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Body implantation tube |
The present invention relates to a body implantation tube to be used for normalizing the flow of fluid in tubular organs of human body, injured by disease or accident, and comprising, a tubular body member with a longitudinal passage; one or more expanding-fixing members surrounding the body member, the expanding-fixing member being expanded, by absorbing the fluid flowing along the passage of the body member, to be fixed, in a tubular organ as a result of expansion; and a plurality of holes connecting the longitudinal passage of the body member to the expanding-fixing member, the holes being formed on the portion of the body member contacting to the expanding-fixing member. |
1. A body implantation tube comprising, a tubular body member with a longitudinal passage; one or more expanding-fixing members surrounding the body member, the expanding-fixing member being expanded, by absorbing the fluid flowing along the passage of the body member, to be fixed in a tubular organ as a result of expansion; and a plurality of holes connecting the longitudinal passage of the body member to the expanding-fixing member, the holes being formed on the portion of the body member contacting to the expanding-fixing member. 2. The body implantation tube according to claim 1, wherein the tubular body member is of a mere cylindrical shape, or a funnel shape in which one or both ends of the body member have a relatively larger diameter than a middle portion thereof. 3. The body implantation tube according to claim 1, wherein the plane of the distal end is not vertical but inclined to be easily inserted into the tubular organ. 4. The body implantation tube according to claim 1, wherein the expanding-fixing member is further coated with a material with the good elasticity and biocompatibility or covered a thin sheet to prevent the expanding-fixing member from contacting directly to in vivo tissues and restrict the expansion thereof to the appropriate extent and prevent the calcification thereof caused by contacting to calcium. 5. The body implantation tube according to claim 1, wherein the tubular organ, into which the body implantation tube is inserted, is lacrimal tube, urethral canal, nasolacrimal duct, ductus pancreaticus, ureter, parotid duct, fallopian tube, deferent duct, etc. 6. A body implantation tube comprise, a tubular body member with a longitudinal passage; one or more expanding-fixing members surrounding the body member, the expanding-fixing member being expanded, by absorbing the fluid flowing along the passage of the body member, to be fixed in a tubular organ as a result of expansion; and a water-supplying means supplying water to the expanding-fixing member, the water-supplying means being joined to the expanding-fixing member and being able to be removed therefrom after the supply of water. 7. A body implantation tube comprising a first implantation tube (A) of the relatively small dimension and a second implantation tube (B) of the relatively large dimension, the first and second implantation tube (A), (B) being almost identical with the implantation tube of claim 1, the first implantation tube (A) having a longitudinal passage or not so, wherein the outer diameter of the first implantation tube (A) is smaller than the inner diameter of the second implantation tube (B) so that, in the state that the second implantation tube (B) is fixed in the human body, the first implantation tube (A) is inserted and fixed in the longitudinal passage of the second implantation tube (B). |
<SOH> BACKGROUND ART <EOH>Human body is an organization of continuing the life action in which liquid phase materials such as bloods, body fluids, secreting fluids, excretions, etc. flow continuously. There are many tubular organs, as passages for movement of these liquid phase materials, in the human body: for example, lacrimal tube, urethral canal, biliary tract, etc. When one or more these tubular organs are clogged by a disease or accident, the liquid phase material cannot be circulated, whereby a patient suffers pain and may be attacked with other diseases. For example, when the lacrimal tube is clogged, tears, being a secreting fluid secreted toward the eyes, cannot flow inside the nasal cavity and instead flows along the surface of face, whereby the nasal cavity becomes dry. It has been reported that the obstruction of lacrimal tube is a very general phenomenon which occurs in one or two peoples per one hundred of traffic accident patients. Meanwhile, when the urethral canal is clogged, the urine filtered in the kidney cannot move toward the urinary bladder so that the kidney tissue may be destroyed, whereby a patient may lose his life ultimately. Such occlusion phenomenon of tubular organs is generally treated by a physical operation, and assistant devices are generally used to penetrate the clogged site. For example, as methods of treating the clogged lacrimal tube, there are the method of inserting a funnel-shaped silicone tube (so called, “Olive tube”) or a glass tube (so called, “Jones tube”) into the clogged lacrimal tube, and the method of inserting the silicone tube of an open loop shape into the lacrimal tube and then binding both ends of loop inside or outside the nasal cavity. These tubes remain in the insertion state for a certain period (generally three weeks, in any case six weeks) and then are removed when the injured site recovers. However, in the Olive tube, the funnel-shaped end which is fixed on the entrance of lacrimal tube disturbs the blinking of eye to suffer a patient and also tends to fall out in sneezing or other external imparts. In the silicone tube of the loop shape, the part of the silicone tube is externally exposed, thereby having a bad effect on a patient's appearance or act. Also, external materials or germs may enter the human body along the loop due to the movement of loop. In order to solve these problems, U.S. Pat. No. 3,726,284 provides a lacrimal drainage duck having an expanded portion, being made of glass or rigid plastic, on the center of a cylindrical tube. However, it is difficult to insert this duck into the lacrimal tube because the expanded portion must have a large dimension for its fixation in the lacrimal tube so that the injured region needs to be incised to the fair extent for its insertion. U.S. Pat. No. 5,318,513 provides a fixation stent including a flexible tube having a proximal end, a distal end, an inflatable portion in fluid communication with the distal end, and a plug for sealing and anchoring the proximal end within a body canal. However, a portion of the stent is exposed to the eye, thereby disturbing the blinking of eye. Meanwhile, as a method of treating the clogged urethral canal, there is the method of using a long, cylindrical tube, in which both ends of the tube are rolled like the pig tail and a wire is inserted into a longitudinal passage of the tube. In operation, the tube is inserted into the urethral canal, and when the wire is removed from the tube, the both ends are rolled to their original shape, with one of end hanging on the entrance of the kidney and the other end hanging on the entrance of the urinary bladder, so that the tube passes the urethral canal. However, germs in the urinary bladder may enter the kidney along the tube and pollute it. Moreover, the tube inhibits or damages the action of sphincter around the urinary bladder and, as a result, the urine may flow continuously in the urinary bladder. As a device of expanding the blood vessel where the occlusion phenomenon takes place, a tubular unit is disclosed in U.S. Pat. No. 3,889,684, which comprises a tube having an open end and a closed end, a compressible cuff surrounding the tube and mounted on the tube adjacent the closed end thereof. This tubular unit works as expanding the blood vessel where the occlusion phenomenon takes place now, and simultaneously removing the thrombus accumulated therein, by inserting the unit into the blood vessel beyond the occluded region thereof, and injecting water through the open end to expand the cuff, and then drawing the unit out the vessel. However, the expanded region of the blood vessel may shrink after the operation, and the interior surface of vessel is damaged so that new tissues may grow thereon. Furthermore, this tubular unit cannot be used in other tubular organs such as lacrimal tube, urethral canal, etc. |
<SOH> SUMMARY OF INVENTION <EOH>The objects of the present invention are to solve the problems described above for once and all. An object of the present invention is to provide a novel body implantation tube of being inserted in the injured region of human body in an endoscopic operation and then being automatically fixed therein to make the flow of body fluids, secreting fluids, excretions, etc. smooth. Another object of the present invention is to provide a novel body implantation tube of being impanted in the human body to substitute a tubular organ, the tubular organ being unable to regenerate because of the serious injury thereof. A still further object of the present invention is to provide a novel body implantation tube of blocking the inflow of external materials to accelerate the regeneration rate of a tubular organ, the tubular organ having a long length and a large injured region. In order to accomplish these objects, the body implantation tube of the present invention comprises, a tubular body member with a longitudinal passage; one or more expanding-fixing members surrounding the body member, the expanding-fixing member being expanded, by absorbing the fluid flowing along the passage of the body member, to be fixed in a tubular organ as a result of expansion; and a plurality of holes connecting the longitudinal passage of the body member to the expanding-fixing member, the holes being formed on the portion of the body member contacting to the expanding-fixing member. The length of tubular body member may change depending on the length of a tubular organ on which the tube of the present invention will be implanted. One of the features of the present invention is to be able to treat an injured region just by installing simply the implanting tube on the injured region of the tubular organ, so that the implanting tube needs not to extend from the entrance of the tubular organ to its exit. For example, when the middle region of the lacrimal tube is injured, the implanting tube of the present invention needs not to be exposed at the entrance of the lacrimal tube, i.e., a region adjacent to the eye, unlike methods of the prior art, thereby reducing a patient's pain. When the middle region of urethral canal is injured, the implanting tube of the present invention needs not to extend to the entrance of urethral canal and the exit of urethral canal, in which the entrance means a region adjacent to the kidney and the exit means a region adjacent to the urinary bladder, thereby not damaging the action of sphincter. The tubular body member may be of a mere cylindrical shape, or be of a funnel shape in which one or both ends of the body member have a relatively larger diameter than a middle portion thereof. Especially, the funnel-shaped body member is available to gather the secretion such as tears through a funnel-shaped end (“proximal end”) and to send it toward the opposite end (“distal end”). In another embodiment, in order to facilitate insertion into the tubular organ, the plane of the distal end is not vertical but inclined. The outer surface of this end is preferably round so as to not damage the interior surface of the tubular organ in insertion. The diameter of the tubular body member is not particular limited. One of the features of the present invention is to be able to guide the flow of fluid, without having a reverse effect on the action of tubular organ, even in the case that the outer diameter of the body member is smaller than the inner diameter of the tubular organ. In the tubular organs of the human body, such as urinary canal, the peristalsis occurs, i.e., a series of normal coordinated, rhythmic muscle contractions that occurs automatically to move food through the digestive tract, urine from the kidneys through the ureters into the bladder, and bile from the gallbladder into the duodenum. When the outer diameter of implantation tube is the same or a little smaller than the inner diameter of tubular organ, as in the conventional implantation tube, the peristalsis is inhibited and thus the smooth flow of fluid cannot be induced. However, in the implantation tube of the present invention, the fluid can also flow through the expanding-fixing member so that, as a result, the fluid can flow on the interior and exterior of the tubular body member, respectively. Therefore, even in the case that the outer diameter of body member is further smaller than the inner diameter of tubular organ, the body member can be fixed to the interior of tubular organ by the expanding-fixing member, thereby guiding the flow of fluid without disturbing the peristalsis of tubular organ. The expanding-fixing member has a little larger diameter than the outer diameter than of body member in the state of not absorbing a fluid, but expands to about three-fold to twenty-fold extent in the state of absorbing a fluid. In consideration that the expanding-fixing member expands, with the implantation tube inserted in the tubular organ, the expansibility is remarkably restricted by the tubular organ, but the implantation tube can be fixed in the tubular organ due to such expansion. Body fluids, secreting fluids and the like in vivo contain the quite amount of water component, and the water component flows through a plurality of holes perforated on the body member to swell the expanding-fixing member. The shape of the expanding-fixing member is not particularly limited, but preferably, the overall shape is a cylinder being concentric to the tubular body member and its both ends are inclined so as to contact gently to the body member. The joining between the expanding-fixing member and the body member can be achieved in various ways; attaching the expanding-fixing member to the body member with an adhesive, making the outer surface of body member irregular and then molding the expanding-fixing member thereon, etc. In the attaching way, the biocompatible adhesive should be used because the components of adhesive may bleed from the joining portion in expansion of the expanding-fixing member. As a commercial adhesive available, is there Silastic® (DowCorning Corporation). In the molding way, the body member with the irregular surface is first molded and then the expanding-fixing member is incorporated therewith by molding. Because the implantation tube of the present invention is a device to be inserted in the human body, it should be biocompatible. Many materials with the biocompatibility have been known in the art: for the body member, styrene/ethylene/butylenes copolymer (C-Flex®), polyethylene copolymer (Percuflex®), polyester copolymer (Silitek®), etc. can be used but not limited to them. Silicone of them is particularly desirable because of its good resilience, easy moldability and low price. The expanding-fixing member should be expanded in absorption of water, as well as biocompatibility. Preferable examples of them include porous polyvinyl alcohol, and porous polymers obtained by partially crosslinking polyvinyl alcohol with formaldehyde, acetyl aldehyde and the like. The commercial material available is Merocel® (Merocel Corporation) of which the detailed information is disclosed in U.S. Pat. No. 4,098,728, which is incorporated with the present invention as a reference. In a embodiment, the expanding-fixing member is further coated with a material with the good elasticity and biocompatibility or covered a thin sheet to prevent the expanding-fixing member from contacting directly to in vivo tissues and restrict the expansion thereof to the appropriate extent and prevent the calcification thereof caused by contacting to calcium. Such configuration protects the interior wall of tubular organ from the implantation tube efficiently. In another embodiment, a plurality of holes are not formed between the tubular body member and expanding-fixing member and instead a water-supplying means is further included, the water-supplying means supplying water to the expanding-fixing member and then being able to be removed. The implantation tube of this configuration comprises, a tubular body member with a longitudinal passage; one or more expanding-fixing members surrounding the body member, the expanding-fixing member being expanded, by absorbing the fluid flowing along the passage of the body member, to be fixed in a tubular organ as a result of expansion; and a water-supplying means supplying water to the expanding-fixing member, the water-supplying means being joined to the expanding-fixing member and being able to be removed therefrom after the supply of water. The water-supplying means is positioned inside or outside the longitudinal passage of the body member. The joining portion between the expanding-fixing member and the water-supplying means is configured to be readily divided in applying a pulling force thereto. In another embodiment, an implantation tube of the present invention comprises a first implantation tube (A) of the relatively small dimension and a second implantation tube (B) of the relatively large dimension, wherein the outer diameter of the first implantation tube (A) is smaller than the inner diameter of the second implantation tube (B) so that, in the state that the second implantation tube (B) is fixed in the human body, the first implantation tube (A) is inserted and fixed in the longitudinal passage of the second implantation tube (B). While the second implantation tube (B) is almost identical with the implantation tube as illustrated earlier, the first implantation tube (A) may have a longitudinal passage as in the second implantation tube (B) or may not so. The implantation tube combination of this configuration is useful to control the amount of fluid which flows through the longitudinal passage of the second implantation tube (B) having been already fixed in the human body. The implantation tubes of the present invention are used to treat the tubular organs in the human body, such as, in addition to lacrimal tube and urethral canal as mentioned earlier, nasolacrimal duct, ductus pancreaticus, ureter, parotid duct, fallopian tube, deferent duct, etc. but are not limited them. When a tubular organ has regenerated with the aid of an implantation tube and needs to be removed, it can be removed by applying a biocompatible lubricant on the outer surface of expanding-fixing member and then pulling the tube. As shown below, the description refers to the drawing in order to describe the present invention more in detail, thereby, the scope of the invention is however not to be interpreted as a limitation of the invention. |
Photoresists processable under biocompatible conditions for multi-biomolecule patterning |
Novel photoresist materials, which can be photolithographically processed in biocompatible conditions are presented in this invention. Suitable lithographic scheme for the use of these and analogous resists for biomolecule layer patterning on solid substrates are also described. The processes described enable micropatterning of more than two different proteins on solid substrates without denaturation of the proteins. The preferred resist materials are based on (meth)acrylate copolymers that contain at least one acid cleavable ester group and at least one hydrophilic group such as an alcoholic or a carboxylic group. |
1. Photoresist comprising a copolymer synthesized from selected monomers, where at least one of these monomers contains an acid cleavable group and at least one of these monomers container a hydrophilic group selected from the class of hydroxyls and carboxyls, said photoresist characterized in that it is processed with dilute aqueous base developers of less than 0.02 N base concentration and is used for the mircropatterning of biomolecules on solid substrate. 2. Photoresist according to claim 1 which is used for the micropatterning of more than one kind of biomolecules on solid substrate. 3. Photoresist according to claim 1 comprising a copolymer synthesized from the monomers 2-hydroxyethyl-methacreylate, isobornyl-methacrylate, t-butyl-methacrylate, and acrylic acid. 4. Photoresist according to claim 1 which is used for micropatterning proteins. 5. Photoresist according to claim 1 which is used for micropatterning nucleic acid chain parts. 6. Method of photolithographic processing using photoresist according to claim 1 comprising the steps of exposure of selected photoresist areas, dissolution of said photoresist areas and deposition of biomolecules on the substrate. 7. Method according to claim 6, where the exposure of selected photoresist areas and the subsequent dissolution of said photoresist areas can follow the deposition of biomolecules on the substrate without deactivating the deposited biomolecules. 8. Method according to claim 7, where the exposure of selected photoresist areas and the subsequent dissolution of said photoresist areas can be repeated more that once without deactivating the deposited biomolecules. 9. Photoresist according to claim 2 comprising a copolymer synthesized from the monomers 2-hydroxyethyl-methacreylate, isobornyl-methacrylate, t-butyl-methacrylate, and acrylic acid. 10. Photoresist according to claim 2 which is used for micropatterning proteins. 11. Photoresist according to claim 3 which is used for micropatterning proteins. 12. Photoresist according to claim 2 which is used for micropatterning nucleic acid chain parts. 13. Photoresist according to claim 3 which is used for micropatterning nucleic acid chain parts. 14. Method of photolithographic processing using photoresist according to claim 2 comprising the steps of exposure of selected photoresist areas, dissolution of said photoresist areas and deposition of biomolecules on the substrate. 15. Method of photolithographic processing using photoresist according to claim 3 comprising the steps of exposure of selected photoresist areas, dissolution of said photoresist areas and deposition of biomolecules on the substrate. 16. Method of photolithographic processing using photoresist according to claim 4 comprising the steps of exposure of selected photoresist areas, dissolution of said photoresist areas and deposition of biomolecules on the substrate. 17. Method of photolithographic processing using photoresist according to claim 5 comprising the steps of exposure of selected photoresist areas, dissolution of said photoresist areas and deposition of biomolecules on the substrate. |
<SOH> BRIEF DESCRIPTION OF THE INVENTION FIGURES <EOH>FIG. 1 . The chemical structure of the (meth)acrylate copolymer invented, which allow the photoresist to be photolithographically processed in biocompatible conditions. FIG. 2 . The lithographic scheme for patterning two different proteins on APTES-treated silicon surface with the biocompatible photolithographic processing (lift-off) of the (meth)acrylate photoresist. FIG. 3 . The lithographic scheme for patterning three different proteins on APTES-treated silicon surface with the biocompatible photolithographic processing (lift-off) of the (meth)acrylate photoresist. FIG. 4 . The lithographic scheme for the definition of two protein “bands” on capillary inner surface with the biocompatible photolithographic processing (lift-off) of the (meth)acrylate photoresist. FIG. 5 . Microstructures of 3.75 μm lines/spaces of two different proteins: rabbit-IgG (green lines—active protein) and bovine serum albumin (black lines—inert protein) obtained by the biocompatible photolithographic processing of the (meth)acrylate photoresist on APTES-treated silicon surface. FIG. 6 . Microstructures of 22.5 μm lines/spaces of three different proteins: mouse-IgG green lines—first active protein), biotinylated bovine serum albumin (red lines—second active protein) and bovine serum albumin (black lines—inert protein) resulted by the biocompatible photolithographic processing of the (meth)acrylate photoresist onto APTES-treated silicon surface. FIG. 7 Two rabbit-IgG (active protein) “bands” defined among bovine serum albumin (inert protein) areas on poly(methyl-pentene) capillary inner surface by the biocompatible photolithographic processing of the (meth)acrylate photoresist. The two protein “bands” are visualized by introduction of anti-rabbit-FITC conjugate and subsequent fluorescence scanning of the whole capillary showing two distinct signals. detailed-description description="Detailed Description" end="lead"? |
Sample concentration maldi plates for maldi mass spectrometry |
A novel Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) sample support plate is described. The plate comprises a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample. The aperture extends through and between the top sample presentation surface and the bottom surface, and contains a porous material that retains and concentrates at the target spot analyte and matrix molecules contained in the sample on the surface of the aperture. Methods for making and using the sample support plate in conventional and automated MALDI-MS are also described. |
1. A sample support plate, for use in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS), comprising a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample, wherein the aperture extends through and between the top sample presentation surface and the bottom surface, and wherein the aperture contains a porous material that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture. 2. The sample plate of claim 1, wherein the porous material is sufficiently porous to allow penetration in or through the porous material or retention on the porous material of selected molecules. 3. The sample plate of claim 2, wherein the porous material is selected from the group consisting of a porous monolith and a bed of particles. 4. The sample plate of claim 2, wherein the molecules that penetrate the porous material are selected from the group consisting of salts, solvents and combinations thereof, and the molecules that are retained on the surface of the porous material are the analyte and the matrix. 5. The sample plate of claim 3, wherein the porous material is a porous monolith. 6. The sample plate of claim 5, wherein the porous monolith is prepared by admixing, a monomer, a porogen, and an initiator. 7. The sample plate of claim 6, wherein the monomer is selected from the group consisting of a monovinyl monomer, a polyvinyl monomer, and a mixture of monovinyl and polyvinyl monomers. 8. The sample plate of claim 7, wherein the monovinyl monomer is selected from the group consisting of styrene, N-vinylpyrrolidone, methacrylate, vinylacetate, glycidyl methacrylate, and any combination thereof. 9. The sample plate of claim 7, wherein the polyvinyl monomer is selected from the group consisting of divinylbenzene, ethylene dimethacrylate, bis-acrylamide, divinylpyridine, ethylene dimethacrylate, hydroxyalkylene dimethacrylate, and any combination thereof. 10. The sample plate of claim 6, wherein the porogen is selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, esters, alcohols, ketones, ether, and any combination thereof. 11. The sample plate of claim 6, wherein the initiator is selected from the group consisting of benzoyl peroxide, lauroyl peroxide, peroxodisulfate, Vazo 52, Vazo 64, Vazo 67, Vazo 88, V70, and any combination thereof. 12. The sample plate of claim 1, wherein the aperture is in a precisely defined location. 13. The sample plate of claim 7, wherein the precisely defined location of the aperture facilitates automated analysis. 14. The sample plate of claim 12, comprising a plurality of apertures, such that a grid of target spots is formed on the top sample presentation surface. 15. The sample plate of claim 14, wherein the grid comprises 96 apertures. 16. The sample plate of claim 14, wherein the plurality of apertures facilitates high through-put analysis. 17. The sample plate of claim 1, wherein the aperture is oriented through the plate in a vertical path, perpendicular to the surface of the plate. 18. The sample plate of claim 2, wherein a vacuum is applied to the aperture to assist in the penetration of selected molecules into or through the porous material. 19. The sample plate of claim 18, wherein the vacuum is applied using a vacuum manifold. 20. A method for preparing a sample for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) comprising: providing the sample support plate of claim 1; applying a sample to the aperture; and allowing selected molecules in the sample to penetrate or pass through the porous material in the aperture, and allowing other selected molecules in the sample to be retained on top of the porous material, thereby concentrating the other selected molecules on the surface of the aperture; to thereby prepare a sample for MALDI-MS. 21. The method of claim 20, further comprising applying a vacuum to the sample support plate prior to applying the sample to the aperture. 22. The method of claim 21, wherein the vacuum is applied by placing the sample support plate on a vacuum manifold. 23. The method of claim 21, wherein the sample comprises an analyte of interest, a matrix material, one or more salts and one or more solvents. 24. The method of claim 23, wherein vacuum is applied at a rate that allows the sample to pass into or through the sorbent material gradually, thereby allowing one or more salts and one or more solvents to pass into or through the porous material and allowing the analyte of interest and the matrix material to be retained on top of the porous material, thereby concentrating the analyte of interest on the surface of the aperture. 25. The method of claim 21, wherein the sample contains a solution of a matrix material. 26. The method of claim 25, wherein vacuum is applied at a rate that allows the sample to pass into or through the porous material gradually, thereby allowing the matrix material to be retained on top of the porous material and form crystals on the top of the porous material, thereby concentrating crystals of the matrix material on the surface of the aperture. 27. The method of claim 26, further comprising applying a second sample containing a solution of an analyte of interest to the aperture, and applying a vacuum at a rate that allows the second sample to pass into or through the porous material gradually, thereby allowing the analyte of interest to be retained on top of the porous material, thereby concentrating the analyte of interest on top of the porous material and incorporating the analyte of interest with the crystals of matrix material on the surface of the aperture. 28. The method of claim 21, wherein the sample contains a solution of an analyte of interest. 29. The method of claim 28, wherein vacuum is applied at a rate that allows the sample to pass into or through the porous material gradually, thereby allowing the analyte of interest to be retained on top of the porous material, thereby concentrating the analyte of interest on the surface of the aperture. 30. The method of claim 29, further comprising applying a second sample containing a solution of a matrix material to the aperture, and applying a vacuum at a rate that allows the second sample to pass into or through the porous material gradually, thereby allowing the matrix material to be retained on top of the porous material and form crystals on the top of the porous material, thereby concentrating crystals of the matrix material and incorporating the matrix material with the analyte of interest on the surface of the aperture. 31. The method of claim 30, wherein prior to applying the second sample containing the solution of the matrix material, water is applied to the aperture, and vacuum is applied to allow the water to pass through the porous material. 32. A method for preparing the sample support plate of claim 1 comprising: providing a sample support plate comprising a top sample presentation surface and a lower surface; forming on the top sample presentation surface at least one aperture for receiving a sample, wherein the aperture extends through and between the top sample presentation surface and the bottom surface; and applying a porous material to the aperture. 33. A method for preparing the sample support plate of claim 1 comprising: forming, on a sample support plate having a top sample presentation surface and a bottom surface, at least one aperture, such that the aperture extends through and between the top sample presentation surface and bottom surface; and applying a porous material to the aperture. 34. The method of claim 32, wherein the porous material comprises a porous monolith. 35. The method of claim 34, further comprising admixing a monomer, a porogen and an initiator; filling the aperture with the admixture; initiating a polymerization reaction to form a porous monolith plug; and washing the porous polymer sorbent plug to remove residual monomer, porogen and initiator. 36. The method claim 35, wherein the monomer is selected from the group consisting of a monovinyl monomer, a polyvinyl monomer, and a mixture of monovinyl and polyvinyl monomers. 37. The method of claim 36, wherein the monovinyl monomer is selected from the group consisting of styrene, N-vinylpyrrolidone, methacrylate, vinylacetate, glycidyl methacrylate, and any combination thereof. 38. The method of claim 36, wherein the polyvinyl monomer is selected from the group consisting of divinylbenzene, ethylene dimethacrylate, bis-acrylamide, divinylpyridine, ethylene dimethacrylate, hydroxyalkylene dimethacrylate, and any combination thereof. 39. The method of claim 35, wherein the porogen is selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, esters, alcohols, ketones, ether, and any combination thereof. 40. The method of claim 39, wherein the initiator is selected from the group consisting of benzoyl peroxide, lauroyl peroxide, peroxodisulfate, Vazo 52, Vazo 64, Vazo 67, Vazo 88, V70, and any combination thereof. 41. A sample plate of claim 1, wherein the aperture may be any shape that allows the penetration of selected molecules and the retention of other selected molecules. 42. A method for performing Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) on an analyte of interest, comprising: providing a sample support plate, wherein the plate comprises a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample, and wherein the aperture extends through and between the top sample presentation surface and the bottom surface, and contains a porous material that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture; applying a sample comprising an analyte of interest to the aperture; allowing selected molecules in the sample to penetrate or pass through the porous material in the aperture, and allowing the analyte of interest in the sample to be retained on top of the porous material, thereby concentrating the analyte of interest on the surface of the aperture; and performing MALDI-MS on the analyte of interest. 43. A sample support plate, for use in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS), comprising a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample, wherein the aperture extends through and between the top sample presentation surface and the bottom surface, and wherein the aperture contains a porous monolith that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture. 44. A sample plate of claim 5, wherein the porous monolith is a macroporous polymer plug. 45. The method or sample plate of claim 1, wherein the top sample presentation surface comprises at least one sample target spot wherein the aperture is located within the target spot. 46. A sample support plate, for use in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS), comprising a monolithic support plate having a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample, wherein the aperture extends through and between the top sample presentation surface and the bottom surface, and wherein the aperture contains a porous monolith that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Mass spectrometry (MS) with ionization by matrix-assisted laser desorption and ionization (MALDI) has become a useful tool for the analysis of large molecules such as proteins, peptides, oligonucleotides, DNA, RNA, etc. It is well known that the sensitivity of the analysis and the speed of automation are highly dependent on preparation of the sample on the MALDI plate. The issues associated with sample preparation for MALDI Mass Spectrometry are summarized in published British patent application GB 2332273A. For example, when a drop of sample and matrix solution is placed onto a clean metal sample support plate, the drop wets an area on the metal surface. After the solution dries, the sample spot consisting of small matrix crystals spreads over the formerly wet area. In general, the wetted area is not uniformly coated. In aqueous solutions, most of the small crystals of the matrix generally begin to grow at the margin of the wet area on the metal plate and continue to grow toward the center of the wet area. Thus, the analyte molecules are irregularly distributed, and the center of the spot is frequently devoid of crystals or covered with small, fine crystals that are practically useless for MALDI ionization because of the high concentration of alkali salts also present. This type of coating requires visual observation of the sample using a microscope. Furthermore, the MALDI ionization yield and mass resolution fluctuate in the sample spot from site to site. In fact, it is often a troublesome process to find a favorable location on the sample spot with good analyte ion yield and good mass resolution. Consequently, high sample throughput automation of MALDI mass spectrometry analysis is hindered, if not impossible. A number of devices have been developed in an attempt to alleviate the aforementioned difficulties. For example, published PCT application WO 96/40888, and related U.S. Pat. Nos. 6,004,770 and 6,093,770, disclose a sample presentation device having a surface-bound complex that includes at least one molecule that can chemically modify a biomolecule. A biomolecule is exposed to the surface-bound complex, and the chemically modified biomolecule resulting from such exposure is then analyzed by mass spectrometry, for example, MALDI-MS. British patent application GB 2332273A describes a MALDI plate, coated with a Teflon-like hydrophobic coating having hydrophilic patches (“anchors”), that utilizes surface property (hydrophilic or hydrophobic) modification on the plate. After sample droplets are deposited onto the anchors, the droplets shrink during solvent evaporation, thereby centering themselves onto the anchor positions. Thus, MS detection sensitivity increases 10 to 100 times as compared to the conventional dried sample droplet preparation method described above, because the analyte is concentrated in smaller spots. The sample spots can be arranged in a precise grid to facilitate rapid, automated MALDI-MS. Such coated plates (Anchor Chip™) are marketed by Bruker Daltonics®. Published PCT Application WO 01/19520 A1 describes a high density cast-in-place sample preparation card useful in a variety of analytical methods, including MALDI-MS. In particular, the patent application describes the use of the surface of a housing insert containing a plug of silica for direct MALDI-time of flight-MS analysis using a system designed by PE Biosystems. The system comprises a sample plate holder to hold the housing, and a Mass Spectrometer, designed to accommodate analysis using the sample plate holder. However, many existing sample plates are limited to use with hydrophilic compounds or to specific MS instruments, require special surface modification, or have other disadvantages. Therefore, a need exists for a MALDI-MS sample plate that is capable of concentrating and locating a vast array of analytes in a small spot precisely segregating alkali salts and other undesired materials from the analyte and matrix, and being used in virtually any type of MALDI-MS instrument. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention is directed to a sample support plate and method for concentrating a sample at one or more discrete locations for analysis by MALDI-MS. The invention also provides convenient methods for the preparation and use of the support plate. Additionally, the invention provides methods of sample preparation and analysis of the samples. Furthermore, the methods of sample preparation and analysis of the present invention are capable of concentrating and locating a large range of analytes in a small spot precisely, segregating salts and other undesired molecules from the analyte and matrix, and being useful for analysis in virtually any type of MALDI-MS. Thus, in one aspect, the invention is a sample support plate for use in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). The MALDI plate comprises a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample. The aperture extends through and between the top sample presentation surface and the bottom surface, and contains a porous material that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture. In a related aspect, the invention is a sample support plate for use in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). The plate comprises a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample. The aperture extends through and between the top sample presentation surface and the bottom surface. In addition, the aperture contains a porous monolith that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture. In another related aspect, the invention is a monolithic sample support plate, for use in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). The monolithic plate comprises a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample. The aperture extends through and between the top sample presentation surface and the bottom surface. In addition, the aperture contains a porous monolith that retains and concentrates analyte and matrix molecules contained in the sample on the surface of the aperture. In another aspect, the invention is a method for preparing a sample for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). The method comprises: providing the sample support plate described above; applying a sample to the aperture; and allowing selected molecules in the sample to penetrate or pass through the porous material in the aperture, and allowing other selected molecules in the sample to be retained on top of the porous material, thereby concentrating the other selected molecules on the surface of the aperture. In yet another aspect, the invention is a method for preparing the sample support plate of the invention described above. The method comprises: providing a sample support plate comprising a top sample presentation surface and a lower surface; forming on the top sample presentation surface at least one aperture for receiving a sample, wherein the aperture extends through and between the top sample presentation surface and the bottom surface; and applying a porous material to the aperture. In a related aspect, the invention is directed to a method for preparing the sample support plate of the invention by: forming, on a sample support plate having a top sample presentation surface and a bottom surface, at least one aperture on the sample presentation surface, such that the aperture extends through and between the top sample presentation surface and bottom surface; and applying a porous material to the aperture. Another aspect of the invention is a method for performing Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) on an analyte of interest. The method comprises: providing a sample support plate, wherein the plate comprises a top sample presentation surface and a lower surface, wherein the top sample presentation surface comprises at least one aperture for receiving a sample, and wherein the aperture extends through and between the top sample presentation surface and the bottom surface, and contains a porous material that retains and concentrates analyte and matrix molecules contained in the sample; applying a sample comprising an analyte of interest to the aperture; and allowing selected molecules in the sample to penetrate or pass through the porous material in the aperture, and allowing the analyte of interest in the sample to be retained on top of the porous material, thereby concentrating the analyte of interest on the surface of the aperture; and performing MALDI-MS on the analyte of interest. |
Bcl-2-modifying factor (bmf) sequences and their use in modulating apoptosis |
The present invention relates generally to novel molecules capable of, inter alia, modulating apoptosis in mammalian cells and to genetic sequences encoding same. More particularly, the present invention relates to a novel member of the Bcl-2 family of proteins, referred to herein as “Bmf”, and to genetic sequences encoding same and to regulatory sequences such as a promoter sequence directing expression of Bmf. Bmf comprises a BH3 domain which facilitates interaction to pro-survival Bcl-2 family members thereby triggering apoptosis. Bmf is regarded, therefore, as a BH3-only molecule. The molecules of the present invention are useful, for example, in therapy, diagnosis, antibody generation and as a screening tool for therapeutic agents capable of modulating physiological cell death or survival and/or modulating cell cycle entry. The present invention further contemplates genetically modified animals in which one or both alleles of Bmf are mutated or partially or wholly deleted alone or in combination with a mutation in one or both alleles of another Bcl-2-type molecule such as but not limited to Bim. The genetically modified animals are useful inter alia in screening for agents which ameliorate the symptoms of diseases caused by defects in apoptosis or which specifically promote apoptosis of target cells. |
1. A nucleic acid molecule comprising a nucleotide sequence encoding or complementary to a sequence encoding an amino acid sequence substantially as set forth in one of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or a derivative or homolog thereof or having at least about 45% or greater similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or a derivative or homolog thereof. 2. The nucleic acid molecule of claim 1 comprising a nucleotide sequence which encodes the amino acid sequence set forth in SEQ ID NO:2. 3. The nucleic acid molecule of claim 1 comprising a nucleotide sequence which encodes the amino acid sequence set forth in SEQ ID NO:4. 4. The nucleic acid molecule of claim 1 comprising a nucleotide sequence which encodes the amino acid sequence set forth in SEQ ID NO:6. 5. The nucleic acid molecule of claim 1 comprising a nucleotide sequence which encodes the amino acid sequence set forth in SEQ ID NO:8. 6. The nucleic acid molecule of claim 1 comprising a nucleotide sequence set forth in SEQ ID NO:1 or a nucleotide sequence having at least about 45% similarity thereto or a nucleotide sequence capable of hybridizing to SEQ ID NO:1 or its complementary form under low stringency conditions. 7. The nucleic acid molecule of claim 1 comprising a nucleotide sequence set forth in SEQ ID NO:3 or a nucleotide sequence having at least about 45% similarity thereto or a nucleotide sequence capable of hybridizing to SEQ ID NO:3 or its complementary form under low stringency conditions. 8. The nucleic acid molecule of claim 1 comprising a nucleotide sequence set forth in SEQ ID NO:5 or a nucleotide sequence having at least about 45% similarity thereto or a nucleotide sequence capable of hybridizing to SEQ ID NO:5 or its complementary form under low stringency conditions. 9. The nucleic acid molecule of claim 1 comprising a nucleotide sequence set forth in SEQ ID NO:7 or a nucleotide sequence having at least about 45% similarity thereto or a nucleotide sequence capable of hybridizing to SEQ ID NO:7 or its complementary form under low stringency conditions. 10. The nucleic acid molecule of claim 1 comprising the nucleotide sequence set forth in SEQ ID NO:1. 11. The nucleic acid molecule of claim 1 comprising the nucleotide sequence set forth in SEQ ID NO:3. 12. The nucleic acid molecule of claim 1 comprising the nucleotide sequence set forth in SEQ ID NO:5. 13. The nucleic acid molecule of claim 1 comprising the nucleotide sequence set forth in SEQ ID NO:7. 14. An isolated protein comprising an amino acid sequence encoded by a nucleotide sequence set forth in SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or a nucleotide sequence having at least about 45% similarity to the nucleotide sequence set forth in SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or a nucleotide sequence capable of hybridizing to SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or a complement thereof under low stringency conditions. 15. The isolated protein of claim 14 comprising an amino acid sequence encoded by the nucleotide sequence set forth in SEQ ID NO:11. 16. The isolated protein of claim 14 comprising an amino acid sequence encoded by the nucleotide sequence set forth in SEQ ID NO:3. 17. The isolated protein of claim 14 comprising an amino acid sequence encoded by the nucleotide sequence set forth in SEQ ID NO:5. 18. The isolated protein of claim 14 comprising an amino acid sequence encoded by the nucleotide sequence set forth in SEQ ID NO:7. 19. The isolated protein of claim 14 comprising an amino acid sequence as set forth in SEQ ID NO:2 or having at least 45% similarity thereto. 20. The isolated protein of claim 14 comprising an amino acid sequence as set forth in SEQ ID NO:4 or having at least 45% similarity thereto. 21. The isolated protein of claim 14 comprising an amino acid sequence as set forth in SEQ ID NO:6 or having at least 45% similarity thereto. 22. The isolated protein of claim 14 comprising an amino acid sequence as set forth in SEQ ID NO:8 or having at least 45% similarity thereto. 23. The isolated protein of claim 14 having an amino acid sequence as set forth in SEQ ID NO:2. 24. The isolated protein of claim 14 having an amino acid sequence as set forth in SEQ ID NO:4. 25. The isolated protein of claim 14 having an amino acid sequence as set forth in SEQ ID NO:6. 26. The isolated protein of claim 14 having an amino acid sequence as set forth in SEQ ID NO:8. 27. A variant of an isolated bmf nucleic acid molecule comprising one or more nucleotide mutations in said nucleic acid molecule resulting in at least one amino acid addition, substitution and/or deletion to the polypeptide encoded by said variant wherein said polypeptide cannot bind, couple or otherwise associate with a dynein light chain, such as DLC2. 28. The variant of claim 28 wherein the mutation results in an altered amino acid sequence in the region which binds to the dynein light chain. 29. A variant of an isolated Bmf polypeptide comprising at least one amino acid addition, substitution and/or deletion wherein said polypeptide cannot bind, couple or otherwise associate with the dynein light chain. 30. A method of modulating activity of Bmf in a mammal, said method comprising administering to said mammal a modulating effective amount of an agent for a time and under conditions sufficient to increase or decrease Bmf activity. 31. A method of modulating apoptosis in a mammal, said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of a nucleotide sequence encoding bmf. 32. A method of modulating apoptosis in a mammal, said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the activity of Bmf. 33. A method of treating a mammal, said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of bmf wherein said modulation results in modulation of apoptosis. 34. A method of treating a mammal, said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the activity of Bmf wherein said modulation results in modulation of apoptosis. 35. The method of claim 30 or 31 or 32 or 33 or 34 wherein the mammal is a human. 36. A pharmaceutical composition comprising bmf, Bmf or derivative thereof or an agent capable of modulating bmf expression or Bmf activity together with one or more pharmaceutically acceptable carriers and/or diluents, bmf, Bmf or said agent are referred to as the active ingredients. 37. A monoclonal antibody having specificity for Bmf or bmf or derivative thereof. 38. A method of detecting an immunointeractive molecule, in a sample, specific for a protein of interest produced by a cell, said method comprising contacting the sample to be tested with a population of cells comprising a defined ratio of cells producing the protein of interest and cells not producing the protein of interest for a time and under conditions sufficient for immunointeractive molecules, if present in said sample, to interact with said protein of interest and the subjecting said immunointeractive molecule-protein complex to detecting means. 39. The method of claim 38 wherein the interactive molecule is an antibody. 40. A genetically modified animal in which one or both alleles of bmf are mutated alone or in combination with another mutation in one or both alleles for another Bcl-2 molecule such as but not limited to genes encoding Blk, Bad, Bik, Hrk, Bid, Bim, Noxa and/or Puma. 41. The genetically modified animal of claim 40 wherein said animal is a mouse. 42. The genetically modified animal of claim 40 wherein said animal is a rat. 43. The genetically modified animal of claim 40 wherein said animal is a pig. 44. A method of producing a genetically modified non-human animal, said method comprising introducing into embryonic, stern cells of an animal a genetic construct comprising a bmf nucleotide sequence carrying a single or multiple nucleotide substitution, addition and/or deletion or inversion or insertion wherein there is sufficient bmf nucleotide sequences to promote homologous recombination with a bmf gene within the genome of said embryonic stem cells selecting for said homologous recombination and selecting embryonic stem cells which carry a mutated bmf gene and then generating a genetically modified animal from said embryonic stem cell. 45. The method of claim 44 wherein the genetically modified animal is a mouse or rat. 46. Use of Bmf in the manufacture of a medicament for the treatment of a condition in a human. 47. Use of Bmf in the manufacture of a medicament for the treatment of a condition in a non-human. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in any country. Apoptosis, the physiologic and genetically modulated process of cell death, is of central importance for modelling tissues and maintaining homeostasis in multicellular organisms (Kerr et al., Br. J. Cancer 26: 239-257, 1972; Jacobson et al., Cell 88: 347-354, 1997). Great progress is being made towards understanding the biochemistry underlying this intrinsic suicide program. The cellular apoptotic effector molecules include a set of cysteine proteinases, termed caspases, that degrade critical cellular substrates (Nicholson et al., Trends Biochem. Sci. 22: 299-306, 1997). The regulatory machinery that governs the activation of the caspases is less well understood. However, a family of proteins of which Bcl-2 is the prototypic molecule (and is referred to as the Bcl-2 family of proteins) plays a central role (Jacobson, Curr. Biol. 7: R277-R281, 1997; Reed, Nature 387: 773-776, 1997; Kroemer, Nature Med. 3: 614-620, 1997; Adams and Cory, Science 281: 1322-1326, 1998). Bcl-2 was the first intracellular regulator of apoptosis to be identified (Vaux et al., Nature 335: 440-442, 1988) and high levels enhance cell survival under diverse cytotoxic conditions. Other cellular homologs, such as BCl-x L (Boise et al., Cell 74: 597-608, 1993) and Bcl-w (Gibson et al., Oncogene 13: 665675, 1996), also enhance cell survival, as do more distantly related viral homologs, such as the adenovirus E1B 19K protein (White et al., Mol. Cell. Biol. 12: 2570-2580, 1992) and Epstein-Barr virus BHRF-1 (Henderson er al., Proc Natl. Acad. Sci. USA 90: 8479-8483, 1993). Pro-apoptotic BH3-only members of the Bcl-2 family are essential for initiation of apoptosis in species as distantly related as mice and C. elegans (Huang and Strasser, Cell 103: 839, 2000). EGL-1, the so far only recognized BH3-only protein in C. elegans , is required for all developmentally programmed cell deaths in this organism. In contrast, a number of BH3-only proteins have already been identified in mammals: Blk, Bad, Bik, Hrk, Bid, Bim, Noxa and Puma. Experiments with knock-out mice have shown that different apoptotic stimuli require distinct BH3-only proteins for their initiation. (Huang and Strasser, 2000, supra). For example, Bim is essential for apoptosis induced by cytokine withdrawal or antigen receptor stimulation, but is dispensable for cell death induced by glucocorticoids (Bouillet et al., Science 286: 1735, 1999; Bouillet et al., Nature 415, 922, 2002). In contrast, Bid is involved in Fas-induced killing of hepatocytes (Yin et al., Nature 400: 886, 1999). Moreover, different cell types may require distinct BH3-only proteins for their developmentally programmed death. Consistent with this idea, Bim-deficient mice have an abnormal accumulation of lymphoid and myeloid cells but erythropoiesis appears normal (Bouillet et al., 1999, supra). These results indicate that individual mammalian BH3-only proteins have specific functions. The pro-apoptotic activity of BH3-only proteins is subject to stringent control. In C. elegans , EGL-1 is regulated by the transcriptional represser TRA-1A in a group of neurons that is required for egg-laying (Conradt and Horvitz, Cell 93: 519, 1998). Some mammalian BH3-only proteins are also subject to transcriptional regulation. For example, Noxa was discovered as a p53-inducible gene and is therefore a prime candidate for mediating DNA damage-induced apoptosis (Oda et al., Science 288: 1053, 2000). Several mammalian BH3-only proteins can also be regulated post-translationally (Huang and Strasser, 2000, supra). In growth factor-stimulated cells, Bad is phosphorylated and sequestered away from pro-survival Bcl-2 family members by binding to 14-3-3 scaffold proteins (Zha et al, Cell 87: 619, 1996). In healthy cells, Bim is sequestered to the microtubular dynein motor complex by binding to dynein light chain, DLC1/LC8 (Puthalakath et al., Mol. Cell 3: 287, 1999). Certain apoptotic stimuli, such as UV-radiation or treatment with taxol, free Bim (still bound to DLC1) and allow it to translocate to, bind and inactivate pro-survival Bcl-2 family members. This process occurs independently of the cell death executioner cysteine proteases (caspases) and therefore constitutes an upstream signalling event in apoptosis (Puthalakath et al., 1999, supra). In contrast, the pro-apoptotic activity of Bid is unleashed upon cleavage by a variety of caspases (e.g. caspase-8) or by the serine protease granzyme B (Li et al., Cell 94: 491-501, 1998; Luo et al., Cell 94: 481-490, 1998), indicating that it functions as part of an amplification mechanism rather than as an initiator of apoptosis. These observations demonstrate that through sequestration to specific sites in the cell, different BH3-only proteins function as sensors for distinct forms of intracellular stress. In work leading to the present invention, the inventors sought novel BH3-only proteins which played a role in embryogenesis. In accordance with the present invention, the inventors cloned “Bmf” (Bcl-2 modifying factor) which was identified through yeast 2-hybrid screening of a day 17 mouse embryonic library using Mcl-1 as bait. Bmf is proposed to induce cell death and act as a “death-ligand” for certain or all members of the pro-survival Bcl-2 family. The identification of this new gene permits the identification and rational design of a range of products for use in therapy, diagnosis, antibody generation and involving modulation of physiological cell death. These therapeutic molecules may act as either, antagonists or agonists of Bmf's friction and will be useful in cancer, autoimmune or degenerative disease therapy. |
<SOH> SUMMARY OF THE INVENTION <EOH>Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers. Nucleotide and amino acid sequences are referred to by a sequence identifier number (SEQ ID NO:). The SEQ ID NOs: correspond numerically to the sequence identifiers <400>1 (SEQ ID NO:1), <400>2 (SEQ ID NO:2), etc. A sequence listing is provided after the claims. Specific mutations in an amino acid sequence are represented herein as “X 1 nX 2 ” where X 1 is the original amino acid residue before mutation, n is the residue number and X 2 is the mutant amino acid. Reference to Xn is a reference to a particular amino acid in an amino acid sequence where X is the amino acid and n is the residue number. The abbreviation X may be to the three letter or single letter amino acid code. The present invention is predicated in part on the identification of a novel member of the pro-survival Bcl-2 family. This protein is referred to herein as “Bcl-2 modifying factor” or “Bmf”. The protein was identified by yeast 2-hybrid screening of a mouse embryonic library using Mcl-1 as bait. Bmf is an apoptosis-inducing BH3-only protein and is activated by anoikis. Accordingly, one aspect of the present invention provides a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide having one or more of the identifying characteristics of Bmf or a derivative or homolog thereof. Another aspect of the present invention provides a nucleic acid molecule comprising a nucleotide sequence encoding or complementary to a sequence encoding an no acid sequence substantially as set forth in one of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or a derivative or homolog thereof or having at least about 45% or greater similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or a derivative or homolog thereof. Yet another aspect of the present invention contemplates a nucleic acid molecule comprising a nucleotide sequence substantially as set forth in one of SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or a derivative or homolog thereof capable of hybridising to one of SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 under low stringency conditions and which encodes an amino acid sequence corresponding to an amino acid sequence set forth in one of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or a sequence having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or 8. Still yet another aspect of the present invention contemplates a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ ID NOS:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7. Still another aspect of the present invention is directed to an isolated nucleic acid molecule encoding bmf or a derivative thereof, said nucleic acid molecule selected from the list consisting of:— (i) a nucleic acid molecule comprising a nucleotide sequence encoding the amino acid sequence set forth in one of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or a derivative or homolog thereof or having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8; (ii) a nucleic acid molecule comprising a nucleotide sequence substantially as set forth in one of SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or a derivative or homolog thereof; (iii) a nucleic acid molecule capable of hybridizing under low stringency conditions to the nucleotide sequence substantially as set forth in one of SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 a derivative or homolog and encoding an amino acid sequence corresponding to an amino acid sequence as set forth in one of SEQ ID NO:SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 a derivative or homolog, or a sequence having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8; (iv) a nucleic acid molecule capable of hybridizing to the nucleic acid molecule of paragraphs (i) or (ii) or (iii) under low stringency conditions and encoding an amino acid sequence having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8; and (v) a derivative or mammalian homolog of the nucleic acid molecule of paragraphs (i) or (ii) or (iii) or (iv). A further aspect of the present invention is directed to an isolated polypeptide selected from the list consisting of:— (i) a polypeptide having an amino acid sequence substantially as set forth in one of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or derivative or homolog thereof or a sequence having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8; (ii) a polypeptide encoded by a nucleotide sequence substantially as set forth in one of SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or derivative or homolog thereof or a sequence encoding an amino acid sequence having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8; (iii) a polypeptide encoded by a nucleic acid molecule capable of hybridizing to the nucleotide sequence as set forth in one of SEQ ID NO:1 or SEQ ID NO:3 or SEQ ID NO:5 or SEQ ID NO:7 or derivative or homolog thereof under low stringency conditions and which encodes an amino acid sequence substantially as set forth in SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8 or derivative or homolog thereof or an amino acid sequence having at least about 45% similarity to one or more of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8; (iv) a polypeptide as defined in paragraphs (i) or (ii) or (iii) in homodimeric form; and (v) a polypeptide as defined in paragraphs (i) or (ii) or (iii) in heterodimeric form. Yet another aspect of the present invention provides a method of producing a genetically modified non-human animal, said method comprising introducing into embryonic stem cells of an animal a genetic construct comprising a bmf nucleotide sequence carrying a single or multiple nucleotide substitution, addition and/or deletion or inversion or insertion wherein there is sufficient bmf nucleotide sequences to promote homologous recombination with a bmf gene within the genomic of said embryonic stem cells selecting for said homologous recombination and selecting embryonic stem cells which carry a mutated bmf gene and then generating a genetically modified animal from said embryonic stem cell. |
Over-clocking in a microdeposition control system to improve resolution |
A microdeposition system (20) and method deposits precise amounts of fluid material onto a substrate. A microdeposition head (50) includes a plurality of spaced nozzles that fire droplets having a deposited width when deposited on the substrate. A positioning device moves the microdeposition head (50) relative to the substrate at a head speed. A controller (22) generates over-clocking signals at a rate that is substantially greater than the head speed divided by the droplet width to improve resolution. The controller (22) includes a positioning module that generates position control signals for the positioning device. The controller (22) includes a nozzle firing module (114) that generates nozzle firing commands based on the over-clocking rate to fire the nozzles to form droplets that define features on the substrate. |
1. A microdeposition system for depositing precise amounts of fluid material onto a substrate, comprising: a microdeposition head that includes a plurality of spaced nozzles that fire droplets having a width when deposited on said substrate; a positioning device that moves said microdeposition head relative to said substrate at a head speed; and a controller that generates over-clocking signals at a rate that is substantially greater than said head speed divided by said droplet width, that includes a positioning module that generates position control signals for said positioning device, and that includes a nozzle firing module that generates nozzle firing commands based on said over-clocking rate to fire said nozzles to form droplets that define features on said substrate. 2. The microdeposition system of claim 1 wherein said over-clocking signal is greater than three times said head speed divided by said droplet width. 3. The microdeposition system of claim 1 wherein said microdeposition system forms part of a layer of an electrical device, and wherein said droplets form at least one of a light emitter, an electrical conductor, resist, an electrical trace, an insulator, a capacitor and a resistor. 4. The microdeposition system of claim 1 further comprising a head assembly that is connected to said head, wherein said positioning module adjusts a pitch of said head by rotating said head assembly. 5. The microdeposition system of claim 4 wherein said over-clocking signal is approximately ten times said head speed divided by said droplet width. 6. The microdeposition system of claim 4 wherein said nozzle firing module adjusts timing of said nozzle firing commands using said over-clocking signal to compensate for changes to said pitch. 7. The microdeposition system of claim 1 further comprising: a first camera that generates digital images of said droplets; and a droplet analysis module that uses optical character recognition to analyze at least one of shape, size, position and speed of said droplet and that adjusts at least one nozzle firing parameter. 8. The microdeposition system of claim 7 wherein said nozzle firing parameters include at least one of timing, amplitude, duration, rise slope and fall slope. 9. The microdeposition system of claim 1 wherein said microdeposition head is selected from the group consisting of thermal microdeposition heads, bubble microdeposition heads, continuous drop microdeposition heads, piezotranducer valves, and microelectromechanical valves. 10. The microdeposition system of claim 1 further comprising a waveform generator that allows adjustment of at least one nozzle firing waveform for each of said nozzles. 11. The microdeposition system of claim 1 wherein said waveform generator includes a selector that selects one of a plurality of nozzle firing waveforms for each of said nozzles based on operating conditions of said nozzle. 12. A method for depositing precise amounts of fluid material onto a substrate, comprising: providing a head including nozzles; moving said microdeposition head relative to said substrate at a head speed; generating over-clocking signals at a rate that is substantially greater than said head speed divided by a deposited droplet width; generating nozzle firing commands based on said over-clocking rate to fire said nozzles; and forming features on said substrate. 13. The method of claim 12 wherein said over-clocking signal is greater than approximately three times said head speed divided by said droplet width. 14. The method of claim 12 wherein said microdeposition system forms part of an electrical device, and wherein said droplets form at least one of a light emitter, an electrical conductor, resist, an electrical trace, an insulator, a capacitor and a resistor. 15. The method of claim 12 further comprising adjusting a pitch of said head. 16. The method of claim 12 wherein said over-clocking signal increases feature resolution. 17. The method of claim 15 wherein said nozzle firing module adjusts timing of said nozzle firing commands using said over-clocking signal to compensate for changes to said pitch. 18. The method of claim 12 further comprising: generating digital images of said droplets; using optical character recognition to analyze at least one of shape, size, position and speed of said droplet; and adjusting at least one nozzle firing parameter. 19. The method of claim 18 wherein said nozzle firing parameters include at least one of timing, amplitude, duration, rise slope and fall slope. 20. The method of claim 12 wherein said microdeposition head is selected from the group consisting of thermal microdeposition heads, bubble microdeposition heads, continuous drop microdeposition heads, piezotranducer valves, and microelectromechanical valves. 21. The method of claim 12 further comprising adjusting at least one nozzle firing waveform of said nozzles. 22. The method of claim 12 further comprising selecting one of a plurality of nozzle firing waveforms for each of said nozzles based on operating conditions of said nozzle. 23. The method of claim 12 wherein said over-clocking signal is approximately ten times said head speed divided by said droplet width. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Manufacturers have developed various techniques for fabricating microstructures that have small feature sizes on substrates. Typically the microstructures form one of more layers of an electronic circuit. Examples of these structures include light-emitting diode (LED) display devices, polymer light-emitting diode (PLED) display devices, liquid crystal display (LCD) devices, printed circuit boards and the like. Most of these manufacturing techniques are relatively expensive to implement and require high production quantities to amortize the cost of the fabrication equipment. One technique for forming microstructures on a substrate includes screen printing. During screen printing, a fine mesh screen is positioned on the substrate. Fluid material is deposited through the screen and onto the substrate in a pattern defined by the screen. Screen printing requires contact between the screen and the substrate. Contact also occurs between the screen and the fluid material, which contaminates both the substrate and the fluid material. While screen printing is suitable for forming some microstructures, many manufacturing processes must be contamination-free to produce operational devices. Therefore, screen printing is not a viable option for the manufacture of certain microstructures. For example, polymer light-emitting diode (PLED) display devices require a contamination-free manufacturing process. Certain polymeric substances can be used in diodes to generate visible light of different wavelengths. Using these polymers, display devices having pixels with sub-components of red, green, and blue can be created. PLED fluid materials enable full-spectrum color displays and require very little power to emit a substantial amount of light. It is expected that PLED displays will be used in the future for various applications, including televisions, computer monitors, PDAs, other handheld computing devices, cellular phones, and the like. It is also expected that PLED technology will be used for manufacturing light-emitting panels that provide ambient lighting for office, storage, and living spaces. One obstacle to the widespread use of PLED display devices is the difficulty encountered to manufacture PLED display devices. Photolithography is another manufacturing technique that is used to manufacture microstructures on substrates. Photolithography is also not compatible with PLED display devices Manufacturing processes using photolithography generally involve the deposition of a photoresist material onto a substrate. The photoresist material is cured by exposure to light. A patterned mask is used to selectively apply light to the photo resist material. Photoresist that is exposed to the light is cured and unexposed portions are not cured. The uncured portions are removed from the substrate. An underlying surface of the substrate is exposed through the removed photoresist layer. The cured portions of the photoresist layer remain on the substrate. Another material is then deposited onto the substrate through the opened pattern on the photoresist layer, followed by the removal of the cured portion of the photoresist layer. Photolithography has been used successfully to manufacture many microstructures such as traces on circuit boards. However, photolithography contaminates the substrate and the material formed on the substrate. Photolithography is not compatible with the manufacture of PLED displays because the photoresist contaminates the PLED polymers. In addition, photolithography involves multiple steps for applying and processing the photoresist material. The cost of the photolithography process can be prohibitive when relatively small quantities are to be fabricated. Spin coating has also been used to form microstructures. Spin coating involves rotating a substrate while depositing fluid material at the center of the substrate. The rotational motion of the substrate causes the fluid material to spread evenly across the surface of the substrate. Spin coating is also an expensive process because a majority of the fluid material does not remain on the substrate. In addition, the size of the substrate is limited by the spin coating process to less than approximately 12″, which makes spin coating unsuitable for larger devices such as PLED televisions. |
<SOH> SUMMARY OF THE INVENTION <EOH>A microdeposition system and method deposits precise amounts of fluid material onto a substrate. A microdeposition head includes a plurality of spaced nozzles that fire droplets having a deposited width when deposited on the substrate. A positioning device moves the microdeposition head relative to the substrate at a head speed. A controller generates over-clocking signals at a rate that are substantially greater than the head speed divided by the droplet width. The controller includes a positioning module that generates position control signals for the positioning device. The controller includes a nozzle firing module that generates nozzle firing commands based on the over-clocking rate to fire the nozzles to form droplets that define features on the substrate. In other features of the invention, the over-clocking signal is greater than three times the head speed divided by the droplet width. Alternately the over-clocking signal is approximately 10 times the head speed divided by the droplet width. In still other features, the microdeposition system forms part of a layer of an electrical device. The droplets form at least one of a light emitter, an electrical conductor, resist, an electrical trace, an insulator, a capacitor and a resistor. A head assembly is connected to the head. A head positioning module adjusts a pitch of the head by rotating the head assembly. In other features, the nozzle firing module adjusts timing of the nozzle firing commands using the over-clocking signal to compensate for changes to the pitch. A first camera generates digital images of the droplets. A droplet analysis module uses optical character recognition to analyze at least one of shape, size, position and speed of the droplet and adjusts at least one nozzle firing parameter. The nozzle firing parameters include at least one of timing, amplitude, duration, rise slope and fall slope. In yet other features, the microdeposition head is selected from the group consisting of thermal microdeposition heads, bubble microdeposition heads, continuous drop microdeposition heads, piezotranducer valves, and microelectromechanical valves. In other features, a waveform generator allows adjustment of at least one nozzle firing waveform for each of the nozzles. The waveform generator includes a selector that selects one of a plurality of nozzle firing waveforms for each of the nozzles based on operating conditions of the nozzle. Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. |
Device for storing objects |
A device for storing articles comprises at least one box for storing the articles. The box comprises an outer shell removably mounted on a support by interfitting engagement, and a moving portion connected to the outer shell. The device further comprises at least one lock secured to the support or to the box, the lock being adapted firstly to allow the moving portion to be opened and closed relative to the outer shell, and secondly to allow the outer shell of the box to be unlocked from the support. |
1. A device for storing articles comprising at least one box for storing said articles, the box comprising an outer shell that is removably mounted on a support by interfitting engagement, and a moving portion connected to the outer shell, said moving portion being movable between an open position giving access to the inside of the box and a closed position in which said moving portion is held to the outer shell to prevent access to the inside of the box, and the device including at least one lock secured to the support or to the box, said lock being adapted firstly to allow the moving portion to be opened and closed relative to the outer shell, and secondly to allow the outer shell of the box to be unlocked relative to the support. 2. A device according to claim 1, wherein the lock is secured to the support, said lock having a bolt suitable for occupying at least one of the following positions: a closing position in which the bolt of the electric lock fixes the moving portion of the box which is associated therewith to the outer shell; an opening position in which the bolt of the lock releases the moving portion of the box from the outer shell of the box; and an unlocking position in which the bolt of the lock releases the outer shell of the box with which it is associated from the support. 3. A device according to claim 1, including at most N boxes and at least N locks. 4. A device according to claim 3, wherein each lock is an electric lock, and the device further comprises a control system for selectively controlling the electric locks. 5. A device according to claim 4, wherein the support comprises at least two substantially parallel beams, and the outer shell of each box has two grooves of shape complementary to the shape of the beams to enable boxes to be engaged and aligned on the two beams. 6. A device according to claim 5, wherein the N electric locks are received in one of the two beams which has N openings through which the bolts of said locks can pass, the bolt of each electric lock being designed to co-operate with a through hole formed in the bottom of one of the two grooves in the outer shell of each box. 7. A device according to claim 5, wherein a cross-member is mounted in releasable manner on the ends of the two beams to enable the boxes to be engaged thereon, said cross-member being secured to the ends of the beams by means of a lock. 8. A device according to claim 4, wherein the support comprises two substantially parallel beams and N pairs of carrier elements, each carrier element being disposed substantially perpendicularly to the beam with which it is associated, and the outer shell of each box has at least two grooves of shape complementary to the shape of the carrier elements so as to enable each box to be engaged on at least one pair of carrier elements (12). 9. A device according to claim 8, wherein the N electric locks are housed respectively in the N pairs of carrier elements, the bolt of each electric lock being designed to co-operate with a through hole formed in the bottom of one of the two grooves in the outer shell of each box. 10. A device according to claim 6, wherein the moving portion of each box presents an opening designed to be placed in register with the through hole of the outer shell when the moving portion is in the closed position, said opening receiving a portion of the bolt of the lock with which it is associated. |
Waveform generator for microdeposition control system |
A microdeposition system (20) and method includes a head with a plurality of nozzles (230). A controller (22) generates nozzle firing commands that selectively fire the nozzles to create a desired feature pattern. Configuration memory stores voltage waveform parameters that define a voltage waveform (280) for each of the nozzles. A digital to analog converter (DAC) sequencer communicates with the configuration memory and the controller and outputs a first voltage waveform for a first nozzle when a nozzle firing command for the first nozzle is received from the controller (22). A resistive ladder DAC receives the voltage waveforms from the DAC sequencer. An operational amplifier (opamp) communicates with the resistive ladder DAC and amplifies the voltage waveforms. The nozzles fire droplets when the voltage waveforms received from the opamp exceed a firing threshold of the nozzle (230). |
1. A microdeposition system that deposits droplets of fluid material on a substrate, comprising: a nozzle including a common line and a nib line; and a waveform generator that communicates with said common line and said nib line and that generates an adjustable voltage waveform that causes said nozzle to fire said droplets. 2. The microdeposition system of claim 1 wherein said common line is connected to one of earth ground and a floating positive voltage relative to a system power ground. 3. The microdeposition system of claim 3 wherein said waveform generator drives said nib line to a negative voltage that exceeds a firing threshold voltage to fire said nozzle. 4. The microdeposition system of claim 1 wherein said waveform generator includes an operational amplifier (opamp). 5. The microdeposition system of claim 4 wherein said waveform generator further includes a resistive ladder digital to analog converter (DAC) that communicates with said opamp. 6. The microdeposition system of claim 5 wherein said waveform generator includes a configuration memory with a first configuration set that defines a first voltage waveform. 7. The microdeposition system of claim 6 wherein said waveform generator further includes a DAC sequencer that generates a voltage waveform based on said first configuration set when a firing command is received. 8. The microdeposition system of claim 6 wherein said first configuration set includes voltage and duration pairs that define rise slope, fall slope, amplitude and timing of said voltage waveform. 9. A microdeposition system, comprising: a head including a plurality of nozzles; a controller that generates nozzle firing commands that selectively fire said nozzles to create a desired feature pattern; and configuration memory that stores voltage waveform parameters that define a voltage waveform for each of said nozzles. 10. The microdeposition system of claim 9 further comprising a digital to analog converter (DAC) sequencer that communicates with said configuration memory and said controller and that outputs a first voltage waveform for a first nozzle when a nozzle firing command for said first nozzle is received from said controller. 11. The microdeposition system of claim 10 further comprising a resistive ladder DAC that receives said voltage waveforms from said DAC sequencer. 12. The microdeposition system of claim 10 further comprising an operational amplifier (opamp) that communicates with said resistive ladder DAC and that amplifies said voltage waveforms, wherein said nozzles fire droplets when said voltage waveforms received from said opamp exceed a firing threshold of said nozzle. 13. The microdeposition system of claim 12 wherein said nozzles include a common line and a nib line, and wherein said common line is connected to one of earth ground and a floating positive voltage relative to a system power ground. 14. The microdeposition system of claim 13 wherein said opamp drives said nib line to a negative voltage that exceeds said firing threshold voltage to fire said nozzle. 15. The microdeposition system of claim 12 wherein said opamp is a high voltage opamp. 16. The microdeposition system of claim 9 wherein a first voltage waveform that is associated with a first nozzle includes at least one of a positive pulse and a negative conditioning pulse that does not exceed said firing threshold. 17. The microdeposition system of claim 16 wherein said at least one of said positive conditioning pulse and said negative conditioning pulse precedes a firing pulse that exceeds said firing threshold. 18. The microdeposition system of claim 17 wherein said at least one of said positive conditioning pulse and said negative conditioning pulse follows a firing pulse that exceeds said firing threshold. 19. The microdeposition system of claim 9 further comprising a configuration latch that receives a set of voltage waveform parameters from said controller and that loads said set of voltage waveform parameters in said configuration memory. 20. The microdeposition system of claim 10 further comprising a pixel latch that receives nozzle firing commands from said controller, wherein said pixel latch communicates with said DAC sequencer. 21. The microdeposition system of claim 9 wherein said configuration memory stores a plurality of sets of voltage waveform parameters for each of said nozzles. 22. The microdeposition system of claim 21 further comprising a configuration set selector that selects one of said sets of voltage waveform parameters based on operating conditions of said nozzle. 23. A method for firing droplets of fluid material in a microdeposition system, comprising: providing a nozzle including a common line and a nib line; and generating an adjustable voltage waveform that causes said nozzle to fire said droplets. 24. The method of claim 23 further comprising connecting said common line to one of earth ground and a floating positive voltage relative to a system power ground. 25. The method of claim 24 further comprising driving said nib line to a negative voltage that exceeds a firing threshold voltage to fire said nozzle. 26. The method of claim 25 further comprising: storing a first configuration set that defines a first voltage waveform; and generating a voltage waveform based on said first configuration set when a firing command is received. 27. The method of claim 26 wherein said first configuration set includes voltage and duration pairs that define rise slope, fall slope, amplitude and timing of said voltage waveform. 28. A method for operating a microdeposition system, comprising: providing a head including a plurality of nozzles; generating nozzle firing commands that selectively fire said nozzles to create a desired feature pattern; and storing voltage waveform parameters that define a voltage waveform for each of said nozzles. 29. The method of claim 9 further comprising generating a first voltage waveform for a first nozzle when a nozzle firing command for said first nozzle is received from said controller. 30. The method of claim 28 wherein said nozzles include a common line and a nib line, and further comprising connecting said common line to one of earth ground and a floating positive voltage relative to a system power ground. 31. The method of claim 30 further comprising driving said nib line to a negative voltage that exceeds said firing threshold voltage to fire said nozzle. 32. The method of claim 28 further comprising generating a first voltage waveform that is associated with a first nozzle and that includes at least one of a positive conditioning pulse and a negative conditioning pulse that does not exceed said firing threshold. 33. The method of claim 32 wherein said at least one of said positive conditioning pulse and said negative conditioning pulse precedes a firing pulse that exceeds said firing threshold. 34. The method of claim 33 wherein said at least one of said positive conditioning pulse and said negative conditioning pulse follows a firing pulse that exceeds said firing threshold. 35. The method of claim 28 further comprising storing a plurality of sets of voltage waveform parameters for each of said nozzles. 36. The method of claim 35 further comprising selecting one of said sets of voltage waveform parameters based on operating conditions of said nozzle. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Manufacturers have developed various techniques for fabricating microstructures that have small feature sizes on substrates. Typically the microstructures form one of more layers of an electronic circuit. Examples of these structures include light-emitting diode (LED) display devices, polymer light-emitting diode (PLED) display devices, liquid crystal display (LCD) devices, printed circuit boards and the like. Most of these manufacturing techniques are relatively expensive to implement and require high production quantities to amortize the cost of the fabrication equipment. One technique for forming microstructures oh a substrate includes screen printing. During screen printing, a fine mesh screen is positioned on the substrate. Fluid material is deposited through the screen and onto the substrate in a pattern defined by the screen. Screen printing requires contact between the screen and the substrate. Contact also occurs between the screen and the fluid material, which contaminates both the substrate and the fluid material. While screen printing is suitable for forming some microstructures, many manufacturing processes must be contamination-free to produce operational devices. Therefore, screen printing is not a viable option for the manufacture of certain microstructures. For example, polymer light-emitting diode (PLED) display devices require a contamination-free manufacturing process. Certain polymeric substances can be used in diodes to generate visible light of different wavelengths. Using these polymers, display devices having pixels with sub-components of red, green, and blue can be created. PLED fluid materials enable full-spectrum color displays and require very little power to emit a substantial amount of light. It is expected that PLED displays will be used in the future for various applications, including televisions, computer monitors, PDAs, other handheld computing devices, cellular phones, and the like. It is also expected that PLED technology will be used for manufacturing light-emitting panels that provide ambient lighting for office, storage, and living spaces. One obstacle to the widespread use of PLED display devices is the difficulty encountered to manufacture PLED display devices. Photolithography is another manufacturing technique that is used to manufacture microstructures on substrates. Photolithography is also not compatible with PLED display devices Manufacturing processes using photolithography generally involve the deposition of a photoresist material onto a substrate. The photoresist material is cured by exposure to light. A patterned mask is used to selectively apply light to the photo resist material. Photoresist that is exposed to the light is cured and unexposed portions are not cured. The uncured portions are removed from the substrate. An underlying surface of the substrate is exposed through the removed photoresist layer. The cured portions of the photoresist layer remain on the substrate. Another material is then deposited onto the substrate through the opened pattern on the photoresist layer, followed by the removal of the cured portion of the photoresist layer. Photolithography has been used successfully to manufacture many microstructures such as traces on circuit boards. However, photolithography contaminates the substrate and the material formed on the substrate. Photolithography is not compatible with the manufacture of PLED displays because the photoresist contaminates the PLED polymers. In addition, photolithography involves multiple steps for applying and processing the photoresist material. The cost of the photolithography process can be prohibitive when relatively small quantities are to be fabricated. Spin coating has also been used to form microstructures. Spin coating involves rotating a substrate while depositing fluid material at the center of the substrate. The rotational motion of the substrate causes the fluid material to spread evenly across the surface of the substrate. Spin coating is also an expensive process because a majority of the fluid material does not remain on the substrate. In addition, the size of the substrate is limited by the spin coating process to less than approximately 12″, which makes spin coating unsuitable for larger devices such as PLED televisions. |
<SOH> SUMMARY OF THE INVENTION <EOH>A microdeposition system and method includes a head with a plurality of nozzles. A controller generates nozzle firing commands that selectively fire the nozzles to create a desired feature pattern. Configuration memory stores voltage waveform parameters that define a voltage waveform for each of the nozzles. In other features, a digital to analog converter (DAC) sequencer communicates with the configuration memory and the controller and outputs a first voltage waveform for a first nozzle when a nozzle firing command for the first nozzle is received from the controller. A resistive ladder DAC receives the voltage waveforms from the DAC sequencer. An operational amplifier (opamp) communicates with the resistive ladder DAC and amplifies the voltage waveforms. The nozzles fire droplets when the voltage waveforms received from the opamp exceed a firing threshold of the nozzle. In other features, the nozzles include a common line and a nib line. The common line is connected to one of earth ground and a floating positive voltage relative to a system power ground. The opamp drives the nib line to a negative voltage that exceeds the firing threshold voltage to fire the nozzle. In still other features, a first voltage waveform that is associated with a first nozzle includes at least one of a positive conditioning pulse and a negative conditioning pulse that does not exceed the firing threshold. The positive conditioning pulse or the negative conditioning pulse precedes or follows a firing pulse that exceeds the firing threshold. In still other features, a configuration latch receives a set of voltage waveform parameters from the controller and loads the set of voltage waveform parameters in the configuration memory. A pixel latch communicates with the DAC sequencer and receives nozzle firing commands from the controller. The configuration memory stores a plurality of sets of voltage waveform parameters for each of the nozzles. A configuration set selector selects one of the sets of voltage waveform parameters based on operating conditions of the nozzle. Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. |
Aerosol composition comprising silicate particles and surfactants |
The invention concerns a cosmetic composition, in particular for the hair, packaged in an aerosol device containing a propellant and a liquid phase which comprises, in a cosmetically acceptable medium: (i) solid particles containing at least 10 wt. % of at least a silicate, and (ii) at least a surfactant; said solid particles containing less than 1 wt. % of aluminium. |
1. A composition, comprising a propellant and a liquid cosmetic composition, wherein the liquid cosmetic composition comprises, in a cosmetically acceptable medium: (i) solid particles comprising at least 10% by weight of at least one silicate, and (ii) at least one surfactant; wherein said solid particles comprise less than 1% by weight of aluminum. 2. The composition as claimed in claim 1, wherein the silicate is at least one of a sodium, magnesium or lithium silicate. 3. The composition as claimed in claim 1, wherein the solid particles have a number-average primary size of between 2 nm and 1 μm. 4. The composition as claimed in claim 1, wherein the solid particles comprising at least 10% by weight of at least one silicate have a number-average primary size of between 5 and 500 nm. 5. The composition as claimed in claim 1, wherein the solid particles comprise at least 50% by weight of at least one silicate. 6. The composition as claimed in claim 1, wherein the silicate comprising particles are present in an amount of between 0.01% and 10% by weight relative to the total weight of the composition. 7. The composition as claimed in claim 1, wherein the surfactant is present in an amount of between 0.1% and 10% by weight, relative to the total weight of the composition. 8. The composition as claimed in claim 1, wherein the surfactant is an amphoteric or nonionic surfactant. 9. The composition as claimed in claim 1, wherein the propellant is at least one selected from the group consisting of dimethyl ether, a C3 to C5 alkane, n-butane, propane, isobutane, a halohydrocarbon, 1,1-difluoroethane, a mixture of dimethyl ether and a C3-5 alkane, and a mixture of 1,1-difluoroethane and at least one of dimethyl ether or a C3-5 alkane. 10. The composition as claimed in claim 1, wherein the propellant is at least one of dimethyl ether, a C3 to C5 alkane, or a mixture thereof. 11. The composition as claimed in claim 1, wherein the propellant is present in an amount of between 2% and 90% by weight, relative to the total weight of the composition. 12. The composition as claimed in claim 1, further comprising one or more cosmetic additives selected from the group consisting of an adhesive; a reducing agent; a thio; a fatty substance; a thickener; a softener; an antifoam; a screening agent; an antiperspirant; an acidifying agent; a basifying agent; a dye; a pigment; a fragrance; a preserving agent; an anionic, cationic, nonionic or amphoteric, fixing or nonfixing polymer; volatile or nonvolatile, modified or unmodified, soluble or insoluble silicone; a plant, animal, mineral or synthetic oil, fragrance; protein; vitamin; or glycerol; and mixtures thereof. 13-15. (canceled) 16. The cosmetic composition as claimed in claim 1, in the form of an aerosol. 17. The composition as claimed in claim 1, wherein the solid particles comprising at least 10% by weight of at least one silicate have a number-average primary size of between 10 and 250 nm. 18. The composition as claimed in claim 1, wherein the solid particles comprise at least 70% by weight of at least one silicate. 19. The composition as claimed in claim 1, wherein the solid particles comprise at least 90% by weight of at least one silicate. 20. The composition as claimed in claim 1, wherein the silicate-comprising particles are present in an amount of between 0.5% and 3% by weight relative to the total weight of the composition. 21. The composition as claimed in claim 1, wherein the surfactant is present in an amount of between 0.5% and 8% by weight relative to the total weight of the composition. 22. The composition as claimed in claim 1, wherein the surfactant is present in an amount of between 1% and 5% by weight relative to the total weight of the composition. 23. The composition as claimed in claim 1, wherein the propellant is present in an amount of between 4% and 80% by weight relative to the total weight of the composition. 24. The composition as claimed in claim 1, wherein the propellant is present in an amount of between 30% and 70% by weight relative to the total weight of the composition. 25. A cosmetic hair treatment process comprising: applying the composition as claimed in claim 1 to hair. 26. A process comprising applying the composition as claimed in claim 1 to hair in an amount effective for at least one of shaping or holding the hair. 27. An aerosol device comprising a container containing a cosmetic composition in the liquid phase and a propellant, wherein the cosmetic composition comprises, in a cosmetically acceptable medium: (i) solid particles comprising at least 10% by weight of at least one silicate, and (ii) at least one surfactant; wherein said solid particles comprise less than 1% by weight of aluminum. 28. The aerosol device as claimed in claim 27, wherein the silicate is at least one of a sodium, magnesium or lithium silicate. 29. The aerosol device as claimed in claim 27, wherein the solid particles have a number-average primary size of between 2 nm and 1 μm. 30. The aerosol device as claimed in claim 27, wherein the solid particles comprising at least 10% by weight of at least one silicate have a number-average primary size of between 5 to 500 nm. 31. The aerosol device as claimed in claim 27, wherein the solid particles comprise at least 50% by weight of at least one silicate. 32. The aerosol device as claimed in claim 27, wherein the silicate—comprising particles are present in an amount of between 0.01% and 10% by weight relative to the total weight of the composition. 33. The aerosol device as claimed in claim 27, wherein the surfactant is present in an amount of between 0.1% and 10% by weight relative to the total weight of the composition. 34. The aerosol device as claimed in claim 27, wherein the surfactant is an amphoteric or nonionic surfactant. 35. The aerosol device as claimed in claim 27, wherein the propellant is at least one selected from the group consisting of dimethyl ether, a C3 to C5 alkane, n-butane, propane, isobutene, halohydrocarbon, 1,1-difluoroethane, a mixture of dimethyl ether and a C3-5 alkane, and a mixture of 1,1-difluoroethane and at least one of dimethyl ether or a C3-5 alkane. 36. The aerosol device as claimed in claim 27, wherein the propellant is at least one of dimethyl ether, a C3 to C5 alkane, or a mixture thereof. 37. The aerosol device as claimed in claim 27, wherein the propellant is present in an amount between 2% and 90% by weight relative to the total weight of the composition. 38. The aerosol device as claimed in claim 27, wherein the composition, further comprises one or more cosmetic additives selected from the group consisting of an adhesive, a reducing agent, a thiol; a fatty substance; a thickener; a softener; an antifoam; a screening agent; an antiperspirant; an acidifying agent; a basifying agent; a dye; a pigment; a fragrance; a preserving agent; an anionic, cationic, nonionic or amphoteric, fixing or nonfixing polymer; volatile or nonvolatile, modified or unmodified, soluble or insoluble silicone; a plant, animal, mineral or synthetic oil, fragrance, protein, vitamin or glycerol; and mixtures thereof. 39. The aerosol device as claimed in claim 27, wherein the solid particles comprising at least 10% by weight of at least one silicate have a number-average primary size of between 10 and 250 nm. 40. The aerosol device as claimed in claim 27, wherein the solid particles comprise at least 70% by weight of at least one silicate. 41. The aerosol device as claimed in claim 24, wherein the solid particles comprise at least 90% by weight of at least one silicate. 42. The aerosol device as claimed in claim 27, wherein the silicate-comprising particles are present in an amount of between 0.5% and 3% by weight relative to the total weight of the composition. 43. The aerosol device as claimed in claim 27, wherein the surfactant is present in an amount of between 0.5% and 8% by weight relative to the total weight of the composition. 44. The aerosol device as claimed in claim 27, wherein the surfactant is present in an amount of between 1% and 5% by weight relative to the total weight of the composition. 45. The aerosol device as claimed in claim 27, wherein the propellant is present in an amount of between 4% and 80% by weight relative to the total weight of the composition. 46. The aerosol device as claimed in claim 27, wherein the propellant is present in an amount of between 30% and 70% by weight relative to the total weight of the composition. |
Torsional vibration damper |
The invention relates to a hydraulic torsional vibration damper which is characterized in that the secondary mass is guided by a pair of slotted plastic flange sleeves with an L-shaped cross-section. The damper is characterized in that the butt joint is closed by a bridge temporarily formed onto it that will either break or deform in an elastic plastic manner when thermal length changes occur, thereby allowing transport of the sleeves in a pile and an automatic assembly of the damper. |
1-11. (cancelled). 12. A viscosity-type torsional vibration damper, comprising: a damper housing; a rotating ring; flange sleeves for guiding the rotating ring in the damper housing, the flange sleeves being inserted loosely without prestress between the damper housing and the ring, and simultaneously maintaining defined shearing gaps between the housing and the ring, each flange sleeve being made of a plastic material, and having an L-shaped cross-section, and including a butt joint at one circumferential location; and wherein the butt joint is bridged by at least one material web, the material web penetrating the butt joint only in sections. 13. The viscosity-type torsional vibration damper according to claim 12, wherein the butt joint is bridged by the at least one material web, which tears during a thermal length increase of the sleeve. 14. The viscosity-type torsional vibration damper according to claim 12, wherein the butt joint is bridged by the at least one material web, which deforms in an elastic-plastic manner during a thermal length increase of the sleeve. 15. The viscosity-type torsional vibration damper according to claim 13, wherein the butt joint is bridged by two material webs, which are constructed as tear webs and which are situated in an alignment with a radial bearing part and in an alignment with an axial bearing part of the flange sleeve. 16. The viscosity-type torsional vibration damper according to claim 13, wherein the butt joint is bridged by the at least one material web, which is constructed as a tear web and is situated in an alignment with a radial bearing part or in an alignment with an axial bearing part of the flange sleeve. 17. The viscosity-type torsional vibration damper according to claim 14, wherein the butt joint is bridged by the at least one material web, which is constructed as a meandering web and which is situated in an alignment with a radial bearing part of the flange sleeve. 18. The viscosity-type torsional vibration damper according to claim 14, wherein the butt joint is bridged by the at least one material web, which is constructed as a meandering web and which is situated in an alignment with an axial bearing part of the flange sleeve. 19. The viscosity-type torsional vibration damper according to claim 17, wherein the butt joint is bridged by two material webs, which are constructed as meandering webs and which are situated in an alignment with a radial bearing part and an axial bearing part of the flange sleeve, respectively. 20. The viscosity-type torsional vibration damper according to claim 14, wherein the butt joint is bridged by two material webs, which are constructed as foil-type webs and which are situated in an alignment with a radial bearing part and in an alignment with an axial bearing part of the flange sleeve, respectively. 21. The viscosity-type torsional vibration damper according to claim 14, wherein the butt joint is bridged by the at least one material web constructed as a foil-type web, which is situated either in an alignment with a radial bearing part or in an alignment with an axial bearing part of the flange sleeve. 22. The viscosity-type torsional vibration damper according to claim 18, wherein the butt joint is bridged by two material webs, which are constructed as meandering webs and which are situated in an alignment with a radial bearing part and an axial bearing part of the flange sleeve, respectively. |
<SOH> BACKGROUND AND SUMMARY OF THE INVENTION <EOH>The invention relates to a torsional vibration damper with flange sleeves for guiding a rotating ring in a damper housing, the flange sleeves guiding the rotating ring with respect to the damper housing and being inserted loosely, that is, without prestress, between the housing and the ring, and simultaneously maintaining defined shearing gaps between the housing and the ring. The shearing gap damper, traditionally called a visco or torsional vibration damper, is usually flanged at an output side of diesel engine crankshafts with respect to the power and reduces their torsional vibration amplitudes. As a result of an oscillating shearing of the silicone oil damping medium in the interior of the damper, the oscillation energy is converted to heat which, as a result of convection, is conveyed to the ambient air or to another cooling medium. Shearing gap dampers normally consist of a ring-shaped housing ( 1 in FIG. 1 ) which encloses a secondary mass 2 called a “rotating ring”. The housing is connected with the crankshaft M in a torsion-proof manner. The damper housing and the rotating ring follow the mean rotational speed of the crankshaft without any slip. In contrast, their torsional vibrations, which are superimposed on the uniform rotation, are first communicated only to the housing. The rotating ring would rotate in a uniform manner if it were not coupled to the housing by the damping medium which fills the narrow shearing gap 3 . This coupling is elastic and subject to damping. As a result, relative angles of rotation of an angular degree of up to ±1° in time with the exciting oscillations occur between the housing and the rotating ring. Since the rotating ring can therefore rotate in an oscillating manner with respect to the housing, it requires guiding elements. From European Patent Document EP-PS 0 745 784 B1, a rotating ring bearing in the manner of a “flange sleeve” is known which is made of plastic and has an L-shaped cross-section. A pair of such flange sleeves are part of the equipment of a shearing gap damper. These flange sleeves are inserted without prestress, that is, loosely between the housing and the ring, so that, during relative movements, both metal parts slide on the flange sleeve with the smallest possible coefficient of friction. The flange sleeves according to European Patent Document EP-PS 0 745 784 B1 provide the best conditions for an uncomplicated fully automatic assembly of shearing gap dampers. However, it was found that the flange sleeves did not yet meet all requirements of an economical manufacturing. In particular, the closed angle rings according to European Patent Document EP-PS 0 745 784 B1 are not optimal with respect to the excessively different linear coefficients of thermal expansion of the participating materials: Steel α = 0.0115 mm/(m × ° C.) cast iron α = 0.0105 mm/(m × ° C.) PA 66 α = 0.070 mm/(m × ° C.) PTFE α = 0.130 mm/(m × ° C.) According to the temperature range to be assumed—from an arctic −50° C. through +20° C. during the assembly, to +100° C. in the engine, plastic rings grow with, for example, 160 mm bearing diameter by ΔI=5 to 9 mm in comparison to the housing and rotating ring. Such an increase in length would not take place without any constraints or compression of the bushing cross-section and cannot be accepted. The straight or diagonally slotted butt joint of the flange sleeves according to European Patent Document EP-PS 0 745 784 was sufficiently wide for easily compensating the temperature-caused length increase of the plastic material. However, the incompatible instability of the cut-open angle rings was a disadvantage. They interlocked and deformed during transport and resisted the grippers of the assembling devices. It is an object of the present invention to provide a torsional vibration damper of this type, which has a flange sleeve as a bearing device, in such a manner that it accomplishes the required length compensation and, simultaneously, is sufficiently dimensionally stable in order to be able to be processed by a fully automatic production facility. The invention achieves this task by providing a viscosity-type torsional vibration damper with flange sleeves for guiding a rotating ring in a damper housing, the flange sleeves guiding the rotating ring with respect to the damper housing and being inserted loosely, that is, without prestress, between the housing and the ring, and simultaneously maintaining defined shearing gaps between the housing and the ring. The flange sleeves are formed of a plastic material, and have a preferably L-shaped cross-section, as well as having a butt joint at one point of the circumference. The butt joint is bridged by at least one or more material webs. Accordingly, the butt joint is bridged by at least one or more material webs which, however, do not extend along the above-mentioned width of the flange sleeve. In a simple manner, the material webs permit good storage properties and easy transportability of the flange sleeves, and also decisively facilitate assembly because deformation and warpage of the slotted rings is prevented. Advantageous further developments of the invention are described herein. Essentially two types of approaches present themselves. The butt gap of the flange sleeve is bridged by webs which break at the operating temperature, or deform in an elastic-plastic manner at the operating temperature. The flange sleeves are preferably L-shaped. However, the invention is theoretically also suitable for slotted plane axial or radial bearing rings. |
<SOH> BACKGROUND AND SUMMARY OF THE INVENTION <EOH>The invention relates to a torsional vibration damper with flange sleeves for guiding a rotating ring in a damper housing, the flange sleeves guiding the rotating ring with respect to the damper housing and being inserted loosely, that is, without prestress, between the housing and the ring, and simultaneously maintaining defined shearing gaps between the housing and the ring. The shearing gap damper, traditionally called a visco or torsional vibration damper, is usually flanged at an output side of diesel engine crankshafts with respect to the power and reduces their torsional vibration amplitudes. As a result of an oscillating shearing of the silicone oil damping medium in the interior of the damper, the oscillation energy is converted to heat which, as a result of convection, is conveyed to the ambient air or to another cooling medium. Shearing gap dampers normally consist of a ring-shaped housing ( 1 in FIG. 1 ) which encloses a secondary mass 2 called a “rotating ring”. The housing is connected with the crankshaft M in a torsion-proof manner. The damper housing and the rotating ring follow the mean rotational speed of the crankshaft without any slip. In contrast, their torsional vibrations, which are superimposed on the uniform rotation, are first communicated only to the housing. The rotating ring would rotate in a uniform manner if it were not coupled to the housing by the damping medium which fills the narrow shearing gap 3 . This coupling is elastic and subject to damping. As a result, relative angles of rotation of an angular degree of up to ±1° in time with the exciting oscillations occur between the housing and the rotating ring. Since the rotating ring can therefore rotate in an oscillating manner with respect to the housing, it requires guiding elements. From European Patent Document EP-PS 0 745 784 B1, a rotating ring bearing in the manner of a “flange sleeve” is known which is made of plastic and has an L-shaped cross-section. A pair of such flange sleeves are part of the equipment of a shearing gap damper. These flange sleeves are inserted without prestress, that is, loosely between the housing and the ring, so that, during relative movements, both metal parts slide on the flange sleeve with the smallest possible coefficient of friction. The flange sleeves according to European Patent Document EP-PS 0 745 784 B1 provide the best conditions for an uncomplicated fully automatic assembly of shearing gap dampers. However, it was found that the flange sleeves did not yet meet all requirements of an economical manufacturing. In particular, the closed angle rings according to European Patent Document EP-PS 0 745 784 B1 are not optimal with respect to the excessively different linear coefficients of thermal expansion of the participating materials: Steel α = 0.0115 mm/(m × ° C.) cast iron α = 0.0105 mm/(m × ° C.) PA 66 α = 0.070 mm/(m × ° C.) PTFE α = 0.130 mm/(m × ° C.) According to the temperature range to be assumed—from an arctic −50° C. through +20° C. during the assembly, to +100° C. in the engine, plastic rings grow with, for example, 160 mm bearing diameter by ΔI=5 to 9 mm in comparison to the housing and rotating ring. Such an increase in length would not take place without any constraints or compression of the bushing cross-section and cannot be accepted. The straight or diagonally slotted butt joint of the flange sleeves according to European Patent Document EP-PS 0 745 784 was sufficiently wide for easily compensating the temperature-caused length increase of the plastic material. However, the incompatible instability of the cut-open angle rings was a disadvantage. They interlocked and deformed during transport and resisted the grippers of the assembling devices. It is an object of the present invention to provide a torsional vibration damper of this type, which has a flange sleeve as a bearing device, in such a manner that it accomplishes the required length compensation and, simultaneously, is sufficiently dimensionally stable in order to be able to be processed by a fully automatic production facility. The invention achieves this task by providing a viscosity-type torsional vibration damper with flange sleeves for guiding a rotating ring in a damper housing, the flange sleeves guiding the rotating ring with respect to the damper housing and being inserted loosely, that is, without prestress, between the housing and the ring, and simultaneously maintaining defined shearing gaps between the housing and the ring. The flange sleeves are formed of a plastic material, and have a preferably L-shaped cross-section, as well as having a butt joint at one point of the circumference. The butt joint is bridged by at least one or more material webs. Accordingly, the butt joint is bridged by at least one or more material webs which, however, do not extend along the above-mentioned width of the flange sleeve. In a simple manner, the material webs permit good storage properties and easy transportability of the flange sleeves, and also decisively facilitate assembly because deformation and warpage of the slotted rings is prevented. Advantageous further developments of the invention are described herein. Essentially two types of approaches present themselves. The butt gap of the flange sleeve is bridged by webs which break at the operating temperature, or deform in an elastic-plastic manner at the operating temperature. The flange sleeves are preferably L-shaped. However, the invention is theoretically also suitable for slotted plane axial or radial bearing rings. |
Surgicals metals with improved hardness and methods for making same |
A surgical device includes a structural portion which is formed of a first element, such as titanium, which has an outer surface and an inner core. A second element, such as oxygen, is combined with the first element without creating a shear plane, to create a concentration of the second element in the first element which varies from the outer surface to the inner core. In an associated method, the second element is driven into the first element under other than ambient conditions to develop a concentration gradient of the second element between the outer surface and the inner core of the first element. |
1. A surgical device, comprising: a structural portion formed of a first element and having an outer surface and an inner core; a second element combined with a first element without creating a shear plane between the first element and the second element; the second element, with the first element providing the structural portion with a physical property which changes between the outer surface and the inner core of the structural portion. 2. The surgical device recited in claim 1, wherein: the physical property is a coefficient of friction; and the coefficient of friction decreases between the outer surface and the inner core. 3. The surgical device recited in claim 2, wherein the coefficient of friction decreases with progressive positions towards the outer surface. 4. The surgical device recited in claim 1, wherein the second element is impregnated into the first element in an amount which decreases from the outer surface to the inner core. 5. The surgical device recited in claim 1, wherein the first element is a metal. 6. The surgical device recited in claim 2, wherein the second element is a gas. 7. The surgical device recited in claim 1, wherein the surgical device comprises a clip. 8. The surgical device recited in claim 6, wherein the metal is titanium and the gas is oxygen. 9. The surgical device recited in claim 1, wherein the physical property is strength, and the strength changes between the outer surface and the inner core. 10. The surgical device recited in claim 9, wherein the strength changes in a gradient which decreases with progressive positions toward the inner core. 11. A method for manufacturing a surgical device, including the steps of: forming the surgical device of a metal having an outer surface and an inner core; exposing the metal of the surgical device to an interstitial element; and driving the interstitial element into the outer surface of the metal to form a combination of the metal and the interstitial element which has a physical property that changes with progressive positions toward the core of the metal. 12. The method recited in claim 11, wherein during the driving step, the method further comprises the steps of: creating a gradient of the interstitial element in the metal, the gradient having a concentration of the interstitial element in the metal which decreases from the other surface toward the inner core. 13. The method recited in claim 11, wherein the metal includes titanium. 14. The method recited in claim 13, wherein the interstitial element includes oxygen. 15. The method recited in claim 12, wherein the driving step includes the step of heating the metal and the interstitial element. 16. The method recited in claim 12, wherein the driving step includes the step of pressurizing the metal and the interstitial element. 17. The method recited in claim 11, wherein the physical property includes at least one of friction, strength and ductility. 18. The method recited in claim 17, wherein: the strength increases with progressive positions toward the outer surface; and the ductility increases with progressive positions toward the inner core. 19. A method recited in claim 12 wherein the surgical device is one of a clip, clamp, needle and staple. 20. A method for increasing the strength of a surgical device, comprising the steps of: forming the device of a wire having an outer surface and an inner core; heating the wire in the presence of an interstitial element to drive the interstitial element into the outer surface of the wire; and during the heating step, creating in the wire a concentration of the interstitial element, the concentration being characterized by a first concentration of the interstitial element at the outer surface and a second concentration of the interstitial element at the inner core; and the first concentration of the interstitial element being greater than the second concentration of the interstitial element. 21. The method recited in claim 20, wherein the creating step includes the step of: creating a concentration gradient in the wire which varies progressively between the first concentration at the outer surface and the second concentration at the inner core. 22. The method recited in claim 20, wherein prior to the heating step, the method includes the step of coating the wire with a material including the interstitial element. 23. The method recited in claim 22, wherein the heating step includes the steps of: heating the coating material to a temperature and for a time sufficient to generally free the interstitial element from the coating material; and heating the wire to a temperature and for a time sufficient to drive the freed interstitial element into the wire. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention relates generally to surgical devices formed of metals and to methods for improving the hardness of surgical metals. 2. Discussion of Relevant Art Safety and efficacy are of primary concern with respect to the use of all surgical instruments and devices. Where surgical metals are included in these instruments and devices, increased hardness for a given size may offer significant advantages. However, if ductility is desired, the increased hardness must be balanced against the need for bendability. Consider, for example, surgical clips and staples. Clips are typically used to occlude or ligate body conduits such as blood vessels. Staples usually function to close wounds or otherwise bring tissue together to promote healing. As used herein, the word “clip” shall refer to both clips and staples, as well as any other medical device formed of wire, such as a spring. With respect to efficacy, a clip needs to have a size and shape that permits easy access to the operative site. It must be bendable at the operative site to engage tissue and must otherwise perform its intended function at the operative site. Finally, the clip must remain at the operative site and continue performing that function until it is removed or its function is no longer desired. These criteria speak mainly to the ability of the clip to accomplish its function. For example, if the clip is intended to occlude a blood vessel, it must be small enough to facilitate insertion into the body to gain access to the blood vessel. At the operative site, the clip must be capable of engaging the blood vessel where it can then be bent to pinch the blood vessel and thereby occlude blood flow. Continued effectiveness relies on the ability of the clip to remain at the operative site and to occlude blood flow until the clip is removed. With respect to safety, some of these same factors come into play. For example, it is important that the clip remain where it is placed so that it does not fall into a body cavity. This can be of particular concern in open procedures where there is generally more movement of hands and organs around the operative site, and consequently a greater probability of dislodging the clip. The clips of the past have been provided with a size facilitating insertion and placement. The clips have also been provided in different forms, but in general they have a U-shape configuration with a back section connecting opposing leg sections that initially extend in a common direction. In some configurations, a locking element is provided at the free end of each leg portion, but this feature tends to complicate ultimate removal of the clip By comparison, clips configured with leg sections having free ends are more easily removed, but rely to a greater extent on the strength of the surgical metal for occlusion and retention. Thus, for a given cross section, a metal wire with increased strength will grip the tissue, such as the blood vessel, with a greater force. This will facilitate retention of the clip, meaning that it will have increased properties for staying in place, as well as better performance of the intended function, such as occlusion. In U.S. Pat. No. 4,188,953 Klieman, et al. disclosed a clip which its uncrimped state is typical of many of the clips in that it includes a back section and opposing leg sections which initially extend generally in a common direction. A clip disclosed by Chen et al. in U.S. Pat. No. 5,160,339, is also worthy of note. This clip includes a resilient hinge means at the proximal ends of the legs and a latch means at the distal ends of the legs. It will be noted that the latch or locking means provides increased retention but tends to inhibit removability of the clips. In the absence of a latch or locking means, clips rely even more heavily on the strength of the surgical metal for retention. Clips of the past, have been made of biocompatible materials, and have typically been formed of titanium. This metal is non-ferromagnetic and consequently does not interfere with magnetic resonance imaging. Titanium is also more stable than stainless steel. Many of these advantages can be achieved by other metals or metal alloys which might also be used for clips. Titanium is known to be highly reactive with oxygen. In fact, titanium in air will rapidly form a naturally occurring, micro-thin layer of titanium oxide on its surface. This natural layer functions as a barrier against further oxygen penetration so the titanium tends to remain relatively pure and inert with this micro-thin oxidation layer. Manufacturers of titanium medical devices have gone to great lengths to maintain the material in its “as bought” condition. Thus, when the metal is purchased as titanium Grade 1, every effort has been made to maintain the ductility and other properties associated with that grade. Bending operations which induce stress into the material have typically been followed by high temperature heating to relieve those stresses. In order to avoid altering the physical properties and chemical makeup of the titanium, this heating has been done in a vacuum or inert gas. This is only one example of the vast teachings of the past which encourage one to avoid oxygen penetration beyond the natural layer. In these teachings, the coating is commonly referred to as “corrosion” and several methods are offered either to avoid the “corrosion” or eliminate the “corrosion” once it has occurred. In many settings, pride is taken in the ability to heat titanium without developing this corrosive layer. Hence, in the procedures of the past, a vacuum has been strictly and laboriously applied in order to limit exposure to gases during the heating step. The manufacturing steps are all undertaken with the intent of providing the clip with desirable properties which can optimize its performance in the operative environment. One of these desirable properties is an ability to absorb mending stresses during crimping so that the clip does not tend to open slightly when the placement force is relieved. This phenomena, commonly referred to as spring-back, results when the stresses induced by the crimping force cause the clip to open when the crimping force is removed. Another property of particular interest relates to the holding force which opposes removal of the clip from a vessel, for example. It is desirable to maintain this holding force relatively high in order that the clip can provide the desired inclusion inoperatively disposed. Unfortunately, this holding force is typically reduced when the clip has a high degree of bendability. A pull test can be performed to measure the holding strength of a particular clip design. In such a test, a clip is crimped onto a vessel or tube and the back section of the clip engaged by a small wire or other tension element. When this tension element is pulled in a direction parallel to the crimped legs of the clip, the force required to remove the clip can be measured to provide a relative indication of holding. Another test which would demonstrate the advantages of the present invention is a micro-hardness test. In this test, a diamond, the hardest material known to man, is pressed with a known force against the target material. Measurement of the resulting indentation provides a quantifiable measurement of the hardness of the material. Thus, this micro-hardness test can be used to measure the hardness at any point on the cross-sectional area of the clip wire. For example, hardness can be measured at the outer surface of the wire as well as at the core of the wire or any point-therebetween. Suffice it to say, that with respect to clips, greater strength for a given size is always desirable where sufficient ductility remains to facilitate bending the clip into its operative form. This is particularly true for open configurations of clips where retention is even more dependent upon strength. |
<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the present invention, the strength of surgical metals can be significantly increased. With respect to clips and other wire devices, the increased strength will provide better strength, reduced bendability and higher retention. Compared to clips of the past, the clips of the present invention will hold the vessels tighter, given the same cross-sectional area. With greater strength, one might expect that there would be increased spring-back. This does not appear to be the case as the spring-back is actually reduced with this process. As a result, retention is facilitated not only by the increased strength, but also the reduced spring-back. In one aspect of the invention, a surgical device includes a structural portion formed of a first element and having an outer surface disposed outwardly of an inner core. A second element is combined with the first element without creating a sure plane between the first element and the second element. This second element in combination with the first, provides the structural portion with a physical property which changes between the outer surface and the inner core. This physical property may be a co-efficient of friction, strength, or ductility, for example. In another aspect of the invention, a method for manufacturing a surgical device includes the step of forming the surgical device of a metal having an outer surface and an inner core. The metal of the surgical device is exposed to an interstatial element which is driven into the outer surface of the metal to form a combination of the metal and the interstitial element which has a physical property that changes with progressive positions toward the core of the metal. The metal may include titanium while the interstitial element may include oxygen which is driven into the titanium under high temperature to create an oxygen gradient from the outer surface to the inner core. In a further aspect, the invention includes a method for increasing the strength of a surgical device. The method includes the step of forming the device of a wire having an outer surface and an inner core. The wire is heated in the presence of an interstitial element which is driven into the outer surface of the wire. During the heating step, a concentration of the interstitial element is creased in the wire, the concentration being characterized by a first concentration at the outer surface and a second concentration less than the first concentration at the inner core. |
Hand and platform trolley |
A trolley (10) having both a hand trolley configuration, where frame (15-19) is substantially non-horizontal and only two wheels contact the ground, and a platform configuration, with frame (15-19) horizontal and trolley (10) supported on four wheels. (The drawing shows an intermediate configuration.) In the hand trolley configuration main wheels (22) are latched to spacers (28) preventing smaller wheels (25) contacting the ground: To convert to the platform configuration, main wheels (22) are swung on arms (23), which are pivotted to the middle of frame (15-19), until arms (23) about handles (20) at the other end of frame (15-19). The trolley (10) is now supported on two wheel sets (22,25) at opposite ends of frame (15-19). |
1. A trolley apparatus having a hand trolley use configuration and a platform trolley use configuration, said apparatus having a body adapted to be loaded with goods or the like when in either said platform trolley configuration where the body is substantially horizontal or in said hand trolley use configuration where the body is substantially non-horizontal, a first set of ground engaging wheels having a common axis, said first set of wheels being adapted to be attached to the body movable between two positions, a first position adjacent one end of the body when in the hand trolley use configuration and a second position adjacent the other end of the body when in the platform trolley use configuration, said first set of wheels being adapted to engage the ground when in either the hand trolley use configuration or the platform trolley use configuration, and a second set of ground engaging wheels having a common axis, said second set of wheels being attached to said one end of said body and being adapted to engage the ground when in the platform trolley use configuration. 2. The trolley according to claim 1, wherein the first set of wheels are attached to the body by pivotal arm means. 3. The trolley according to claim 2, wherein the first set of wheels are a pair of wheels attached to a pair of pivotal arms, whereby the pivotal arms are parallel and coupled together, the pivotal arms being pivotal about pivotal connections positioned substantially between the first and second positions of the first set of wheels. 4. The trolley according to clam 3, wherein axis of the first pair of wheels is spaced downwardly from the body when the wheels are in both the had trolley use configuration and the platform trolley use configuration. 5. The trolley according to claim 4, wherein the first pair of wheels have a fixed axis and are not able to be steered. 6. The trolley according to claim 1, wherein the second set of wheels do not engage the ground when in the hand trolley use configuration. 7. The trolley according to claim 6, wherein the second set of wheels are smaller in diameter than the first set of wheels and are attached to the body by brackets extending downwardly from said body when in the platform trolley use configuration. 8. The trolley according to claim 7, wherein, the second set of wheels are a pair of castor type wheels. 9. The trolley according to claim 1, wherein the body is a frame having parallel arms with cross braces therebetween. 10. The trolley according to claim 9, wherein the cross braces are adapted such that the trolley can be used in both use configurations. 11. The trolley according to claim 10, wherein a flange is provided at the one end to assist in the carrying of goods when in the hand trolley use configuration. 12. The trolley according to claim 11, wherein the flange extends perpendicularly from the frame. 13. The trolley according to claim 12, wherein the flange is pivotal about the edge of the frame to be moved to a position where it is abutting against the frame in a parallel manner. 14. The trolley according to claim 10, wherein one of the cross braces located at the other end of the frame, this cross brace acting as a handle means. 15. The trolley according to claim 14, wherein the two parallel arms and the cross brace acting as the handle means are formed from one piece of material in a U-shape. 16. The trolley according to claim 1, wherein a pair of pistol grip handles are provided adjacent the other end of the frame, the pistol grip handles extending downwardly from the frame. 17. The trolley according to claim 2, wherein the pistol grit handles provide spacers between the frame and the axis of the first pair of wheels, the ends of the spacers abutting against the pair of pivotal arms when in the platform trolley use configuration. 18. The trolley according to claim 1, wherein the fit pair of wheels are latched into the fist position when in the hand trolley use configuration. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Trolleys used to carry goods and the like include so-called hand trolleys and platform trolleys, as well as other types. A hand trolley is one which is usually has a pair of wheels attached to a pair of parallel handles or the like which are able to be gripped. In some examples, the handles are joined at their extremities with a cross member and so-called pistol grips can also be attached to the handles for ease of use. The hand trolley is generally used to tort relatively light pulled. A platform trolley is one which has a chassis or frame placed on wheels such that when the chassis or frame is loaded with goods, the platform trolley can be pushed or pulled appropriately. Such trolleys generally have three or more wheels and as well as being used to transport goods and the like can be used as mobile storage devices or mobile work platforms. It is believed that it would be advantageous to have a hand trolley which could be easily converted into a platform trolley such that the one trolley having different configurations can have multiple uses. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>An embodiment of the present invention will now be described with reference to the drawings in which FIG. 1 is a schematic side view of the trolley when in the bad trolley use configuration; FIG. 2 is a schematic front view of the trolley when in the hand trolley use configuration; FIG. 3 is a of schematic side perspective view of the trolley as it is converted from the hand trolley use configuration to the platform trolley use configuration; FIG. 4 is a schematic front perspective view of the trolley in the platform trolley use configuration; and FIG. 5 is a schematic plan perspective view of the trolley in the platform trolley configuration. detailed-description description="Detailed Description" end="lead"? |
System and method of anatomical modeling |
Methods of modeling anatomical structures, along with pathology including the vasculature, spine and internal organs, for visualization and manipulation in simulation systems. A representation of on the human vascular network is built up from medical images and a geometrical model produced therefrom by extracting topological and geometrical information. The model is constructed using topological and geometrical information. The model is constructed using segments containing topology structure information, flow domain information contour domain information and skeletal domain information. A realistic surface is then applied to the geometric model, by generating a trajectory along a central axis of the geometric model, conducting moving trihedron modeling along the generated trajectory and then creating a sweeping surface along the trajectory. A novel joint reconstruction approach is also proposed whereby a part surface sweeping operation is performed across branches of the joint and then a surface created over the resultatn holes therebetween. A 3-D mesh may also be generated, based upon this model, for finite element analysis and pathology creation. |
1. In a biomedical simulation environment, a method of forming a visually continuous surface across a joint of a plurality of anatomical branches, the method including the steps of: generating surfaces for the anatomical branches using a part-surface sweeping operation; and constructing surfaces across any holes in the surface across the joint using a patch filling method to complete the joint surface. 2. Method of claim 1 wherein the surfaces are generated by: determining an appropriate cross-section for each branch; dividing the cross-sections into portions, such that each portion is associated with a corresponding portion of a neighboring branch; performing the part-surface sweeping operation along a trajectory relating to each of the associated portions. 3. Method of claim 2 wherein the trajectories are generated using a cubic Bezier curve, and include the steps of: generating branch trajectories through vertices of each branch; determining at least one control point on each branch trajectory; forming a cubic Bezier curve between each set of neighbouring branches using the at least one control point relating to each branch. 4. Method of claim 2 wherein the part-surface sweeping operation is performed using moving trihedron modelling. 5. Method of claim 4 wherein the moving trihedron modeling includes the following steps: initiating a trihedron (Ti0, Ni0, Bi0) at an end of the trajectory with parameter t=0, such that T, N and B are unit tangent, normal and binormal vectors of the trajectory at a given point, respectively; projecting a vector Bi0 onto the plane defined by tangent vector Ti1 with parameter t=⅓, in order to obtain a new vector Bi1=Bi0−(Bi0•Ti1)Ti1; calculating vector Ni1 as the cross-product of Bi1 and Ti1; projecting the vector Bi1 onto the plane defined by tangent vector Ti2 with parameter t=⅔ in order to obtain a new vector Bi2=Bi1−(Bi1•Ti2)Ti2; calculating vector Ni2 as the cross-product of Bi2 and Ti2; projecting the vector Bi2 onto the plane defined by tangent vector Ti3 with parameter t=1 in order to obtain a new vector Bi3=Bi2−(Bi2•Ti3) Ti3; calculating vector Ni3 as the cross-product of Bi3 and Ti3. 6. Method of claim 5 wherein (Ti3, Ni3, Bi3) is used as the new start trihedron for trihedron (Ti+10, Ni+10, Bi+10). 7. Method of claim 2 wherein the construction of surfaces across any holes includes the steps of: dividing each Bezier curve of each branch surface in two on the boundary with the hole at a particular point; determining a center vertex of the hole; dividing the hole into a plurality of subpatches, using the particular points and the center vertex, the number of depending upon the number of branches; and constructing a surface across each subpatch. 8. In a biomedical simulation environment, a method of constructing a surface of a 3D object using a segmented geometrical model, including the steps of undertaking segment reconstruction and joint reconstruction using the segmented geometric model such that the joint reconstruction is in accordance with claim 2. 9. Method of claim 8 wherein the segment reconstruction includes the steps of: generating a trajectory along a central axis of the geometric model; conducting moving trihedron modeling along the generated trajectory; and creating a sweeping surface along the trajectory. 10. Method of claim 9 wherein the trajectory is generated using a piecewise Bezier curve, and further includes the steps of: creating a tangent node vector for each node of the central axis; generating at least one control point between each pair of neighbouring nodes using the tangent node vectors of the applicable pair of neighbouring nodes; forming a cubic Bezier curve using the at least one control point. 11. Computer program product including a computer usable medium having computer readable program code and computer readable system code embodied on said medium for constructing a surface on a virtual geometric anatomical model, said computer program product further including computer readable code within said computer usable medium for: undertaking the method according to claim 1. 12. In a biomedical simulation environment, a method of pathological modeling for use in the simulation of the growth of a pathology, the method including: creating a 3D surface model of the pathology; applying outward force at one or more surface points of the model; and calculating the degree of each force and the degree of deformation of the model at the one or more surface points as a result of each force. 13. In a biomedical simulation environment, a method of pathological modeling for use in the simulation of the growth of a pathology, the method including: creating a 3D surface model of the pathology; applying an appropriate weight function to the model, the weight function relating to the shape of the pathology being modeled. 14. Method of claim 13 wherein the pathology is a tumor or aneurysm and the weight function applied is a Gaussian filter. 15. Method of claim 14 wherein the Gaussian filter is G ( r , θ ) = R 0 ⅇ - r 2 2 σ 2 such that R0 is a maximum deformable position of a point on the model and a relates to the shape of the deformable surface. 16. In a biomedical simulation environment, a method of interactive pathological modeling, the method including: obtaining angiographic observations relating to a pathology; extracting geometric parameter bounds relating to the pathology from the angiographic observations; incorporating the pathological parameters into a geometric anatomical model; constructing a 3D anatomical model including the pathology from the geometric model such that the shape of the pathology is capable of modification by a user within the geometric parameter bounds. 17. In a biomedical simulation environment, a method of automatically generating FEM mesh on a virtual anatomical object model for use in simulating deformation of at least a portion of the object, the model being formed from a plurality of cross-sections each having a plurality of points on the edges of the cross-sections with edge lengths between adjacent points on each cross-section, the method including the steps of: undertaking 2D mesh generation at each cross-section; and undertaking 3D mesh generation between two adjacent cross sections by subdividing edge lengths of each cross-section to form one or more additional points and connecting corresponding points between adjacent cross-sections; and undertaking mesh refinement and/or optimization of the resultant 3D mesh. 18. Method of claim 17 wherein the 2D mesh generation is undertaken with a flexible resolution. 19. Computer program product including a computer usable medium having computer readable program code and computer readable system code embodied on said medium for generating a mesh on a virtual geometric model for FEM analysis, the model formed from a plurality of cross-sections each having a plurality of points on the edges of the cross-sections with edge lengths between adjacent points on each cross-section, said computer program product further including computer readable code within said computer usable medium for: undertaking 2D mesh generation at each cross-section; and undertaking 3D mesh generation between two adjacent cross sections by subdividing edge lengths of each cross-section to form one or more additional points and connecting corresponding points between adjacent cross-sections; and undertaking mesh refinement and/or optimization of the resultant 3D mesh. 20. Method of automatically generating a surface mesh on a object model for use in FEM analysis, the model being formed from a plurality of cross-sections each having a plurality of points on the edges of the cross-sections with edge lengths between adjacent points on each cross-section, the method including the steps of: undertaking 3D mesh generation between two adjacent cross sections by subdividing edge lengths of each cross-section to form one or more additional points and connecting corresponding points between adjacent cross-sections. 21. Method of validating the accuracy of a geometric model, including the steps of: generating a first binary volume image relating to the geometric model; generating a second binary volume image relating to a validation threshold; comparing the first binary volume image with the second binary volume image in order to obtain an indication relating to the degree of accuracy of the geometric model. 22. Method of claim 21 wherein the step of comparing the first and second volume images further includes determining the number of voxels in the first volume image that have values different from equivalent voxels in the second volume image. 23. Method of claim 22 wherein the indication is a factor achieved by dividing the number of voxels with different values by the total number of voxels, whereby the factor approaches zero for an accurate model. 24. Method of claim 21 wherein the geometric model is constructed from one or more volume images, and the steps of generating the first and second binary volume images utilize a volume model derived from parameters of the one or more volume images. 25. Method of claim 24 wherein the parameters include volume size, length, width and height. 26. In a biomedical simulation environment, a method of constructing a surface of a 3D object using a segmented geometrical model, including the steps of undertaking segment reconstruction and joint reconstruction using the segmented geometric model such that the joint reconstruction is in accordance with claim 1. 27. Computer program product including a computer usable medium having computer readable program code and computer readable system code embodied on said medium for constructing a surface on a virtual geometric anatomical model, said computer program product further including computer readable code within said computer usable medium for: undertaking the method according to claim 2. |
<SOH> BACKGROUND <EOH>Medical simulators have significant potential in reducing the cost of health care through improved training and better pretreatment planning. Further, image guided procedures, such as vascular catheterization, angioplasty and stent placement are especially suited for simulation because it is possible to place the physician at a distance from the operative site, thereby remotely manipulating surgical instruments and viewing the procedure on video monitors. For real-time and useful simulation of interventional procedures, such as catheterization, vasculature within the environment should be properly manipulated and accurately visualized. A geometric model can provide good support to these functions. In general, this requires the segmentation of topological and geometrical information from medical images before constructing a geometric model of the vasculature. In surgical simulation applications, there are several methods of geometrical modeling for visualization and manipulation. These methods can generally be divided into two types. One type builds the geometrical model up directly from original image data. This can provide an accurate representation of the anatomical structure, but the model is usually intended for specific cases and cannot be applied generally. Further, processing the three-dimensional data directly from original medial images, such as medical resonance images (MRI), computerized tomography (CT) or ultrasound scan images, is computationally demanding. For example a 512×512×64×16 bit magnetic resonance angiogram is 32 MB. This size will prohibit the implementation in real-time. The other type extracts or segments the topological and geometrical information first, then builds up the geometrical modeling from the segmented result. In this regard, it is to be appreciated that the topological information specifies vertices, edges and faces and indicates their incidence and connectivity, while the geometry specifies the equations of the surface and orientation. One way to create an object is by utilising Constructive Solid Geometry (CSG). The CSG method utilises boolean operations to construct a logical binary tree of the primitives such as spheres and cylinders, in order to represent an object by its topological and geometrical description. In this regard, the technique represents a solid 3-D object by a functional definition identifying the set of points that lie within the object. For example, the object may be defined by a Boolean function which returns a “true” if applied to a point within the object and returns a “false” otherwise. Boolean operations for medical objects, however, are not particularly meaningful. An alternative approach is that of boundary representations (B-reps). B-reps, explicitly describe the adjacency relationship of object topology and the hierarchical structure of the object geometry. An example of a B-reps based modeling system is BUILD developed by a CAD group at the University of Cambridge. This system produces a wing-edged data structure, which is a primary example of edge-based boundary models. A problem with boundary representations is that they are usually computationally expensive. For instance, the ability to compute the intersection of two surfaces usually forms the heart of a solid modeling system. Hence, the internal or core representation may significantly influence the efficiency of computation and storage for tasks like surface intersection and blending. These prior methods generally work well in engineering drafting and manufacturing where interactive design is of utmost importance. However, they do have deficiencies, particularly in medical applications, where model reconstruction from various modalities of images is an important issue. There is therefore a need for an improved approach for creating a virtual representation of an anatomical structure. There is also a need for creating improved building blocks for use in forming these anatomical-structures. Another problem that needs to be addressed in geometrical modeling is that of surface reconstruction from cross-sections. The cross-sections from the scanned medical image can be parallel or non-parallel. Based on the segmentation algorithm used, there are generally two types of extracted geometrical information, being cross-contours on each slice (i.e. parallel cross contours) or cross contours that are perpendicular to the skeleton (i.e. non-parallel). It has been found that a surface reconstructed from parallel cross-contours may not be good for visualization, especially if the central axis of the human vasculature is slanted with the slice. Further, if the scanned medical image includes different kinds of human anatomy, to date a suitable automated process for reconstructing the desired component of the image has not been developed. Surface reconstruction may be volume based or surface based. Volume based reconstruction directly triangulates the set of points making up each of the cross sections, such that they become vertices of the surface mesh. The volume-based approach is difficult to use in cases where the cross-sectional shape varies between planes and where the cross sections are non-parallel. Further, it is difficult to constrain the aspect ratios of the generated triangles, since the vertices are defined by the positions of the cross sections. This can lead to poor quality surface displays if Gouraud shading is used. In this regard, much effort is also required to detect and correct special cases where the triangulation of complex shapes might otherwise fail. Surface based reconstruction extracts the contours from the cross-sections and then connects the neighboring contours to form the surface. It can be applied to simple and complex shapes and can provide visually appealing results using computation geometry and graph theory. One problem with existing surface reconstruction methods, however is that they do not adequately allow branching junctions to be reconstructed. In this regard, the modeling of the branching junction is a challenging issue. Therefore, an improved surface based reconstruction approach is required, in order to obtain a more general and complete solution for smooth surface reconstruction. It is therefore an object of this invention to provide an improved surface based reconstruction approach as used in geometrical modeling. There is also a need for an improved surface reconstruction approach that can be used for both parallel and non-parallel cross-contours. In medical simulation environments, meshes for Finite Element Modeling (FEM), which are generally used for enhanced realism in a virtual reality environment, can be generated using the reconstructed surface. FEM analysis is an essential method for deformation simulation. Hence, in such simulation environments, it is necessary to generate the FEM meshes of anatomical structures automatically. To date a mature FEM mesh generation model has not been developed for human anatomical structures, so an automatic modeling procedure is required in medical simulation environments. It is therefore another object of this invention to provide a complete automatic FEM mesh generation method. It is also an object of this invention to provide an improved geometrical model including information relating to pathology derived from medical images of specific patients. |
<SOH> SUMMARY OF THE INVENTION <EOH>Overall the invention relates to geometrical modeling of anatomical structures for computer aided clinical applications, particularly in medical simulation environments. According to one aspect, the present invention provides, in a biomedical simulation environment, a method of forming a visually continuous surface across a joint of a plurality of anatomical branches, the method including the steps of: generating surfaces for the anatomical branches using a part-surface sweeping operation; and constructing surfaces across any holes in the surface across the joint using a patch filling method to complete the joint surface. In essence, this aspect of the invention allows information regarding the representation of the anatomical structure to be conveniently stored and compiled. It provides a solution for the problem of surface reconstruction from parallel-and non-parallel cross-sections with visually smooth surfaces rendered, wherein a novel joint construction approach deals with the difficult branching problem. The reconstructed geometrical surface allows visualization and manipulation flexibly performed, and the computational demand is within a standard PC. According to a second aspect, the present invention proposes, in a biomedical simulation environment, a method of pathological modeling for use in the simulation of the growth of a pathology, the method including: creating a 3D surface model of the pathology; applying outward force at one or more surface points of the model; and calculating the degree of each force and the degree of deformation of the model at the one or more surface points as a result of each force. According to a second aspect, the present invention provides, in a biomedical simulation environment, a method of pathological modeling for use in the simulation of the growth of a pathology, the method including: creating a 3D surface model of the pathology; and applying an appropriate filter to the model, the filter relating to the shape of the pathology being modeled. According to a third aspect, the present invention provides, in a biomedical simulation environment, a method of interactive pathological modeling, the method including: obtaining angiographic observations relating to a pathology; extracting geometric parameter bounds relating to the pathology from the angiographic observations; incorporating the pathological parameters into a geometric anatomical model; and constructing a 3D anatomical model including the pathology from the geometric model such that the shape of the pathology is capable of modification by a user within the geometric parameter bounds. In particular, the second and third aspects of the invention provide for pathology modeling in respect of vasculature. This aspect of the invention further allows models of pathology to be developed, which incorporate patient specific data, and hence are more suitable for and characteristic of patient specific applications. According to a fourth aspect, the present invention provides, in a biomedical simulation environment, a method of automatically generating FEM mesh on a virtual anatomical object model for use in simulating deformation of at least a portion of the object, the model being formed from a plurality of cross-sections each having a plurality of points on the edges of the cross-sections with edge lengths between adjacent points on each cross-section, the method including the steps of: undertaking 2D mesh generation at each cross-section; undertaking 3D mesh generation between two adjacent cross sections by subdividing edge lengths of each cross-section to form one or more additional points and connecting corresponding points between adjacent cross-sections; and undertaking mesh refinement and/or optimization of the resultant 3D mesh. According to a fifth aspect, the present invention provides a computer program product including a computer usable medium having computer readable program code and computer readable system code embodied on said medium for generating a mesh on a virtual geometric model for FEM analysis, the model formed from a plurality of cross-sections each having a plurality of points on the edges of the cross-sections with edge lengths between adjacent points on each cross-section, said computer program product further including computer readable code within said computer usable medium for: undertaking 2D mesh generation at each cross-section; undertaking 3D mesh generation between two adjacent cross sections by subdividing edge lengths of each cross-section to form one or more additional points and connecting corresponding points between adjacent cross-sections; and undertaking mesh refinement and/or optimization of the resultant 3D mesh. According to a sixth aspect, the present invention provides a method of automatically generating a surface mesh on a object model for use in FEM analysis, the model being formed from a plurality of cross-sections each having a plurality of points on the edges of the cross-sections with edge lengths between adjacent points on each cross-section, the method including the steps of: undertaking 3D mesh generation between two adjacent cross sections by subdividing edge lengths of each cross-section to form one or more additional points and connecting corresponding points between adjacent cross-sections. The fourth, fifth and sixth aspects of invention provide a general and complete FEM mesh generation method for anatomical structures from medical images. The 3D FEM mesh generation is also suitable for complex anatomy. |
Integral formwork system for the construction of pits for loading ramps |
An integral formwork system for the construction of pits (20) for loading ramps (10), comprising a set of appropriately reinforced sheet metal panels, piping and sections, bolted to each other; in particular, the formwork is of disposable type, built with specific construction, lightweight, resistant, and compact in size, in order to permit single operation casting for paving (PCL), from the pit level of the formwork without the need to provide special and expensive connecting structures such as flexible joints. Moreover, the system in question also permits the construction of overhang ledges (23) without special moulds; when work is completed, these overhang ledges (23) are able to bear the weight of the loading ramp (10) and the vehicle positioned on it (17). |
1. Integral formwork for the construction of pits (20) for loading ramps (10), wherein each ramp (10) comprises at least one metal platform (11) on which an articulated extension (12) is applied so that the flatbeds (13) of vehicles (14) can be connected to a platform (15) for the transporting of goods, said formwork including a set of reinforced panels, piping and sections, assembled together to form a disposable structure, and said pits (20) including at least one recess (18, 22) for the insertion of a tailgate (19), characterised in that said formwork further includes at least two rigid side panels (FF1, FF2), a front connecting beam (IAN), composed of at least a first horizontal metal section (TPR) whose ends are fixed to second shaped sections (PRA1, PRA2) defining a width of at least one space (VSM) for the insertion of said tailgate (19), and third sections (AP1, AP2), fixed to said first section (TPR), suitable for connecting all the elements of the formwork and for fixing a plurality of front buffers (PA1, PA2) and side plates (LAT1, LAT2). 2. Integral formwork according to claim 1, characterised in that said pits (20) are prefabricated or they are built so that said formwork remains included inside a cast concrete. 4. Integral formwork according to claim 3 characterised in that said pits (20) can also include at least one recess (18, 22) for the insertion of a tailgate (19). 5. Integral formwork according to claim 4, characterised in that it includes at least two rigid side panels (FF1, FF2), a front connecting beam (AN) composed of at least a first horizontal metal section (TPR), whose ends are fixed to second specially shaped sections (PRA1, PRA2), that define the width of at least one space (VSM) for the insertion of said tailgate (19); a third set of sections (AP1, AP2) are fixed to said first section TPR, used to unite the elements of said formwork and to fix a certain number of front buffers (PA1, PA2) and side plates (LAT1, LAT2). 6. Integral formwork according to claim 5 characterised in that said second sections (PRA1, PRA2) and said plates (LAT1, LAT2) terminate with the elements (PP1, PP2, PP3, PP4) folded back towards the rear, said plates (LAT1, LAT2) being configured so that they terminate at the top with a side (LAD1, LAD2) folded backwards with parallelepiped elements (PPP1, PPP2) on the internal side. 7. Integral formwork according to claim 5, characterised in that it also includes two stiffened external sides (FE1, FE2), a head (TE), composed of a metal plate element, possibly reinforced with sections with the application of one or more hinge piping elements (TO1, TO2, TO3) and/or one or more extra strong rod (ZA), two side head plates (LLT1, LLT2), folded over towards the interior of the pit (20), and at least one reinforced joist (TAR1, TAR2) in brick tile and/or concrete, in which gripping iron rods are inserted conformed according to a composition of reinforced prefabricated joists for floor slabs. 9. Integral formwork according to claim 5, characterised in that it includes at least one central joist (TCE) whose ends are fixed to plates (PTZ1, PTZ2) and at least one support flange (FL) of said loading ramp (10) as well as the means for fixing and assembling the various said parts. 9. Integral formwork according to claim 5, characterised in that said front connecting beam (AN) forms an external face on the loading platform (15) for the goods, and is designed to spread the weight of the casting on at least two side portions (AG1, AG2), that form an unsupported overhanging extension (23) that in turn form the space (VSM) for the insertion of the tailgate (19), said space (VSM) being defined by a first external side panel (FE1), by a first head plate (LLT1) by said head (TE), by a second head plate (LLT2), and by a second external side panel (FE2) that is connected to said front connecting beam (AN) to present an opening that is wider than the width of an upper pit (FSR) defined by said formwork, used for the installation of said loading ramp (10), and composed of an initial vertical section (AP1), an internal side panel (FF1), said head (TE) and an external side panel (FF2), that is connected to a second vertical section (AP2) and to said front connecting beam (AN). 10. Integral formwork according to claim 8, characterised in that a joist (TCE) is applied below said side panels (FF1, FF2) and equipped at each end with at least two plates (PTZ1, PTZ2), positioned on the exterior of said side panels (FF1, FF2) and fixed to the sides to bear the weight of the casting that forms said two side portions (AG1, AG2) that form the overhanging extension. 11. Integral formwork according to claim 5, characterised in that it provides for the use of side forms (CAL1, CAL2) and rear form (CAP1), designed to be used for carrying out the casting up to an established height, in order to create single or multiple loading bays through the direct fixing and connection of adjacent formwork, at least one of said forms (CAL1) being maintained at an established distance by an internal perimeter portion of said space (VSM) for tailgate insertion (19), and by a certain number of shims (DIS) and containing within this distance a certain number of rods (TND) previously positioned in a base slab (SOL) 12. Integral formwork according to claim 11, characterised in that a rolled and compacted inert material (IRC) is piled against the casting in rear and side positions where said formwork is the first or last of a row, or in the case of a single formwork. 13. Integral formwork according to claim 9, characterised in that a concrete foundation (STF) is cast in a single operation, to cover all construction around said formwork, including the layer of said rolled and compacted inert material (IRC), as far as an established height that is lower than the pre-established height of the finished flooring surface, an under-paving grid (RET) being laid above said structure, followed by the casting of the final flooring surface (PCL) in a single operation, starting from the edges of the pit. 14. Integral formwork according to claim 9 characterised in that it envisages as an alternative, a certain number of side joists (TAR1, TAR2) or plates (LOC1, LOC2), specially shaped so that they can be positioned over said external sides (FE1, FE2), on the parallelepipeds (PPP1, PPP2) and on the side head plates (LLT1, LLT2), plus complementary reinforcing stiffening means (FSO1, FSO2, PFO), designed to form a slab-beam system. 15. Integral formwork according to claim 9 characterised in that said external sides (FE1, FE2) terminating at the top and bottom with two edges folded over towards the interior of the formwork and said head (TE) composed preferably of a plate that terminates at the bottom with an edge folded inwards towards the interior of the pit (20) and at the top with a folded edge or a reinforcing section on which on which are applied one ore more portions of piping (TO1, TO2, TO3) inserted in comb fashion between other portions of piping present on the platform of the ramp (11), and designed with the insertion of special rods to form a head hinge between the ramp (10) and the platform (15). 16. Integral formwork according to claim 15, characterised in that one or more extra strong rods (ZA) are inserted behind said piping portions (TO1, TO2, TO3). 17. Integral framework for the construction of loading ramp pits as described, illustrated and claimed for the aims as specified. |
Liquid chromatograph and analysis system |
The present invention aims to provide a liquid chromatograph, an analysis system, and a gradient elution method, which are designed to permit a gradient change of eluent with higher precision and also permit a high sensitive detection or analysis. For attaining the object, there are provided: a liquid chromatograph having at least a liquid-feeding means 1 for flowing an eluent E at a predetermined flow rate, a sample-pouring means 9 for pouring a sample Sm into the eluent E, and a separation-column means 13 for separating a solute So contained in the sample Sm into components, comprising an eluent-selecting means 8 for forming branched flow paths 7 having predetermined volumes by dividing a flow path 3 of the eluent E fed from the liquid-feeding means 1, temporally storing eluents E1, E2, and soon in the branched flow paths 7, and pouring the sample Sm into the selected eluents E1, E2, and so on, and means for carrying out a gradient elution of a solute So; an analysis system comprising a mass spectrometer connected to the liquid chromatograph, and a gradient-elution method using the liquid chromatograph. |
1. A liquid chromatograph, for introducing a sample into a separation column with eluents having different compositions successively fed through a flow path and performing a gradient elution of a solute in the sample depending on elution strengths of the eluents, comprising: one high-pressure liquid-feeding pump for feeding the eluent at a constant flow rate: an eluent-storing means for temporally storing the eluents having different compositions in branched flow paths having predetermined volumes, where the branched flow paths are formed by dividing the flow path of the eluents fed from the high-pressure liquid-feeding pump; and an eluent-selecting means for successively selecting the eluents temporally stored in the branched flow paths and feeding the eluents toward the separation column. 2. The liquid chromatograph as described in claim 1, wherein a means for filling the branched flow paths respectively with the eluents from a syringe by a switching movement of a valve. 3. An analysis system, comprising a mass spectrometer connected to the liquid chromatograph described in claim 1 or claim 2. 4. A gradient elution method, comprising the use of the liquid chomatograph described in claim 1. 5. The gradient elution method as described in claim 4, wherein the eluents having different compositions are successively fed from the respective branched flow paths to a flow path extending from discharge orifice of the respective branched flow paths to the separation column and stored therein in advance. |
<SOH> BACKGROUND ART <EOH>There is an analysis technique that utilizes the so-called gradient elution method (a gradient elution technique) in which the composition (the constituent ratio) of an elute is sequentially changed and then flowed into a separation column using a high-performance liquid chromatograph (hereinafter, referred to as “HPLC”) to change the elution strength of a solute kept in the separation column. This analysis technique has been widely applied because of its advantages in that a separation requiring a great elution time can be completed within a short time, a separation between molecules having similar structures can be allowed, and so on. In this analysis technique, currently, it is general to feed the eluent at a flow velocity of about 1 ml/min. However, against the background of technical trends for increasing a sample-detecting accuracy by lowering the flow rate of a eluent in recent years, a HPLC being devised to feed the eluent at a flow velocity of as low as about 5 μl/min has been proposed. However, the HPLC designed for low flow rate had a very complicated device structure, so that there was a basic technical problem in that the operation of the HPLC was difficult. Furthermore, when a gradient elution is carried out under the conditions in which the flow velocity of the eluent is lower than 5 μl/min, it is possible to adapt a technology by which a flow path through which the eluent is transferred is splitted into a main stream and a subsidiary stream having a smaller inner diameter. Then, an analysis column is connected on the subsidary stream side, and then a gradient elution analysis is performed using an eluent flowing through the subsidary stream at a low flow velocity. However, this technology had technical problems in that a gradient elution can be hardly performed at high precision because the subsidary stream tended to be clogged, the desired low flow rate condition of the predetermined (Sub-uL/min) was hardly kept in stable, and it became difficult to confirm whether the flowing was occurred at a predetermined flow rate. Therefore, the present invention intends to provide a liquid chromatograph, an analysis system, and a method for gradient elution, which are designed so as to be allowed to make a change in gradient of an eluent at higher precision and to detect or analyze at high sensitivity by subsequently feeding the eluent under stable conditions of low flow velocity. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a block diagram that simply illustrates the configuration of a liquid chromatograph and the configuration of an analysis system provided with such a liquid chromatograph in accordance with the present invention; FIG. 2 is a schematic diagram showing the situation in which eluents E 1 , E 2 , and so on are stored in the flow path 3 ′. FIG. 3 is a diagram (graph) that shows a base line drawn by he recorder 15 in Example 3; FIG. 4 is a diagram (graph) that shows a base line drawn by the recorder 15 in Example 3; FIG. 5 is a diagram (a graph) showing a chromatograph of each mass component contained in the calmodulin trypsic digest; and FIG. 6 is a diagram (a chromatograph) showing the results in which a peptide with 600 attomol (S/N=2) could be detected when the separated component with a highest total mass was detected by a single ion monitor. detailed-description description="Detailed Description" end="lead"? |
Nsaid formulation comprising a granular composition and an extra-granular composition |
A formulation comprising a granular composition and an extra-granular composition. The granular composition comprises a plurality of solidified melt granules comprising a continuous phase of a non-steroidal anti-inflammatory drug (NSAID)). The extra-granular composition comprises a wicking agent which is insoluble in water and comprises at least one of an inorganic material, stearic acid or an insoluble salt thereof, a starch material, a cellulose material or a mixture thereof. The formulation does not contain silicon dioxide. |
1-40. (canceled) 41. A formulation comprising: (a) a granular composition comprising a plurality of solidified melt granules comprising a continuous phase of a non-steroidal anti-inflammatory drug (NSAID), and (b) an extra-granular composition comprising a wicking agent which is insoluble in water and comprises at least one of an inorganic material, stearic acid or an insoluble salt thereof, a starch material, a cellulose material or a mixture thereof, provided that the formulation does not contain silicon dioxide. 42. A formulation according to claim 41 in the form of a compressed tablet. 43. A formulation according to claim 41, wherein the NSAID has a melting point of from 30 to 300° C. 44. A formulation according to claim 41 further comprising a disintegrant. 45. A formulation according to claim 45, wherein the disintegrant is uniformly dispersed in the granular composition. 46. A formulation according to claim 44, wherein the disintegrant is uniformly dispersed in the extra-granular composition. 47. A formulation according to claim 41 comprising: (a) 30-99.9 wt % granular composition; and (b) 0.1-70 wt % extra-granular composition. 48. A formulation according to claim 44 comprising: (a) 50-99.9 wt % granular composition; and (b) 0.1-50 wt % extra-granular composition. 49. A formulation according to claim 41, wherein the wicking agent is present in an amount of from 0.1 to 30% by weight. 50. A formulation according to claim 41, wherein said extra-granular composition comprises 2-100% wicking agent. 51. A formulation according to claim 41, comprising said NSAID in a weight ratio to said wicking agent of 2.1 to 200:1. 52. A formulation according to claim 41, wherein the NSAID comprises at least one of ibuprofen, flurbiprofen, ketoprofen and naproxen or an enantiomer thereof or a salt thereof. 53. A formulation according to claim 52 comprising racemic ibuprofen or S(+)-ibuprofen. 54. A formulation according to claim 41, wherein said inorganic material comprises at least one of talc, PTFE powder, alkaline earth metal silicates, alkali metal carbonates and alkaline earth metal carbonates. 55. A formulation according to claim 54, wherein the inorganic material comprises at least one of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, magnesium carbonate, calcium carbonate, talc, PTFE powder, magnesium silicate and calcium silicate. 56. A formulation according to claim 41, wherein said stearic acid or insoluble salt thereof comprises at least one of stearic acid, magnesium stearate and calcium stearate. 57. A formulation according to claim 41, wherein the starch material comprises at least one of potato starch, maize starch, pre-gelatinised starch, rice starch and tapioca starch. 58. A formulation according to claim 41, wherein the granular composition comprises 1-25% disintegrant. 59. A formulation according to claim 41, wherein the disintegrant comprises at least one of croscarmellose sodium and sodium starch glycolate. 60. A formulation according to claim 41 further comprising a surfactant. 61. A formulation according to claim 60, wherein the wicking agent comprises at least one of stearic acid, magnesium stearate, calcium stearate, talc, maize starch and pre-gelatinised starch. 62. A formulation according to claim 41 wherein the extra-granular composition comprises: (a) 2-100% w/w said wicking agent; and (b) 0-20% w/w surfactant. 63. A formulation according to claim 41 wherein the extra-granular composition consists essentially of the wicking agent. 64. A formulation according to claim 41 comprising: (a) 50-90% w/w ibuprofen; (b) 5-20% w/w croscarmellose sodium; (c) 0.1-30% w/w said wicking agent; and (d) 0-20% w/w surfactant. 65. A formulation according to claim 62 wherein the surfactant comprises sodium lauryl sulphate or poloxamer or a mixture thereof. 66. A formulation according to claim 41 further comprising a diluent in an amount of 0.1-65% w/w. 67. A process for the preparation of a formulation according to claim 41 comprises: (a) heating a NSAID until it is molten; (b) forming the melt into solidified melt granules; and (c) combining the solidified melt granules with an extra-granular composition comprising the wicking agent. 68. A process according to claim 67 wherein the granular composition includes a disintegrant uniformly dispersed therein, and step (a) comprises: (i) combining the disintegrant with the NSAID in the solid state and heating the mixture until the NSAID is molten; or (ii) heating the NSAID until it is molten and adding the disintegrant thereto with mixing to form a mixture thereof. 69. A process according to claim 68, in which the NSAID and the disintegrant are uniformly mixed in the solid state prior to heating. 70. A process according to claim 68, comprising: (a) heating the NSAID until it is molten and then combining the molten NSAID with the disintegrant to form a mixture thereof; (b) forming said mixture into solidified melt granules with cooling; (c) combining said solidified melt granules with an extra-granular composition comprising the wicking agent. 71. A process according to claim 67, wherein the mixture is cooled to the solid state before being formed into granules. 72. A process according to claim 68, wherein the ingredients of the extra-granular composition are added sequentially to the granular composition with stirring. 73. A process according to claim 67, wherein the NSAID comprises racemic ibuprofen, flurbiprofen, ketoprofen, naproxen and/or an enantiomer thereof and/or a salt thereof. 74. A process according to claim 67, wherein the NSAID comprises ibuprofen. 75. A process according to claim 67, wherein the NSAID is melted completely during the heating step. 76. The use of a formulation according to claim 41 in the treatment of pain and/or inflammation and/or fever. 77. Use according to claim 76 in the treatment of coughs, colds, influenza, migraine, headache, rheumatic pain, neuralgia, period pain, dental pain or backache. 78. A formulation according to claim 41 in the form of a unit dose. |
Remote testing of high speed data and voice communication networks |
Faults or degradation of performance of a voice/data communication network (2) are identified without the need to dispatch service personnel by selectively testing isolated sections of the communication network. For some of these tests, the communication network address of a customer's modem under test (106, 114, 60, 66) is retrieved from a database (88) for use in directing these tests to the customer's modem (106, 114, 60, 66) and for emulating the customer's modem (106, 114, 60, 66) during one or more of the tests. |
1. A method of fault isolation on a communication network having a metallic line tester (MLT) and an Internet Service Provider (ISP) communicatively coupled to an edge gateway that provisions voice and/or data services to a customer via a conductive line, the method comprising the steps of: (a) causing the MLT to retrieve from a database a network address of a modem of the customer on the communication network, the internet protocol (IP) parameters of the customer's modem and the asynchronous transfer mode (ATM) parameters of the customer's modem; (b) synchronizing a modem of the edge gateway with the customer's modem at the network address; (c) installing the IP and ATM parameters in a modem of a test head that is coupled to the edge gateway; (d) synchronizing the test head modem with the edge gateway modem operating at the same synchronization rate that it synchronized with the customer's modem in step (b); (e) following synchronization in step (d) causing the edge gateway modem to issue a Ping test command to an IP address of a data network of the ISP; (f) receiving the result of the Ping test at the test head modem; and (g) logging the result of the Ping test with the MLT. 2. The method as set forth in claim 1, further including the steps of: if synchronization in step (b) is not achieved, causing the test head to perform a metallic test of the conductive line via the edge gateway bypassing its modem; if the metallic test passes, causing the test head to acquire a metallic signature of the customer modem via the edge gateway bypassing its modem; and if the metallic signature is acquired, synchronizing the test head modem with the customer modem whereupon, if synchronization is successful, logging an indication of such with the MLT, wherein said logging indicates the edge gateway modem is not operating properly. 3. The method as set forth in claim 2, further including the steps of: if the metallic test fails, logging an indication of such with the MLT and terminating the method, wherein said logging indicates the conductive line is not operating properly; if the metallic signature is not acquired, logging an indication of such with the MLT and terminating the method, wherein said logging indicates that the customer modem is not connected; and if the metallic signature is acquired and if synchronization between the test head modem and the customer modem is not successful, logging an indication of such with the MLT, wherein said logging indicates that the customer modem is not powered or has failed. 4. The method as set forth in claim 1, further including the step of: if synchronization in step (d) is not achieved, logging an indication of such with the MLT and terminating the method, wherein said logging indicates that the edge gateway modem is not operating properly. 5. The method as set forth in claim 1, further including the step of: if the Ping test fails, logging an indication of such with the MLT and terminating the method, wherein said logging indicates that the data network is not operating properly. 6. A method of fault isolation on a communication network having a metallic line tester (MLT) and an Internet Service Provider (ISP) communicatively coupled to an edge gateway that provisions voice and/or data services to a customer via a conductive line, the method comprising the steps of: (a) causing the MLT to retrieve from a database a network address of a modem of the customer on the communication network, the internet protocol (IP) parameters of the customer modem and the asynchronous transfer mode (ATM) parameters of the customer modem; (b) synchronizing a modem of the edge gateway with the customer modem at the network address; (c) following synchronization in step (b), causing the edge gateway modem to determine an actual data transmission rate of the customer modem; (d) causing a mode of a test head coupled to the edge gateway to perform a metallic test of the conductive line via the edge gateway bypassing its modem; (e) determining from the metallic test a calculated data transmission rate of the customer modem; (f) comparing the calculated and actual data transmission rates; (g) if the calculated and actual data transmission rates are different by more than a predetermined tolerance, adjusting parameters of the edge gateway modem so that the actual data transmission rate is within the predetermined tolerance of the calculated data transmission rate; (h) installing the IP and ATM, parameters of the customer modem in the test head modem; (i) synchronizing the test head modem with the edge gateway modem at the same synchronization rate that it synchronized with the customer modem in step (b); (j) synchronizing the edge gateway modem with an IP address of a data network of the ISP; (k) following synchronization in step (j), logging an indication of the synchronization rate with the MLT; (l) causing the edge gateway modem to issue a file download command to an IP address of the data network; (m) in response to the file download command, downloading a predetermined file to the edge gateway from the data network; (n) determining an actual download data transmission rate of the downloaded file; and (o) comparing the actual download data transmission rate to a predetermined download data transmission rate. 7. The method as set forth in claim 6, further including the step of: if the difference between the actual download data transmission rate and the predetermined data transmission rate is greater than a predetermined tolerance, logging an indication of such with the MLT, wherein said logging indicates that the data network is not operating properly. 8. The method as set forth in claim 6, further including the steps of: if synchronization in step (b) is not achieved, logging an indication of such with the MLT and terminating the method, wherein said logging indicates that the edge gateway modem or the customer modem is not operating properly; and if synchronization in step (j) is not achieved, logging an indication of such with the MLT and terminating the method, wherein said logging indicates that the data network is not operating properly. 9. A method of fault isolation on a communication network having a controller, a data network and a voice network communicatively coupled to a packet switch that facilitates communication with an edge gateway that provisions voice and/or data services to a customer, the method comprising the steps of: (a) causing the controller to retrieve from a database modem parameters of a modem of the customer; (b) synchronizing the customer's modem with a modem of the edge gateway; (c) following synchronization in step (b), determining an actual data transmission rate of the customer modem and an actual cell error rate of a data transmission by the customer modem; (d) causing a test head coupled to the edge gateway to perform a test of a conductive line connected to the customer modem via the edge gateway bypassing its modem; (e) determining from the test in step (d) an estimated data transmission rate of the customer modem; (f) comparing the actual and estimated data transmission rates of the customer modem; (g) configuring the test head modem with the customer modem parameters; (h) synchronizing the test head modem with the edge gateway modem at the same synchronization rate that it synchronized with the customer's modem in step (b); (i) initiating a voice quality test of the voice network from the edge gateway under the control of the test head via the test head modem and the edge gateway modem; (j) synchronizing the test head modem with the edge gateway modem at a data rate that is slower than the synchronization in step (h); (k) causing the edge gateway modem to issue a file download command to an IP address of the data network; (l) in response to the file download command, downloading a predetermined file from the data network to the edge gateway modem; and (m) during download of the file in step (l), initiating a voice quality test of the voice network from the edge gateway under the control of the test head via the test head modem and the edge gateway modem. 10. The method as set forth in claim 9, further including the step of: if synchronization in step (b) is not achieved, logging an indication of such with the controller and terminating the method, wherein said logging indicates that the edges gateway modem or the customer modem is not operating properly. 11. The method as set forth in claim 9, further including the steps of: if the actual cell error rate determined in step (c) is different by more than a predetermined tolerance from a predetermined cell error rate, logging an indication of such with the controller and terminating the method, wherein said logging indicates that the edge gateway modem or the customer modem is not operating properly; and if the comparison in step (f) indicates that the estimated data transmission rate is different by more than a predetermined tolerance from the actual data transmission rate, logging an indication of such with the controller and terminating the method, wherein said logging indicates that the edge gateway modem or the customer modem is not operating property. 12. The method as set forth in claim 9, further including the steps of: if the synchronization in step (h) is not achieved, logging an indication of such with the controller and terminating the method, wherein said logging indicates that the edge gateway modem is not operating properly; and if the synchronization in step (j) is not achieved, logging an indication of such with the controller and terminating the method, wherein said logging indicates that the edge gateway modem is not operating properly. 13. The method as set forth in claim 9, further including the step of: if one of the voice quality test in step (i) fails and the voice quality test in step (m) fails, logging an indication of such with the controller, wherein said logging indicates that the edge gateway, the voice network or the packet switch is not operating properly. 14. A method of fault isolation on a communication network having a controller, a data network, a voice network and an integrated data/voice network communicatively coupled to a packet switch, with the integrated data/voice network including an edge gateway coupled to the packet switch, a test head coupled to the edge gateway, and a customer modem coupled to the edge gateway via a conductive line, with the customer modem residing at a network address of the integrated data/voice network, the method comprising the steps of: (a) causing the controller to retrieve from a database the network address and modem parameters of the customer modem; (b) acquiring synchronization between a modem of the edge gateway and the customer modem via the conductive line; (c) if synchronization in step (b) is not acquired, logging an indication of such with the controller and terminating the method; (d) testing the efficacy of the conductive line between the edge gateway modem and the customer modem with the test head; (e) if the test in step (d) indicates that the efficacy of the conductive line is not within a predetermined tolerance, logging an indication of such with the controller and terminating the method; (f) installing the customer's modem parameters in a modem of the test head; (g) acquiring synchronization between the test head modem and the edge gateway modem at the same synchronization rate as that it acquired synchronization with the customer modem in step (b); (h) if synchronization in step (g) is not acquired, logging an indication of such with the controller and terminating the method; (i) initiating a test of at least one of the data network and the voice network from the edge gateway under the control of the test head via the test head modem and the edge gateway modem; (j) receiving the result of the test initiated in step (i); and (k) if the result of the test received in step (j) is not acceptable logging an indication of such with the controller and terminating the method. 15. The method as set forth in claim 14, wherein, in step (i): the test of the data network includes at least one of a Ping test and determining a data transmission rate of a file download from the data network to the edge gateway modem; and the test of the voice network includes initiating a first voice quality test of the voice network with the edge gateway modem operating at a first data rate. 16. The method as set forth in claim 15, wherein the test of the voice network in step (i) further includes initiating a second voice quality test of the voice network with the edge gateway modem operating at a second, slower data rate concurrent with the download of a file to the edge gateway modem from the data network. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention relates to isolating failures or causes of degraded performance on a voice/data communication network without the need for dispatching service personnel. 2. Description of Related Art Heretofore, one of the problems encountered with deploying and maintaining a digital subscriber line (DSL) service to a customer was the inability to fully and remotely test the communication network that included the DSL service. To this end, the prior art solution for testing DSL services included dispatching service personnel and equipment to various points on the network to determine whether the DSL service was working properly. However, such dispatches are costly and time-consuming. It is, therefore, an, object of the present invention to overcome the above problem and others by providing a method for remotely testing a communication network that provisions DSL service to a customer. Still other objects will become apparent to those of ordinary skill in the art upon reading and understanding the following detailed description. |
<SOH> SUMMARY OF THE INVENTION <EOH>Accordingly, I have invented a method of fault isolation on a communication network having a controller, a data network, a voice network and an integrated data/voice network communicatively coupled to a packet switch. The integrated data/voice network includes an edge gateway coupled to the packet switch, a test head coupled to the edge gateway, and a customer modem coupled to the edge gateway via a conductive line. The customer's modem resides at a network address of the integrated data/voice network. The method includes causing the controller to retrieve from a database the network address and modem parameters of the customer's modem. Next, synchronization is acquired between a modem of the edge gateway and the customer modem at the network address via the conductive line. If synchronization is not acquired, an indication of such is logged with the controller and the method is terminated. However, if synchronization is acquired, the efficacy of the conductive line between the edge gateway modem and the customer modem is tested by the test head. If the efficacy of the conductive lines is not within a predetermined tolerance, an indication of such is logged with the controller and the method is terminated. However, if the efficacy of the conductive line is within the predetermined tolerance, the customer's modem parameters are installed in the test head modem. Next, synchronization is acquired between a modem of the test head and the edge gateway modem at the same synchronization rate that the edge gateway modem synchronized with the customer modem., If synchronization is not acquired, an indication of such is logged with the controller and the method is terminated. However, if synchronization is acquired, a test of the data network or the voice network is initiated from the edge gateway under the control of the test head via the test head modem and the edge gateway modem. The result of the test is received at the test head via the test head modem and the edge gateway modem. If the result of the test is not within a predetermined tolerance therefor, an indication of such is logged with the controller and the method is terminated. The test of the data network can include a Ping test or determining a data transmission rate of a file download from the data network to the edge gateway. The test of the voice network can include initiating a call to the voice network and, thereafter, initiating a first voice quality test of the voice network with the edge gateway modem operating at a first data rate. The test of the voice network can further include initiating a second voice quality test of the voice network with the edge gateway modem operating at a second, slower data rate concurrent with the download of a file to the edge gateway modem from the data network. |
Methods for solubilizing and recovering fluorinate compounds |
Methods of enhancing the solubility of a fluorinated compound in an organic solvent are provided. In one embodiment, carbon dioxide gas pressure is applied to the solvent at a pressure effective to enhance the solubility of the fluorinated compound. The method may further include recrystallizing the fluorinated compound by reducing the pressure of the carbon dioxide gas. Also provided are methods of conducting a reaction using a fluorinated compound in an organic solvent In one embodiment, the method comprises applying carbon dioxide pressure to an organic solvent comprising at least one substrate and a fluorinated catalyst, in an effective amount to solubilize the catalyst; and permitting the fluorinated catalyst to catalyze the reaction of the substrate to form a product. The catalyst is optionally separated from the reaction product and solvent after the reaction by the release of the pressure. |
1. A method of recrystallizing a fluorinated compound in an organic nonhalogenated solvent, the method comprising: applying carbon dioxide gas to the solvent at a pressure effective to enhance the solubility of the fluorinated compound; and recrystallizing the fluorinated compound by reducing the pressure of the carbon dioxide gas. 2. The method of claim 1, wherein the pressure of the carbon dioxide gas is about 30-300 bar. 3. The method of claim 1, wherein the organic solvent is pentane, hexane, heptane, octane, nonane, decane, cyclopentane, cyclohexane, dioxane, benzene, toluene, xylene, ether, diisopropylether, ethyl acetate, tetrahydrofuran, triethylamine, tripropylamine, N,N,N′,N′-tetramethylethylenediamine, methylene chloride, chloroform, chlorobenzene, acetone, nitrobenzene, acetonitrile, formamide, acetamide, dimethylformamide, dimethylacetamide, nitromethane, methanol, ethanol, propanol, butanol, isopropanol, sec-butanol, tert-butanol, ethylene carbonate, propylene carbonate, glyme, diglyme, dimethylsulfone, or dimethylsulfoxide, or a mixture thereof. 4. The method of claim 1, 2, or 3, wherein the fluorinated compound is a catalyst. 5. The method of claim 4, wherein the catalyst is an organometallic complex of a main group metal, main group semimetal, transition metal, actinide or lanthanide. 6. The method of claim 4, wherein the catalyst comprises highly fluorinated ligands. 7. The method of claim 1, 2, or 3, wherein the pressure is released in about 24 hours or less. 8. The method of claim 7, wherein the pressure is released in about 4 hours or less. 9. The method of claim 1, 2, or 3 further comprising providing a plurality of individual sample containers, each container comprising a fluorinated compound in an organic non-halogenated solvent, the method further comprising: applying carbon dioxide gas to the solvent in the individual sample containers at a pressure effective to enhance the solubility of the fluorinated compound; and recrystallizing the fluorinated compounds in the individual sample containers by reducing the pressure of the carbon dioxide gas. 10. The method of claim 9, wherein the method further comprises varying components of the individual samples. 11. The method of claim 9 further comprising screening the recrystallized fluorinated compounds for crystallinity, chemical purity or optical purity. 12. A method of conducting a reaction using a fluorinated compound in an organic solvent, the method comprising applying carbon dioxide gas to an organic solvent comprising a fluorinated compound at a pressure effective to solubilize the fluorinated compound during the reaction. 13. The method of claim 12, wherein the pressure of the carbon dioxide gas is about 40 to 90 bar. 14. The method of claim 12 or 13, wherein the compound is a catalyst. 15. The method of claim 12 or 13, wherein the method comprises: applying carbon dioxide pressure to a non-halogenated organic solvent comprising at least one substrate and a fluorinated organometallic catalyst, in an effective amount to solubilize the catalyst; permitting the catalyst to catalyze the reaction of the substrate to form a product; and reducing the carbon dioxide gaseous pressure, thereby to cause precipitation of the catalyst. 16. The method of claim 15, further comprising recovering the catalyst after the reaction from the solvent. 17. The method of claim 15, wherein carbon dioxide pressure is applied at about 40 to 90 bar. 18. The method of claim 15, wherein the reaction is hydrogenation, hydroboration, hydroformylation, cyclopropanation, C—H insertion reactions, oxidation, hydroxylation, isomerization, coupling reaction, olefin metathesis, polymerization, hydrosilylation, hydrocyanation, epoxidation, or a Diels-Alder reaction. 19. The method of claim 15, wherein the catalyst is an organometallic complex of a main group metal, main group semimetal, transition metal, actinide or lanthanide. 20. The method of claim 12, the method comprising: applying carbon dioxide pressure to an organic solvent comprising at least one substrate and a fluorinated organometallic catalyst, in an effective amount to solubilize the catalyst; permitting the catalyst to catalyze the reaction of the substrate to form a product; and reducing the carbon dioxide gaseous pressure, thereby to cause precipitation of the catalyst. 21. The method of claim 12 or 13, further comprising including a fluorinated support material in the organic solvent, wherein the fluorinated support material is capable of adsorbing the catalyst when the carbon dioxide pressure is reduced. 22. The method of claim 21, wherein the fluorinated support material is a fluorinated polymer, or an inorganic or organic support material comprising fluorinated organic groups. 23. The method of claim 21, wherein the method comprises: applying carbon dioxide pressure to a non-halogenated organic solvent comprising at least one substrate and a fluorinated organometallic catalyst, in an effective amount to solubilize the catalyst; providing a fluorinated support material in the solvent; permitting the catalyst to catalyze the reaction of the substrate to form a product; and reducing the carbon dioxide gaseous pressure, thereby to permit precipitation of the catalyst and adsorption of the fluorinated catalyst on the support material. 24. The method of claim 23, wherein the fluorinated support material is a fluorinated polymer, or an inorganic or organic support material comprising fluorinated organic groups. 25. The method of claim 23, further comprising isolating the support material having the fluorinated catalyst thereon from the solvent. 26. The method of claim 25, further comprising reusing the support material having the fluorinated catalyst thereon to catalyze a second reaction. 27. The method of claim 23, wherein the fluorinated catalyst is adsorbed onto the support material prior to application of the carbon dioxide pressure, and is released from the support material after application of the carbon dioxide pressure. 28. The method of claim 12, wherein the method comprises conducting a plurality of said reactions, wherein individual reactions vary in reaction conditions. 29. The method of claim 28, wherein the plurality of reactions are done in plural different reaction containers; wherein individual reaction containers comprise an organic solvent, at least one reaction substrate, and a fluorinated organometallic catalyst, and wherein the method comprises: applying carbon dioxide pressure to the reaction containers in an effective amount to solubilize the catalyst; permitting the catalyst to catalyze the reaction of the substrate to form a product in the reaction containers; and reducing the carbon dioxide gaseous pressure, thereby to cause precipitation of the catalyst in the reaction containers. 30. The method of claim 29, wherein the reaction containers are provided within a sealable reaction vessel. 31. The method of claim 29, wherein the amount or identity of at least one of the organic solvent, the reaction substrate, or the catalyst vary in the different reaction containers. 32. The method of claim 31, wherein the method comprises varying the solvent in the different reaction containers. 33. The method of claim 31, wherein the method comprises varying the identity of the catalyst in the different reaction containers. 34. The method of claim 31, wherein the method comprises varying the concentration of the catalyst or reaction substrate in different reaction containers. 35. The method of claim 29, wherein the method further comprises screening the reaction for a reaction product in the individual containers. 36. The method of claim 29, wherein the solvent is a non-halogenated organic solvent. 37. The method of claim 10 further comprising screening the recrystallized fluorinated compounds for crystallinity, chemical purity or optical purity. 38. The method of claim 14, wherein the method comprises: applying carbon dioxide pressure to a non-halogenated organic solvent comprising at least one substrate and a fluorinated organometallic catalyst, in an effective amount to solubilize the catalyst; permitting the catalyst to catalyze the reaction of the substrate to form a product; and reducing the carbon dioxide gaseous pressure, thereby to cause precipitation of the catalyst. 39. The method of claim 38, further comprising recovering the catalyst after the reaction from the solvent. 40. The method of claim 38, wherein carbon dioxide pressure is applied at about 40 to 90 bar. 41. The method of claim 38, wherein the reaction is hydrogenation, hydroboration, hydroformylation, cyclopropanation, C—H insertion reactions, oxidation, hydroxylation, isomerization, coupling reaction, olefin metathesis, polymerization, hydrosilylation, hydrocyanation, epoxidation, or a Diels-Alder reaction. 42. The method of claim 38, wherein the catalyst is an organometallic complex of a main group metal, main group semimetal, transition metal, actinide or lanthanide. 43. The method of claim 14, further comprising including a fluorinated support material in the organic solvent, wherein the fluorinated support material is capable of adsorbing the catalyst when the carbon dioxide pressure is reduced. 44. The method of claim 43, wherein the fluorinated support material is a fluorinated polymer, or an inorganic or organic support material comprising fluorinated organic groups. 45. The method of claim 43, wherein the method comprises: applying carbon dioxide pressure to a non-halogenated organic solvent comprising at least one substrate and a fluorinated organometallic catalyst, in an effective amount to solubilize the catalyst; providing a fluorinated support material in the solvent; permitting the catalyst to catalyze the reaction of the substrate to form a product; and reducing the carbon dioxide gaseous pressure, thereby to permit precipitation of the catalyst and adsorption of the fluorinated catalyst on the support material. |
<SOH> BACKGROUND ART <EOH>Fluorous biphasic catalysis methods have been described in the art. A review of fluorous phase separation techniques in catalysis is described in de Wolf et al., Chem. Soc. Rev. 28(1): 37-41(1999); Hope and Stuart, J. Fluorine Chem., 100(1-2): 75-83 (1999); Fish, R. H., Chem. Eur. J, 5:1677-1680 (1999); and Barthel-Rosa and Gladysz, Coord. Chem. Rev., 192: 587-605 (1999). Fluorous biphasic catalysis is a method of homogeneous catalysis that allows the catalyst and the products to be separated after the reaction. In this scheme, shown in FIG. 1 , a highly fluorinated catalyst is dissolved in a highly fluorinated solvent (the fluorous solvent) and organic reagents are dissolved in a traditional organic liquid. The two liquid solutions are placed together, and the reaction takes place, often requiring heating and stirring. After the reaction, the organic products are removed by pipetting off the organic liquid solution. The catalyst remains in the fluorous liquid. Unfortunately, the fluorous solvents used as the lower liquid phase are usually volatile, environmentally damaging and expensive to replace. An example of fluorous biphasic catalysis is the fluorous biphase hydroformylation of olefins as described in Horváth and Rabai (1994), Science 266(5182): 72-75. Supercritical antisolvent precipitation, in which a solid compound is dissolved in an organic solvent and then made to precipitate as a fine powder by the rapid addition of carbon dioxide gas, has been described in Reverchon, E., J. Supercrit. Fluids, 15: 1-21 (1999); Bertucco, A., “Precipitation and crystallization techniques” in Chemical Synthesis using Supercritical Fluids; Jessop and Leitner, Eds.; Wiley-VCH: Weinheim, 1999, pp 108-126; and Field et al. J. Am. Chem. Soc., 122, 2480-2488 (2000). The article by Field also described a somewhat slower addition of carbon dioxide gas in order to obtain very small crystals of the solid compound. Methods of synthesis and separation in which organic/fluorous phase separation techniques are used to effect separations, and compositions of matter comprising fluorous Si, Sn and Ge compounds are described in U.S. Pat. Nos. 6,156,896; 6,376,676; 6,372,906; 5,777,121; and 5,859,247. Crystallizing under gas pressure, in which an organic compound is made to melt by the addition of carbon dioxide pressure and then is made to crystallize by the slow release of the carbon dioxide, is described in Freund and Steiner, Crystallization under Gas Pressure” in High Pressure Engineering, von Rohr and Trepp, Eds., Elsevier Science B. V. (1996). This technique is limited to those few compounds which can be made to melt by carbon dioxide pressure at moderate temperatures. The growth of crystals from supercritical carbon dioxide or related fluids is described in U.S. Pat. No. 4,512,846; Tai and Cheng, AIChE Journal, 41:2227-2236 (1995). In this technique, an organic compound such as naphthalene is dissolved in supercritical carbon dioxide and then made to crystallize by slow release of the carbon dioxide pressure. The observation that highly fluorinated metal complexes have good solubility in supercritical carbon dioxide was described in Laintz et al., J. Supercritical Fluids, 4:194-198 (1991). The observation that highly fluorinated surfactants have good solubility in carbon dioxide is described in Consani, K. A. and Smith, R. D., J. Supercrit. Fluids, 1990, 3: 51-65 (1990). Polymerization of styrene in solutions with compressed carbon dioxide as antisolvent is described in Liu et al., J. Supercritical Fluids, 20:171-176 (2001). Fluorous solvents are disadvantageous because of their long lifetime in the environment, high cost, and contribution to the greenhouse effect. It would be advantageous if the use of fluorous solvents could be avoided in solvation, recrystallization and catalytic reaction techniques using fluorinated compounds. |
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