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V-CAD data is prepared by dividing external data 12 consisting of boundary data of an object into rectangular parallelepiped cells 13 having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into internal cells 13a positioned on the inner side of the object and boundary cells 13b including a boundary face, and a modeling unit quantity of a prototyping material 7 is changed in accordance with sizes of the internal cell 13a and the boundary cell 13b of a modeling portion. The prototyping material 7 is a resin, lumber powder, a low-fusing-point metal, metal powder, ceramics powder or a mixture of a binder and one of these materials, and its modeling unit quantity is set in such a manner that the modeling unit quantity is smaller than a capacity of a corresponding cell and does not protrude from the boundary plane of the cell. As a result, by using the V-CAD data, a program for rapid prototyping can be simplified, and a model production time can be greatly reduced. |
1. A rapid prototyping method using V-CAD data, comprising the steps of: preparing V-CAD data obtained by dividing external data consisting of boundary data of an object into rectangular parallelepiped cells having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into internal cells positioned on the inner side of the object and boundary cells including a boundary face; and changing a modeling unit quantity of a prototyping material in accordance with sizes of the internal cell and the boundary cell of a modeling portion. 2. The rapid prototyping method according to claim 1, wherein the prototyping material is a resin, lumber powder, a low-fusing-point metal, metal powder, ceramics powder, or a mixture of a binder and one of these materials. 3. The rapid prototyping method according to claim 1, wherein a modeling unit quantity of the prototyping material is set in such a manner that the modeling unit quantity is smaller than a capacity of a corresponding cell and does not protrude from the boundary plane of the cell. 4. A rapid prototyping apparatus using V-CAD data, comprising: a storage device which stores V-CAD data obtained by dividing external data consisting of boundary data of an object into rectangular parallelepiped cells having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into internal cells positioned on the inner side of the object and boundary cells including a boundary face; a data generation program which generates a program used to manufacture the object from the V-CAD data by rapid prototyping; a material supply device which changes a modeling unit quantity of a prototyping material in accordance with sizes of the internal cell and the boundary cell of a modeling part and supplies the prototyping material; and an NC control device which controls the material supply device based on the data generation program. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Technical Field of the Invention The present invention relates to a rapid prototyping method and apparatus using V-CAD data, which can store entity data combining a shape and a physical property with a small storage capacity. 2. Description of the Related Art The rapid prototyping is also referred to as a photo-solidification modeling method or stereolithography, and generally creates a three-dimensional object by solidifying a photo-curing resin with light. FIGS. 1A to 1 D are principle views of the rapid prototyping. (A) data of a three-dimensional model 1 produced by three-dimensional CAD or X-ray CT is horizontally sliced by a computer in order to generate cross-sectional shape data. (B) a liquid surface of a liquid photo-curing resin 2 is irradiated with a scanning laser beam 3 along slice data. The photo-curing resin is cured in such a manner that only a part irradiated with the laser beam has a given thickness. In this manner, a solidified layer 4 according to the cross-sectional shape data is formed. (C) Then, a table 5 having the solidified layer 4 (shaped object) mounted thereon is moved by only a distance corresponding to a pitch with which the model 1 was sliced, and an uncured thin resin layer is formed on the upper surface of the solidified layer. At this moment, a flattening operation called recoat is usually performed by using a member called a blade, and the surface of the uncured resin liquid is evenly smoothed. Subsequently, the surface is likewise irradiated with the scanning laser beam 3 according to the cross-sectional shape, and the solidified layer is united with the preceding solidified layer 4 . (D) By repeating the steps B and C, the target three-dimensional model is created. The above-described rapid prototyping is characterized in that a three-dimensional object can be created from the CAD data without using a mold, and used in many fields such as production of a master model for precision casting or the like, manufacture of a map or a stereo object and others. However, the above-described conventional rapid prototyping has a problem that not only steps on the surface of a finished three-dimensional object become large when a slice pitch of the model is roughened but production requires more than several days. Further, on the contrary, when the slice pitch is set small and the solidified layer per one process is thinned in order to increase the precision of the object to be created, not only a program for the rapid prototyping is complicated but introducing of the uncured liquid becomes difficult due to surface tension, and the recoating time becomes long or a remaining surface of recoat is generated. |
<SOH> SUMMARY OF THE INVENTION <EOH>On the other hand, the inventors of the present invention and others invented and filed a “method of storing entity data” by which entity data combining a shape and a physical property with a small storage capacity (Japanese Patent Application No. 025023/2001, not laid-open). This method of storing entity data divides external data consisting of boundary data of an object into rectangular parallelepiped internal cells and boundary cells having boundary planes orthogonal to each other in accordance with octree (oct-tree) division, and stores various physical properties for the respective cells. By this method, a shape, a structure, physical information and history of an object can be managed in an integrated fashion, data concerning a series of processes such as design, processing, assembling, test, evaluation and others can be managed with the same data, and CAD and simulation can be integrated. It is to be noted that the entity data combining the shape and the physical property is referred to as “V-CAD data”. The present invention has been contrived in order to solve the above-described problems by using this method. That is, it is an object of the present invention to provide a rapid prototyping method and apparatus which can simplify a program for rapid prototyping and greatly reduce a model production time. According to the present invention, there is provided a rapid prototyping method using V-CAD data, comprising the steps of: preparing V-CAD data by dividing external data ( 12 ) consisting of boundary data of an object ( 1 ) into rectangular parallelepiped cells ( 13 ) having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into internal cells ( 13 a ) positioned on the inner side of the object and boundary cells ( 13 b ) including a boundary face; and changing a modeling unit quantity of a prototyping material ( 7 ) in accordance with sizes of the internal cell ( 13 a ) and the boundary cell ( 13 b ) of a modeling portion. According to a preferred embodiment of the present invention, the prototyping material ( 7 ) is a resin, lumber powder, low-fusing-point powder, metal power, ceramics power, or a mixture of a binder and one of these materials. Furthermore, the modeling unit quantity of the prototyping material ( 7 ) is set in such a manner that the modeling unit quantity is smaller than a capacity of a corresponding cell and does not protrude from the boundary plane of the cell. Moreover, according to the present invention, there is provided a rapid prototyping apparatus using V-CAD data, comprising: a storage device ( 22 ) which stores V-CAD data obtained by dividing external data ( 12 ) consisting of boundary data of an object ( 1 ) into rectangular parallelepiped cells ( 13 ) having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into internal cells ( 13 a ) positioned on the inner side of the object and boundary cells ( 13 b ) including a boundary face; a data generation program ( 24 ) which generates a program for manufacturing the object from the V-CAD data by rapid prototyping; a material supply device ( 26 ) which supplies a prototyping material ( 5 ) while changing its modeling unit quantity in accordance with sizes of the internal cell ( 13 a ) and the boundary cell ( 13 b ) of a modeling portion; and an NC control device ( 28 ) which controls the material supply device based on the data generation program. According to the method and apparatus of the present invention mentioned above, since the V-CAD data is stored, which is obtained by dividing the external data ( 12 ) of the object ( 1 ) into rectangular parallelepiped cells ( 13 ) having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into the internal cells ( 13 a ) positioned on the inner side of the object and the boundary cells ( 13 b ) including the boundary face, the external data ( 12 ) can be stored by using a small storage capacity as a hierarchy of the cells. In addition, since the program for manufacturing the object by rapid prototyping is generated based on the V-CAD data, the program can be simplified. Additionally, since the modeling unit quantity of the prototyping material ( 7 ) is changed in accordance with sizes of the cells ( 13 a and 13 b ) of the object (modeling portion), the material is laminated so as not to protrude from the boundary planes of the cells with a relatively large agglomerate of the material which substantially corresponds to a capacity of each cell being determined as a modeling unit. Therefore, the number of all cells is small, and the number of laminations is thus small, thereby greatly reducing the model production time. Other objects and advantageous features of the present invention will be apparent from the following description in conjunction with the accompanying drawings. |
Ultra-precision machining method and device for heterogeneous material |
(A) V-CAD data of an object (1) is prepared. (B) A processed surface shape after NC processing is predicted by simulation using the V-CAD data. (C) The object is subjected to NC processing by a predetermined NC program, and a processed surface shape after NC processing is measured, and (D) processing correction data is obtained from a difference between the processed surface shapes acquired by simulation and measurement, and the NC program is corrected based on the processing correction data. As a result, the ultra-precise processing is enabled even if a workpiece or a tool has low rigidity and an inconstant quantity of deformation. |
1. An ultra-precise processing method for an inhomogeneous material, comprising the steps of: (A) preparing V-CAD data obtained by dividing external data consisting of boundary data of an object into rectangular parallelepiped cells having boundary planes orthogonal to each other in accordance with octree division, and separating the respective divided cells into internal cells positioned on the inner side of the object and boundary cells including a boundary face; and (B) generating an NC program by using the V-CAD data and subjecting the object to NC processing by using the NC program. 2. The ultra-precise processing method for an inhomogeneous material according to claim 1, further comprising: (C) predicting a processed surface shape of the object after NC processing by simulation using the V-CAD data; (D) measuring a processed surface shape of the object after NC processing; and (E) obtaining processing correction data from a difference between the processed surface shapes acquired by the simulation and the measurement, and correcting the NC program based on the processing correction data. 3. The ultra-precise processing method for an inhomogeneous material according to claim 2, wherein a stress at the time of attaching the object, a load and a quantity of deformation due to heat generation/vibrations during processing, roughness, a transmittance, and quantities of deformation of a processing tool and a processing system are simulated in the simulation, and prediction data of a quantity of deformation, roughness and a transmittance in each portion of the object is thereby generated. 4. The ultra-precise processing method for an inhomogeneous material according to claim 2, wherein the simulation is carried out by mesh generation based on the V-CAD data of the object by using a finite element method. 5. The ultra-precise processing method for an inhomogeneous material according to claim 2, wherein the simulation is carried out by a finite element method through modeling and mesh generation of the processing tool and the processing system. 6. The ultra-precise processing method for an inhomogeneous material according to claim 2, wherein measurement data of a shape, a dimension error, roughness and a transmittance in each portion of the object after NC processing is generated in the measurement. 7. The ultra-precise processing method for an inhomogeneous material according to claim 2, wherein the measurement performs surface measurement using a contact type probe having a low contact pressure, a laser or a non-contact type probe using the atomic force, and optical measurement of a transmittance. 8. The ultra-precise processing method for an inhomogeneous material according to claim 1, wherein the NC processing includes cutting processing, grinding processing, or a composite process thereof. 9. The ultra-precise processing method for an inhomogeneous material according to claim 8, wherein the grinding processing uses electrolytic dressing using a metal bonded grinding stone. 10. An ultra-precise processing apparatus for an inhomogeneous material, comprising: a storage device which stores V-CAD data obtained by dividing external data consisting of boundary data of an object into rectangular parallelepiped cells having boundary planes orthogonal to each other in accordance with octree division and separating the respective divided cells into internal cells positioned on the inner side of the object and boundary cells including a boundary face, the storage device further storing a simulation program used to predict a processed surface shape after NC processing by simulation using the V-CAD data, and a data correction program used to correct the NC program; an NC processing device which subjects the object to NC processing by a predetermined NC program; and a measurement device which measures a processed surface shape of the object on the NC processing device after NC processing, wherein processing correction data is obtained from a difference between the processed surface shapes acquired by simulation and measurement, and the NC program is corrected based on the processing correction data. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Technical Field of the Invention The present invention relates to an ultra-precise processing method and apparatus for an inhomogeneous material, which can perform ultra-precise processing even when a workpiece or a tool has low rigidity and an inconstant deformation quantity. 2. Description of the Related Art FIG. 1A is a type drawing showing a processing step of a large-diameter lightweight mirror for a large reflecting telescope used in the outer space. This large-diameter lightweight mirror 1 includes a thin reflecting plate 2 (for example, a thickness of 3 to 5 mm) supported by a honey-comb body 3 in order to reduce the weight. Although this large-diameter lightweight mirror has a large diameter of, e.g., 300 to 700 mm, its weight is restricted to less than 150 kg. Conventionally, when processing and forming a high-precision and mirror-surface-like high-quality (which will be simply referred to as “ultra-precise” hereinafter) reflecting surface on the surface of the above-described large-diameter lightweight mirror, a processing tool 4 (for example, a cylindrical grinding stone) is moved along a predetermined curve (for example, a parabola) by an NC control while rotating the large-diameter lightweight mirror 1 around its center axis Z, thereby processing a reflecting plate 2 . In FIG. 1A , however, the reflecting plate 2 is just partially supported by the honey-comb body 3 , and the rigidity of the reflecting plate 2 at a part not supported by the honey-comb body 3 is low. Therefore, during the grinding process using the processing tool, a contact arc length between the processing tool and the reflecting plate 2 (workpiece) largely varies depending on a processing position, and the processing resistance also greatly fluctuates. Therefore, the deformation of the workpiece itself partially differs, and deformation as indicated by a thin line 2 ′ in FIG. 1B is generated, for example. As a result, although the processing tool is subjected to precise positional control by the NC control in order to process the workpiece, ultra-precise processing is difficult when the rigidity of the workpiece or the tool is low and its quantity of deformation is inconstant. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention has been contrived in order to solve the above-described problems. That is, it is an object of the present invention to provide an ultra-precise processing method and apparatus for an inhomogeneous material, which enable ultra-precise processing even when a workpiece or a tool has low rigidity and an inconstant quantity of deformation. The inventors of the present invention and others invented and filed a “method of storing entity data” by which entity data combining a shape and a physical property can be stored with a small storage capacity (Japanese Patent Application No. 025023/2001, not laid-open). This method of storing entity data divides external data consisting of boundary data of an object into rectangular parallelepiped internal cells and boundary cells having boundary planes orthogonal to each other in accordance with octree (oct-tree) division, and stores various physical properties in accordance with the respective cells. By this method, a shape, a structure, physical information and history of an object can be managed in an integrated fashion, data concerning a series of processes such as design, processing, assembling, test, evaluation and others can be managed with the same data, and CAD and simulation can be integrated. It is to be noted that the entity data combining the shape and the physical property is referred to as “V-CAD data” hereinafter. The present invention uses the above-described V-CAD data and performs ultra-precise processing of an inhomogeneous material by utilizing both simulation and measurement. That is, according to the preset invention, there is provided an ultra-precise processing method for an inhomogeneous material, comprising the steps of: (A) preparing V-CAD data obtained by dividing external data consisting of boundary data of an object ( 1 ) into rectangular parallelepiped cells ( 13 ) having boundary planes orthogonal to each other in accordance with octree division, and separating the respective divided cells into internal cells ( 13 a )positioned on the inner side of the object and boundary cells ( 13 b ) including a boundary face; and (B) generating an NC program by using the V-CAD data and subjecting the object to NC processing by the NC program. According to a preferred embodiment of the present invention, (C) a processed surface shape of the object after NC processing is predicted by simulation using the V-CAD data, (D) the processed surface shape of the object after NC processing is measured, and (E) processing correction data is obtained from a difference between processed surface shapes acquired by the simulation and the measurement, and the NC program is corrected based on the processing correction data. Further, according to the present invention, there is provided a ultra-precise processing apparatus for an inhomogeneous material comprising: a storage device ( 24 ) which stores V-CAD data ( 14 ) obtained by dividing external data consisting of boundary data of an object ( 1 ) into rectangular parallelepiped cells ( 13 ) having boundary planes orthogonal to each other in accordance with octree division, and separating the respective divided cells into internal cells ( 13 a )positioned on the inner side of the object and boundary cells ( 13 b ) including a boundary face, the storage device further storing a simulation program ( 20 ) used to predict a processed surface shape after NC processing by simulation using the V-CAD data, and a data correction program ( 22 ) which corrects the NC program; an NC processing device ( 26 ) which subjects the object to NC processing by using a predetermined NC program; and a measurement device ( 28 ) which measures the processed surface shape of the object on the NC processing device after NC processing, wherein processing correction data is obtained from a difference between processed surface shapes acquired by the simulation and the measurement and the NC program is corrected based on the processing correction data. According to the method and apparatus of the present invention mentioned above, since the V-CAD data is stored, which is obtained by dividing the external data of the object ( 1 ) into rectangular parallelepiped cells ( 13 ) having boundary planes orthogonal to each other in accordance with octree division, and separating the respective divided cells into the internal cells ( 13 a )positioned on the inner side of the object and the boundary cells ( 13 b )including the boundary face, the external data can be stored by using a small storage capacity as a hierarchy of the cells. Further, since the processed surface shape after NC processing is predicted by simulation by using the V-CAD data, accurate simulation can be performed taking physical properties of respective portions into consideration even if the object is an inhomogeneous material and has low rigidity and an inconstant quantity of deformation. Furthermore, the object is actually subjected to NC processing by a predetermined NC program, the processed surface shape after this processing is measured, the processing correction data is obtained from a difference between the processed surface shapes acquired by the simulation and the measurement, and the NC program is corrected based on the processing correction data. Therefore, the processing characteristics which cannot be predicted by the simulation can be also taken into consideration for the next NC program. Thus, even if the rigidity of a tool or the like other than a workpiece is low or there is an error factor in the processing system itself, their influence can be avoided and ultra-precise processing is enabled. According to a preferred embodiment of the present invention, in the simulation, a stress when attaching the object, a load and a quantity of deformation due to heat generation/vibrations during processing, roughness, a transmittance, and quantities of deformation of a processing tool and a processing system are simulated, and prediction data of a quantity of deformation, roughness and a transmittance of each portion of the object is thereby generated. Furthermore, the simulation is carried out by using a finite element method by mesh generation based on the V-CAD data of the object. Moreover, the simulation is carried out by using the finite element method through modeling and mesh generation of the processing tool and the processing system. By these methods, the prediction accuracy by simulation can be increased. In addition, in the measurement, measurement data of a shape, a dimension error, roughness and a transmittance at each part of the object after NC processing is generated. Additionally, in the measurement, there are carried out surface measurement using a contact type probe with a low contact pressure, a laser, a non-contact type probe using the atomic force and/or optical measurement of a transmittance. The accuracy of the measurement can be increased by using these measurement means. Additionally, the NC processing includes cutting processing, grinding processing or a composite process thereof. Further, the grinding processing uses electrolytic dressing utilizing a metal bonded grinding stone. The high-precision and high-quality ultra-precise processing is enabled by using the above-described processing means. Other objects and advantageous features of the present invention will be apparent from the following description in conjunction with the accompanying drawings. |
Acrylic polymer latex dispersions as additives for inhibiting paraffin deposits in crude oils and compositions containing same |
This invention relates to latex dispersions that are based on (co)polymers with one or more n-alkyl (meth)acrylate monomers with n a varying from 6 to 40, and optionally one or more monomers that are not very water-soluble of the (meth)acrylic and/or vinyl type, optionally one or more polar monomers that are selected from among the (meth)acrylamides and their derivatives and optionally one or more monomers that are selected from among the ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides. These dispersions are obtained by radical-type emulsion polymerization in the presence of water. They can be used as is for the inhibition of the deposition of paraffins that are contained in the crude petroleum hydrocarbons or else diluted in one or more solvents. |
1. A latex dispersion, comprising: (1) 5 to 70 parts by weight of one or more (co)polymers, whose units come from: A—50 to 100%, by weight of one or more monomers of n-alkyl (meth)acrylate, with n separating the number of carbon atoms in the alkyl and being of 6 to 40, B—0 to 50%, by weight of one or more (meth)acrylic or vinyl monomers (having a water solubility of less than 5% at 20° C.) selected from n-alkyl (meth)acrylates with n less than or equal to 6, 2-ethyl hexyl (meth)acrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl versatates, vinyl pivalate, vinyl laurate, and stryenes, C—0 to 50%, by weight of one or more polar monomers that are selected from (meth)acrylamides and their derivatives, N-methylolacrylamide, dialkylaminoethyl (meth)acrylates, the monoolefinic derivatives of sulfonic acid and phosphoric acid, acrylamidomethyl propane sulfonic acid, N-vinylpyrrolidone, vinylpyridine and its derivatives, and hydroxyalkyl (meth)acrylates, D—either 0 to 0.5% by weight of one or more monomers that are selected from ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides when C=0%, or up to 40% by weight of one or more monomers that are selected from ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides when C # 0%. (2) 0 to 30 parts by weight of a co-solvent or a mixture of co-solvents, parts by weight, selected from ketones, methylethylketone or methylisobutylketone, aromatic solvents, toluene, xylene and mixtures of aromatic hydrocarbons, alcohols, butanol or isopropanol, glycols and polyglycol ethers, ethylene or propylene glycol, diethylene glycol or dipropylene glycol, (3) 0.1 to 10, parts by weight of one or more surfactants (ionic surfactants and/or nonionic surfactants and/or protective colloids such as polyvinyl alcohols and/or amphiphilic polymers that are selected from sulfates or sulfonates of fatty alcohols or alkylphenol, alkylbenzene sulfonates and sulfosuccinates, quaternary ammonium salts, dimethyldialkylammonium chlorides and ethoxylated fatty alcohols). (4) water (sufficient quantity for 100), and optionally other components comprising initiating agents, buffering agents, transfer agents and surfactants with a low hydrophilic-lipophilic balance. 2. A latex dispersion according to claim 1, comprising as co-solvent(s) one or more liquid polyols, for which the amount of water represents more than 40% of the weight of solid polyol(s). 3. A later dispersion according to claim 1, comprising: (1) about 30 to about 35 parts by weight of said (co)polymer(s), (2) about 14 to about 18 parts by weight of said co-solvent or mixture of co-solvents, (3) about 1 to about 4 parts by weight of said surfactants, (4) the addition to 100 parts by weight of water, and at least one initiating agent, at least one transfer agent, and at least one buffering agent. 4. A process for preparation of latex dispersions as defined in claim 1, comprising conducting radical-type emulsion polymerization in water of the monomers in the presence of surfactant(s) and optionally in the presence of one or more co-solvents. 5. A process according to claim 4, wherein the radical-type initiating agents are selected from peroxides persulfates, organic hydroperoxides and peroxides, hydrogen peroxide, peracids, diazo compounds, 4,4′ azobis(4-cyanopentanoic) acid, or 2,2-azobis(2-amidinopropane) hydrochloride or redox systems, or ammonium persulfate combined with sodium metabisulfite. 6. A process according to claim 4, wherein the polymerization reaction is conducted over a range of temperatures of from 20 to 90° C. 7. A process according to claim 4, wherein the polymerization is performed in the presence of at least one buffering agent and/or at least one transfer agent. 8. A process according to claim 4, comprising a post-addition of organic solvent(s), and/or surfactant(s) having an HLB that is less than or equal to 5. 9. A process comprising adding to crude petroleum a latex dispersion as defined in claim 1 to inhibit the deposition of paraffins in the crude petroleum. 10. A process according to claim 9, wherein said adding comprises direct addition in the crude oil, or in the form of dilute compositions that contain said dispersions and one or more solvents such as water and/or one or more organic solvents or latex co-solvents. 11. A crude petroleum comprising a sufficient amount of a latex dispersion according to claim 1, to inhibit deposition of paraffins. 12. A latex dispersion according to claim 1 comprising B, C or D. 13. A latex dispersion according to claim 1, wherein the A monomers comprise benenyl acrylates. 14. A latex dispersion according to claim 3, wherein the A monomers comprise benenyl acrylates. 15. A latex dispersion according to claim 11, comprising 5-25 parts by weight of said co-solvent or mixture of co-solvents. 16. A latex dispersion according to claim 15, wherein said co-solvent or mixture of co-solvents comprises monomethyl ethers of dipropylene glycol. 17. A latex dispersion according to claim 15, wherein said co-solvent or mixture of co-solvents comprise N-vinyl pyrrolidone. 18. A latex dispersion according to claim 1, wherein said dispersion comprises: (1) 5 to 58 parts by weight of one or more (co)polymers, whose units come from: A—70 to 100% by weight of one or more monomers of n-alkyl (meth)acrylate with n being 14 to 30, B—0 to 30% by weight of said one or more (meth)acrylic or vinyl monomers, C—0 to 30% by weight of said one or more polar monomers, D—either 0 to 0.5% by weight of one or more monomers that are selected from ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides when C=0%, or up to 40% by weight of one or more monomers that are selected from ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides when C # 0%. (2) 5 to 25 parts by weight of said co-solvent or said mixture of co-solvents, (3) 0.1 to 8 parts by weight of said one or more surfactants. (4) water (sufficient quantity for 100), and optionally other components comprising initiating agents, buffering agents, transfer agents and surfactants with a low hydrophilic-lipophilic balance. 19. A latex dispersion according to claim 1, wherein said dispersion comprises: (1) 5 to 50 parts by weight of one or more (co)polymers, whose units come from: A—70 to 100% by weight of one or more monomers of n-alkyl (meth)acrylate with n being 14 to 30, B—0 to 30% by weight of said one or more (meth)acrylic or vinyl monomers, C—0 to 30% by weight of said one or more polar monomers, D—either 0 to 0.5% by weight of one or more monomers that are selected from ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides when C=0%, or up to 40% by weight of one or more monomers that are selected from ethylenically unsaturated monocarboxylic and/or dicarboxylic acids or anhydrides when C # 0%. (2) 5 to 20 parts by weight of said co-solvent or said mixture of co-solvents, (3) 0.5 to 5 parts by weight of said one or more surfactants. (4) water (sufficient quantity for 100), and optionally other components comprising initiating agents, buffering agents, transfer agents and surfactants with a low hydrophilic-lipophilic balance. 20. A latex dispersion according to claim 1, wherein said one or more (meth)acrylic or vinyl monomers having a water solubility of less than 5% at 20° C. are selected from n-alkyl (meth)acrylates with n less than or equal to 6,2-ethyl hexyl (meth)acrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl versatates, vinyl pivalate, vinyl laurate, and α-methyl styrene. 21. A latex dispersion according to claim 1, wherein of said co-solvent or mixture of co-solvents are selected from methylethylketone, methylisobutylketone, toluene, xylene, butanoyl, isopropanol, ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, and monomethyl or ethyl propylene or dipropylene glycol. 22. A latex dispersion according to claim 1, comprising as co-solvent(s) one or more liquid polyols, for which the amount of water represents more than 50% of the weight of solid polyol(s). 23. A process according to claim 6, wherein the polymerization reaction is conducted for a period from 0.5 to 4 hours. 24. A process according to claim 7, wherein said at least one buffering as agent is sodium tetraborate and/or said at least one transfer agent is an alkyl mercaptan. 25. A process according to claim 8, wherein said organic solvent(s), and/or surfactant(s) having an HLB that is less than or equal to 5 is a fatty sorbitan esters. |
<SOH> TECHNICAL FIELD <EOH>The technical field of this invention is that of crude petroleum hydrocarbons and additives that are intended to improve their conditions of use. The crude petroleum hydrocarbons can contain significant paraffin fractions, of which the amount and the exact nature are variable according to the extraction fields. At well temperature, the paraffins are liquid and dissolved in the crude oil. During the oil's rise to the surface, its temperature drops, and the paraffins, by crystallizing, form a three-dimensional grid of needles and flakes. This results in a loss of fluidity that makes the production, the transport, the storage and even the treatment of these oils very difficult. The clogging in the pipelines and treatment equipment is frequent. |
Closure cap |
A closure (10) is provided and includes a tamper-evident band (40). The band (40) has a plurality of retaining flaps (60) which engage under a container neck annular retaining bead (23) when the closure is first applied. The flaps have a ratchet surface (86a, 190) for engaging a complimentary surface on the container neck (20). The flaps also have spacer means (85a, 85b, 186) for pushing them into a more vertical inclination under the bead (23). The ratchet arrangement and spacer means ensure reliable separation of the tamper-evident band (40). |
1. A closure cap (10), the closure comprising a top panel (30), a cylindrical skirt (35) depending from the periphery of the top panel, and a tamper-evident band (40) frangibly connected to the open end of the skirt, the tamper-evident band (40) has a plurality of circumferentially spaced retaining flaps (60), in use the retaining flaps extend radially inwardly and are directed towards the top panel (30) so as to engage under an annular retaining bead (23) on a container neck (20), characterised in that the flaps (60) include a ratchet surface (86a, 190) adapted to engage a corresponding surface on the container neck, and in that the retaining flaps include spacer means (85a, 85b, 186) which push the flap away from the neck. 2. The closure cap (10) as defined in claim 1, wherein the flaps (60) are connected to the lower edge of the tamper-evident band (40) for hinged movement so that they can be turned from a downward, as-moulded condition to an upward condition prior to application to the container. 3. The closure cap (10) as defined in claim 1, wherein the ratchet surface (86a, 190) of the flap is its lateral edge. 4. The closure cap (10) as defined in claim 1, wherein the spacer means (85a, 85b) is a fin. 5. The closure cap (10) as defined in claim 4, wherein there are two fins (85a, 85b), located at each lateral edge of the flap (60). 6. The closure cap (10) as defined in claim 1, wherein the spacer means (85a, 85b) is formed by a fold in part of the flap (60). 7. The closure cap (110) as defined in claim 1, wherein the spacer means is a surface projection (186). 8. The closure cap (10) as defined in claim 1, wherein the spacer means increases in width towards the free edge of the flap (60). 9. The closure cap (10) as defined in claim 1, wherein the length of the closure cap is no greater than 15 mm. 10. The closure cap (110) as defined in claim 1, wherein adjacent flaps (160) are interconnected by intermediate web elements (161). 11. In combination, a closure cap (10) and a container neck (20), the closure cap (10) comprising a top panel (30), a cylindrical skirt (35) depending from the periphery of the top panel, and a tamper-evident band (40) frangibly connected to the open end of the skirt, the tamper-evident band (40) has a plurality of circumferentially spaced retaining flaps (60), in use the retaining flaps extend radially inwardly and are directed towards the top panel so as to engage under an annular retaining bead (23) on the container neck (20), characterised in that, the container neck (20) includes one or more ratchet elements (24) mutually spaced under the annular retaining bead (23), the flaps include a ratchet surface (86a, 190) for engaging the ratchet elements, and in that the flaps 60 include spacer means (85a, 85b, 186) which push them away from the neck (20). 12. The closure cap (10) as defined in claim 2, wherein the ratchet surface (86a, 190) of the flap is its lateral edge. |
Method to identify modulators for human 3alpha-hydroxysteroid dehydrogenase |
3 α-hydroxysteroid dehydrogenase (3a-HSD) plays a central role in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The high resolution structure of human type III 3a-HSD crystallized in complex with cofactor NADP is determined by X-ray diffraction. Furthermore the active site is determined. The structure coordinates of the enzyme may be used to design and select novel classes of modulators to human type III 3a-HSD. |
1. A method for identifying an inhibitor to the human type III 3a-HSD enzyme, comprising the steps of a) designing or selecting computationally a potential inhibitor by using the atomic coordinates of the human type III 3a-HSD enzyme or co-complexes, e.g. as described in Table 1; and/or b) obtaining a potential inhibitor by performing a NMR screen with the human type 1113a-HSD and candidate compounds, e.g. from a library of compounds; and/or c) obtaining a potential inhibitor by performing a NMR reporter screen with the human type III 3a-HSD, a first inhibitor candidate to human type III 3a-HSD with a dissociation constant smaller than 2 mM which is either already known or found by a method according to step a) or b) and further a second candidate compound, e.g. from a library of compounds; and/or d) determining the activity of the potential inhibitor from step a), b) or c) at the human type III 3a-HSD enzyme. 2. The method of claim 1, comprising a further step d), said step comprises the step of docking said potential inhibitor to the three-dimensional structure of human type III 3a-HSD enzyme or co-complexes, as described in Table 1, and employing the obtained three-dimensional structure relation to design or select further inhibitors. 3. The method of claim 1, comprising a further step e), said step comprises the step of crystallizing the in step a), b) or c) obtained potential inhibitor with human type III 3a-HSD enzyme or co-complexes, e.g. as described in Table 1, determining the X-ray structure, comparing the three-dimensional structure of the so obtained new co-complex with the formerly known structures of human type III 3a-HSD enzyme and employing the obtained three-dimensional structure difference to design or select further potential inhibitors. 4. The method according to claim 1, wherein said potential inhibitor Is designed de novo. 5. The method according to claim 1, wherein said potential inhibitor is designed from a known inhibitor. 6. The method according to claim 1, wherein said potential inhibitor is a competitive inhibitor of human type III 3a-HSD. 7. The method according to claim 1, wherein said step of employing a three-dimensional structure to design or select said compound comprises the steps of: a) identifying chemical entities or fragments capable of associating with said enzyme; and b) assembling the identified chemical entities or fragments into a single molecule to provide the structure of said potential inhibitor. 8. The method according to claim, wherein said first inhibitor candidate in step c) is 2-acetylbenzofuran. 9. A crystalline complex of human type III 3a-HSD and NADP exhibiting essentially the atomic coordinates listed in Table 1. 10. A process for the production of a crystalline complex according to claim 9, comprising the step of growing the crystalline complex in 50-200 mM ammonium sulfate or ammonium acetate, 25-200 mM MES, pH 6.0 or 25-200 mM sodium citrate, 20-30% PEG monomethylether 2000 or 5000 or 20-30% PEG 2000, 4000, 6000, or 8000; 0-10% additives, and 0-20 mM DTT. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Human 3a-HSD s play central roles in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The 3a-HSD is a member of the aldo-keto reductase (AKR) superfamily. In general, the function of mammalian 3a-HSD s is to convert (reduce) 5α- and 5α,3-ketosteroids into 5α,3α- and 5α,3α-tetrahydrosteroids, respectively, and to further oxidize these 3α-reduced tertrahydrosteroids back to their parent 3-keto steroidal precursors. The steroids that are target substrates of the 3a-HSDs are androgens and progestins. For example, in the prostate the potent androgen 5α-dihidrotestosterone will be converted by the 3a-HSD into the weak androgen 3α-androstanediol. By contrast, in the central nervous system, 3a-HSD can regulate the occupancy of the g-aminobutyric acid (GABA) A receptor by converting 5α-dihydroprogesterone into 3α-hydroxy-5a-pregnan-20-one (allopregnanolone), a potent allosteric effector of the GABA A receptor (K d =10 −9 M) (Majewski, M. D. et al. (1986) Science 232, 1004-1007; Majewski, M. D. (1992) Prog. Neurobiol. 38, 379-395; Lambert, J. J. et al., Trends Pharmacol. Sci. 16, 295-303). In the presence of GABA, allopregnanolone will potentiate GABA A -mediated chloride conductance. As a result 3a-HSD is responsible for the production of anxiolytic steroids, and decreased activity in this pathway has been implicated in the symptoms of pre-menstrual syndrome (Morrow, A. L. et al. (1998) Nature (London) 395, 652-653). Thus 3a-HSD isoforms regulate the occupancy of both a nuclear receptor (androgen receptor) and a membrane-bound chloride-ion gated channel (GABA A receptor) and may have profound effects on receptor function. For these reasons the 3α-HSD is considered a molecular switch turning on and off the function of steroid hormones in the prostate and of neurosteroids in the CNS. Four human 3a-HSD isoforms have been cloned, sequenced and characterized: type-1 3α-HSD (AKR1C4), type-2 3α(17β)-HSD (AKR1C3), type-3 3α-HSD (AKR1C2), and 20α(3α)-HSD (AKR1C1), sharing at least 84% amino acid and sequence identity. Of these isoforms only type-2 and type-3 are expressed in the brain with type-3 being the predominant form present in the CNS. Types-2 and -3 3α-HSDs share almost 90% nucleotide sequence identity and 88% amino acid homology. Their putative substrate binding pockets and catalytic domains are highly conserved (as are among the other members of the AKR superfamily). The type-3 isoform is believed to be the major form responsible for the oxidation (turning off) of the anxiolytic GABA A receptor-active neurosteroid allopregnanolone in the brain. All 3a-HSD s are NAD(P)(H) dependent oxido-reductases implying that NAD + , NADH, NADP + and NADPH are the cofactors. The oxidative function requires the presence of NAD + or NADP + , while NADPH is being utilized for the reduction of 3-ketosteroids. Known inhibitors of the 3a-HSD are the class of the non-steroidal anti-inflamatory drugs (NSAIDs) (Penning et al., PNAS (1983) 80, 4504-4508) and the selective serotonin reuptake inhibitors (SSRIs) that were reported to potentiate and inhibit at the same time the 3a-HSD (Griffin and Mellon, PNAS (1999) 96, 13512-13517. |
<SOH> SUMMARY OF THE INVENTION <EOH>In one aspect the invention comprises the crystalline structure of human type III 3a-HSD and to determine its structure coordinates. The structure coordinates of a human type III 3a-HSD crystal are used to reveal the atomic details of the active site or the cofactor binding site of the enzyme and to solve the structure of a different human type III 3a-HSD crystal, or a crystal of a mutant, homologue or co-complex, of human type III 3a-HSD. It is also an object of this invention to use the structure coordinates and atomic details of human type III 3a-HSD, or its mutants or homologues or co-complexes, to provide potentiators or inhibitors of human type III 3a-HSD. In still a further aspect, the invention provides a method of screening compounds for their ability to modulate the human type III 3a-HSD. detailed-description description="Detailed Description" end="lead"? |
Fungicidal active substance combinations containing trifloxystrobin |
The Present invention relates to novel active compound combinations comprising a known oxime ether derivative (trifloxystrobin) and imidacloprid, which combinations are highly suitable for controlling phytopathogenic fungi and insects. |
1-8. (canceled) 9. An active compound combination comprising at least one compound of the formula (I) and (1) a compound of formula (II) and/or (2) a compound of formula (III) and/or (3) a compound of formula (IV) and/or (4) a compound of formula (V) and/or (5) a compound of formula (VI) and/or (6) a compound of formula (VII) and/or (7) a compound of formula (VIII) 10. An active compound combination according to claim 9 wherein the weight ratio of the active compound of formula (I) to (i) the active compound of the formula (II) is from 1:0.1 to 1:10, (ii) the active compound of the formula (III) is from 1:0.05 to 1:20, (iii) the active compound of the formula (IV) is from 1:0.05 to 1:20, (iv) the active compound of the formula (V) is from 1:0.05 to 1:20, (v) the active compound of the formula (VI) is from 1:0.05 to 1:20, (vi) the active compound of the formula (VII) is from 1:0.05 to 1:20, and/or (vii) the active compound of the formula (VIII) is from 1:0.05 to 1:20. 11. A method for controlling fungi comprising allowing an effective amount of an active compound combination according to claim 9 to act on the fungi and/or their habitat or on the plants, types of plants, seeds, soils, areas, materials, or rooms to be kept free from the fungi. 12. A method for controlling insects comprising allowing an effective amount of an active compound combination according to claim 9 to act on the insects and/or their habitat or on the plants, types of plants, seeds, soils, areas, materials or rooms to be kept free from the insects. 13. A method according to claim 11 comprising applying a compound (I) and compound (II) and/or compound (III) and/or compound (IV) and/or compound (V) and/or compound (VI) and/or compound (VII) and/or compound (VIII) according to claim 9 simultaneously together or separately or successively. 14. A method according to claim 12 comprising applying a compound (I) and compound (II) and/or compound (III) and/or compound (IV) and/or compound (V) and/or compound (VI) and/or compound (VII) and/or compound (VIII) according to claim 9 simultaneously together or separately or successively. 15. Propagation material treated by the method of claim 11. 16. Propagation material treated by the method of claim 12. 17. A fungicidal or insecticidal composition comprising an effective amount of an active compound combination according to claim 9 and one or more extenders and/or surfactants. 18. A process for preparing a fungicidal or insecticidal composition comprising mixing an active compound combination according to claim 9 with one or more extenders and/or surfactants. |
Providing photonic control over wafer borne semiconductor devices |
Disclosed are methods for providing wafer photonic flow control to a semiconductor wafer (1700) having a substrate (1720), at least one active layer (1765) and at least one surface layer (1710). Photonic flow control can be achieved through the formation of trenches (1725) and/or insulating implants (1730) formed in said wafer (1700), whereby active regions (1760) are defined by trenches (1725) that operate as nonconductive areas (1750). Methods of and systems for wafer level burn-in (WLBI) of semiconductor devices are also disclosed. Photonic flow control at the wafer level is important when using WLBI methods and systems. |
1. A method for providing photonic flow control over VCSEL devices borne by a semiconductor wafer (1700) having a substrate (1720), at least one active component layer (1765) and a surface layer (1710), comprising the step of: forming at least one trench (1725) into said semiconductor wafer (1700), thereby defining nonconductive regions (1750) and further defining boundaries between active component regions (1760) thereby separated by said at least one trench (1725), 2. The method of claim 1, wherein said step of forming at least one trench (1725) includes the step of etching said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765). 3. The method of claim 1, wherein said step of forming at least one trench (1725) includes the step of milling said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765). 4. The method of claim 1, wherein said step of forming at least one trench (1725) includes the step of engraving said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765). 5. A method of claim 1, further comprising the step of: implanting isolation material (1730) into said at least one trench (1725). 6. The method of claim 5, wherein said isolation material is an optical absorbing material (1730). 7. A method for providing parasitic current control over photonic devices represented by at least one active component layer (1765) borne by a semiconductor wafer (1700), said semiconductor layer (1700) having a substrate (1720), said at least one active component layer (1765) and at least one surface layer (1710), comprising the steps of: forming at least one trench (1725) extending from said surface layer (1710) through said at least one active component layer (1765) near said substrate (1720), wherein said at least one trench thereby defines lo nonconductive regions (1750) and sets forth a nonconductive area between active component regions (1760) that operate as photonic devices on the semiconductor wafer (1700); and implanting photonic isolation material (1730) into said at least one trench (1725) formed between said photonic devices represented by said is active component regions (1760), wherein said at least one trench (1725) extends from said surface layer (1710) through said at least one active component layer (1765). 8. The method of claim 7, wherein said isolation material (1730) is an optical absorbing material. 9. The method of claim 7, wherein said step of forming at least one trench (1725) includes the step of etching said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765) towards said substrate (1720). 10. The method of claim 9, wherein said isolation material (1730) is an optical absorbing material. 11. The method of claim 7, wherein said step of forming at least one trench (1725) includes the step of milling said at least one trench (1725) into said surface layer (1710) and said active component layers (1765) up to said substrate (1720). 12. The method of claim 11, wherein said isolation material (1730) is an optical absorbing material. 13. The method of claim 7, wherein said step of forming at least one trench (1725) includes the step of engraving said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765). 14. The method of claim 13, wherein said isolation material (1730) is an optical absorbing material. 15. The method of claim 8, wherein said step of forming at least one trench (1725) includes the step of etching said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765). 16. The method of claim 8, wherein said step of forming at least one trench (1725) includes the step of milling said at least one trench (1725) into said surface layer (1710) and said at least one active component layer (1765). 17. The method of claim 8, wherein said step of forming at least one trench (1725) includes the step of engraving said at least one trench (1725) into said surface (1710) layer and said at least one active component layer (1765). 18. A semiconductor wafer (1700) bearing more than one active optical device and optimized for photonic flow control, said semiconductor wafer (1700) comprising: a substrate (1720); at least one active layer (1765) formed above said substrate (1720); a surface layer (1710) formed above said at least one active layer (1765); at least one trench (1725) extending from said at least one surface layer (1710) through said at least one active layer (1765) towards said substrate (1720), said at least one trench (1725) defining space between active regions (1760) formed within said at least one active layer (1765) and separated by said at least one trench (1725); at least one electrical contact (1715) formed on said at least one surface layer 1710 and associated exclusively with each of said at least one active region (1760); and a common contact formed in communication with said substrate 1720. 19. The system of claim 18, wherein said at least one electrical contact (1715) is formed by said at least one trench (1720), wherein said at least one trench (1725) is formed in said wafer (1700) from said at least one electrical contact (1715) through said surface layer (1710) and through said at least one active layer (1740), towards said substrate (1720), said at least one trench (1725) thereby defining nonconductive regions (1750) and separate said at least one electrical contact (1715) associated with each of said active regions (1760) also formed by said at least one trench (1725). 20. The system of claim 18, further including photonic isolation material (1730) implanted into said at least one trench (1720). 21. The system of claim 20, wherein said isolation material (1730) is an optical absorbing material. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Solid-state semiconductor devices are found in most electronic components today. For example, semiconductor lasers are important devices in applications such as optoelectronic communication systems and high-speed printing systems. It is common for more than 60,000 semiconductor laser components to be fabricated on a single wafer. There continues to be increased interest in vertical cavity surface emitting lasers (VCSELs). VCSELs are typically made by growing several layers of reflective material on a substrate material. VCSELs include a first mirrored stack, formed on the substrate by semiconductor manufacturing techniques, an active region, formed on top of the first mirrored stack, and a second mirrored stack, formed on top of the active region. By providing a first contact on top of the second mirrored stack, and a second contact on the backside of the substrate, a current is forced through the active region, thus driving the VCSEL. VCSELs can be fabricated/grown with combinations of gallium, arsenic, nitrogen, aluminum, antimony, phosphorous and/or indium placed within or about a typical GaAs substrate. Historically, the manufacturing of semiconductors has been a very elaborate and expensive multi-step process. Component burn-in generally refers to the process of thermally and/or electrically testing newly fabricated semiconductor components. Burn-in allows for the individual identification of faulty components coming for a lot or batch. Currently, components are burned-in at the “package level”, which means that the individually-packaged devices are typically tested after being derived from a wafer. Each component is tested and placed in sockets to be burned-in either as a packaged unit or to be tested as bare die (before packaging). Either die or package level burn-in can be costly for manufacturers because it is labor intensive. Each component has to be tested, requiring plenary human intervention. Although wafer level burn-in (WLBI) methods and systems are currently being explored by the semiconductor industry, proposed systems and methods generally require that a plurality of electrical probes contact a plurality of electrical contacts on a wafer. Such systems can be complex and require extra care with regard to probe and contact alignment. For example, U.S. Pat. No. 6,339,329 issued to Nakata et al., entitled “Method of testing electrical characteristics of multiple semiconductor integrated circuits simultaneously”, is typical of the technological direction being taken in the industry for WLBI. The Nakata et al. patent teaches simultaneous testing of a plurality of semiconductor integrated circuit elements by bringing a plurality of probe terminals into contact with a plurality of testing electrodes associated respectively with a plurality of semiconductor integrated circuit elements on a wafer and applying a voltage to each of the testing electrodes from the common voltage supply line via a plurality of positive temperature coefficient elements. The semiconductor fabrication industry needs methods and systems for reducing the costs and associated labor currently required to carry out device burn-in. Further, the semiconductor industry needs WLBI methods and systems that can be used in the manufacturing and test of semiconductor components having front and back contacts, such as VCSELs, diodes, LEDs, and other semiconductor devices. The present inventors have recognized that it would be advantageous to remedy current burn-in procedures by describing methods and systems of accomplishing WLBI of components. During WLBI operations, however, the present inventors have discovered that lack of current and/or photonic control between devices borne by a single wafer can be problematic, resulting in inaccurate burn-in and/or damaged devices. The present inventors have therefore invented systems and methods to control photonic flow between wafer borne electronic devices during wafer level burn-in processing. Accordingly, the present invention is described and presented as novel methods and means to address the shortcomings currently found with WLBI processes. |
<SOH> SUMMARY OF THE INVENTION <EOH>The following summary of the invention is provided to facilitate an understanding of some of the innovative features unique to the present invention and is not intended to be a full description. A full appreciation of the various aspects of the invention can be gained by taking the entire specification, claims, drawings, and the abstract as a whole. Additional objects and advantages of the current invention will become apparent to one of ordinary skill in the art upon reading the specification. Wafer level burn-in (WLBI) methods and systems can reduce the need for package level burn-in and can reduce overall component production costs. The WLBI system described herein has two distinct electrodes for the application of electrical bias on each side of a wafer having back and front electrical contacts for a plurality of semiconductor devices born by the wafer. Cooling systems can also enable the application of an uniform temperature to a wafer undergoing burn-in. Yet current and/or photonic flow control throughout wafer-borne devices is generally needed and can generally only be provided directly at the component level. The WLBI contacts apply bias to the full area of the electronic device wafer's device contacts and substrate surfaces. At times, current and/or photonic leakage can occur between neighboring devices on a wafer. The present invention describes a manner in which electronic devices borne on the same wafer can avoid shorting where photonic flow is channeled to the appropriate active regions of each device. Control of photons that flow outside of the intended region can be controlled through the implementation of several designs. It is an object of the present invention to provide means of controlling photon flow between semiconductor devices borne on a semiconductor wafer. Such control is useful when undertaking methods of and systems for conducting WLBI of semiconductor devices. In accordance with addressing the limitations of the prior art, presented are methods and systems for buming-in electronics components at the wafer level, or WLBI, using photonic control means. It is another feature of the present invention to describe a method of achieving WLBI for semiconductor devices wherein a wafer containing semiconductor devices is fabricated, undergoes WLBI, individual devices are derived from the WLBI, and operational devices are made available for use (e.g., shipment or end-use). It is another feature of the present invention to describe WLBI methods including consistent application of electrical power and thermal temperature to wafer-born devices during a WLBI procedure. It is another feature of the present invention to describe WLBI methods including consistent application of thermal temperature to wafer-born devices during a WLBI procedure. In accordance with aspects of the present invention, diffusion patterns on the electronic device wafer surface can create positive and negative polarity regions. In accordance with aspects of the present invention, metallization patterns on the electronic device wafer surface can direct current flow. In accordance with aspects of the present invention, implant patterns (e.g., sacrificial layers) on the electronic device wafer surface can create nonconductive regions. In accordance with aspects of the present invention, trenches, etched, milled, or otherwise engraved into the surface of a wafer between devices represented by active layers can control photonic flow. In accordance with aspects of the present invention, trenches filled with implants can minimize electrical or photonic flow outside of active regions associated with said devices. In accordance with aspects of the present invention, oxidation patterns formed vertically and/or horizontally on a wafer can control photonic flow (These formations can include, but are not limited to, oxidation horizontally from vertical trenches). In accordance with aspects of the present invention, optical barriers, is including but not limited to, trenches can be patterned into the electronic device wafer surface to prevent lateral photon propagation and photogenerated current flow in lateral regions outside of the intended region. In accordance with aspects of the present invention, dielectric patterns can be formed on an electronic device wafer surface. In accordance with aspects of the present invention, dielectric materials can also include, but are not limited to, nitride, oxide, polyamide, and photoresist. |
Tablet dispenser |
The present invention relates to an apparatus (1, 1′) for dispensing tablets, also in the form of pills, dragees or the like, having means for holding a blister pack (20), means for pushing out a tablet (21) from the blister pack and also means for setting taking times and means for displaying taking times. The invention provides for the apparatus (1, 1′) to have a bottom part (11, 101) and a lid (12, 102), removably connected to the bottom part (11), for holding the blister pack (20) and also having means (18, 43) for pushing out the tablets (21) from the blister pack (20), the arrangement of the means (18, 41) being matched to the arrangement of the tablets (21) in the blister pack (20) which is to be held. The present invention also relates to a lid (12, 102) and to a bottom part (11, 101) for such an apparatus. |
1. An apparatus (1, 1′) for dispensing tablets, also in the form of pills, dragees or the like, having means for holding a blister pack (20), means for pushing out a tablet (21) from the blister pack and also means for setting taking times and means for displaying taking times, wherein the apparatus (1, 1′) has a bottom part (11, 101) and a lid (12, 102), removably connected to the bottom part (11), for holding the blister pack (20) and also having means (18, 43) for pushing out the tablets (21) from the blister pack (20), the arrangement of the means (18, 41) being matched to the arrangement of the tablets (21) in the blister pack (20) which is to be held. 2. The apparatus as claimed in claim 1, wherein the lid (12, 102) has recesses (13, 41) having centered holes (14, 42) which hold pushbuttons (18, 43) such that they cannot be lost. 3. The apparatus as claimed in claim 1, wherein the bottom part (11) has at least one support (15). 4. The apparatus as claimed in claim 1, wherein a grid or mesh (16) having holes (17) whose arrangement corresponds to the arrangement of the means (18, 43) is provided. 5. The apparatus as claimed in claim 4, wherein the grid or mesh (16) is provided in the bottom part (11, 101). 6. The apparatus as claimed in claim 4, wherein the grid or mesh (16) is provided in the lid (12, 102). 7. The apparatus as claimed in claim 1, wherein the bottom part (11, 101) has a dispensing chute (11′) and a dispensing opening (11″). 8. The apparatus as claimed in claim 1, wherein the means (18, 43) have at least one lamp element (43′, 43″). 9. The apparatus as claimed in claim 1, wherein the means (18, 43) are made of a transparent, optically conductive plastic. 10. The apparatus as claimed in claim 1, wherein the bottom part (11, 101) or the lid (12, 102) has a display device (103), preferably an LCD display or LED display, and also at least one programming and/or display button (104, 104′, 105, 105′). 11. The apparatus as claimed in claim 1, wherein the inside of the lid (12, 102) is provided with a board (30) having holes whose arrangement corresponds to the arrangement of the means (18, 43). 12. The apparatus as claimed in claim 11, wherein the board (30) is provided for programming the taking cycle for the tablets (21) and for acknowledging tablet removal. 13. The apparatus as claimed in claim 11, wherein the board (30) is provided just for acknowledging tablet removal, and the bottom part (11) contains a further board for programming the taking cycle for the tablets (21), the two boards being in electrical contact with one another. 14. A lid (12, 102) for an apparatus as claimed in claim 1, wherein it is provided for holding the blister pack (20) and has means (18, 43) for pushing out the tablets (21) from the blister pack (20), the arrangement of the means (18, 41) being matched to the arrangement of the tablets (21) in the blister pack (20) which is to be held. 15. The lid as claimed in claim 14, wherein it has recesses (13, 41) having centered holes (14, 42) which hold pushbuttons (18, 43) such that they cannot be lost. 16. The lid as claimed in claim 14, wherein a grid or mesh (16) having holes (17) whose arrangement corresponds to the arrangement of the means (18, 43) is provided. 17. The lid as claimed in claim 14, wherein the means (18, 43) have at least one lamp element (43′, 43″). 18. The lid as claimed in claim 14, wherein the means (18, 43) are made of a transparent, optically conductive plastic. 19. The lid as claimed in claim 14, wherein its inside is provided with a board (30) having holes whose arrangement corresponds to the arrangement of the means (18, 43). 20. The lid as claimed in claim 19, wherein the board (30) is provided for programming the taking cycle for the tablets (21) and for acknowledging tablet removal. 21. The lid as claimed in claim 19, wherein the board (30) is provided just for acknowledging tablet removal. 22. The lid as claimed in claim 14, wherein it has a display device (103), preferably an LCD display, and also at least one programming and/or display button (104, 104′, 105, 105′). 23. A bottom part for an apparatus as claimed in claim 1, wherein a grid or mesh (16) having holes (17) whose arrangement corresponds to the arrangement of the means (18, 43) is provided. 24. The bottom part as claimed in claim 23, wherein it has a dispensing chute (11′) and a dispensing opening (11″). 25. The bottom part as claimed in claim 23, wherein it has a display device (103), preferably an LCD display, and also at least one programming and/or display button (104, 104′, 105, 105′). 26. The bottom part as claimed in one of claims 23 to 25, wherein it has a board for programming the taking cycle for the tablets (21). |
<SOH> Summary of Subfunctions—Variant No 1 <EOH>Blister held in an exactly shaped depression Alignment with new blister format by changing the top shell Indication of the button to be pushed by LED next to it Precisely one pushout button is above each tablet Buttons are locked using a cover above buttons A tapered opening simplifies tablet removal Manual programming is effected using 4 control buttons The computer interface should be matched to the MCU, in this case a serial interface, for example The taking plan is stored in the microcontroller's EEPROM Conceivable controllers e.g. microchip PIC16F871/PIC18F4220 Software controlled locking of the manual control part Alarm generation by means of piezoelectric bleeper Alarm acknowledgment by contacts on the buttons Power supplied using normal batteries (miniature, possibly micro) Low battery warning function performed by the microcontroller (in connection with PIC 18F4220) Data storage upon change of battery is ensured by EEPROM Time measurement performed using the microcontroller's timer in connection with an external clock generator (on account of accuracy) The time is displayed using a conventional LCD display (not pixel-based) |
Systems for wafer level burn-in of electronic devices |
Systems for wafer level burn-in (WLBI) of semiconductor devices (210, 215) are presented. Systems having at least two electrodes for the application of electrical bias and/or thermal power on each side of a wafer (100) having back (105) and front (110) electrical contacts for semiconductor devices borne by the wafer (100) is described. Methods of wafer level burnin using the system are also described. Furthermore, a pliable conductive layer (220) is described for supplying pins or contacts (110) on device side of a wafer with electrical contact. The pliable conductive layer (220) can allow for an effective series R in each of the devices borne by the wafer (100), thus helping keep voltage bias level consistent. The pliable conductive layer can also prevent damage to a wafer when pressure is applied to it by chamber contacts (210, 215) and pressure onto surfaces of the wafer (100) during burn-in operations. A cooling system (660) is also described for enabling the application of a uniform temperature to the wafer (100) undergoing burn-in. |
1. A wafer level burn-in system, comprising: a first electrode plate (210) for providing electrical contact simultaneously to contacts (110) of more than one semiconductor device borne by a semiconductor wafer (100) on a device surface of said semiconductor wafer; a second electrode plate (215) for providing electrical contact to a substrate surface (105) of said semiconductor wafer (100); and means for providing electrical power (610) to said more than one semiconductor device through said contacts (110) and said substrate (105) of said semiconductor wafer (100) through said first (210) and second (215) electrode plates. 2. The wafer level burn-in system of claim 1, wherein said means for providing electrical power (610) comprises a voltage regulator for providing and monitoring electrical power to said more than one semiconductor device through said first (210) and second (215) electrode plates. 3. The wafer level burn-in system of claim 1, further comprising means for providing controlled thermal energy (640) to said semiconductor wafer (100) through at least one of said first (210) and second (215) electrode plates. 4. The wafer level burn-in system of claim 3, further comprising a temperature regulator (630) for enabling the application of a uniform temperature to said semiconductor wafer (100). 5. The wafer level burn-in system of claim 4, wherein said temperature regulator (630) further comprises a thermocouple (650) located with at least one of said first (210) and second (215) electrode plates for enabling the application of a uniform temperature to said semiconductor wafer (100). 6. The wafer level burn-in system of claim 1, further comprising a heat exchanger (660) for controlling thermal energy at said semiconductor wafer (100) through at least one of said first (210) and second (215) electrode plates. 7. The wafer level burn-in system of claim 6, wherein said heat exchanger (660) further comprises a heat sink (900) in thermal contact with at least one of said first (210) or second (215) electrode plates. 8. The wafer level burn-in system of claim 1, further comprising a wafer surface contact material (220) for placement between said more than one semiconductor device (110) and said first electrode contact plate (210) to facilitate thermal and electrical conduction by said semiconductor wafer (100) and said more than one semiconductor device (110) borne by said semiconductor wafer (100), and to minimize damage to said wafer and said more than one semiconductor device (110) from pressure applied by said first (210) and second (215) contact plates. 9. The wafer level burn-in system of claim 1, further comprising: a first wafer surface contact material (220) placed between said device (110) surface of said semiconductor wafer (100) and said first electrode contact plate (210); and a second wafer surface contact material (220) placed between said substrate surface (105) of said semiconductor wafer (100) and said first contact plate (215); wherein said first and said second wafer surface contact materials (220) facilitate thermal and electrical conduction by said semiconductor wafer (100) through said substrate surface (105) and said more than one semiconductor device (110) borne by said semiconductor wafer, and said first and said second wafer surface contact materials (220) minimize damage to said semiconductor wafer and said more than one semiconductor device from pressure applied by said first (210) and second (215) contact plates respectively against said device surface and said substrate surface. 10. The wafer level burn-in system of claim 1, further comprising a wafer contact pressure control assembly (330) for providing self-adjusting contact and pressure control to at least one of said first and second contact plates. 11. The wafer level burn-in system of claim 10, said wafer contact pressure control assembly (330) further comprising a manually controlled system (710). 12. The wafer level burn-in system of claim 10, said wafer contact pressure control assembly (330) further comprising a hydraulic system (710). 13. The wafer level burn-in system of claim 10, said wafer contact pressure control assembly (330) further comprising a pneumatic system (710). 14. A wafer level burn-in system, comprising: upper contact plate (210) for providing physical and electrical contact to a front surface (110) of a semiconductor wafer (100); lower contact plate (215) for providing physical and electrical contact to a back surface (105) of a semiconductor wafer (100); and a voltage source (610) coupled to said upper (210) and said lower (215) contact plates for providing electrical current through said semiconductor wafer (100); wherein said front surface (110) of said semiconductor wafer (100) comprises contacts for more than one semiconductor device borne by said semiconductor wafer and said back surface (105) of said semiconductor wafer comprises a substrate operating as a common contact for said more than one semiconductor device. 15. The system of claim 14 further comprising a voltage regulator (610) for providing controlled electrical power to said more than one semiconductor device. 16. The system of claim 14 further comprising a heat exchanger (660) for providing thermal energy control to said semiconductor wafer (100) through at least one of said upper (210) or lower (215) contact plates. 17. The wafer level burn-in system of claim 14, further comprising a temperature regulator (630) for enabling the application of a uniform temperature to said semiconductor wafer (100) during wafer level burn-in processing. 18. The wafer level burn-in system of claim 17, wherein said temperature regulator (630) further comprises a thermocouple (650) located with at least one of said upper (210) and lower (215) contact plates for enabling said temperature regulator (630) to provide uniform and controlled temperature to said semiconductor wafer (100). 19. The wafer level burn-in system of claim 14, further comprising a heat exchanger (660) for controlling thermal energy at said semiconductor wafer (100) through at least one of said upper (210) or said lower (215) contact plates. 20. The wafer level burn-in system of claim 19, wherein said heat exchanger (660) further comprises a heat sink in thermal contact with at least one of said upper (210) or said lower (215) contact plates. 21. The wafer level burn-in system of claim 14, further comprising a wafer surface contact material (220) for placement between at least one of: said front surface (410) and said upper contact plate (210), and said back surface (420) and said lower contact plate (215); wherein said wafer surface contact material (220) facilitates control over thermal and electrical conduction by said semiconductor wafer (100) and said more than one semiconductor device (110) borne by said semiconductor wafer (100), and said wafer surface contact material (220) further minimizes damage to said wafer (100) and said devices from pressure applied by said upper (210) and said lower (215) contact plates. 22. The wafer level burn-in system of claim 14, further comprising a wafer contact pressure control assembly (230) that provides self-adjusting contact and pressure control to at least one of said first (210) and second (215) contact plates. 23. The wafer level burn-in system of claim 22, said wafer contact pressure control assembly (230) further comprising a manually controlled system. 24. The wafer level burn-in system of claim 22, said wafer contact pressure control assembly further comprising a hydraulic system (710). 25. The wafer level burn-in system of claim 22, said wafer contact pressure control assembly further comprising a pneumatic system (710). 26. A wafer level burn-in system, comprising: a first electrode plate (210) for providing physical and electrical contact to a substrate surface (105) of a semiconductor wafer (100); a second electrode plate (215) for providing physical and electrical contact simultaneously to contacts of more than one semiconductor device (110) borne by said semiconductor wafer (100); means for providing electrical power (610) to said more than one semiconductor device through said first (210) and second (215) electrode plates; and means for providing controlled thermal energy (630) to said semiconductor wafer (100) through at least one of said first (210) and second (215) electrode plates. 27. The wafer level burn-in system of claim 26, wherein said means for providing electrical power (610) further comprises a voltage regulator for providing and monitoring electrical power to said more than one semiconductor device through said first (210) and second (215) electrode plates. 28. The wafer level burn-in system of claim 26, wherein said means for providing controlled thermal energy (630) further comprises a temperature regulator for applying a uniform temperature to said semiconductor wafer. 29. The wafer level burn-in system of claim 28, wherein said temperature regulator further comprises a thermocouple (640) located with at least one of said first (210) and second (215) electrode plates for enabling the application of a uniform temperature to said semiconductor wafer while undergoing burn-in. 30. The wafer level burn-in system of claim 26, wherein said means for providing controlled thermal energy (630) further comprises a heat exchanger (660) for controlling thermal energy at said semiconductor wafer through at least one of said first and second electrode plates. 31. The wafer level burn-in system of claim 30, said heat exchanger (660) further comprising a heat sink in thermal contact with at least one of said first (210) or second (215) electrode plates. 32. The wafer level burn-in system of claim 26, further comprising a wafer surface contact material (220) placed between said semiconductor devices and said second electrode plate (215) to facilitate thermal and electrical conduction by said semiconductor wafer and said semiconductor devices borne by said semiconductor wafer, and to minimize damage to said wafer and said devices from pressure applied by said first (210) and second (215) electrode plates. 33. The wafer level burn-in system of claim 32, wherein said wafer surface contact material (220) is formed in the shape of said semiconductor wafer, said material physically, thermally and electrically contacts said more than one semiconductor device, and wherein said wafer surface contact material (220) can facilitate a consistent voltage bias level across said more than one semiconductor device borne by said semiconductor wafer, said contact material can minimize damage to said more than one device when pressure is applied by said second electrode plate (215) towards said more than one semiconductor device. 34. The wafer level burn-in system of claim 26, further comprising a wafer contact pressure control assembly for providing self-adjusting contact and pressure control to at least one of said first (210) and second (215) electrode plates. 35. The wafer level burn-in system of claim 34, said wafer contact pressure control assembly (710) comprises a manually controlled system. 36. The wafer level burn-in system of claim 34, said wafer contact pressure control assembly (710) comprises a hydraulic system. 37. The wafer level burn-in system of claim 34, said wafer contact pressure control assembly (710) comprises a pneumatic system. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Solid-state semiconductor devices are found in most electronic components today. For example, semiconductor lasers are important devices in applications such as optoelectronic communication systems and high-speed printing systems. There continues to be increased interest in vertical cavity surface emitting lasers (VCSELs) although edge emitting lasers are currently used in the vast majority of applications. A reason for the interest in VCSELs is that edge-emitting lasers produce a beam with a large angular divergence, making efficient collection of the emitted beam more difficult. Furthermore, edge emitting lasers cannot be tested until the wafer is cleaved into individual devices, the edges of which form the mirror facets of each device. On the other hand, not only does the beam of a VCSEL have a small angular divergence, a VCSEL emits light normal to the surface of the wafer. In addition, since VCSELs incorporate the mirrors monolithically in their design, they allow for on-wafer testing and the fabrication of one-dimensional or two-dimensional laser arrays. It is common for more than 60,000 semiconductor laser components to be fabricated on a single wafer. VCSELs are typically made by growing several layers of reflective material on a substrate material. VCSELs include a first mirrored stack, formed on the substrate by semiconductor manufacturing techniques, an active region, formed on top of the first mirrored stack, and a second mirrored stack, formed on top of the active region. By providing a first contact on top of the second mirrored stack, and a second contact on the backside of the substrate, a current is forced through the active region, thus driving the VCSEL. VCSELs can be fabricated/grown with combinations of gallium, arsinide, nitrogen, aluminum, antimony, phosphorous and/or indium placed within or about a typical GaAs substrate. Historically, the manufacturing of semiconductors has been a very elaborate and expensive multi-step process. Component burn-in generally refers to the process of thermally and/or electrically testing newly fabricated semiconductor components. Burn-in allows for the individual identification of faulty components coming for a lot or batch. Currently, components are burned-in at the “package level”, which means that the individually-packaged devices are typically tested after being derived from a wafer. Each component is tested and placed in sockets to be burned-in either as a packaged unit or to be tested as bare die (before packaging). Either die or package level burn-in can be costly for manufacturers because it is labor intensive. Each component has to be tested, requiring plenary human intervention. Although wafer level burn-in (WLBI) methods and systems are currently being explored by the semiconductor industry, proposed systems and methods generally require that a plurality of electrical probes contact a plurality of electrical contacts on a wafer. Such systems can be complex and require extra care with regard to probe and contact alignment. For example, U.S. Pat. No. 6,339,329 issued to Nakata et al., entitled “Method of testing electrical characteristics of multiple semiconductor integrated circuits simultaneously”, is typical of the technological direction being taken in the industry for WLBI. The Nakata et al. patent teaches simultaneous testing of a plurality of semiconductor integrated circuit elements by bringing a plurality of probe terminals into contact with a plurality of testing electrodes associated respectively with a plurality of semiconductor integrated circuit elements on a wafer and applying a voltage to each of the testing electrodes from the common voltage supply line via a plurality of positive temperature coefficient elements. The semiconductor fabrication industry needs methods and systems for reducing the costs and associated labor currently required to carry out device burn-in. Further, the semiconductor industry needs a wafer level burn-in (WLBI) method and systems that can be used in the manufacturing and test of semiconductor components having front and back contacts, such as VCSELs, diodes, LEDs, and other semiconductor devices. The present inventors have recognized that it would be advantageous to remedy current burn-in procedures by providing methods and systems of accomplishing wafer level burn-in of components. Accordingly, the present invention is described and presented as a novel method and means to address the shortcomings currently found in the art. |
<SOH> SUMMARY OF THE INVENTION <EOH>The following summary of the invention is provided to facilitate an understanding of some of the innovative features unique to the present invention and is not intended to be a full description. A full appreciation of the various aspects of the invention can be gained by taking the entire specification, claims, drawings, and abstract as a whole. Additional objects and advantages of the current invention will become apparent to one of ordinary skill in the art upon reading the specification. It is a feature of the present invention to provide systems for conducting wafer level burn-in of semiconductor devices. In accordance with addressing the limitations of the prior art, presented are systems for burning-in electronics components at the wafer level, or wafer level burn-in (WLBI). It is a feature of the present invention to provide a WLBI system including top and bottom contact plates for making electrical contact with a semiconductor wafer having front and back contacts. It is another feature of the present invention to provide a WLBI system including a heat exchanger for assisting in the regulation of wafer temperature during burn-in procedures. It is another feature of the present invention to optionally provide a graphite foil for facilitating contact between contact plates and/or wafer contacts. It is another feature of the present invention to provide an electrical power regulator for providing current and voltage through components on a wafer undergoing a burn-in procedure. It is another feature of the present invention to provide monitoring and automated adjustment apparatuses necessary for maintaining current and temperature level requirements during wafer level burn-in. It is another feature of the present invention to provide a wafer level burn-in system including wafer support hardware for providing mechanical retention of a wafer undergoing burn-in procedures. It is yet another feature of the present invention to provide a wafer support that provides controlled mechanical clamping force, electrical contact and temperature interface to a wafer undergoing burn-in procedures. It is another feature of the present invention to describe methods of achieving wafer level burn-in for semiconductor devices wherein a wafer containing semiconductor devices is fabricated, undergoes wafer level burn-in, individual devices are derived from the wafer after burn-in, and operational devices are made available for use (shipment). Wafer level burn-in reduces the need for package level burn-in and reduces component production costs. A WLBI system having distinct contact plates serving as electrodes for the application of electrical bias on each surface/side of a wafer having back and front electrical contacts for semiconductor devices borne by the wafer is described. Furthermore, a pliable conductive layer, such as a graphite, felt material that can appear disk-like in form, is described for simultaneously supplying pins on the device side and/or substrate side of a wafer with electrical contact. The pliable conductive layer can allow for an effective series resistance, R, in each of the devices borne by the wafer, thus helping maintain voltage bias level consistent. The pliable conductive layer also prevents damage to the wafer when pressure is applied by chamber contacts onto the wafer during burn-in operations, because the pliable conductive layer can deform to absorb contact surfaces of the pins on the device side of a wafer. A cooling system is also described for enabling the application of a uniform temperature to a wafer undergoing burn-in. |
Signal transmitting cable |
A fibre optic cable includes a core of primary coated optical fibres embedded in an inner layer of acrylate material, having sufficient tensile strength when cured to lock at least the outermost fibres in place and still allow the fibres to be easily broken out of the assembly for termination and splicing purposes. The hardness of the acrylate layer is such that at least the outermost fibres of the bundle are restricted from moving axially relative to the inner layer. The inner layer is then surrounded by a loose thin jacket formed from a mixture of high density polyethylene having a Shore hardness greater than or equal to 60 and a generally uniformly distributed slip agent, including a polyether modified poly (dimethylsiloxane) material such as polyether modified hydroxy functional poly (dimethylsiloxane) material. The mixture from which the outer layer is formed is compacted by means of heat and pressure. The outer layer may also contain a mineral filler, such as calcium carbonate and/or titanium dioxide, in order to improve the stability of the dimensions of the outer layer as the temperature changes. |
1. A cable assembly, comprising a plurality of flexible signal transmitting members surrounded by a first layer, wherein axial movement of at least the outermost of said signal transmitting members relative to said first layer is restricted, and further comprising a continuous thermoplastic polymer second layer arranged outwardly of said first layer, wherein the hardness of the polymer of said second layer is greater than or equal to a Shore D hardness of 60. 2. The cable assembly of claim 1, wherein the hardness of the polymer of said second layer is greater than or equal to a Shore hardness of 60 as measured by means of ISO R868. 3. The cable assembly of claim 1, wherein the thickness of said second layer is less than 400 microns around at least 10% of the circumference of said cable assembly. 4. The cable assembly of claim 3, wherein said second layer has a thickness of less than 200 microns around at least 10% of the circumference of said cable assembly. 5. The cable assembly of claim 4, wherein said second layer has a thickness of less than 125 microns around at least 10% of the circumference of said cable assembly. 6. The cable assembly of claim 1, wherein said second layer is adapted to be removed from said first layer by sliding over said first layer. 7. The cable assembly of claim 6, wherein the inner periphery of said second layer is longer than the outer periphery of said first layer. 8. The cable assembly of claim 1, wherein said inner layer comprises at least one acrylate material. 9. A cable assembly, comprising a plurality of flexible signal transmitting members surrounded by a first layer, wherein axial movement of at least the outermost of said signal transmitting members relative to said first layer is restricted, and further comprising a continuous thermoplastic polymer second layer arranged outwardly of said first layer, said second layer having a thickness of less than 400 microns around at least 10% of the circumference of said cable assembly. 10. The cable assembly of claim 9, wherein said second layer has a thickness of less than 200 microns around at least 10% of the circumference of said cable assembly. 11. The cable assembly of claim 10, wherein said second layer has a thickness of less than 125 microns around at least 10% of the circumference of said cable assembly. 12. The cable assembly of claim 9, wherein the hardness of the polymer of said second layer is greater than or equal to a Shore D hardness of 60. 13. The cable assembly of claim 9, wherein the hardness of the polymer of said second layer is greater than or equal to a Shore hardness of 60 as measured by means of ISO R868. 14. The cable assembly of claim 9, wherein said second layer is adapted to be removed from said first layer by sliding over said first layer. 15. The cable assembly of claim 14, wherein the inner periphery of said second layer is longer than the outer periphery of said first layer. 16. A cable assembly, comprising a plurality of flexible signal transmitting members surrounded by a first layer such that axial movement of at least the outermost signal transmitting members relative to said first layer is restricted, and further comprising a continuous thermoplastic polymer second layer arranged outwardly of said first layer and adapted to be removed from said first layer by sliding over said first layer. 17. The cable assembly of claim 16, wherein the inner periphery of said second layer is longer than the outer periphery of said first layer to enable removal of said second layer from said assembly. 18. The cable assembly of claim 16, wherein said second layer has a Shore hardness greater than 60. 19. The cable assembly of claim 18, wherein the hardness of the polymer of said second layer is greater than or equal to a Shore hardness of 60 as measured by means of ISO R868. 20. The cable assembly of claim 16, wherein the thickness of said second layer is less than 400 microns around at least 10% of the circumference of said cable assembly. 21. The cable assembly of claim 20, wherein said second layer has a thickness of less than 200 microns around at least 10% of the circumference of said cable assembly. 22. The cable assembly of claim 21, wherein said second layer has a thickness of less than 125 microns around at least 10% of the circumference of said cable assembly. 23. The assembly of claim 16, wherein said second layer comprises at least one polymer material. 24. The assembly of claim 23, wherein said at least one polymer material comprises a thermoplastic material. 25. The assembly of claim 23, wherein said at least one polymer material comprises high-density polyethylene. 26. The assembly of claim 16, wherein said signal transmitting members are embedded in said first layer. |
Treatment of muscular dystrophies and related disorders |
The invention provides, among other aspects, compositions and methods for treating, preventing, and diagnosing diseases or conditions associated with an abnormal level or activity of biglycan; diseases or conditions associated with an abnormal level or activity of collagen VI; disorders associated with an unstable cytoplasmic membrane, due, e.g., to an unstable dystrophin associated protein complex (DAPC); and disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. |
1. A method for stabilizing collagen VI-deficient dystrophin-associated protein complexes (DAPCs) on the surface of a cell, comprising contacting the cell with an effective amount of a biglycan therapeutic, such that the collagen VI-deficient DAPCs are stabilized. 2. The method of claim 1, wherein the biglycan therapeutic is a polypeptide including a biglycan amino acid sequence which is at least about 90% identical to SEQ ID No. 9, or a portion thereof. 3. The method of claim 2, wherein the biglycan therapeutic binds to MuSK. 4. The method of claim 2, wherein the biglycan therapeutic binds to a α-sarcoglycan and/or γ-sarcoglycan. 5. The method of claim 2, wherein the biglycan therapeutic binds to a collagen VI polypeptide. 6. The method of claim 2, wherein the biglycan therapeutic induces phosphorylation of sarcoglycans. 7. The method of claim 2, wherein the biglycan therapeutic upregulates utrophin levels. 8. The method of claim 2, wherein the biglycan amino acid sequence includes one or more LLRs of human biglycan having SEQ ID NO: 9. 9. The method of claim 2, wherein the polypeptide is derivatized with one or more glycosaminoglycan (GAG) side chains. 10. The method of claim 2, wherein the biglycan amino acid sequence is at least about 90% identical to amino acids 38-365 of SEQ ID NO: 9. 11. The method of claim 2, wherein the biglycan amino acid sequence is at least about 95% identical to amino acids 38-365 of SEQ ID NO: 9. 12. The method of claim 2, wherein the biglycan amino acid sequence is encoded by a nucleic acid which hybridizes to SEQ ID NO: 8. 13. The method of claim 1, wherein the cell is a muscle cell. 14. A method for treating or preventing a condition associated with a collagen VI deficiency, comprising administering to the subject a pharmaceutically effective amount of biglycan therapeutic. 15. The method of claim 14, wherein the biglycan therapeutic is a polypeptide including a biglycan amino acid sequence which is at least about 90% identical to SEQ ID No. 9, or a portion thereof. 16. The method of claim 15, wherein the biglycan therapeutic binds to MuSK. 17. The method of claim 15, wherein the biglycan therapeutic binds to a α-sarcoglycan and/or γ-sarcoglycan. 18. The method of claim 15, wherein the biglycan therapeutic binds to a collagen VI polypeptide. 19. The method of claim 15, wherein the biglycan therapeutic induces phosphorylation of sarcoglycans. 20. The method of claim 15, wherein the biglycan therapeutic upregulates utrophin levels. 21. The method of claim 14, wherein the condition associated with a collagen VI deficiency is selected from the group consisting of Bethlem myopathy, Ullrich Congenital Muscular Dystrophy and Sorsby's fundus dystrophy. 22. A method for treating or preventing a condition associated with an abnormal dystrophin-associated complex (DAPC) in cells of a subject, comprising administering a pharmaceutically effective amount of a collagen VI therapeutic. 23. The method of claim 22, wherein the collagen VI therapeutic comprises a polypeptide that is at least 90% identical to a polypeptde selected from the group consisting of: SEQ ID NO: 12, SEQ ID NO: 14 and SEQ ID NO: 16. 24. The method of claim 23, wherein the collagen VI therapeutic binds to biglycan. 25. The method of claim 22, wherein the condition is selected from the group consisting of Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Congenital Muscular Dystrophy, Limb-girdle Muscular Dystrophy, and mytonic dystrophy. 26. A composition comprising a pharmaceutically efficient amount of collagen VI therapeutic that is sufficient for stabilizing DAPCs or activating postsynatpic membranes. 27. The composition of claim 26, further comprising a biglycan therapeutic. 28. A method for identifying an agent which modulates the interaction between a collagen VI polypeptide and a biglycan, comprising contacting a collagen VI polypeptide with a biglycan or a portion thereof sufficient for binding to collagen VI and a test compound in conditions under which the collagen VI polypeptide and the biglycan interact in the absence of the test compound, wherein a difference in the level of binding between the collagen VI polypeptide and the biglycan in the presence of the test compound relative to the absence of the test compound indicates that the test compound is an agent which modulates the interaction between collagen VI and biglycan. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The dystrophin-associated protein complex (DAPC) links the cytoskeleton to the extracellular matrix and is necessary for maintaining the integrity of the muscle cell\plasma membrane. The core DAPC consists of the cytoskeletal scaffolding molecule dystrophin and the dystroglycan and sarcoglycan transmembrane subcomplexes. The DAPC also serves to localize key signaling molecules to the cell surface, at least in part through its associated syntrophins (Brenman, et al. (1996) Cell. 84: 757-767; Bredt, et al. (1998), Proc Natl Acad Sci USA. 95: 14592). Mutations in either dystrophin or any of the sarcoglycans result in muscular dystrophies characterized by breakdown of the muscle cell membrane, loss of myofibers, and fibrosis (Hoffman, et al. 1987 . Cell 51: 919; Straub, and Campbell (1997) Curr Opin Neurol. 10: 168). Moreover, mutations in the extracellular matrix protein laminin-α2, which associates with the DAPC on the cell surface, is the basis of a major congenital muscular dystrophy (Helbling-Leclerc, et al. (1995) Nat Genet. 11:216). The α-/β-dystroglycan subcomplex forms a critical structural link in the DAPC. The transmembrane β-dystroglycan and the wholly extracellular α-dystroglycan arise by proteolytic cleavage of a common precursor (Ibraghimov, et al. (1992) Nature 355: 696; Bowe, et al. (1994) Neuron 12: 1173). The cytoplasmic tail of β-dystroglycan binds dystrophin, while the highly glycosylated, mucin-like α-dystroglycan binds to several ECM elements including agrin, laminin, and perlecan (Ervasti and Campbell, (1993) J Cell Biol 122: 809; Bowe, et al. (1994) Neuron 12: 1173; Gee, et al. (1994) Cell 77: 675; Hemler, (1999) Cell 97: 543). This binding to matrix proteins appears to be essential for assembly of basal lamina, since mice deficient in dystroglycan fail to form these structures and die very early in development (Henry, M. D. and K. P. Campbell. 1998 . Cell. 95: 859). β-Dystroglycan can bind the signaling adapter molecule Grb2 and associates indirectly with p125FAK (Yang, et al. (1995) J Biol Chem. 270: 11711; Cavaldesi, et al. (1999), J. Neurochem. 72: 01648). Although the significance of these associations remains unknown, these binding properties suggest that dystroglycan may also serve to localize signaling molecules to the cell surface. Several lines of evidence suggest that dystroglycan may also function in neuromuscular junction formation, in particular, in postsynaptic differentiation. For purposes of clarity, the components of the neuromuscular junction are summarized here. The major structural features of the neuromuscular junction (NMJ) or nerve-muscle synapse are the pre- and post-synaptic specializations of the motor neuron and muscle, respectively, the intervening synaptic basal lamina, and the specialized Schwann cell cap (Salpeter, et al (1987) The Vertebrate Neuromuscular Junction . New York, Alan R. Liss.). The presynaptic apparatus is marked by ordered arrays of synaptic vesicles, a subset of which are poised to fuse with the plasma membrane at the active zones, and release acethylcholine that is recognized by acetylcholine receptors (AChRs) on the muscle, and ultimately results in electrical activation and contraction of the muscle (Heuser, et al (1981) J. Cell Biol. 88: 564). Immediately across the 50 nm synaptic cleft from these zones are the crests of the postjunctional folds. These crests bristle with Acetylcholine receptors (AChRs), which can reach densities of >10,000 molecules/μm 2 (Fertuck, et al (1976) J. Cell. Biol. 69: 144). The localized and tightly regulated secretion of acetylcholine into the narrow synaptic cleft, coupled with the high ACHR density in the postsynaptic membrane, ensures rapid and reliable synaptic transmission between neuron and muscle. Perturbations of these specializations, such as the decrease in the number of functional AChRs seen in myasthenia gravis, can lead to debilitating and often fatal clinical outcomes (Oosterhuis, et al (1992) Neurology & Neurosurgery 5: 638). The synaptic basal lamina (SBL) is interposed between the pre- and post-synaptic membranes and contains molecules important for the structure, function, and regulation of the neuromuscular junction (Bowe, M. A & Fallon, J. R., (1995) Ann. Rev. Neurosci. 18: 443; Sanes, et al. (1999) Ann. Rev. Neurosci. 22: 389). It consists of a distinct set of extracellular matrix molecules including specialized laminins, proteoglycans and collagens (Hall, et al (1993) Neuron 10: (Suppl.) 99). The SBL also contains molecules essential for the regulation of synaptic structure and function including ACHE, neuregulins, and agrin. The SBL thus serves both as a specialized structure for maintaining the localized differentiation of the synapse as well as a repository for essential regulatory molecules. The molecular composition of the postsynaptic membrane is known in considerable detail. As noted above, the most abundant membrane protein is the AChR. The cytosolic AChR associated protein rapsyn (formerly known as the 43kD protein) is present at stoichiometric levels with the receptor and is likely to form a key link between the cytosolic domain of the AChR and the cytoskeleton (Froehner, et al (1995) Nature 377: 195; Gautam, et al. (1995) Nature 377: 232). The postsynaptic membrane is also enriched in erbB2-4, some or all of which serve as neuregulin receptors (Altiok, et al. (1995) EMBO J. 14: 4258; Zhu, et al. (1995) EMBO J. 14: 5842). ACHR and other molecules essential for nerve-muscle communication. The cytoskeletal elements can be broadly grouped into two subsets. Dystrophin and utrophin are members of the dystrophin-associated protein complex, or DAPC, and are linked to the synaptic basal lamina via the transmembrane heteromer α-/β-dystroglycan. The postsynaptic cytoskeleton is also enriched in several focal adhesion-associated molecules including α-actinin, vinculin, talin, paxillin, and filamin (Sanes, et al (1999) Ann. Rev. Neurosci. 22: 389). The latter proteins probably communicate, directly or indirectly, with the extracellular matrix through integrins, some of which are enriched at synapses (Martin, et al. (1996) Dev. Biol. 174: 125). Actin is associated with both sets of cytoskeletal molecules (Rybakova et al. (1996) J. Cell Biol. 135: 661; Amann, et al. (1998) J. Biol. Chem. 273: 28419-23; Schoenwaelder et al. (1999) Curr. Opin. Cell. Biol. 11: 274). The functions of these specialized sets of proteins are considered below. α-Dystroglycan binds the synapse organizing molecule agrin (Bowe, et al. (1994) Neuron. 12: 1173; Campanelli, et al. (1994) Cell. 77: 663; Gee, et al. (1994) Cell. 77: 675; Sugiyama, et al. (1994) Neuron. 13: 103; O'Toole, et al. (1996) Proc Natl Acad Sci USA. 93: 7369) (reviewed in Fallon and Hall, (1994) Trends Neurosci. 17: 469), and β-dystroglycan binds to the AChR-associated protein rapsyn (Cartaud, et al. (1998) J Biol Chem. 273: 11321). Further, agrin-induced ACHR clustering on the postsynaptic membrane is markedly decreased in muscle cells expressing reduced levels of dystroglycan (Montanaro, et al. (1998) J Neurosci. 18: 1250). The precise role of dystroglycan in this process is unknown. Currently available evidence suggests that dystroglycan is not part of the primary agrin receptor, but rather may play a structural role in the organization of postsynaptic specializations (Gesemann, et al. (1995) Biol. 128: 625; Glass, et al. (1996) Cell. 85: 513; Jacobson, et al. (1998) J Neurosci. 18: 6340). Another molecule that plays an important role in neuromuscular junction formation is the tyrosine kinase receptor MuSK, which becomes phosphorylated in response to agrin. However, agrin does not bind to MuSK and it is unclear how agrin stimulates MuSK. The existence of a co-receptor had been suggested. Activation of MuSK by antibody cross-linking is sufficient to induce the clustering of AChRs on cultured myotubes (Xie et al. (1997) Nat. Biotechnol. 15:768 and Hopf and Hoch (1998) J. Biol. Chem. 273: 6467) and a constitutively active MuSK can induce postsynaptic differentiation in vivo (Jones et al. (1999) J. Neurosci. 19:3376). However, MuSK phosphorylation is necessary but not sufficient for agrin-induced AChR clustering. The realm of dystroglycan function ranges far beyond muscle. As noted above, mice defective in dystroglycan die long before muscle differentiation. In a surprising development, α-dystroglycan in non-muscle cells has been shown to function as a receptor for Lassa Fever and choriomeningitis fever viruses (Cao, W., et al., 1998 , Science. 282: 2079), and on Schwann cells as a co-receptor for Mycobacterium leprae (Rambukkana, et al. (1998) Science. 282: 2076). Dystroglycan is also abundant in brain, but its function there is not understood (Gorecki, et al. (1994) Hum Mol Genet. 3: 1589; Smalheiser and Kim (1995) J Biol Chem. 270:15425). α-Dystroglycan is comprised of three known domains. An amino-terminal domain folds into an autonomous globular configuration (Brancaccio, et al. (1995) Febs Lett. 368: 139). The middle third of the protein is serine- and threonine-rich, and is highly glycosylated (Brancaccio, et al. (1997) Eur J Biochem. 246: 166). Indeed, the core molecular weight of α-dystroglycan is ˜68 kDa, but the native molecule migrates on SDS-PAGE as a polydisperse band whose size ranges from 120-190 kDa, depending upon the species and tissue source (Ervasti and Campbell (1993) J Cell BioL 122: 809; Bowe, et al. (1994) Neuron. 12: 1173; Gee, et al. (1994) Cell. 77: 675; Matsumura, et al. (1997) J Biol Chem. 272: 13904). Glycosylation of α-dystroglycan, probably in this middle third, is essential for its laminin- and agrin-binding properties. While it is clear that dystroglycan and the DAPC play crucial roles in a variety of processes in muscle as well as in other tissues, the underlying mechanisms remain obscure. |
<SOH> SUMMARY OF THE INVENTION <EOH>In certain aspects, the invention provides methods and compositions for stabilizing dystrophin-associated protein complexes (DAPCs) on the surface of a cell. Stabilizing DAPC complexes on cell membranes allows membranes to be less “leaky” and thus, provides a longer life span to cells. In certain aspects, the invention also provides methods for activating a postynaptic membrane, such as to render the membrane more sensitive to an incoming signal from a neural cell (e.g., at a neuromuscular junction). Activating a postsynaptic membrane may comprise stimulating aggregation of AChR on the cell membrane and/or activating MuSK, such as by phosphorylation. In certain aspects, the invention provides methods for treating a condition associated with a collagen VI abnormality, such as a deficiency or structural disorganization. In one embodiment, the method comprises contacting the target cell with a biglycan polypeptide comprising an amino acid sequence which is at least about 90% identical to the biglycan sequence of SEQ ID NO: 9 or a portion thereof. In a preferred method, the biglycan polypeptide binds to α-dystroglycan; collagen VI; α-sarcoglycan and/or γ-sarcoglycan. In an even more preferred embodiment, the biglycan polypeptide stimulates phosphorylation of α-sarcoglycan on a cell membrane. The biglycan polypeptide also preferably potentiates agrin-induced AChR aggregation on the surface of the cell; stimulate the phosphorylation of MuSK on the cell; and/or potentiates agrin-induced phosphorylation of MuSK. In certain preferred embodiments, the biglycan polypeptide interacts with and/or stimulates the expression of collagen VI. The biglycan polypeptide may comprise one or more 24 amino acid repeat motifs in the Leucine Rich Repeat (LRR) of human biglycan having SEQ ID NO: 9. In another embodiment, the biglycan polypeptide comprises a cysteine-rich region, e.g., the C-terminal or the N-terminal Cysteine-rich region. The biglycan polypeptide may include one or more glycosaminoglycan (GAG) chains. In an even more preferred embodiment, the biglycan polypeptide comprises an amino acid sequence which is at least about 90% identical to amino acids 20-368 or 38-368 of SEQ ID NO: 9, even more preferably at least 95% identical or 100% identical to amino acids 20-368 or 38-368 of SEQ ID NO: 9. In another embodiment, the biglycan polypeptide is encoded by a nucleic acid which hybridizes to SEQ ID NO: 8. The biglycan polypeptide can be Torpedo DAG-125, or the human biglycan of SEQ ID NO: 9, or a portion thereof having at least one biological activity of biglycan. In other embodiments, the biglycan therapeutic is a peptide fragment of the full length protein. Preferably it is a fragment which retains the ability to induce phosphorylation of sarcoglycans and upregulate utrophin activity/expression. For instance, a preferred peptide fragment binds to and activates MuSK. In certain preferred embodiments the peptide fragment has the ability to upregulate collagen VI activity/expression. In further embodiments, the method comprises contacting the target cell with a collagen VI polypeptide comprising an amino acid sequence which is at least about 90% identical to a collagen α1 (VI) sequence, a collagen α2(VI) sequence or a collagen α3(VI) sequence, exemplified by SEQ ID Nos: 11 and 12, 13 and 14, and 15 and 16, respectively, or a portion thereof. In a preferred method the collagen VI polypeptide is a portion of a mature collagen peptide (e.g. signal sequence is removed). In a preferred method, the collagen VI polypeptide binds to bigycan. In certain embodiments, the method comprises contacting the target cell with a collagen VI therapeutic comprising a collagen VI monomer, the monomer comprising a collagen α1(VI) chain, a collagen α2(VI) chain and a collagen α3(VI) chain in a 1:1:1 ratio. Optionally, the therapeutic comprises multimers of collagen VI monomers. In other embodiments, the collagen VI therapeutic is a peptide fragment of a full length collagen VI α1(VI) chain α2(VI) chain or α3(VI) chain. Preferably it is a fragment which retains the ability to bind biglycan. In other embodiments, the subject biglycan or collagen VI therapeutics are peptidomimetics of a portion of a biglycan or collagen VI protein, respectively. Peptidomimetics are compounds based on, or derived from, peptides and proteins. The peptidomimetics of the present invention typically can be obtained by structural modification of a known biglycan or collagen VI peptide sequence using unnatural amino acids, conformational restraints, isosteric replacement, and the like. The subject peptidomimetics constitute the continum of structural space between peptides and non-peptide synthetic structures; biglycan and collagen VI peptidomimetics may be useful, therefore, in delineating pharmacophores and in helping to translate peptides into nonpeptide compounds with the activity of the parent biglycan or collagen VI peptides. Moreover, as is apparent from the present disclosure, mimetopes of the subject biglycan and collagen VI peptides can be provided. Such peptidomimetics can have such attributes as being non-hydrolyzable (e.g., increased stability against proteases or other physiological conditions which degrade the corresponding peptide), increased specificity and/or potency, and increased cell permeability for intracellular localization of the peptidomimetic. For illustrative purposes, peptide analogs of the present invention can be generated using, for example, benzodiazepines (e.g., see Freidinger et al. in Peptides: Chemistry and Biology, G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), substituted gama lactam rings (Garvey et al. in Peptides: Chemistry and Biology , G. R Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988, p 123), C-7 mimics (Huffman et al. in Peptides: Chemistry and Biologyy , G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988, p. 105), keto-methylene pseudopeptides (Ewenson et al. (1986) J Med Chem 29:295; and Ewenson et al. in Peptides: Structure and Function (Proceedings of the 9th American Peptide Symposium) Pierce Chemical Co. Rockland, Ill., 1985), β-turn dipeptide cores (Nagai et al. (1985) Tetrahedron Lett 26:647; and Sato et al. (1986) J Chem Soc Perkin Trans 1:1231), β-aminoalcohols (Gordon et al. (1985) Biochem Biophys Res Commun 126:419; and Dann et al. (1986) Biochem Biophys Res Commun 134:71), diaminoketones (Natarajan et al. (1984) Biochem Biophys Res Commun 124:141), and methyleneamino-modifed (Roark et al. in Peptides: Chemistry and Biology , G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988, p 134). Also, see generally, Session III: Analytic and synthetic methods, in in Peptides: Chemistry and Biology , G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988) In addition to a variety of sidechain replacements which can be carried out to generate the subject biglycan and collagen VI peptidomimetics, the present invention specifically contemplates the use of conformationally restrained mimics of peptide secondary structure. Numerous surrogates have been developed for the amide bond of peptides. Frequently exploited surrogates for the amide bond include the following groups (i) trans-olefins, (ii) fluoroalkene, (iii) methyleneamino, (iv) phosphonamides, and (v) sulfonamides. Examples of Surrogates Additionally, peptidomimietics based on more substantial modifications of the backbone of the biglycan or collagen VI peptide can be used. Peptidomimetics which fall in this category include (i) retro-inverso analogs, and (ii) N-alkyl glycine analogs (so-called peptoids). Examples of Analogs Furthermore, the methods of combinatorial chemistry are being brought to bear, c.f. Verdine et al. PCT publication WO9948897, on the development of new peptidomimetics. For example, one embodiment of a so-called “peptide morphing” strategy focuses on the random generation of a library of peptide analogs that comprise a wide range of peptide bond substitutes. In certain embodiments, the invention also provides a method for treating or preventing a condition associated with an abnormal dystrophin-associated protein complex (DAPC) in cells of a subject, comprising administering to the subject a pharmaceutically efficient amount of a biglycan polypeptide, peptide or peptidomimetic or a biglycan agonist (collectively referred to herein as “biglycan therapeutics”) which stabilizes the DAPC. In certain embodiments, the invention provides a method for treating or preventing a condition associated with an abnormal dystrophin-associated protein complex (DAPC) in cells of a subject, comprising administering to the subject a pharmaceutically efficient amount of a collagen VI polypeptide, peptide or peptidomimetic or a biglycan agonist (collectively referred to herein as “collagen VI therapeutics”) which stabilizes the DAPC. Optionally, the DAPC is of a type that is deficient in collagen VI function. Examples of diseases that can be treated or prevented include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Congenital Muscular Dystrophy, Ullrich Congenital Muscular Dystrophy, Limb-girdle Muscular Dystrophy, and mytonic dystrophy; cardiomyopathies, Bethlem myopathy and Sorsby's fundus dystrophy. In certain embodiments, the invention relates to a combination therapy comprising administering a collagen VI therapeutic and a biglycan therapeutic, optionally as a single combination therapeutic composition. In another example, the invention provides a method for treating or preventing a condition characterized by an abnormal neuromuscular junction or synapse in a subject, comprising administering to the subject a pharmaceutically efficient amount of a biglycan therapeutic which binds to, and/or induces phosphorylation of MuSK and/or which induces aggregation of acetylcholine receptors (AChRs), or a collagen VI therapeutic. The condition can be a neuromuscular or neurological disease. The invention also provides methods for treating, preventing and diagnosing diseases or disorders that are associated with abnormal levels or activity of biglycan; with unstable cytoplasmic membranes, due in particular, to unstable DAPCs; or abnormal synapses or neuromuscular junctions. In yet another example, the invention provides a diagnostic method for determining whether a subject has or is at risk of developing a condition associated with an abnormal DAPC or abnormal synapse or neuromuscular junction, or other disease associated with an abnormal biglycan level or activity, comprising determining the level or activity of biglycan in a tissue of the subject, wherein the presence of an abnormal level and/or activity of biglycan in the tissue of a subject indicates that the subject has or is at risk of developing a condition associated with an abnormal DAPC or abnormal synapse or neuromuscular junction or other disease associated with an abnormal biglycan level or activity. In further embodiments, the invention provides screening methods for identifying agents with inhibit or potentiate the activity of biglycan, such as a human biglycan or Torpedo DAG-125, such as agents which potentiate or inhibit biglycan binding to another molecule, such as a member of a DAPC or MuSK. Agents identified in these assays can be used, e.g., in therapeutic methods, as biglycan therapeutics. Screening methods for identifying agents which modulate phosphorylation induced by biglycan are also within the scope of the invention. In additional embodiments, the invention relates to screening methods for identifying agents with inhibit or potentiate the activity of collagen VI, such as a human collagen VI, such as agents which potentiate or inhibit collagen VI binding to biglycan. Agents identified in these assays can be used, e.g., in therapeutic methods, as collagen VI therapeutics. Other aspects of the invention are described below or will be apparent to those skilled in the art in light of the present disclosure. |
Self-attaching fastener systems |
Methods of forming and feeding self-attaching fasteners are disclosed wherein the strip includes a plurality of spaced abutment surfaces, preferably notches, which may be used both during the manufacturing process and feeding of a strip of fasteners to an installation head. Where the fasteners are interconnected in a strip, by frangible wires, the wires are located in the bottom wall of the panel receiving grooves in the flange portions on opposed sides of the projecting pilot portion. A self-attaching fastener having deformable inclined lip portions which extend upwardly and toward the pilot portion from the flange portions which are deformed during installation to provide further securement for the panel when deformed in the grooves. |
1. A preoriented strip of self-attaching fasteners for attachment to a panel, each of said fasteners including a projecting pilot portion adapted to be received through an opening in a panel, a flange portion adjacent said pilot portion having a panel receiving surface, a substantially continuous wire groove in said panel receiving surface, and a frangible continuous wire in said wire groove interconnecting said fasteners in a continuous preoriented strip. 2. The preoriented strip of self-attaching fasteners as defined in claim 1, wherein each of said fasteners include two flange portions on opposed sides of said projecting pilot portion each having a panel receiving surface, a wire receiving groove in each panel receiving surface and a continuous frangible wire in each wire receiving groove on opposed sides of said projecting pilot portion interconnecting said fasteners. 3. The preoriented strip of self-attaching fasteners as defined in claim 1, wherein each of said fasteners includes a panel receiving groove in said panel receiving surface of said flange portion adjacent said pilot portion having a bottom wall and said wire groove located in bottom wall of said panel receiving groove. 4. The preoriented strip of self-attaching fasteners as defined in claim 3, wherein said wire receiving groove is adjacent said pilot portion. 5. The preoriented strip of self-attaching fasteners as defined in claim 1, wherein said wire receiving groove includes a bottom wall and said bottom wall of said wire-receiving groove includes a plurality of spaced pockets. 6. The preoriented strip of self-attaching fasteners as defined in claim 4, wherein said wire is deformed into said plurality of spaced pockets in said wire groove bottom wall preventing said fasteners from moving on said wire. 7. The preoriented strip of self-attaching fasteners as defined in claim 1, wherein said wire is located below said panel receiving surface. 8. A fastener and panel assembly, comprising: a fastener including a projecting pilot portion, a flange portion adjacent said pilot portion having a panel receiving surface, a substantially continuous wire groove in said panel receiving surface and a frangible wire in said wire groove; and a panel having an opening therein receiving said projecting pilot portion of said fastener and said panel having a portion overlying and contacting said panel receiving surface and overlying said wire. 9. The fastener and panel assembly as defined in claim 8, wherein said frangible wire is spaced below said panel receiving surface and said portion of said panel is deformed into said wire grove. 10. The fastener and panel assembly as defined in claim 8, wherein each of said fasteners includes a panel receiving groove in said panel receiving surface of said flange portion having a bottom wall, said wire groove located in said bottom wall of said panel receiving groove and said panel portion adjacent said pilot portion of said fastener deformed into said panel receiving groove overlying said bottom wall of said panel receiving groove and said frangible wire. 11. The fastener and panel assembly as defined in claim 10, wherein said wire receiving groove is adjacent said pilot portion. 12. The fastener and panel assembly as defined in claim 8, wherein said wire receiving groove includes a bottom surface and said bottom surface of said wire receiving groove includes a plurality of spaced pockets. 13. The fastener and panel assembly as defined in claim 12, wherein said wire is deformed into said plurality of spaced pockets in said bottom surface of said wire receiving groove preventing said fasteners from moving on said wire. 14. A method of forming a continuous strip of self-attaching fasteners, comprising the following steps: forming a plurality of discrete self-attaching fasteners, each fastener including a projecting pilot portion and a flange portion having a panel receiving surface adjacent said projecting pilot portion; forming a substantially continuous wire groove in said panel receiving surface of each of said self-attaching fasteners; aligning said discrete self-attaching fasteners with said wire grooves substantially coaxially aligned; and inserting a continuous frangible wire in said wire grooves of said discrete self-attaching fasteners and securing said wire to said fasteners forming a continuous strip of self-attaching fasteners. 15. The method of forming a continuous strip of self-attaching fasteners as defined in claim 14, wherein said method includes forming a panel receiving groove in said panel receiving surface adjacent said pilot portion having a bottom surface in each of said fasteners, forming said wire groove in said bottom surface of said panel receiving groove, and inserting said continuous frangible wire into said wire groove through said panel receiving groove. 16. The method of forming a continuous strip of self-attaching fasteners as defined in claim 14, wherein said method includes forming a plurality of spaced pockets in a bottom surface of said wire retaining groove of each of said fasteners and deforming said continuous frangible wire against said bottom surface and into said plurality of spaced pockets, thereby preventing said fasteners from moving on said wire. 17. The method of forming a continuous strip of self-attaching fasteners as defined in claim 14, wherein said method includes deforming said continuous frangible wire against a bottom surface of said wire retaining groove with said wire spaced below said panel receiving surface. 18. A method of feeding a preoriented strip of self-attaching fasteners to an installation head, said method comprising the following steps: forming a continuous strip of self-attaching fasteners interconnected by frangible connectors, each fastener having a bore and a sidewall extending generally perpendicular to said bore; forming a plurality of substantially equally spaced abutment surfaces in at least one side of said side walls of said preoriented strip of self-attaching fasteners and receiving a driving member seriatim against at least one of said abutment surfaces and moving said driving member to drive said strip of self-attaching fasteners to an installation head. 19. The method of feeding a preoriented strip of self-attaching fasteners to an installation head as defined in claim 18, wherein said method includes forming notches between adjacent fasteners in said continuous strip of said self-attaching fasteners. 20. The method of feeding a preoriented strip of self-attaching fasteners to an installation head as defined in claim 19, wherein said method includes forming a plurality of generally rectangular self-attaching fasteners each fastener having an end face in nearly abutting relation in said strip of self-attaching fasteners and forming a chamfered surface at said end faces of said fasteners forming said abutment surfaces. 21. The method of feeding a preoriented strip of self-attaching fasteners to an installation head as defined in claim 18, wherein said method includes forming a plurality of spaced notches in said sidewalls of each of said fasteners. 22. The method of feeding a preoriented strip of self-attaching fasteners to an installation head as defined in claim 18, wherein said driving member comprises a rotatable member having a plurality of spaced radial spokes, said method including forming equally spaced notches in said side wall of said strip of self-attaching fasteners including said abutment surfaces, rotating said driving member to receive said radial spokes in said plurality of substantially equally spaced notches in said continuous strip of fasteners, driving said strip of fasteners to an installation head. 23. The method of feeding a preoriented strip of self-attaching fasteners to an installation head as defined in claim 18, wherein said drive member includes a reciprocal pawl having an end portion configured to be received against said abutment surfaces, and said method including receiving said end portion of said pawl against one of said abutment surfaces and moving said pawl to drive said strip of fasteners. 24. A continuous strip of fasteners for attachment to a panel, comprising: a plurality of generally rectangular fasteners, each fastener including end faces and side faces, a central projecting pilot having a bore therethrough and a flange portion on opposed sides of said pilot portion having a panel engaging surface adjacent said pilot portion, a frangible connector interconnecting said fasteners in end to end relation in a continuous strip, and a plurality of substantially equally spaced notches in said strip of fasteners at said side faces for driving said strip of fasteners to an installation head. 25. The continuous strip of fasteners for attachment to a panel as defined in claim 24, wherein said plurality of substantially equally spaced notches is defined by a chamfer in the end faces of adjacent fasteners in said continuous strip of fasteners. 26. The continuous strip of fasteners for attachment to a panel as defined in claim 24, wherein said substantially equally spaced notches comprise a plurality of spaced notches defined in said side faces of each of said fasteners. 27. The continuous strip of fasteners for attachment to a panel as defined in claim 24, wherein said panel engaging surface of each of said fasteners includes a wire groove and said frangible connector comprises a continuous frangible wire in said wire grooves interconnecting adjacent fasteners in said continuous strip of fasteners. 28. The continuous strip of fasteners for attachment to a panel as defined in claim 27, wherein each of said fasteners includes a panel receiving groove extending into said flange portions on opposed sides of said pilot portion adjacent said pilot portion and said wire grooves located in a lower surface of said panel receiving grooves. 29. A self-attaching fastener, comprising: a central projecting pilot portion having an end face, a bore extending through said pilot portion through said end face, flange portion on opposed sides of said pilot portion each having a panel supporting face, panel receiving grooves in said panel supporting faces of said flange portions on opposed sides of said pilot portion adjacent said pilot portion, said panel receiving grooves each including a bottom wall and opposed side walls including an inner side wall adjacent said pilot portion and an outer side wall, at least one of said side walls of said panel receiving grooves being inclined and overlying said bottom wall, and said outer side wall including a deformable lip inclined upwardly from said panel supporting faces and overlying said bottom wall. 30. The self-attaching fastener as defined in claim 29, wherein said bottom wall of each of said panel receiving grooves includes a wire retaining groove. 31. The self-attaching fastener as defined in claim 30 wherein said wire retaining grooves include spaced pockets and said wire retaining grooves each including a frangible wire deformed into said spaced pockets in said bottom wall of said wire retaining groove. 32. The self-attaching fastener as defined in claim 29, wherein said flange portions include spaced grooves in a side wall of said flange portions extending generally perpendicular to said panel supporting faces. 33. A method of forming self-attaching female fasteners, comprising the following steps: forming a continuous metal strip having a cross-section of the self-attaching fasteners to be formed including a continuous pilot portion projecting from a central portion of said strip and flange portions on opposed sides of said pilot portion, said flange portions each including a bearing face spaced below and end face of said pilot portion and a side face; forming a plurality of equally spaced notches in at least one of said side faces of said strip; locating a first portion of said strip opposite a cylindrical punch by receiving a locating member in one of said notches, then moving said punch to pierce a cylindrical bore in said strip, advancing said strip and locating a second portion of said strip opposite said punch by receiving said locating member in a second one of said notches, thereby forming a plurality of equally spaced cylindrical bores in said strip; and locating said strip opposite a cut-off tool by receiving a locating member in one of said notches and moving said cut-off tool to at least partially severe said strip spaced equidistant between two of said plurality of equally spaced bores, forming a self-attaching fastener. 34. The method of forming self-attaching fasteners as defined in claim 33, wherein said method includes advancing said strip by moving said locating member. 35. The method of forming self-attaching fasteners as defined in claim 33, wherein said method includes severing said strip by moving said cut-off tool through said strip, thereby forming a plurality of discreet self-attaching fasteners, then interconnecting said self-attaching fasteners by attaching a frangible connector element extending between said self-attaching fasteners. 36. The method of forming self-attaching fasteners as defined in claim 35, wherein said method includes forming a groove in said flange portions of said strip and locating a wire in said groove of adjacent fasteners. 37. The method of forming self-attaching fasteners as defined in claim 33, wherein said method includes forming a plurality of equally spaced U-shaped notches in said at least one side face of said strip. 38. The method of forming attaching fasteners as defined in claim 37, wherein said method includes forming said plurality of equally spaced V-shaped notches in each of said side faces of said strip. 39. The method of forming self-attaching fasteners as defined in claim 38, wherein said method includes forming said V-shaped notches in each of said side faces of said strip, locating said strip opposite said cut-off tool with said cut-off tool aligned with said V-shaped notches and severing said strip through said V-shaped notches forming a plurality of discreet self-attaching fasteners each having a chamfered surface at the corners of said self-attaching fasteners. 40. A method of forming self-attaching fasteners, comprising the following steps: forming a continuous metal strip having a cross-section of the fasteners to be formed including a pilot portion projecting from a central portion of said strip and flange portions on opposed sides of said pilot portion, said flange portions each including a bearing surface spaced below an end face of said pilot portion and a side face; forming a plurality of equally spaced notches in said side faces of said strip; locating a first portion of said strip opposite a punch by receiving a locating member in one of said notches in each of said side faces of said strip, then moving said punch to pierce a first bore in said strip, advancing said strip by moving said locating member and moving said punch to form a second bore in said strip; and locating said strip opposite a cut-off tool by receiving a locating member in one of said notches on opposed sides of said strip and moving said cut-off tool to severe said strip equidistant between two of said plurality of equally spaced bores forming discreet self-attaching fasteners. 41. The method of forming self-attaching fasteners as defined in claim 40, wherein said method further includes forming a groove in said flange portions of said strip and interconnecting said discreet self-attaching fasteners by locating a continuous frangible connector element in said groove of adjacent fasteners. 42. The method of forming self-attaching fasteners as defined in claim 40, wherein said method includes forming a plurality of equally spaced U-shaped notches, in said side faces of said strip. 43. The method of forming self-attaching fasteners as defined in claim 40, wherein said method includes forming V-shaped notches in said side faces of said strip and locating said strip opposite said cut-off tool with said cut-off tool aligned with said V-shaped notches and severing said strip through said V-shaped notches forming a plurality of discreet self-attaching fasteners each having a chamfered surface at the corners of said self-attaching fasteners. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Self-attaching fastener systems developed by the predecessor in interest of the applicant (Multifastener Corporation) have been used for many years in mass production applications, including the automotive industry. Such fasteners generally include a central projecting pilot portion having a threaded or unthreaded bore therethrough and flange portions on opposed sides of the pilot portion. Universal™ pierce and clinch nuts commercially available from the assignee of this application include a groove extending into opposed sides of the projecting pilot portion adjacent the flange portions. When used as a clinch nut, the pilot portion is received through an opening in a panel and the panel is then received on panel supporting or engaging surfaces of the flange portions. The panel is then deformed by a die button into the grooves in the pilot portion, permanently attaching the fastener to the panel. When used as a pierce nut, the end of the pilot portion is used as a punch, piercing an opening in the panel, which receives the pilot portion as described. In the Hi-Stress™ nut, also commercially available from the Assignee of the present application, the panel receiving grooves are located in the flange portions on opposed sides of the pilot portion. In the preferred embodiment of the Hi-Stress™ nut, the grooves are dovetail-shaped having a restricted opening at the panel receiving surface of the flange portions providing significantly improved pull-off strength. When used as a pierce nut, the pilot portion pierces an opening in the panel and the panel adjacent the opening is then deformed by a die member into the dovetail-shaped grooves and against the bottom wall of the grooves providing improved push-off strength. Both types of pierce and clinch nuts described above are generally installed in mass production applications by a die press. One platen of the die press includes an installation head which receives the pierce or clinch nuts and the opposed die platen includes a die button which deforms the metal into the grooves of the nut as described above. U.S. Pat. No. 3,140,010, describes a method and apparatus for dispensing fasteners of the type described above which includes adhesively fixing the fasteners to a continuous web. The prior patents describe a number of methods of preorienting fasteners in a carrier strip, including an integral frangible carrier portion or methods of attaching fasteners on a wire or plurality of wires. U.S. Pat. No. 3,711,931, assigned to the predecessor in interest of the applicant, describes a method of forming a continuous strip of preoriented self-attaching fasteners including pierce and clinch nuts of the type described above, wherein wire grooves are formed on the back bearing surface of the nut opposite the pilot portion. The pierce or clinch nuts are then oriented in end to end relation with the wire grooves coaxially aligned and a frangible continuous wire is then inserted or rolled into the wire grooves and the back face of the fastener is deformed over the wires by a knurling tool. Self-attaching fasteners of the type described above are now supplied by the assignee of this application in bulk and strip form as disclosed in the above referenced U.S. Pat. No. 3,711,931. The self-attaching fasteners described above are fed to the installation head by a reciprocal pawl having a finger received in the threaded bore. In a typical installation, the installation head includes a chuck or feeder which, upon opening of the die press, feeds a nut into the plunger passage of the installation head, such that a nut is located in the “ready position” following each stroke of the press. Self-attaching fasteners of the type described above are presently formed by a rolling process, starting with a continuous metal wire, wherein the desired cross-section of the fastener is first formed in a continuous strip of metal, which is then rolled into a coil. The coil is then fed through a punch, which punches or pierces the nut bore, and the strip is then fed to a cut-off tool which cuts the strip into discreet fasteners each having a projecting pilot portion and flange portions on opposed sides of the pilot portion. One problem with this method of forming self-attaching fasteners, particularly in mass production applications, is that the bore may not be accurately centered in the pilot portion because the exact position of the strip is difficult to control. At present, the strip is positioned opposite the punch by moving the strip until it contacts a stop. However, the strip may not fully engage the stop or bounce off the stop. This is a particular problem in mass production applications because only two bores are punched at a time and therefore the strip must be repeatedly located opposite the punches. As will be understood, the bore of a nut must be accurately located in the pilot for proper function. There are several problems associated with the present method of forming a preoriented fastener strip as disclosed in the above referenced U.S. Pat. No. 3,711,931, and the feeder system described above. The method of installing a self-attaching fastener of the type described above is disclosed in U.S. Pat. No. 3,648,747 assigned to the predecessor-in-interest of the assignee of this application. First, location of the wires on the rear bearing face of the pierce or clinch nut reduces the bearing area for the punch which installs the fastener in a panel. During installation of a fastener strip of the type described in the above referenced U.S. Pat. No. 3,711,931, the reciprocating punch of the installation head engages and drives the rear face of the fastener into the panel or panel opening. It would therefore be desirable to eliminate the wire grooves and wires from the rear face of the fastener to increase the bearing area. It should also be understood that following installation of the pierce or clinch nut to a panel, a second panel, such as a bracket or other component, is secured to the panel which receives the self-attaching fastener. It would thus be desirable to increase the bearing area of the self-attaching fastener by eliminating the wire grooves. Another problem associated with forming a preoriented strip of fasteners as disclosed in the above referenced patent is that the frangible wires interconnecting the self-attaching fasteners may be pulled out of the wire grooves during installation of the fastener in a panel, creating a sharp wire end on the rear surface of the fastener. Further, the adjacent surfaces of the fasteners in the preoriented strip are spaced a predetermined distance for installation. Thus, when the frangible wires are severed during the installation process, these sharp wire ends protrude from the wire grooves adjacent the rear bearing surface of the fastener following installation which also creates a potential handling hazard. Another problem with the method of attaching the self-attaching fasteners in a preoriented fastener strip as disclosed in the above referenced patent is movement of the nuts on the wires prior to and during feeding of the nuts to the installation head which may cause misfeeding. Finally, another problem with the present method of feeding self-attaching nuts to an installation head is damage to the thread cylinder of the threaded bore through the pilot portion. As set forth above, self-attaching fasteners are normally fed to the installation head by a feed pawl having a finger received in the threaded bore. The feed pawl may damage the thread cylinder. |
<SOH> SUMMARY OF THE INVENTION <EOH>The preoriented strip of self-attaching fasteners of this invention for attachment to a panel, method of forming self-attaching fasteners, method of forming a strip of self-attaching fasteners and method of feeding a strip of fasteners to an installation head of this invention solve the above problems associated with the prior art without additional expense. As set forth above, the self-attaching fasteners of this invention preferably includes a projecting pilot portion adapted to be received through an opening in a panel, and a flange portion adjacent the pilot portion having a panel receiving or bearing surface. In the continuous preoriented strip of self-attaching fasteners of this invention, however, the wire groove is formed in the panel receiving surface adjacent the pilot portion, such that upon installation of the fastener to a panel, the panel overlies the wire groove and the wire. This method of installation thus eliminates the problems associated with sharp wire ends or tangs because the wire ends are completely covered by the panel following installation. The preferred method of forming a preoriented strip of self-attaching fasteners of this invention thus includes forming a wire groove in the panel receiving surface of the flange portion of the self-attaching fastener and inserting a continuous frangible wire in the wire groove, interconnecting the fasteners in a continuous preoriented strip. The preferred embodiments of self-attaching fasteners, as described above, include a flange portion on opposed sides of the projecting pilot portion. In such embodiments, the fastener strip preferably includes a wire groove in the panel receiving surface on opposed sides of the pilot portion and parallel continuous frangible wires are received in the wire grooves and secured to the fasteners. The method further includes preorienting or aligning the fasteners, such that the wire grooves are coaxially aligned and the continuous frangible wires are preferably installed in the grooves by rolling. The self-attaching fasteners of this invention and method of forming same may be used with various embodiments of fasteners, including both the Universal™ fastener systems and the HI-Stress™ fastener systems described above and other self-attaching fastener systems. In the Hi-Stress™ fastener system, the method includes first forming a panel receiving groove in the flange portions adjacent the pilot portion, preferably on both sides of the pilot portion. The method then includes forming a wire groove in the lower surface or bottom wall of the panel receiving groove, preferably both grooves, and then inserting a continuous frangible wire in the wire grooves through the panel receiving grooves and securing the wires to the fasteners. In the most preferred embodiment of this invention, the bottom wall of the wire groove or grooves includes a plurality of spaced pockets. As used herein, the term “pockets” may include either depressions or upstanding ribs, defining pockets therebetween. The continuous frangible wire is then deformed against the bottom wall of the wire groove, filling the pockets, and preventing movement of the fasteners on the wires. The method of feeding a preoriented strip of fasteners to an installation head and preoriented fastener strip of this invention also eliminates damage to the thread cylinder. The method of forming a preoriented strip of fasteners of this invention includes forming a plurality of discreet self-attaching fasteners, preferably of the type described above, wherein each of the fasteners includes a projecting pilot portion, a flange portion on opposed sides of the pilot portion having a panel receiving surface adjacent the pilot portion and side surfaces. The method then includes forming a plurality of preferably equally spaced abutment surfaces on at least one of the sides of each of the fasteners, orienting the fasteners in end to end relation, preferably in nearly abutting relation, and then interconnecting the fasteners by a frangible connector element forming a preoriented strip of fasteners having abutment surfaces on at least one side of the preoriented fastener strip. The preoriented fastener strip is then fed to an installation head by receiving a driving member seriatim in the spaced abutment surfaces and moving the driving member to drive the strip of preoriented fasteners to the installation head. In the preferred embodiment, the abutment surfaces are equally spaced notches or grooves in the side wall of the fasteners. This method thus eliminates contact of the driving member with the bore of the fasteners. Another advantage of the method of forming and feeding a preoriented strip of fasteners of this invention is that the abutment surfaces may be formed in the rolled metal strip from which the fasteners are formed and used to accurately locate the nut bore in the fasteners formed from the strip. This method includes forming a continuous metal strip having the cross-section of the self-attaching fasteners to be formed including a continuous central projecting pilot portion and flange portions on opposed sides of the pilot portion, wherein the flange portions include a bearing face spaced below the end face of the pilot portion and side faces. The method of forming self-attaching female fasteners of this invention then includes forming a plurality of equally spaced notches in at least one side face of the continuous strip, locating the continuous strip opposite a cylindrical punch by receiving a locating member in one of the notches and moving the punch to punch a cylindrical bore in the strip, then moving the strip to successively receive the locating member in a second notch in the strip opposite the punch to punch a plurality of equally spaced cylindrical bores in the strip and finally locating the strip opposite a cut-off tool by receiving a locating member in a notch in the strip and then moving the cut-off tool to at least partially severe the self-attaching female fasteners from the strip, preferably completely severing the strip to form discreet fasteners. This method assures that the nut bore is accurately located through the pilot portion of each nut, eliminating a problem with the present method of forming self-attaching female fasteners. In the preferred method, the fasteners are completely severed from the strip and the fasteners are then interconnected by frangible connectors as described above. In the preferred embodiments of the method of forming self-attaching fasteners or a preoriented strip of fasteners and method of feeding a preoriented strip of fasteners of this invention, the abutment surfaces are defined by substantially equally spaced notches or grooves in the side wall of the continuous metal strip from which the fasteners are formed or the preoriented strip which is fed to the installation head, the method includes receiving a drive member seriatim in the spaced notches and moving the drive member to drive the strip, thus eliminating contact between the drive member and the thread cylinder of the fasteners. In one embodiment, each of the fasteners in the strip includes a plurality of equally spaced grooves or notches. In another embodiment, the notches are formed between adjacent fasteners by chamfering the adjacent ends of the fasteners. In one embodiment, the drive member is a rotatable wheel having a plurality of radial spokes which are received in the notches in the fastener strip, such that rotating the drive member drives the fastener strip. In another embodiment, the drive member is a pawl having a finger configured to be received in the notches and the pawl is reciprocated to drive the fasteners or the fastener strip. As will be understood, however, the abutment surfaces can also be defined by protuberances or projections extending from the side walls of the nut strip. Other advantages and meritorious features of the present invention will be more fully understood from the following description of the preferred embodiments, the appended claims and the drawings, a brief description of which follows. |
Method for the fabrication of a "lab on chip" from photoresist material for medical diagnostic applications |
The present invention relates to a device for performing immuno assays (“biochip” or “lab on chip” respectively), a procedure for its fabrication and the use of the device for performing immuno assays. Furthermore the present invention relates to the use of a photo lithographically patternable dry film photo resist based on a material with functional chemical groups for the immobilization of biomolecules. |
1. A method for the fabrication of a device for performing immuno assays comprising: (a) providing a micro structured substrate having predefined indentations and/or through holes, (b) applying at least one layer of a dry film photo resist material with functional chemical groups onto said substrate, (c) light exposing the dry film photo resist using a photo mask with a different predefined pattern, (d) developing the dry film photo resist layer, (e) repeating step (b) and step (c) using a photo mask with a different predefined pattern and step (d), so that substrate and dry film photo resist material form a capillary structure or capillary channel structure, respectively, with at least one inlet and outlet, (f) localized immobilizing biomolecules to at least one region of the inner surface of the dry film photo resist material channel structure generated in step (e) by chemical coupling via the functional groups of the dry film photo resist material, wherein a device for performing immuno assays is obtained. 2. The method according to claim 1, wherein the dry film photo resist is based on a negative photo resist. 3. The method according to claim 1 or 2, wherein the functional chemical groups are selected from carboxylic acids, carboxylic acids anhydrids, carboxylic acid chlorides, aldehydes, glyoxals, N-hydroxy succinimide esters, hydrazides, imidates, isothiocyanates, isocyanates, maleinimides, halogenquinones, epoxides, aziridines, acylazides, phenoles, amino groups, thiol groups, hydroxyl groups, sulfhydryl-reactive bromium and iodine and biotin groups, preferably thiol groups (—SH) and groups derived therefrom and carboxylic acid groups (—COOH) and groups derived therefrom. 4. The method according to claim 1, wherein the dry film photo resist is based on a mixture of polymers and optionally oligomers and/or monomers, wherein at least one of the polymers, oligomers or monomers comprises thiol-, carboxylic acid-, anhydride-, acid-amide- or imide ester groups, preferably acrylic acid-, methacrylic acid-, maleic acid anhydride-, maleic acid imide- or N-hydroxy succinimide ester groups. 5. The method according to claim 1, wherein the functional chemical groups are activated before step (f). 6. The method according to claim 3, wherein the activation, if the functional groups are carboxylic acid groups, is carried out by reaction with a carbodiimide compound. 7. The method according to claim 1, wherein step (f) is performed by using an immersion or pouring process and the channels of the capillary structure are subsequently closed with either a top layer of at least one dry film photo resist layer or with a self sealing film. 8. The method according to claim 1, wherein in the course of step (e) the predefined channels of the capillary structure are closed, with the exception of the channels provided as inlets and outlets, and subsequently step (f) is performed by using pumping techniques. 9. The method according to claim 1, wherein in step (f) a solution of biomolecules is delivered to one or more capillaries of the capillary structure obtained in step (e) by means of at least one needle or an arrangement of needles utilizing capillary forces. 10. The method according to claim 1, wherein the biomolecules used in step (e) are DNA, RNA, PNA, saccharides, peptides, proteines, cellular components, cells, multicellular organisms and cell assemblies. 11. The method according to claim 1, wherein by binding of biomolecules, at least one capillary of the capillary structure is made as affinity capillary and at least one capillary is made as amplification capillary. 12. The method according to claim 11, wherein the amplification capillary is functionalized by immobilization of at least two enzymes. 13. The method according to claim 12, wherein the immobilization of the enzymes to at least one region of the inner surface of the capillary structure formed by the dry film photo resist material, is carried out by chemical linking via the functional groups of the dry film photo resist material or by entrapment into a membrane that covers one or more of the inner surfaces of the capillary structure. 14. The method according to claim 13, wherein the membrane is fabricated photo lithographically. 15. The method according to claim 1, wherein the chemical signal, generated due to the interaction of the bound biomolecules with a passing fluid to be analyzed, is measured electrochemically, preferably amperometrically, or fluorescence spectrophotometrically. 16. A device for performing immuno assays, comprising at least one substrate and provided thereon at least one dry film photo resist polymer material layer comprising functional chemical groups, wherein substrate and dry film photo resist polymer material together form a capillary structure with at least one inlet and one outlet, wherein biomolecules are bound to at least one region of the inner surface of the capillary structure, formed by the dry film photo resist material, by a chemical link via the functional groups of the dry film photo resist material. 17. The device according to claim 16, wherein the dry film photo resist is based on a negative photo resist. 18. The device according to claim 16 or 17, wherein the functional chemical groups are selected from carboxylic acids, carboxylic acids anhydrids, carboxylic acid chlorides, aldehydes, glyoxals, N-hydroxy succinimide esters, hydrazides, imidates, isothiocyanates, isocyanates, maleinimides, halogenquinones, epoxides, aziridines, acylazides, phenoles, amino groups, thiol groups, hydroxyl groups, sulfhydryl-reactive bromium and iodine and biotin groups, preferably thiol groups (—SH) and groups derived therefrom and carboxylic acid groups (—COOH) and groups derived therefrom. 19. The device according to claim 16, wherein the dry film photo resist is based on a mixture of polymers and optionally oligomers and/or monomers, wherein at least one of the polymers, oligomers or monomers comprises thiol-, carboxylic acid-, anhydride-, acid-amide- or imide ester groups, preferably acrylic acid-, methacrylic acid-, maleic acid anhydride-, maleic acid imide- or N-hydroxy succinimide ester groups. 20. The device according to claim 16, wherein the biomolecules are selected from DNA, RNA, PNA, saccharides, peptides, proteines, cellular components, cells, multicellular organisms and cell assemblies. 21. The device according to claim 16, wherein, by binding of biomolecules, at least one capillary of the capillary structure is made as affinity capillary and at least one capillary as made as amplification capillary. 22. The device according to claim 21, wherein the amplification capillary is functionalized by immobilization of at least two enzymes. 23. The device according to claim 16, further comprising at least two electrodes that can be adopted for one or for more capillaries. 24. The device according to claim 23, wherein the electrodes are designed as micro electrodes or micro electrode arrays. 25. Use of the device according to claim 16 for performing immuno assays. 26. Use of a photo lithographically patternable dry film photo resist based on a material with functional chemical groups for the immobilization of biomolecules. 27. The use according to claim 26, wherein the dry film photo resist is based on a negative photo resist. 28. The use according to claim 26 or 27, wherein the functional chemical groups are selected from carboxylic acids, carboxylic acids anhydrids, carboxylic acid chlorides, aldehydes, glyoxals, N-hydroxy succinimide esters, hydrazides, imidates, isothiocyanates, isocyanates, maleinimides, halogenquinones, epoxides, aziridines, acylazides, phenoles, amino groups, thiol groups, hydroxyl groups, sulfhydryl-reactive bromium and iodine and biotin groups, preferably thiol groups (—SH) and groups derived therefrom and carboxylic acid groups (—COOH) and groups derived therefrom. 29. The use according to claim 26, wherein the dry film photo resist is based on a mixture of polymers and optionally oligomers and/or monomers, wherein at least one of the polymers, oligomers or monomers comprises thiol-, carboxylic acid-, anhydride-, acid-amide- or imide ester groups, preferably acrylic acid-, methacrylic acid-, maleic acid anhydride-, maleic acid imide- or N-hydroxy succinimide ester groups. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is an example scheme showing the fabrication of a capillary channel system according to the present invention. FIG. 2 is an example scheme showing the procedure for performing an ELISA using a capillary channel system according to the present invention. detailed-description description="Detailed Description" end="lead"? The dry film photo resist materials used in the method of the present invention are based on photo patternable polymers that comprise functional chemical groups which are able to form a chemical link with respective biomolecules. Preferably a dry film photo resist based on a negative photo resist is used in the method according to the present invention. In particular dry film photo resists based on polymeric materials comprising functional groups selected from carboxylic acids, carboxylic acids anhydrids, carboxylic acid chlorides, aldehydes, glyoxals, N-hydroxy succinimide esters, hydrazides, imidates, isothiocyanates, isocyanates, maleinimides, halogenquinones, epoxides, aziridines, acylazides, phenoles, amino groups, thiol groups, hydroxyl groups, sulfhydryl-reactive bromium and iodine, and biotin groups. Preferably, the chemical functional groups are thiol groups (—SH) and groups derived therefrom as e.g. pyridyl thio groups, carboxylic acid groups (—COOH) and groups derived therefrom such as e.g. carboxylic acid anhydride groups like maleic acid anhydride or succinic acid anhydride, imide ester groups such as e.g. N-hydroxy-succinimide ester groups, and carboxylate groups. Especially preferred are carboxylic acid groups. In a preferred embodiment of the present invention the dry film photo resist is based on a mixture of polymers and optionally oligomers and/or monomers, wherein at least one of the polymers, oligomers or monomers comprises thiol-, carboxylic acid-, anhydride-, acid-amide-or imide ester groups, preferable acrylic acid-, methacrylic acid-, maleic acid anhydride-, maleic acid imide- or N-hydroxy succinimide ester groups. The polymers used in such mixture may be block polymers, copolymers or graft copolymers, in particular copolymers, preferably random or block-copolymers which preferably comprise carboxylic acid-, anhydride-, acid amide- or imide ester groups. For example, photo resist materials on the basis of styrene/maleic acid anhydride-copolymers can be mentioned. Of course such mixture may comprise additional additives as e.g. fillers, cross linkers, plasticizers, and photo initiators, as well known to an expert in the field of dry film photo resists. In the course of the present invention, there is included the mixing or compounding of an aforementioned dry film photo resist material based on polymers with a monomer or oligomer, that on the one side is capable of being incorporated into the polymer network in the light induced cross linking reaction and on the other side comprises one of the aforementioned functional chemical groups which are capable to form a chemical link with respective biomolecules. Examples are γ-malein imido butyric acid-N-hydroxy succinimide, γ-malein imido capronic-acid-N-hydroxy succinimide oder N-acryloxy succinimide. |
Radiation-curable coating composition for optical filers comprising all-in-one oligomeric system |
A radiation-curable coating composition containing an oligomeric system containing (a) individual oligomers that each contain an oligomeric backbone having chemically tethered thereto one or more radiation-curable components and (b) individual oligomers that each contain an oligomeric backbone having chemically tethered thereto one or more formulation components of a radiation-curable coating composition, wherein each individual oligomer of the group of individual oligomers (a) may be the same as or different from each individual oligomer of the group of individual oligomers (b), and each formulation component is a photoinitiator group, an adhesion promoter group, or a fullerene. |
1. A radiation-curable coating composition for optical fibers comprising an oligomeric system comprising (a) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more radiation-curable groups and (b) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more formulation components of a radiation-curable coating composition, wherein each individual oligomer of the group of individual oligomers (a) may be the same as or different from each individual oligomer of the group of individual oligomers (b), and each formulation component is selected from the group consisting of a photoinitiator group, an adhesion promoter group, and a fullerene, wherein at least one formulation component is a photoinitiator group or a fullerene, or more than one formulation component are adhesion promoter groups. 2. The radiation-curable coating composition of claim 1, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) comprises (i) at least one backbone group, (ii) at least two linking groups, and (iii) at least two end groups. 3. The radiation-curable coating composition of claim 2, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) is independently represented by the following structure: X1-A1-(R-A2)n-X2 wherein X1 and X2 are end groups, which may be the same or different, A1 and A2 are linking groups, which may be the same or different, R is a backbone group, n≧1, and the end groups X1 and X2 are independently selected from the group consisting of a photoinitiator group, an adhesion promoter group, a radiation-curable end group, and a fullerene, provided that, in the case of an individual oligomer of the group of individual oligomers (a), at least one of end groups X1 and X2 is a radiation-curable group, and in the case of an individual oligomer of the group of individual oligomers (b), at least one of end groups X1 and X2 is selected from the group consisting of a photoinitiator group and a fullerene, or both of end groups X1 and X2 are adhesion promoter groups. 4. The radiation-curable coating composition of claim 3, wherein at least 90% of the individual oligomers, based on the combined total amount of individual oligomers (a) and individual oligomers (b) in the oligomeric system, contain, as the end groups X1 and X2, at least one radiation-curable group. 5. The radiation-curable coating composition of claim 3, wherein at most 10% of the individual oligomers, based on the combined total amount of individual oligomers (a) and individual oligomers (b) in the oligomeric system, contain, as the end groups X1 and X2, a photoinitiator group and an adhesion promoter group, two photoinitiator groups, two adhesion promoter groups, or a fullerene group and either a photoinitiator group or an adhesion promoter group. 6. The radiation-curable coating composition of claim 3, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) is the reaction product of (i) at least one polyhydroxy functionalized compound that reacts to provide the backbone group R, (ii) at least one diisocyanate, and (iii) at least one hydroxy-, thiol-, amino-, or isocyano-functionalized compound that reacts to provide the end groups X1 and X2. 7. The radiation-curable coating composition of claim 6, wherein the at least one diisocyanate is selected from the group consisting of toluene diisocyanate and isophorone diisocyanate. 8. The radiation-curable coating composition of claim 6, wherein the at least one polyhydroxy functionalized compound that reacts to provide the backbone group R is a diol selected from the group consisting of polyether diols, polyester diols, polycarbonate diols, hydrocarbon diols, and mixtures thereof. 9. The radiation-curable coating composition of claim 8, wherein the diol is a polyethylene-polypropylene glycol. 10. The radiation-curable coating composition of claim 3, wherein n is on average from about 2 to about 25. 11. The radiation-curable coating composition of claim 3, wherein the linking groups A1 and A2 are urethane linking groups. 12. The radiation-curable coating composition of claim 3, wherein a photoinitiator reacts to provide the photoinitiator group, and the photoinitiator is selected from the group consisting of benzoin, 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl propan-1-one, 1-{4-(2-hydroxyethoxy)phenyl}-2-hydroxy-2-methylpropan-1-one, and 2-hydroxythioxanthen-9-one. 13. The radiation-curable coating composition of claim 3, wherein an adhesion promoter reacts to provide the adhesion promoter group, and the adhesion promoter is an hydroxy-, thiol-, amino-, or isocyano-fimctionalized dialkoxysilane or an hydroxy-, thiol-, amino-, or isocyano-fimctionalized trialkoxysilane. 14. The radiation-curable coating composition of claim 13, wherein the adhesion promoter is selected from the group consisting of N-beta(aminoethyl)-gamma-aminopropylmethyldimethoxysilane, N-beta(aminoethyl)-gamma-aminopropyltrimethoxysilane, and isocyanopropyltriethoxysilane. 15. The radiation-curable coating composition of claim 3, wherein a radiation-curable compound reacts to provide the radiation-curable group, and the radiation-curable compound is selected from the group consisting of 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, pentanediol mono(meth)acrylate, 2-hydroxy-3-phenyloxypropyl (meth)acrylate, 2-hydroxyalkyl(meth)acryloyl phosphate, 4-hydroxycyclohexyl (meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, and pentaerythritol tri(meth)acrylate. 16. The radiation-curable coating composition of claim 1, wherein the coating composition does not contain photoinitiator that is not chemically tethered to an oligomer backbone. 17. The radiation-curable coating composition of claim 1, wherein the coating composition does not contain adhesion promoter that is not chemically tethered to an oligomer backbone. 18. The radiation-curable coating composition of claim 17, wherein the coating composition comprises each of reactive diluent(s), antioxidant(s), flow control agent(s), sensitizer(s), stabilizer(s), lubricant(s) and wetting agent(s) in amounts of 5 wt % or less, based on the total weight of the coating composition. 19. The radiation-curable coating composition of claim 18, wherein the coating composition comprises each of reactive diluent(s), antioxidant(s), flow control agent(s), sensitizer(s), stabilizer(s), lubricant(s) and wetting agent(s) in amounts of 3 wt % or less, based on the total weight of the coating composition. 20. The radiation-curable coating composition of claim 1, wherein the coating composition does not contain a reactive diluent(s). 21. A coated optical fiber, comprising an optical fiber having coated thereon a radiation-curable coating composition for optical fibers comprising an oligomeric system comprising (a) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more radiation-curable groups and (b) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more formulation components of a radiation-curable coating composition, wherein each individual oligomer of the group of individual oligomers (a) may be the same as or different from each individual oligomer of the group of individual oligomers (b), and each formulation component is selected from the group consisting of a photoinitiator group, an adhesion promoter group, and a fullerene, wherein at least one formulation component is a photoinitiator group or a fullerene, or more than one formulation component are adhesion promoter groups. 22. The coated optical fiber of claim 21, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) comprises (i) at least one backbone group, (ii) at least two linking groups, and (iii) at least two end groups. 23. The coated optical fiber of claim 22, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) is independently represented by the following structure: X1-A1-(R-A2)n-X2 wherein X1 and X2 are end groups, which may be the same or different, A1 and A2 are linking groups, which may be the same or different, R is a backbone group, n≧1, and the end groups X1 and X2 are independently selected from the group consisting of a photoinitiator group, an adhesion promoter group, a radiation-curable end group, and a fullerene, provided that, in the case of an individual oligomer of the group of individual oligomers (a), at least one of end groups X1 and X2 is a radiation-curable group, and in the case of an individual oligomer of the group of individual oligomers (b), at least one of end groups X1 and X2 is selected from the group consisting of a photoinitiator group and a fullerene, or both of end groups X1 and X2 are adhesion promoter groups. 24. The coated optical fiber of claim 23, wherein at least 90% of the individual oligomers, based on the combined total amount of individual oligomers (a) and individual oligomers (b) in the oligomeric system, contain, as the end groups X1 and X2, at least one radiation-curable group. 25. The coated optical fiber of claim 23, wherein at most 10% of the individual oligomers, based on the combined total amount of individual oligomers (a) and individual oligomers (b) in the oligomeric system, contain, as the end groups X1 and X2, a photoinitiator group and an adhesion promoter group, two photoinitiator groups, two adhesion promoter groups, or a fullerene group and either a photoinitiator group or an adhesion promoter group. 26. The coated optical fiber of claim 23, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) is the reaction product of (i) at least one polyhydroxy functionalized compound that reacts to provide the backbone group R, (ii) at least one diisocyanate, and (iii) at least one hydroxy-, thiol-, amino-, or isocyano-functionalized compound that reacts to provide the end groups X1 and X2. 27. The coated optical fiber of claim 26, wherein the at least one diisocyanate is selected from the group consisting of toluene diisocyanate and isophorone diisocyanate. 28. The coated optical fiber of claim 26, wherein the at least one polyhydroxy functionalized compound that reacts to provide the backbone group R is a diol selected from the group consisting of polyether diols, polyester diols, polycarbonate diols, hydrocarbon diols, and mixtures thereof. 29. The coated optical fiber of claim 28, wherein the diol is a polyethylene-polypropylene glycol. 30. The coated optical fiber of claim 23, wherein n is on average from about 2 to about 25. 31. The coated optical fiber of claim 23, wherein the linking groups A1 and A2 are urethane linking groups. 32. The coated optical fiber of claim 23, wherein a photoinitiator reacts to provide the photoinitiator group, and the photoinitiator is selected from the group consisting of benzoin, 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl propan-1-one, 1-{4-(2-hydroxyethoxy)phenyl}-2-hydroxy-2-methylpropan-1-one, and 2-hydroxythioxanthen-9-one. 33. The coated optical fiber of claim 23, wherein an adhesion promoter reacts to provide the adhesion promoter group, and the adhesion promoter is an hydroxy-, thiol-, amino-, or isocyano-fimctionalized dialkoxysilane or an hydroxy-, thiol-, amino-, or isocyano-functionalized trialkoxysilane. 34. The coated optical fiber of claim 33, wherein the adhesion promoter is selected from the group consisting of N-beta(aminoethyl)-gamma-aminopropylmethyldimethoxysilane, N-beta(aminoethyl)-gamma-aminopropyltrimethoxysilane, and isocyanopropyltriethoxysilane. 35. The coated optical fiber of claim 23, wherein a radiation-curable compound reacts to provide the radiation-curable group, and the radiation-curable compound is selected from the group consisting of 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, pentanediol mono(meth)acrylate, 2-hydroxy-3-phenyloxypropyl (meth)acrylate, 2-hydroxyalkyl(meth)acryloyl phosphate, 4-hydroxycyclohexyl (meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, and pentaerythritol tri(meth)acrylate. 36. The coated optical fiber of claim 21, wherein the coating composition does not contain photoinitiator that is not chemically tethered to an oligomer backbone. 37. The coated optical fiber of claim 21, wherein the coating composition does not contain adhesion promoter that is not chemically tethered to an oligomer backbone. 38. The coated optical fiber of claim 37, wherein the coating composition comprises each of reactive diluent(s), antioxidant(s), flow control agent(s), sensitizer(s), stabilizer(s), lubricant(s) and wetting agent(s) in amounts of 5 wt % or less, based on the total weight of the coating composition. 39. The coated optical fiber of claim 38, wherein the coating composition comprises each of reactive diluent(s), antioxidant(s), flow control agent(s), sensitizer(s), stabilizer(s), lubricant(s) and wetting agent(s) in amounts of 3 wt % or less, based on the total weight of the coating composition. 40. The coated optical fiber of claim 21, wherein the coating composition does not contain a reactive diluent(s). 41. A telecommunications cable, comprising a glass optical fiber having coated thereon a radiation-curable coating composition for optical fibers comprising an oligomeric system comprising (a) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more radiation-curable groups and (b) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more formulation components of a radiation-curable coating composition, wherein each individual oligomer of the group of individual oligomers (a) may be the same as or different from each individual oligomer of the group of individual oligomers (b), and each formulation component is selected from the group consisting of a photoinitiator group, an adhesion promoter group, and a fullerene, wherein at least one formulation component is a photoinitiator group or a fullerene, or more than one formulation component are adhesion promoter groups. 42. The telecommunications cable of claim 41, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) comprises (i) at least one backbone group, (ii) at least two linking groups, and (iii) at least two end groups. 43. The telecommunications cable of claim 42, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) is independently represented by the following structure: X1-A1-(R-A2)n-X2 wherein X1 and X2 are end groups, which may be the same or different, A1 and A2 are linking groups, which may be the same or different, R is a backbone group, n≧1, and the end groups X1 and X2 are independently selected from the group consisting of a photoinitiator group, an adhesion promoter group, a radiation-curable end group, and a fullerene, provided that, in the case of an individual oligomer of the group of individual oligomers (a), at least one of end groups X1 and X2 is a radiation-curable group, and in the case of an individual oligomer of the group of individual oligomers (b), at least one of end groups X1 and X2 is selected from the group consisting of a photoinitiator group and a fullerene, or both of end groups X1 and X2 are adhesion promoter groups. 44. The telecommunications cable of claim 43, wherein at least 90% of the individual oligomers, based on the combined total amount of individual oligomers (a) and individual oligomers (b) in the oligomeric system, contain, as the end groups X1 and X2, at least one radiation-curable group. 45. The telecommunications cable of claim 43, wherein at most 10% of the individual oligomers, based on the combined total amount of individual oligomers (a) and individual oligomers (b) in the oligomeric system, contain, as the end groups X1 and X2, a photoinitiator group and an adhesion promoter group, two photoinitiator groups, two adhesion promoter groups, or a fullerene group and either a photoinitiator group or an adhesion promoter group. 46. The telecommunications cable of claim 43, wherein each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) is the reaction product of (i) at least one polyhydroxy functionalized compound that reacts to provide the backbone group R, (ii) at least one diisocyanate, and (iii) at least one hydroxy-, thiol-, amino-, or isocyano-functionalized compound that reacts to provide the end groups X1 and X2. 47. The telecommunications cable of claim 46, wherein the at least one diisocyanate is selected from the group consisting of toluene diisocyanate and isophorone diisocyanate. 48. The telecommunications cable of claim 46, wherein the at least one polyhydroxy functionalized compound that reacts to provide the backbone group R is a diol selected from the group consisting of polyether diols, polyester diols, polycarbonate diols, hydrocarbon diols, and mixtures thereof. 49. The telecommunications cable of claim 48, wherein the diol is a polyethylene-polypropylene glycol. 50. The telecommunications cable of claim 43, wherein n is on average from about 2 to about 25. 51. The telecommunications cable of claim 43, wherein the linking groups A1 and A2 are urethane linking groups. 52. The telecommunications cable of claim 43, wherein a photoinitiator reacts to provide the photoinitiator group, and the photoinitiator is selected from the group consisting of benzoin, 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl propan- 1-one, 1-{4-(2-hydroxyethoxy)phenyl}-2-hydroxy-2-methylpropan-1-one, and 2-hydroxythioxanthen-9-one. 53. The telecommunications cable of claim 43, wherein an adhesion promoter reacts to provide the adhesion promoter group, and the adhesion promoter is an hydroxy-, thiol-, amino-, or isocyano-functionalized dialkoxysilane or an hydroxy-, thiol-, amino-, or isocyano-functionalized trialkoxysilane. 54. The telecommunications cable of claim 53, wherein the adhesion promoter is selected from the group consisting of N-beta(aminoethyl)-gamma-aminopropylmethyldimethoxysilane, N-beta(aminoethyl)-gamma-aminopropyltrimethoxysilane, and isocyanopropyltriethoxysilane. 55. The telecommunications cable of claim 43, wherein a radiation-curable compound reacts to provide the radiation-curable group, and the radiation-curable compound is selected from the group consisting of 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, pentanediol mono(meth)acrylate, 2-hydroxy-3-phenyloxypropyl (meth)acrylate, 2-hydroxyalkyl(meth)acryloyl phosphate, 4-hydroxycyclohexyl (meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, and pentaerythritol tri(meth)acrylate. 56. The telecommunications cable of claim 41, wherein the coating composition does not contain photoinitiator that is not chemically tethered to an oligomer backbone. 57. The telecommunications cable of claim 41, wherein the coating composition does not contain adhesion promoter that is not chemically tethered to an oligomer backbone. 58. The telecommunications cable of claim 57, wherein the coating composition comprises each of reactive diluent(s), antioxidant(s), flow control agent(s), sensitizer(s), stabilizer(s), lubricant(s) and wetting agent(s) in amounts of 5 wt % or less, based on the total weight of the coating composition. 59. The telecommunications cable of claim 58, wherein the coating composition comprises each of reactive diluent(s), antioxidant(s), flow control agent(s), sensitizer(s), stabilizer(s), lubricant(s) and wetting agent(s) in amounts of 3 wt % or less, based on the total weight of the coating composition. 60. The telecommunications cable of claim 41, wherein the coating composition does not contain a reactive diluent(s). |
<SOH> BACKGROUND <EOH>The invention relates to optical fiber coating compositions. In particular, the invention relates to radiation-curable primary or secondary optical fiber coating compositions comprising an oligomeric system, wherein individual oligomers of the oligomeric system have formulation components of the coating composition chemically tethered thereto. Optical fibers made from drawn glass have been used as a reliable transmission medium in telecommunications cables. Glass optical fibers are useful because they have the ability to carry large amounts of information over long distances. To facilitate these long-distance transmissions, optical fiber waveguides have been coated with plastic compositions of various materials in order to protect the fiber. Optical glass fibers are usually coated with two superposed coatings. The coating which contacts the glass is a relatively soft, primary coating that must satisfactorily adhere to the fiber and be soft enough to resist microbending, especially at low service temperatures. The outer, exposed coating is a much harder secondary coating, and it provides resistance to handling forces, while possessing sufficient flexibility to enable the coated fiber to withstand repeated bending without cracking the coating. Optical fiber coating compositions, whether primary coating compositions, single coating compositions, or secondary coating compositions, typically comprise, prior to being cured, one or more oligomers, photoinitiator(s) or a photoinitiator system, adhesion promoter(s), and reactive diluent(s). Optical fiber coating compositions also typically comprise flow control additive(s), antioxidant(s), and stabihzer(s). The coating composition is applied to the optical glass fiber in a liquid state, and is thereafter exposed to actinic radiation to effect cure. Specifically, coatings are applied to the fiber in-line during fiber drawing. As the state of fiber drawing technology has allowed for increased draw speeds to effectuate longer optical fibers, however, the need for coating compositions that can cure at faster rates coincident with the faster draw speeds has become more urgent. Thus, as draw speeds have increased, a need has developed for materials that cure at faster rates while retaining the desired chemical and mechanical properties. One method of effecting photopolymerization, and thereby curing the coating composition, is to create free radicals. It is known that a photoinitiator(s) or photoinitiator system may be included in a coating composition in order to generate free radicals upon the absorption of light, e.g. ultraviolet light. When the photoinitiator molecule absorbs radiation, electrons are promoted to higher energy levels in the molecule and the molecule becomes unstable, i.e. very reactive. So, for example, a photoinitiator molecule becomes electronically excited upon the absorption of light and undergoes alpha-cleavage to form two free radicals. One or both of these free radicals are capable of initiating polymerization. Other more complicated processes employ photoinitiator systems, which include co-initiators, from which a photoinitiator molecule may abstract a hydrogen (electron) to form a radical pair. Amines are typical co-initiators. Although the prior art discloses various curable coating compositions with photoinitiators or a photoinitiator system dissolved therein, the effectiveness of the photoinitiators has not always been maximized. For example, problems sometimes exist with initiating the cure. In addition, free residual photoinitiator has a tendency to leach from the cured composition, thereby deteriorating the coating. Still further, photoinitiators may sometimes remain as low molecular weight inclusions in the cured polymer, thereby reducing the maximum physical properties obtainable in the cured system by adversely affecting properties such as hardness, abrasion resistance, etc. A similar problem exists for the inclusion of one or more adhesion promoters in a coating composition. In the case of primary coating compositions, it is important that the cured coating adhere well to the glass cladding. Otherwise, the cured coating will have a tendency to delaminate from the glass fiber. Although the prior art discloses various curable coating compositions with adhesion promoters dissolved therein, the effectiveness of the adhesion promoters has not always been maximized. Thus, a need still exists for adhesion promoters that provide even stronger adhesion to glass at relatively low concentrations. |
<SOH> SUMMARY <EOH>A radiation-curable coating composition comprising an oligomeric system comprising (a) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more radiation-curable components and (b) individual oligomers that each comprise an oligomeric backbone having chemically tethered thereto one or more formulation components of a radiation-curable coating composition, wherein each individual oligomer of the group of individual oligomers (a) may be the same as or different from each individual oligomer of the group of individual oligomers (b), and each formulation component is selected from the group consisting of a photoinitiator group, an adhesion promoter group, and a fullerene. Each individual oligomer of the group of individual oligomers (a) and each individual oligomer of the group of individual oligomers (b) may be independently represented by the following structure: in-line-formulae description="In-line Formulae" end="lead"? X 1 -A 1 -(R-A 2 ) n -X 2 in-line-formulae description="In-line Formulae" end="tail"? wherein X 1 and X 2 are end groups, which may be the same or different, A 1 and A 2 are linking groups, which may be the same or different, R is a backbone group, n≧1, and the end groups X 1 and X 2 are independently selected from the group consisting of a photoinitiator group, an adhesion promoter group, a radiation-curable end group, and a fullerene, provided that, in the case of an individual oligomer of the group of individual oligomers (a), at least one of end groups X 1 and X 2 is a radiation-curable end group, and in the case of an individual oligomer of the group of individual oligomers (b), at least one of end groups X 1 and X 2 is selected from the group consisting of a photoinitiator group, an adhesion promoter group, and a fullerene. |
Optical fibre means |
The present invention relates to a method and a device for detecting damages in an optical fibre (1,2) made for transmitting high optical power, specifically power exceeding 1 kW, and where the optical fibre (1,2) has an entrance end (7) for incident optical radiation (4) and an exit end where the optical radiation is leaving the fibre. According to the invention substantially radially spread radiation in connection with the entrance and/or exit parts of the fibre is detected, and if this radiation exceeds a certain level this is used as an indication of a damage in the entrance and/or exit zone of the fibre. |
1. A method for detecting damages in an optical fiber made for transmitting high optical power, specifically power exceeding 1 kW, and where the optical fiber has an entrance end for incident optical radiation and an exit end where the optical radiation is leaving the fiber wherein substantially, radially reflected radiation from said incident optical radiation is detected in connection with the entrance and/or exit parts of the fiber, and if this radiation exceeds a certain level this is used as an indication of a damage in the entrance and/or exit zone of the fiber. 2. The method according to claim 1 wherein the radially reflected radiation is arranged to hit a diffuser surface before it is detected. 3. A device for detecting damages in an optical fiber made for transmitting high optical power, specifically power exceeding 1 kW, and where the optical fiber has an entrance end for incident optical radiation and an exit end where the optical radiation is leaving the fiber characterized by a detector for sensing substantially radially reflected radiation from said incident optical radiation in connection with the entrance and/or exit parts of the fiber, and if this sensed radiation exceeds a certain level this is used as an indication of a damage in the entrance and/or exit zone of the fiber. 4. The device according to claim 3 wherein a diffusor surface arranged in front of the detector. 5. The device according to claim 4 wherein the diffusor surface is transparent. 6. The device according to claim 4 wherein the diffusor surface is reflecting. 7. The device according to claim 3 wherein the detector is arranged in connection to the entrance end and/or the exit end of the fiber. 8. The device according to claim 3 wherein the detector is arranged at a distance from the entrance or exit end of the fiber, in which case the radially reflected radiation is arranged to be transmitted to the detector via optics. |
Thin film electromagnet and switching device comprising it |
The present invention provided a thin-film electromagnet including a magnetic yoke and a thin-film coil, characterized in that the magnetic yoke is comprised of a first magnetic yoke and a second magnetic yoke making contact with the first magnetic yoke, the first magnetic yoke is located at a center of a winding of which the thin-film coil is comprised, and the second magnetic yoke is arranged above or below the thin-film coil such that the second magnetic yoke faces the thin-film coil, and overlaps at least a part of the thin-film coil. |
1. A thin-film electromagnet comprising a magnetic yoke and a thin-film coil, characterized in that said magnetic yoke is comprised of a first magnetic yoke and a second magnetic yoke making contact with said first magnetic yoke, said first magnetic yoke is located at a center of a winding of which said thin-film coil is comprised, and said second magnetic yoke is arranged above or below said thin-film coil such that said second magnetic yoke faces said thin-film coil, and overlaps at least a part of said thin-film coil. 2. The thin-film electromagnet as defined in claim 1, wherein said thin-film electromagnet has magnetic poles at a surface of said first magnetic yoke which surface is opposite to a surface at which said first and second magnetic yokes make contact with each other, and further at an outer surface of said second magnetic yoke. 3. The thin-film electromagnet as defined in claim 2, wherein said magnetic pole generated at said surface of said first magnetic yoke is out of a center of said winding of which said thin-film coil is comprised. 4. The thin-film electromagnet as defined in any one of claims 1 to 3, further comprising a substrate, wherein said first and second magnetic yokes are arranged on said substrate. 5. The thin-film electromagnet as defined in claim 4, wherein said substrate constitutes said second magnetic yoke. 6. The thin-film electromagnet as defined in any one of claims 1 to 5, further comprising an insulating layer formed on said first or second magnetic yoke, wherein said thin-film coil is formed on said insulating layer. 7. The thin-film electromagnet as defined in any one of claims 1 to 6, further comprising a protection layer covering said first magnetic yoke, said second magnetic yoke and said thin-film coil therewith, wherein said protection layer is planarized at a surface thereof, and said surface of said first magnetic yoke, constituting said magnetic pole, is exposed to a planarized surface of said protection layer. 8. The thin-film electromagnet as defined in any one of claims 1 to 7, wherein said first and second magnetic yokes have a thickness in the range of 0.1 micrometer to 200 micrometers both inclusive. 9. The thin-film electromagnet as defined in claim 8, wherein said first and second magnetic yokes have a thickness in the range of 1 micrometer to 50 micrometers both inclusive. 10. The thin-film electromagnet as defined in any one of claims 1 to 9, wherein said first magnetic yoke is arranged above said second magnetic yoke, and said first magnetic yoke is comprised of a central portion located at a center of said winding of which said thin-film coil is comprised, a body portion making contact above said central portion with said central portion, and extending in parallel with said second magnetic yoke in a direction in which said second magnetic yoke extends, and projecting portions upwardly projecting at opposite ends of said body portion. 11. A method of fabricating a thin-film electromagnet comprising a magnetic yoke and a thin-film coil, said magnetic yoke being comprised of a first magnetic yoke and a second magnetic yoke making contact with said first magnetic yoke, said first magnetic yoke being located at a center of a winding of which said thin-film coil is comprised, said method comprising: the first step of forming said second magnetic yoke on a substrate; the second step of forming an insulating layer on said second magnetic yoke for electrically insulating said second magnetic yoke and said thin-film coil from each other; the third step of forming said thin-film coil on said insulating layer; the fourth step of forming an insulating layer covering said thin-film coil therewith; the fifth step of forming said first magnetic yoke on said second magnetic yoke; the sixth step of forming a protection film entirely covering a resultant resulted from said fifth step; and the seventh step of planarizing said protection film such that said first magnetic yoke is exposed to a surface of said protection film. 12. A switching device comprising a thin-film electromagnet defined in any one of claims 1 to 10, and a swingable unit, wherein said swingable unit is comprised of a pillar, and a swinger supported on said pillar for making swing-movement about said pillar, and switching is carried out by turning on and off electromagnetic force generated between said thin-film electromagnet and said swinger. 13. The switching device as set forth in claim 12, wherein said first magnetic yoke faces said swinger. 14. The switching device as set forth in claim 12 or 13, wherein said swinger is supported on said pillar with a spring being arranged therebetween. 15. The switching device as set forth in claim 14, wherein said spring is composed of amorphous metal. 16. The switching device as set forth in claim 14, wherein said spring is composed of shape memory metal. 17. The switching device as set forth in any one of claims 12 to 16, wherein said swinger has magnetic substance. 18. The switching device as set forth in claim 17, wherein said magnetic substance has remanent magnetism. 19. A switching device comprising: a first thin-film electromagnet; a substrate in which said first thin-film electromagnet is buried; a first electrical contact formed on a surface of said substrate; a swinger rotatable in a plane vertical to said substrate by virtue of magnetic force generated by said first thin-film electromagnet; and a second electrical contact formed on said swinger such that said second electrical contact makes contact with said first electrical contact when said swinger rotates towards said substrate; wherein said first thin-film electromagnet is comprised of a thin-film electromagnet defined in any one of claims 1 to 10. 20. The switching device as set forth in claim 19, wherein said first electrical contact is formed on a surface of said substrate above said first thing-film electromagnet in electrical insulation from said first thin-film electromagnet. 21. The switching device as set forth in claim 19, wherein said first electrical contact is formed on a surface of said substrate away from said first thin-film electromagnet, and said swinger rotates about an intermediate point between said first thin-film electromagnet and said first electrical contact. 22. A switching device comprising: a first thin-film electromagnet; a second thin-film electromagnet; a substrate in which said first and second thin-film electromagnets are buried; a first electrical contact formed on a surface of said substrate above said first thin-film electromagnet in electrical insulation from said first thin-film electromagnet; a second electrical contact formed on a surface of said substrate above said second thin-film electromagnet in electrical insulation from said second thin-film electromagnet; a swinger rotatable in a plane vertical to said substrate about an intermediate point between said first thin-film electromagnet and said second thin-film electromagnet; a third electrical contact formed on said swinger such that said third electrical contact makes contact with said first electrical contact when said swinger rotates towards said first thin-film electromagnet; and a fourth electrical contact formed on said swinger such that said fourth electrical contact makes contact with said second electrical contact when said swinger rotates towards said second thin-film electromagnet, wherein each of said first and second thin-film electromagnets is comprised of a thin-film electromagnet defined in any one of claims 1 to 10. 23. The switching device as set forth in any one of claims 19 to 22, further comprising connectors formed on opposite ends of said swinger, and extensions extending in a direction in which said swinger extends and attached to said swinger through said connectors, wherein said third and fourth electrical contacts are formed on said extensions. 24. The switching device as set forth in any one of claims 12 to 18, wherein said swinger has a light-reflective surface. 25. A switching device comprising: a first thin-film electromagnet; a substrate in which said first thin-film electromagnet is buried; and a swinger rotatable in a plane vertical to said substrate by virtue of magnetic force generated by said first thin-film electromagnet, wherein said swinger has a light-reflective surface, and said first thin-film electromagnet is comprised of a thin-film electromagnet defined in any one of claims 1 to 10. 26. The switching device as set forth in claim 24 or 25, wherein said swinger is covered partially or wholly at a surface thereof with gold or silver. 27. The switching device as set forth in any one of claims 12 to 18, wherein said swinger has a mirror unit for reflecting light. 28. A switching device comprising: a first thin-film electromagnet; a substrate in which said first thin-film electromagnet is buried; a swinger rotatable in a plane vertical to said substrate by virtue of magnetic force generated by said first thin-film electromagnet, and a mirror unit mounted on said swinger for reflecting light, wherein said first thin-film electromagnet is comprised of a thin-film electromagnet defined in any one of claims 1 to 10. 29. The switching device as set forth in claim 28, wherein said mirror unit is formed by forming a sacrifice layer on said swinger, forming a metal or insulating film on said sacrifice layer which film will make said mirror unit, patterning said metal or insulating film, and removing said sacrifice layer. 30. The switching device as set forth in any one of claims 19 to 29, further comprising a pair of pillars arranged facing each other outside said swinger in a width-wise direction of said swinger, and a pair of springs mounted on said pillars and extending towards said swinger, wherein said swinger is supported at its opposite edges in its width-wise direction by said springs arranged such that a line connecting said springs to each other passes a center of said swinger in its length-wise direction. 31. A switching device comprising a thin-film electromagnet defined in any one of claims 1 to 10, and a swingable unit, wherein said swingable unit is comprised of a pillar, and a cantilever supported on said pillar for making swing-movement about said pillar, and switching is carried out by turning on and off electromagnetic force generated between said thin-film electromagnet and a free end of said cantilever. 32. A method of fabricating a switching device defined in any one of claims 19 to 31, said method comprising: the first step of forming said second magnetic yoke on a substrate; the second step of forming an insulating layer on said second magnetic yoke for electrically insulating said second magnetic yoke and said thin-film coil from each other; the third step of forming said thin-film coil on said insulating layer; the fourth step of forming an insulating layer covering said thin-film coil therewith; the fifth step of forming said first magnetic yoke on said second magnetic yoke; the sixth step of forming a protection film entirely covering a resultant resulted from said fifth step; the seventh step of planarizing said protection film such that said first magnetic yoke is exposed to a surface of said protection film; the eighth step of forming an electrical contact on said protection layer; the ninth step of forming a sacrifice layer on said protection layer, said sacrifice layer having a pattern in which openings are formed in predetermined areas; the tenth step of filling said openings with a predetermined material to form a pillar by which said swinger is supported; the eleventh step of forming said swinger on said sacrifice layer; and the twelfth step of removing said sacrifice layer. |
<SOH> FIELD OF THE INVENTION <EOH>The invention relates to a thin-film electromagnet and a switching device including the same, and more particularly to a switch for turning on or off a current signal covering a dc current to an ac current having a frequency in the range of zero to a GHz or greater, and a micro electronics mechanical system (MEMS) switch applicable to an optical device such as a semiconductor laser which is capable of varying a wavelength of laser beams, an optical filter and an optical switch. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 ( a ) is a plan view of a thin-film electromagnet in accordance with the first embodiment of the present invention, and FIG. 1 ( b ) is a cross-sectional view taken along the line 1 B- 1 B in FIG. 1 ( a ). FIGS. 2 ( a ) to 2 ( h ) are cross-sectional views showing respective steps of a method of fabricating the thin-film electromagnet in accordance with the first embodiment of the present invention, illustrated in FIGS. 1 ( a ) and 1 ( b ). FIG. 3 ( a ) is a plan view of a thin-film electromagnet in accordance with the second embodiment of the present invention, and FIG. 3 ( b ) is a cross-sectional view taken along the line 3 B- 3 B in FIG. 3 ( a ). FIG. 4 ( a ) is a plan view of a thin-film electromagnet in accordance with the third embodiment of the present invention, and FIG. 4 ( b ) is a cross-sectional view taken along the line 4 B- 4 B in FIG. 4 ( a ). FIG. 5 ( a ) is a plan view of a thin-film electromagnet in accordance with the fourth embodiment of the present invention, and FIG. 5 ( b ) is a cross-sectional view taken along the line 5 B- 5 B in FIG. 5 ( a ). FIG. 6 ( a ) is a plan view of a thin-film electromagnet in accordance with the fifth embodiment of the present invention, and FIG. 6 ( b ) is a cross-sectional view taken along the line 6 B- 6 B in FIG. 6 ( a ). FIG. 7 ( a ) is a plan view of a thin-film electromagnet in accordance with the sixth embodiment of the present invention, and FIG. 7 ( b ) is a cross-sectional view taken along the line 7 B- 7 B in FIG. 7 ( a ). FIG. 8 ( a ) is a plan view of a switching device in accordance with the seventh embodiment of the present invention, and FIG. 8 ( b ) is a cross-sectional view taken along the line 8 B- 8 B in FIG. 8 ( a ). FIGS. 9 ( a ) to 9 ( n ) are cross-sectional views showing respective steps of a method of fabricating the switching device in accordance with the seventh embodiment of the present invention, illustrated in FIGS. 8 ( a ) and 8 ( b ). FIG. 10 ( a ) is a plan view of a switching device in accordance with the eighth embodiment of the present invention, and FIG. 10 ( b ) is a cross-sectional view taken along the line 10 B- 10 B in FIG. 10 ( a ). FIG. 11 ( a ) is a plan view of a switching device in accordance with the ninth embodiment of the present invention, and FIG. 11 ( b ) is a cross-sectional view taken along the line 11 B- 11 B in FIG. 11 ( a ). FIG. 12 ( a ) is a plan view of a switching device in accordance with the tenth embodiment of the present invention, and FIG. 12 ( b ) is a cross-sectional view taken along the line 12 B- 12 B in FIG. 12 ( a ). FIG. 13 ( a ) is a plan view of a switching device in accordance with the eleventh embodiment of the present invention, and FIG. 13 ( b ) is a cross-sectional view taken along the line 13 B- 13 B in FIG. 13 ( a ). FIG. 14 ( a ) is a plan view of a switching device in accordance with the twelfth embodiment of the present invention, and FIG. 14 ( b ) is a cross-sectional view taken along the line 14 B- 14 B in FIG. 14 ( a ). FIG. 15 ( a ) is a plan view of a switching device in accordance with the thirteenth embodiment of the present invention, and FIG. 15 ( b ) is a cross-sectional view taken along the line 15 B- 15 B in FIG. 15 ( a ). FIG. 16 ( a ) is a plan view of a switching device in accordance with the fourteenth embodiment of the present invention, and FIG. 16 ( b ) is a cross-sectional view taken along the line 16 B- 16 B in FIG. 16 ( a ). FIG. 17 ( a ) is a plan view of a switching device in accordance with the fifteenth embodiment of the present invention, and FIG. 17 ( b ) is a cross-sectional view taken along the line 17 B- 17 B in FIG. 17 ( a ). FIG. 18 ( a ) is a plan view of a conventional MEMS switching device, and FIG. 18 ( b ) is a cross-sectional view taken along the line 18 B- 18 B in FIG. 18 ( a ). FIG. 19 is a cross-sectional view of another conventional MEMS switching device. FIG. 20 is a cross-sectional view of still another conventional MEMS switching device. FIG. 21 is a graph showing comparison between electromagnetic force and electrostatic force. detailed-description description="Detailed Description" end="lead"? |
Humanised baculovirus |
The invention relates to a genetically engineered baculovirus wherein said virus is engineered to target therapeutic agents to cells, typically cancer cells, for example prostate cancer cells. |
1. A baculovirus wherein the baculovirus genome has been modified to comprise a first polynucleotide which encodes a therapeutic agent and a second polynucleotide which encodes a polypeptide which functions to target said baculovirus to at least one cell type. 2. A baculovirus according to claim 1 wherein said genome is adapted for eukaryotic gene expression of said first and second polynucleotides. 3. A baculovirus according to claim 2 wherein the expression of said first polynucleotide is controlled by a cancer specific promoter. 4. A baculovirus according to claim 3 wherein said cancer specific promoter is a prostate cancer cell specific promoter. 5. A baculovirus according to claim 3 wherein said promoter is a promoter listed in Table 1. 6. A baculovirus according to claim 1 wherein said therapeutic agent is a polypeptide. 7. A baculovirus according to claim 6 wherein said therapeutic agent is a tumor suppressor polypeptide listed in Table 2. 8. A baculovirus according to claim 7 wherein said therapeutic agent is an antigenic polypeptide. 9. A baculovirus according to claim 8 wherein said antigenic polypeptide is a prostate tumor rejection antigen. 10. A baculovirus according to claim 6 wherein said therapeutic agent is a cytotoxic polypeptide. 11. A baculovirus according to claim 10 wherein said cytotoxic polypeptide is selected from the group consisting of: pseudomonas exotoxin; ricin toxin; and diptheria toxin (Genbank ace.#: A04646). 12. A baculovirus according to claim 6 wherein said therapeutic agent is a polypeptide which induces cell-cycle arrest. 13. A baculovirus according to claim 12 wherein said therapeutic agent is a polypeptide listed in Table 4. 14. A baculovirus according to claim 6 wherein said therapeutic agent is a pharmaceutically active polypeptide. 15. A baculovirus according to claim 14 wherein said therapeutic agent is a cytokine. 16. A baculovirus according to claim 15 wherein said therapeutic agent is a cytokine listed in Table 5. 17. A baculovirus according to claim 6 wherein said therapeutic agent is an antibody or active binding fragment thereof. 18. A baculovirus according to claim 17 wherein said fragment is a Fab fragment. 19. A baculovirus according to claim 6 wherein said therapeutic agent is a polypeptide which induces apoptosis. 20. A baculovirus according to claim 19 wherein said therapeutic agent is an apoptosis-inducing polypeptide listed in Table 6. 21. A baculovirus according to claim 6 wherein said therapeutic agent is a pro-drug activating polypeptide. 22. A baculovirus according to claim 21 wherein said therapeutic agent is a prodrug-activating polypeptide listed in Table 7. 23. A baculovirus according to claim 22 wherein said prodrug-activating polypeptide has antiangiogenic activity. 24. A baculovirus according to claim 23 wherein said prodrug-activating polypeptide is selected from the group consisting of angiostatin (Genbank accANM007037), Tie2 (Genbank acc.#: AF451865), and endostatin (Genbank acc.#: NM130445). 25. A baculovirus according to claim 1 wherein said therapeutic agent is an antisense nucleic acid molecule. 26. A baculovirus according to claim 25 wherein said antisense nucleic acid molecule binds a nucleic acid molecule encoding a cell-cycle regulatory gene. 27. A baculovirus according to claim 26 wherein said antisense nucleic acid molecule binds a cell-cycle regulatory gene listed in Table 4. 28. A baculovirus according to claim 25 wherein said antisense nucleic acid molecule binds a nucleic acid molecule encoding an apoptosis inhibitor. 29. A baculovirus according to claim 28 wherein said apoptosis inhibitor is caveolin (Genbank ace.#: AF095591) 30. A baculovirus according to claim 1 wherein said therapeutic agent is a double stranded RNA molecule. 31. A baculovirus according to any claim 1 wherein said therapeutic agent is a ribozyme. 32. A baculovirus according to any of claim 1 wherein said baculovirus genome further comprises a third polynucleotide which encodes a polypeptide which binds the baculovirus to the cell surface of at least one cell type. 33. A baculovirus according to claim 32 wherein said nucleic acid encodes a polypeptide selected from the group consisting of. GnRH (Genbank ace.#: L03380), fibroblast growth factors; insulin, an insulin-like growth factor; neurotensin; platelet derived growth factor (Genbank acc.#:NM 002609 & NM 006206); and somatostatin (Genbank acc.#: BC032625). 34. A baculovirus according to claim 32 wherein said third polynucleotide is inserted into the baculovirus genome at a site such that said polypeptide which binds the baculovirus to the cell surface is fused to a baculovirus capsid polypeptide. 35. A baculovirus according to claim 34 wherein said capsid polypeptide is gp64. 36. A pharmaceutical composition comprising the baculovirus according to claim 1 and a pharmaceutically acceptable excipient. 37-38. (Cancelled) 39. A method of treatment comprising the administration of a therapeutically effective amount of a pharmaceutical composition of claim 36. 40. A method according to claim 39 wherein said method is for the treatment of cancer. 41. A method according to claim 40 wherein said cancer is prostate cancer. |
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