A system for pumping or mixing a fluid using a levitating, rotating magnetic bearing and various other components for use in a pumping or mixing system are disclosed. The magnetic bearing is placed in a fluid-containing vessel in close proximity to a superconducting element. A separate cooling source thermally linked to the superconducting element provides the necessary cooling to induce levitation in the magnetic bearing. The superconducting element may be thermally isolated, such that the bearing, the vessel, and any fluid contained therein are not exposed to the cold temperatures required to produce the desired superconductive effects and the resulting levitation. By using means external to the vessel to rotate and/or stabilize the magnetic bearing levitating in the fluid, including possibly rotating the superconducting element itself or moving it relative to the vessel, the desired effective pumping or mixing action may be provided.

The present invention relates generally to the mixing or pumping of fluids or the like and, more particularly, to a number of systems, related components, and related methods for pumping or mixing fluids using a rotating magnetic bearing levitated by a superconducting element.
Most pharmaceutical solutions and suspensions manufactured on an industrial scale require highly controlled, thorough mixing to achieve a satisfactory yield and to ensure a uniform distribution of ingredients in the final product. Agitator tanks are frequently used to complete the mixing process, but a better degree of mixing is normally achieved by using a mechanical stirrer or impeller (e.g., a set of mixing blades attached to a metal rod). Typically, the mechanical stirrer or impeller is simply lowered into the fluid through an opening in the top of the vessel and rotated by an external motor to create the desired mixing action.
One significant limitation or shortcoming of such an arrangement is the danger of contamination or leakage during mixing. The rod carrying the mixing blades or impeller is typically introduced into the vessel through a dynamic seal or bearing. This opening provides an opportunity for bacteria or other contaminants to enter, which of course can lead to the degradation of the product. A corresponding danger of environmental contamination exists in applications involving hazardous or toxic fluids, or suspensions of pathogenic organisms, since dynamic seals or bearings are prone to leakage. Cleanup and sterilization are also made difficult by the dynamic bearings or seals, since these structures typically include folds and crevices that are difficult to reach. Since these problems are faced by all manufacturers of sterile solutions, pharmaceuticals, or the like, the U.S. Food and Drug Administration (FDA) has consequently promulgated strict processing requirements for such fluids, and especially those slated for intravenous use.
Recently, there has also been an extraordinary increase in the use of biosynthetic pathways in the production of pharmaceutical materials, but problems plague those involved in this rapidly advancing industry. The primary problem is that suspensions of genetically altered bacterial cells frequently used to produce protein pharmaceuticals (insulin is a well-known example) require gentle mixing to circulate nutrients. If overly vigorous mixing or contact between the impeller and the vessel wall occurs, the resultant forces and shear stresses may damage or destroy a significant fraction of the cells, as well as protein molecules that are sensitive to shear stresses. This not only reduces the beneficial yield of the process, but also creates deleterious debris in the fluid suspension that requires further processing to remove.
In an effort to overcome this problem, others have proposed alternative mixing technologies. The most common proposal for stirring fluids under sterile conditions is to use a rotating, permanent magnet bar covered by an inert layer of TEFLON, glass, or the like. The magnetic bar is placed on the bottom of the agitator vessel and rotated by a driving magnet positioned external to the vessel. Of course, the use of such an externally driven magnetic bar avoids the need for a dynamic bearing, seal or other opening in the vessel to transfer the rotational force from the driving magnet to the stirring magnet. Therefore, a completely enclosed system is provided. This of course prevents leakage and the potential for contamination created by hazardous materials (e.g., cytotoxic agents, solvents with low flash points, blood products, etc.), eases clean up, and allows for the desirable sterile interior environment to be maintained.
However, several well-recognized drawbacks are associated with this mixing technology, making it unacceptable for use in many applications. For example, the driving magnet produces not only torque on the stirring magnetic bar, but also an attractive axial thrust force tending to drive the bar into contact with the bottom wall of the vessel. This of course generates substantial friction at the interface between the bar and the bottom wall of the vessel. This uncontrolled friction generates unwanted heat and may also introduce an undesirable shear stress in the fluid. Consequently, fragile biological molecules, such as proteins and living cells that are highly sensitive to temperature and shear stress, are easily damaged during the mixing process, and the resultant debris may contaminate the product. Moreover, the magnetic bar stirrer may not generate the level of circulation provided by an impeller, and thus cannot be scaled up to provide effective mixing throughout the entire volume of large agitation tanks of the type preferred in commercial production operations.
In yet another effort to eliminate the need for dynamic bearings or shaft seals, some have proposed mixing vessels having external magnets that remotely couple the mixing impeller to a motor located externally to the vessel. A typical magnetic coupler comprises a drive magnet attached to the motor and a stirring magnet carrying an impeller. Similar to the magnetic bar technology described above, the driver and stirrer magnets are kept in close proximity to ensure that the coupling between the two is strong enough to provide sufficient torque. An example of one such proposal is found in U.S. Pat. No. 5,470,152 to Rains.
As described above, the high torque generated can drive the impeller into the walls of the vessel creating significant friction. By strategically positioning roller bearings inside the vessel, the effects of friction between the impeller and the vessel wall can be substantially reduced. Of course, high stresses at the interfaces between the ball bearings and the vessel wall or impeller result in a grinding of the mixing proteins and living cells, and loss of yield. Further, the bearings may be sensitive to corrosive reactions with water-based solutions and other media and will eventually deteriorate, resulting in frictional losses that slow the impeller, reduce the mixing action, and eventually also lead to undesirable contamination of the product. Bearings also add to the cleanup problems.
In an effort to address and overcome the limitations described above, still others have proposed levitated bearings designed to reduce the deleterious effects of friction resulting from magnetically coupled mixers. By using a specially configured magnetic coupler to maintain only a repulsive levitation force in the vertical direction, the large thrust force between the stirring and driving magnets can be eliminated, along with the resultant shear stress and frictional heating. An example of one such arrangement is shown in U.S. Pat. No. 5,478,149 to Quigg.
However, one limitation remaining from this approach is that only magnet-magnet interactions provide the levitation. This leads to intrinsically unstable systems that produce the desired levitation in the vertical direction, but are unable to control side-to-side movement. As a result, external contact bearings in the form of bearing rings are necessary to laterally stabilize the impeller. Although this xe2x80x9cpartialxe2x80x9d levitation reduces the friction between the impeller and the vessel walls, it does not totally eliminate the drawbacks of the magnetically coupled, roller bearing mixers previously mentioned.
In an effort to eliminate the need for contact or other types of mechanical roller bearings, complex feedback control has been proposed to stabilize the impeller. Typical arrangements use electromagnets positioned alongside the levitating magnet. However, the high power level required to attain only sub-millimeter separations between the levitating magnet and the stabilizing magnets constitutes a major disadvantage of this approach. Furthermore, this solution is quite complex, since the stabilizing magnets must be actively monitored and precisely controlled by complex computer-implemented software routines to achieve even a moderate degree of stability. As a consequence of this complexity and the associated maintenance expense, this ostensible solution has not been accepted in the commercial arena, and it is doubtful that it can be successfully scaled up for use in mixing industrial or commercial scale process volumes.
Still others have proposed the use of superconductive materials to levitate magnetic bearings. Despite recent advances in the art, significant limitation on the application of this technology to mixing systems results from the extraordinarily cold temperatures required to create the desired superconductive effects. Even the recently discovered xe2x80x9chigh temperaturexe2x80x9d superconductors require temperatures on the order of 77 to 130 Kelvin to induce reliable, stable levitation in a magnetic bearing. In the past, the relatively wide separation distance required between the bearing, the cryostat outer wall, and the superconducting element necessary to prevent unwanted cooling of the fluid has limited the industrial applicability of this approach. To date, applications of this technology to fluids have been primarily in the pumping of cryogens or the like, such as those typically used in cold fusion experiments, in flywheels or other energy storage devices, or for space travel (see representative U.S. Pat. No. 5,747,426 to Abboud or U.S. Pat. No. 4,365,942 to Schmidt), where there is of course little concern for the inevitable cooling effect created.
In my prior U.S. Pat. No. 5,567,672, I describe levitating a magnet above a superconducting element in a cryostat, which contains the cooling source used to cool the superconducting element. This arrangement could possibly be used as part of a system for mixing temperature sensitive fluids, such as cell suspensions or blood, as disclosed herein. However, the resultant increased separation created by the double wall vacuum gap may decrease the stability and the load capacity of the levitating magnet. This may limit the applications in which this arrangement is useful, and could especially preclude use with particularly viscous fluids or with the large volumes of fluid typically present in commercial scale operations.
Thus, a need is identified for an improved system having a levitating magnetic bearing for mixing or pumping fluids, and especially ultra-pure, hazardous, or delicate fluid solutions or suspensions. The system would preferably employ a magnetic bearing that levitates in a stable fashion to avoid contact with the bottom or side walls of the vessel. Since the bearing would levitate in the fluid, no mixing rod or other structure penetrating the mixing vessel would be necessary, thus eliminating the need for dynamic bearings or seals and all potentially deleterious effects associated therewith. Since penetration is unnecessary, the vessel could be completely sealed prior to mixing to avoid the potential for contamination and reduce the chance for exposure in the case of hazardous or biological fluids, such as contaminated blood or the like. The vessel and magnetic bearing could also be made of disposable materials and discarded after each use, which would eliminate the need for cleaning or sterilization. The absence of a mixing or stirring rod penetrating through the vessel would also allow a slowly rotating impeller to be held at an off-axis position in a sealed vessel, thus making it possible to independently rotate the vessel about its central axis to achieve very gentle, yet thorough, mixing.
In the case of warm or temperature-sensitive fluids, the use of superconductivity to provide the desired levitation would be possible by thermally isolating and separating the superconducting element from the magnetic bearing and providing a separate, substantially isolated cooling source. This combined thermal isolation and separation would avoid creating any significant cooling in the vessel, the magnetic bearing or the fluid being mixed or pumped. The use of a superconductor would also eliminate the sole reliance on magnet-magnet repulsion to provide the levitation force and the concomitant need for active electronic control systems to ensure stable levitation. Overall, the proposed system would have superior characteristics over existing mixing or pumping technologies, especially in terms of sterility, mixing quality, safety and reliability, and would be readily adaptable for use in larger, industrial scale operations.
To meet these needs, and in accordance with a first aspect of the present invention as described herein, a number of systems that are capable of pumping or mixing fluids, including temperature sensitive fluids, using a magnetic bearing, impeller, rotor or other element or device capable of generating a pumping or mixing action in a fluid (hereinafter generically referred to as a xe2x80x9cmagnetic bearingxe2x80x9d) levitated by a superconducting element are disclosed. The magnetic bearing may be placed in a vessel positioned adjacent to the wall of a cryostat or other housing for the superconducting element. A separate cooling source thermally linked to the superconducting element provides the necessary cooling to create the desired superconductive effects and induce levitation in the magnetic bearing. The cryostat outer wall or other housing may define a chamber around the superconducting element. This chamber thermally isolates the superconducting element from the vessel containing the bearing. To minimize thermal transfer from the superconducting element to the outer wall or housing, this chamber is preferably evacuated, but may be instead filled with an insulating material. This thermal isolation and separation means that the superconducting element may be placed in close proximity to the outer wall of the cryostat or other housing adjacent to the vessel to achieve a significant reduction in the separation distance between the levitating bearing and the superconducting element. This advantageously enhances the magnetic stiffness and loading capacity of the bearing as it levitates. However, since the superconducting element may be thermally isolated from the wall or housing, the magnetic bearing, and hence the vessel and fluid contained therein, are not exposed to the cold temperatures required to generate the desired superconductive effects. By using means external to the vessel to rotate one of the levitating magnetic bearing or the superconducting element, the desired pumping or mixing action is provided.
As should be appreciated from reviewing the foregoing description, several advantages may possibly be provided through the use of the mixing or pumping system of the present invention, depending in part upon the particular application. Since the rotating magnetic bearing levitates in the fluid, there is no mechanical stirrer or mixing rod extending through any wall of the vessel, which means that the vessel can be completely sealed from the outside environment, if desired. This eliminates the need for a dynamic bearing or seal and the concomitant problems with leakage, sterility, and the like, which makes the present arrangement particularly well suited for use in pumping or mixing ultra-pure or hazardous fluids. Furthermore, exceptionally stable levitation of the magnetic bearing is provided by the minimal separation distance between the superconducting element and the magnetic bearing. Due to the thermal isolation and separation of the superconducting element from the cryostat wall, the system may even be used to pump or mix temperature sensitive fluids. In any case, contact-free, stable levitation reduces the incidence of frictional heating or unwanted shear stresses, both of which can have a significant deleterious effect on sensitive fluids, such as cell suspensions or the like.
In one possible embodiment, the magnetic bearing includes first and second spaced permanent magnets, which may be mounted at the opposite ends of a support shaft. The first magnet is placed in the fluid vessel closest to the outer wall of the cryostat such that it is levitated by the superconducting element. While those of skill in the art will understand that the polarity of the first permanent magnet is not critical for producing the desired levitation, it is preferred that it is disk-shaped and polarized in the vertical direction. This ensures that the magnetic field generated is substantially symmetrical and the desired stable levitation and free rotation relative to the vertical axis results.
The second permanent magnet forms a magnetic coupling with the motive device for rotating the magnetic bearing, which is preferably a drive magnet coupled to the rotating shaft of a motor. In applications where the stability of the magnetic bearing is particularly important, the drive magnet includes more than one magnet, and in the one embodiment has at least two sub-magnets that correspond to opposite polarity sub-magnets forming a part of the second permanent magnet. In addition to creating the desired magnetic coupling for transmitting the driving torque, these cooperating sub-magnets produce an attractive force that balances with the levitational force provided by the superconducting element to keep the bearing properly balanced in the vertical direction. The cooperating sub-magnet pairs also keep the levitating bearing axially aligned and prevent side-to-side movement without the need for active control. In combination, the magnetic couplings created by the sub-magnet pairs allow the bearing to rotate in an exceptionally stable fashion. This reduces the chances of the bearing inadvertently contacting between the bottom and side walls of the vessel, and eliminates the need for electromagnets, roller bearings, or like structures found in prior art pumps or mixers.
In an alternate version of the magnetic bearing, at least one, and preferably a plurality of chambers are provided for holding a gas or other substance that is lighter than the fluid or other substance surrounding the bearing. These chambers serve to assist in levitating the magnetic bearing in the fluid, while the pinning forces created by the superconducting element simultaneously assist in keeping the magnetic bearing properly positioned at the desired location in the vessel. The chamber or chambers thus effectively reduce the amount of levitation force that must be supplied by the superconducting element.
The superconducting element may be formed of melt-textured Yttrium-Barium Copper Oxide (YBCO), which is a well-known high temperature, or xe2x80x9cType II,xe2x80x9d superconducting material, formed into a relatively thin pellet. The thermal link between the superconducting element and the cooling source is created by an elongate rod formed of a material having desirable thermal transfer characteristics. Metals, such as copper, brass, aluminum, or the like, are particularly well-suited for this purpose, but the use of any other material having good thermal conductance/low thermal resistance is possible. The rod may be cylindrical in shape such that one end has a relatively large surface area that fully contacts and engages an entire face of the superconducting element to maximize thermal transfer. While one end of the rod supports the superconducting element in the chamber defined by the outer wall of the cryostat or other housing, which remains at room temperature, the opposite end is kept in thermal contact with the cooling source. The cooling source may take the form of a separate cooling chamber in the cryostat holding a cryogen ataur between 4.2 and 130 Kelvin, and most preferably liquid nitrogen at a temperature between approximately 65-80 Kelvin. Instead of liquid cryogens, the use of alternate means for cooling the rod is possible, such as providing a separate closed cycle refrigerator that is kept entirely outside of the cryostat or other housing for the superconducting element.
Since the magnetic bearing levitates without the need for a mixing rod or other form of driving shaft, it should be appreciated that the vessel containing the fluid may be completely sealed from the outside environment and used to mix, rather than pump, the fluid. By using such an arrangement, the potential for leakage or contamination during mixing is eliminated, as is the risk of exposing hazardous or biologically active fluids to the environment. Forming the sealed vessel and the magnetic bearing from disposable materials is also possible, such that both can simply be discarded after mixing is complete and the fluid is retrieved or recovered, if necessary. This advantageously avoids the need for clean up or sterilization of the vessel and bearing.
Also, since there is no need for a dynamic bearing or seal for any drive shaft penetrating through a wall of the vessel, the vertical center axis of rotation of the magnetic bearing can be easily offset from the vertical center axis of the vessel. The vessel can then be rotated in a direction counterclockwise to the rotation of the bearing mounted in such an offset position. By doing so, gentle, yet thorough mixing may be provided in an efficient manner.
It should also be appreciated that other alternatives to a sealed vessel are possible. Of course, the vessel may simply be open to the ambient environment, as may be desired during the mixing of some solutions or suspensions that require exposure to open air to achieve a desired result. Alternatively, the vessel may be substantially sealed with only an inlet and an outlet, such that the rotating magnetic bearing/impeller provides pumping action to move the fluid through the vessel. Manufacturing the open top or substantially sealed vessel of disposable materials is also possible, such that both the vessel and magnetic bearing can simply be discarded after use to avoid the need for clean up or sterilization. The vessel can also be a flexible bag or other non-rigid type of container, the dimensions of which are essentially defined by the volume of fluid held therein.
As should further be appreciated, the system described above is based on the use of a stationary superconducting element and a magnetic bearing that includes a levitation magnet and separate xe2x80x9cdrivenxe2x80x9d magnets. The driving force is applied to the driven magnets from adjacent the top of the vessel, while the levitation force is provided by the other, levitating magnet adjacent to the bottom of the vessel. While this system provides the several advantages described above, in many practical applications, it is advantageous to keep the top of the mixing vessel or pumping head substantially clear from obstructions. For instance, if the mixing vessel includes a number of different ports and connections on the top, such as a filling port, temperature sensor connector, pH sensor connector, or the like, driving the levitating magnetic bearing from the top may interfere with these structures, thus possibly making operation somewhat inconvenient. This is also true in the case where the levitating magnetic bearing is used in a pumping chamber or centrifugal pumping head, where it is often desirable to place the fluid inlet in the top or upper wall of the vessel.
Moreover, in case of accidental decoupling of the driving magnet with the driven magnet at the opposite side of the levitating magnetic bearing, the shaft may lose vertical stability and fall into contact with the bottom or sides of the container. If this occurs, it is impossible to recover the stable levitation without opening the container, if sealed, or otherwise disturbing the fluid. This, of course, can lead to deleterious contamination.
Yet another reason for providing an alternative to the top driven arrangement is that it eliminates the need for a fixed height vessel or container for holding the fluid. For example, in the case of where the vessel is in the form of a flexible bag, the vertical dimension of the bag often depends on the amount of fluid present, as well as the size and overall geometry of the bag itself. By magnetically driving a low-profile, levitating bearing or impeller in a stable, non-contact fashion from only the bottom of such a flexible plastic container, it could be of a reduced vertical dimension without compromising the degree of pumping or mixing action created.
Driving and levitating a magnetic bearing from the same side of the vessel also reduces the number of permanent magnets required. This is because the levitation magnets may simultaneously serve as the xe2x80x9cdrivenxe2x80x9d magnets. Eliminating the total number of magnets required not only reduces the materials cost, but also creates a bearing that is less complicated to manufacture.
Thus, another purpose of the present invention is to provide a magnetic bearing, and most preferably a low-profile, disk-shaped magnetic bearing or impeller (with or without blades, vanes, or the like) that is both levitated by a superconducting element and magnetically driven by means located outside of the vessel, and preferably on the same side of the vessel as the superconducting element. The magnetic bearing can thus be used for mixing or pumping fluids in a variety of vessels without regard to height, including flexible containers, such as bags or the like. Also, as described above, the magnetic bearing can be used along with a disposable plastic container (or with disposable impeller blades along with a disposable plastic pumping chamber or head).
To achieve this second goal, another version of a pumping or mixing system using a levitating magnetic bearing is disclosed. In this version, the thermally isolated superconducting element is contained within a wall defining a chamber that may be evacuated or insulated to create the desired thermal separation, as above, but instead of rotating the magnetic bearing including separate drive magnets, the motive device rotates both the wall and the superconducting element together. Accordingly, both the levitation and motive forces for the magnetic bearing are supplied by the same superconducting element (which actually can be formed of several component parts). To ensure proper rotation of the bearing, it includes at least two permanent magnets having different polarities that together create a non-symmetrical magnetic field with respect to the axis of rotation of the superconducting element. The bearing may also carry one or more blades or vanes to enhance the mixing or pumping action. In an alternate version of this embodiment, the cooling source may also be rotated along with the wall creating the chamber for thermally isolating the superconducting element (or may serve to couple the chamber to the motive device). In either case, the low-profile, magnet-carrying bearing may thus be efficiently and effectively levitated and rotated from the bottom of a vessel (or pumping chamber/head) resting on a stable support structure, while at all times remaining thermally separated and isolated from the cold superconducting element.
When using a vessel having a narrow opening, it may be difficult or impossible to insert the typical pancake or disk-shaped magnetic bearing in the fluid. Thus, an alternate version of a magnetic bearing, and one especially adapted for use in the pumping or mixing system of this second embodiment, is disclosed. The magnetic bearing is in the form of a low-profile rod. Each end of the rod carries a magnet. These magnets may serve as both the levitating and the driven magnets in the case where the bearing is positioned above a rotating superconducting element.
In another version, two of the low-profile rods, each carrying at least two magnets having identical polarities, are pinned together, preferably at their centers. The rods are thus capable of rotating relative to each other to form a low-profile magnetic bearing that can easily pass through a narrow opening in a vessel. Since the magnets at the end of each rod have the same polarity, they not only serve to levitate and drive the bearing, but also repel each other to keep the rods from aligning when rotating in the vessel. Instead of or in addition to pinning the rods together, it is also possible to fabricate one or both rods of a flexible material, and possibly a single integral piece of material. As a result of the flexibility, the bearing formed from the rigidly coupled rods can be deformed to pass through any narrow opening in a vessel or container.
Despite the preference for using the system of this second possible embodiment for pumping or mixing temperature sensitive fluids in view of the beneficial nature of the thermal separation, it should be appreciated that it is possible to use it for pumping or mixing non-temperature sensitive or cryogenic fluids as well. For example, the evacuated housing or like chamber surrounding the rotating superconducting element can be eliminated altogether, since there is no need to thermally separate it from the support structure for the vessel containing the magnetic bearing when a cold or non-temperature sensitive fluid is being pumped or mixed. Nevertheless, the desired stable, contact free levitation is still achieved.
In accordance with a third aspect of the present invention, the thermally isolated superconducting element provides the levitation, substantially as described above, while a separate motive device positioned adjacent to the superconducting element serves to rotate the magnetic bearing. In a most preferred version of this embodiment, the superconducting element is annular and positioned in a correspondingly shaped chamber defined by the outer wall of a cryostat or like device. This chamber may be evacuated or insulated to provide the desired thermal separation and isolation for the superconducting element. The wall also defines a bore or opening in the center of the chamber housing the superconducting element for receiving a portion of a motive device, such as a shaft carrying alternating polarity driving magnets at one end. The opposite end of the shaft is coupled to a motor also forming a part of the motive device. The magnetic bearing, in turn, carries a first xe2x80x9clevitatingxe2x80x9d magnet corresponding in shape to the superconducting element, as well as at least two alternating polarity xe2x80x9cdrivenxe2x80x9d magnets that couple with the corresponding driving magnets. This magnetic coupling with the driven shaft serves to provide the desired rotation for the levitating bearing, while the superconducting element simultaneously serves to levitate the bearing in the vessel.
To provide the necessary cooling, a thermal link connects the superconducting element with a separate cooling source, such as a container holding a suitable liquid cryogen or a closed-cycle refrigerator. Preferably, like the superconducting element, the rod and cooling source are each held in evacuated or insulated chambers to prevent any thermal transfer to or from the outside environment. In the case of evacuation, all three chambers are preferably in communication, but each may also be kept separate, such as by partitions, and individually evacuated or insulated. Thus, like the second embodiment, this system can also efficiently and effectively rotate a thermally isolated and separated magnetic bearing in a vessel containing a fluid to provide the desired pumping or mixing action. However, it should be appreciated that, like in the second embodiment, thermal separation is not a critical requirement, since the system of this embodiment could also be used to pump or mix non-temperature sensitive or cryogenic fluids as well.
In accordance with a fourth aspect of the invention, the vessel is in the form of a pipe containing a stationary or passing fluid. A correspondingly shaped superconducting element, which is preferably provided in two spaced component parts, surrounds the pipe. Each element is thermally separated and isolated from the outer surface of the pipe, such as by evacuating a chamber defined by a wall surrounding the element or filling it with insulation. A bearing positioned in the pipe carries levitating magnets corresponding in number to the components of the superconducting element and preferably positioned at each end of the bearing to ensure that a stable levitation force is achieved. As described above, the superconducting element may be thermally linked to a separate cooling source, such as a liquid nitrogen container, refrigerator, or the like. This link provides the necessary cooling such that the superconducting element causes the magnetic bearing to levitate in the pipe in a stable and non-contact fashion.
To rotate the bearing, it may also carry a plurality of driven magnets that correspond to driving magnets positioned externally to the vessel and rotated by a motive device. Alternatively, a winding may be provided around the vessel and supplied with an electrical current to create an electric field that induces rotation in the driven magnets carried on or attached to the bearing. In either case, a levitating, rotating magnetic bearing is provided for xe2x80x9cinlinexe2x80x9d use in a pipe or other narrow, elongated vessel.
In an alternate xe2x80x9cinlinexe2x80x9d embodiment, the cryostat or other wall defining a chamber for housing the superconducting element is positioned in the vessel, such that the superconducting element aligns with and corresponds to a levitation magnet in the bearing, while separate, room-temperature driving magnets forming a part of a motive device correspond to and align with opposite polarity driven magnets in the bearing to form a magnetic coupling. The chamber is preferably evacuated or insulated to thermally isolate the superconducting element from the bearing and the surrounding fluid. A separate cooling source is also provided to supply the necessary cooling to the superconducting element to induce levitation in the bearing. The superconducting element and surrounding chamber may both be annular, as in the third embodiment. The inner wall creating this annular chamber also defines a bore for receiving the end of a driven shaft carrying the driving magnets for coupling with the adjacent driven magnets on the bearing. The bearing may also carry one or more blades or vanes to enhance the pumping or mixing action.
In accordance with a fifth aspect of the present invention, an assembly for use in containing a fluid undergoing pumping or mixing is provided. The assembly comprises a vessel formed of a flexible disposable material capable of holding a fluid and a magnetic bearing positioned in the vessel. Thus, when used in conjunction with a pumping or mixing system wherein the magnetic bearing is levitated in the vessel by an adjacent superconducting element, both the vessel and the bearing can be disposed of when the pumping or mixing operation is complete and the fluid is recovered. While not an exhaustive list, the vessel can be selected from the group of an open-top container, a pipe, a container having an inlet for receiving a flow of fluid and an outlet for expelling a flow of fluid, a sealed container, or a flexible bag. An attachment or cover containing a coupler comprised of a ferromagnetic material or the like may also be provided to keep the bearing in the proper position relative to the bag or vessel, such as during shipping or the like.
Ensuring that the magnetic bearing used in each system is both the proper one for that particular system and is sized appropriately may also be important. To do so, and in accordance with a sixth aspect of the invention, it is possible to provide a transmitter in one of the magnetic bearing or the vessel for generating a signal that is received by a receiver positioned elsewhere in the system (or vice versa), such as one positioned adjacent to the superconducting element. A controller for the system, such as a computer, can then be used to maintain the system in a non-operational, or xe2x80x9clock-out,xe2x80x9d condition until such time as the appropriate signal is received.
In accordance with a seventh aspect of the invention, a kit is also provided to assist in the set-up of any of the systems previously described. Specifically, it is necessary during field cooling to cool the superconducting element to below its transition temperature in the presence of a magnetic field in order to induce levitation in a permanent magnet producing the same magnetic field. This cooling process causes the superconducting element to xe2x80x9crememberxe2x80x9d the magnetic field, and thus produce the desired stable and reliable levitation each time a similar field is present. While it is possible to use the magnetic bearing to produce the magnetic field during field cooling, oftentimes the bearing will be pre-sealed in the vessel or container. This makes it difficult, if not impossible, to ensure that the magnet is properly aligned and spaced from the superconducting element during field cooling.
To overcome this problem, the kit of the present invention comprises at least one charging magnet having a size, shape, and magnetic field distribution identical to the levitation magnet contained in the particular bearing slated for use in one of the pumping or mixing systems previously described. The charging magnet is placed adjacent to the superconducting element during cooling, such as on the upper surface of the cryostat or other chamber surrounding the superconducting element (or a stable support structure for the bearing). Once cooling below the transition temperature is complete, the charging magnet may be removed and replaced with the vessel containing the corresponding magnetic bearing.
The kit or charging magnet may also comprise a spacer. This spacer allows the charging magnet to simulate the spacing of the magnetic bearing above the superconducting element to ensure that the desired levitation height is achieved once the vessel containing the actual bearing to be levitated is in position. The spacer is fabricated of a non-magnetic material to avoid interfering with the charging process. By also providing a variety of different sizes, shapes, and configurations of charging magnets (e.g., annular magnets), it is possible to easily perform field cooling for any size or shape of levitation magnet in the corresponding magnetic bearing.
During field cooling, and regardless of whether the magnetic bearing or a separate charging magnet is used to produce the charging magnetic field, it is possible to induce an undesired magnetic state in the superconducting element, such as if the position of the bearing or charging magnet is not correct during cooling. Since improper charging may prevent the magnetic bearing from levitating in a stable fashion, xe2x80x9crechargingxe2x80x9d the superconducting element may be required.
In accordance with an eighth aspect of the present invention, a heater may be provided adjacent to the superconducting element for use in facilitating recharging. More specifically, by activating this heater, the superconducting element may be quickly brought up from the transition temperature for recharging. Once the position of the bearing or charging magnet is adjusted or corrected, the heater may be turned off and the superconducting element once again allowed to cool to the transition temperature in the presence of the desired magnetic field. Of course, this operation may be repeated as necessary until the desired stable levitation is achieved.
In many of the above-described embodiments, the pumping or mixing action is essentially localized in nature, since the bearing is rotated on a fixed axis relative to the vessel. This may be undesirable in some situations, such as where the vessel is relatively large, as compared to the magnetic bearing. Thus, in accordance with a ninth aspect of the invention, the particular system used to supply the pumping or mixing action may be provided with a motive device for physically moving the superconducting element (which may also be simultaneously rotated). Moving the superconducting element relative to the vessel will cause the levitating magnetic bearing to follow a similar path.
In accordance with a tenth aspect of the present invention, a method of levitating and rotating a magnetic bearing, such as for pumping or mixing a fluid in a vessel, is disclosed. The method includes the steps of placing a magnetic bearing in the vessel. Levitation is induced in the magnetic bearing by a superconducting element, which may be positioned in an insulated or evacuated chamber defined by the outer wall of a cryostat or other housing. If present, the chamber serves to thermally isolate and separate the vessel, fluid, and magnetic bearing from the superconducting element, which is thermally linked to a separate cooling source. Upon rotating one of the levitating magnetic bearing or the superconducting element in the vessel, the desired mixing or pumping action is provided. As described above, the magnetic bearing and vessel may also be formed of disposable materials and discarded once mixing is complete and the fluid is recovered. Other methods are also disclosed for accomplishing the goals of the other embodiments previously described.

Pumping or mixing system using a levitating magnetic element, related system components, and related methods


A nonvolatile memory device includes a memory cell array and a voltage controller. The memory cell array includes a plurality of memory blocks each including a plurality of cell strings, where each of the cell strings includes a first selection transistor, a second selection transistor, and at least one memory cell transistor connected in series between the first and second selection transistors. The voltage controller applies a first selection voltage to first selection lines connected to the first selection transistors, a second selection voltage to second selection lines connected to the second selection transistors, and a word line voltage to word lines connected to the memory cell transistors, in response to a plurality of block selection signals corresponding to the memory blocks. The voltage controller precharges the second selection lines to a precharge voltage by applying the second selection line voltage to the second selection lines in a standby state, where the second selection line voltage is equal to the precharge voltage.

1. Field of the Invention
The present invention relates to nonvolatile memory devices, and more particularly, the present invention relates to a voltage controller of a nonvolatile memory device and a method of reading a non-volatile memory device.
A claim of priority is made to Korean Patent Application No. 10-2006-0106715, filed Oct. 31, 2006, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference in its entirety.
2. Description of the Related Art
F-N tunneling is utilized to program and erase cell transistors contained in non-volatile memory devices, such as NAND type flash memory devices.
For example, F-N tunneling is induced in an erase operation by applying a low voltage (e.g., 0V or ground) to a control gate of a cell transistor, and by applying a high voltage (e.g., 20V) which exceeds a supply voltage to a semiconductor substrate (or bulk) containing the cell transistor. The resultant large voltage differential causes a strong electric field to be formed between the floating gate and the bulk, and F-N tunneling occurs in which electrons are discharged from the floating gate to the bulk. This causes the threshold voltage (Vth) of the erased cell transistor to shift in a negative direction (e.g., Vth≦−3V). In conventional terms, the erased state is designated as data "1", and a cell transistor in this state is referred to as an "ON" cell.
In a program operation, for example, a high voltage (e.g., 18V) which exceeds a supply voltage is applied to the control gate of the cell transistor, and a low voltage (e.g., 0V or ground) is applied to the drain of the cell transistor and to the semiconductor bulk. When the cell transistor is biased in this manner, F-N tunneling results and electrons are injected to a floating gate of the cell transistor. This causes the threshold voltage (Vth) of the programmed cell transistor to shift in a positive direction (e.g., Vth≧+1V). The programmed state is conventionally designated as data "0", and the cell transistor is referred to as an "OFF" cell.
FIG. 1 is a block diagram of a conventional NAND type flash memory device 100. The NAND type flash memory device 100 includes a memory cell array 110, a row selecting circuit 130, a row decoder circuit (not shown), a page buffer circuit 150 (or a data sensing and latching circuit), and a column decoder circuit 170.
The memory cell array 110 includes a plurality of memory blocks BLK0 through BLKn each having a plurality of cell strings (n is a positive integer). As illustrated in FIG. 1, each of the cell strings includes of a string selection transistor SST connected to a corresponding bit line, e.g., a bit line BL0, a ground selection transistor GST connected to a common source line CSL, and memory cell transistors MC15 through MC0 connected between the string selection transistor SST and the ground selection transistor GST. Each of the memory cell transistors MC15 through MC0 forms a memory cell. FIG. 1 illustrates the example of 16 memory cells per cell string, but the number of memory cells contained in each string may vary among different NAND flash memory devices.
As shown in FIG. 1, the string selection transistor SST, the memory cells MC15 through MC0, and the ground selection transistor GST are respectively gated to a string selection line SSL, word lines WL15 through WL0, and a ground selection line GSL. Further, as shown, block selection transistors BS17 through BS0 are respectively connected between the lines SSL, WL15 through WL0, and GSL, and lines SS, Si15 through Si0, and GS. The block selection transistors BS17 through BS0 are commonly controlled by a block selection signal BS.
The row selecting circuit 130 is responsive to the row decoder (not shown) to select a word line (or a page) from among the word lines WL0 through WL15 via block selection transistors BS0 through BS17. In a programming mode, the page buffer circuit 150 temporarily stores data to be stored in memory cells of the selected word line (or page). In a read mode, the page buffer circuit 150 senses data stored in the memory cells of the selected word line (or page). The page buffer circuit 150 includes a plurality of page buffers (or data sensing and latching blocks) which respectively correspond to rows (bit lines) related to the selected page. Data bits that are sensed (read) from the memory cells of the selected page are output via the column decoder circuit 170 in predetermined units, e.g., in units of bytes X8.
The conventional NAND-type flash memory device described above requires substantial time to execute a read operation. This is because read operations are performed in units of memory blocks (and not in units of memory cells), and read data must typically be fetched from the flash memory and loaded into main memory (e.g., DRAM) prior to execution by a processor. In an effort to overcome this drawback, a type of flash memory device having an execute-in-place (XIP) structure has been introduced.
FIG. 2 is a circuit diagram for explaining a read operation of one type of flash memory device 200 having an XIP structure. As shown, a single memory cell transistor is connected in each cell string, thus allowing processor access to the stored data at relatively high speeds. Also, wirings for providing voltages to the string selection lines SSL are metal-strapped to one another, as are the wirings for providing voltages to the ground selection lines GSL.
Further, the string selection lines SSL are directly connected to the row selecting circuit. In a standby state prior to the read operation, both the string selection lines SSL and the ground selection lines GSL are discharged to ground voltage. When the read operation is performed, a supply voltage (e.g., VPP) is applied as a block selection signal to the selection transistors of a selected block, while a ground voltage (e.g., 0V) is applied as a block selection signal to the selection transistors of a non-selected block
During the read operation, the voltages of the string selection line SSL and the ground selection line GSL of the selected block are increased from the ground voltage (0 V) to a read voltage VREAD. Further, the ground voltage (0V) is applied to the word line WL of the selected block. In this state, data is read out from the cell transistor(s) of a selected bit line(s).
In the configuration described above, coupling noise may be generated in the word line WL of the selected block during the read operation, since the word line WL is influenced by coupling between the string selection line SSL and the ground selection line GSL. This can inhibit accurate execution of the read operation.

Nonvolatile memory device and method of reading information from the same


A blower assembly includes a housing including an inner shell and an outer shell that define a flow passage therebetween. The inner shell also at least partially defines a cavity. The blower assembly also includes a fan coupled within the housing such that the fan also at least partially defines the cavity. The blower assembly further includes a motor configured to rotate about an axis. The motor is coupled to the inner shell and is positioned within the cavity radially inward of the flow passage.

The field of the disclosure relates generally to air handling systems, and more specifically, to air handling systems that include a compact mixed flow blower assembly positioned between a pair of heat exchangers.
At least some known air handling systems and furnaces include a blower assembly and a plurality of heat exchangers downstream from the blower assembly. In at least some such air handling systems, the heat exchangers are sequentially positioned downstream of the blower assembly such that the airflow is channeled through one heat exchanger after another. Additionally, in at least some known systems, the heat exchangers operate at different temperatures to gradually cause the air being channeled therethrough to increase in temperature. However, after each heat exchanger encountered, the airflow experiences a relatively large pressure drop. In order to maintain the airflow at a desired pressure and velocity, the blower assembly is operated at a higher than desired rotating speeds. In at least some known blower assemblies, operating at a higher than desired rotating speeds causes a decrease in the aerodynamics efficiency of the entire system and an increase in the noise level generated by the blower assembly, which is undesirable.
Furthermore, at least some known blower assemblies used in air handling systems include a mixed flow fan for channeling air through the air handling system. At least some known mixed flow fans include an externally mounted motor and occupy a relatively large amount of space within the air handling system. Additionally, in order to channel air through the air handling system at a desired rate, at least some known mixed flow fans operate at a relatively high speed, which may generate undesirable noise.

Blower assembly for use in an air handling system and method for assembling the same


A wireless IC tag reader includes a receiving antenna, a transmitting antenna and a beam direction control unit. The receiving antenna has a maximum beam direction and a half-value angle. The transmitting antenna has a maximum beam direction and a half-value angle narrower than the half-value angle of the receiving antenna. The beam direction control unit changes the maximum beam direction of the transmitting antenna.

1. Field of the Invention
The present invention relates to a wireless IC tag reader, and more specifically relates to a wireless IC tag reader having a function for reading information stored in a wireless IC tag (the wireless IC tag is also called an electronic tag or a radio frequency identification (RFID) tag).
2. Description of the Related Art
An RFID technique is recently used. In the RFID technique, a tag communication device (wireless IC tag reader) which is a reader or a reader/writer carries out wireless-communication with a wireless IC tag to read information stored in the wireless IC tag remotely. Especially, the wireless IC tag is expected as an alternative to a bar-code in a physical distribution field. In the near feature, it is predicted that the RFID technique spreads widely.
For example, the RFID technique is applied to detection to be carried out when a product enters into or leaves from a warehouse or a store. In this case, it is important to surely read multiple pieces of information stored in wireless IC tags incorporated in products within a communication area. Generally, in the communication area, there are weaker radio wave spot areas (these areas are also called field holes, dead spots or null points) where radio waves from a wireless IC tag reader interfere with each other on multiple paths by reflection phenomena and the radio waves are almost canceled. If a wireless IC tag is located in a dead spot, it is difficult or impossible for the wireless IC tag reader to read information stored in the wireless IC tag.
As a method for resolving the above-described problem, Japanese Patent Application Laid-Open No. 2006-20083 discloses a control method for electronically controlling directional characteristics (angular characteristics) of radio waves to be transmitted by a wireless IC tag reader (see paragraphs [0054] to [0059] and FIG. 2).
In the control method, a common type in which antennas for transmitting radio waves and receiving response waves are commoditized is employed. However, it is difficult to separate a response wave transmitted by a wireless IC tag from a radio wave transmitted by a wireless IC tag reader because the intensity of response wave is remarkably lower than that of radio waves transmitted by the wireless IC tag reader. In order to resolve the above-described problem, a separate type in which antennas for transmitting radio waves and receiving response waves are separated is recently employed.
The separate type however increases a cost because the antennas for transmitting radio waves and receiving response waves are separated. Further, if a radio wave transmitted from the separate type antenna has relatively high intensity so as to be uniformly transmitted to a wide area while being kept at a certain level, the dead spots still appear in a communication area.


The present invention provides an intra-ocular lens (IOL) whose focusing performance can be modified after its implantation in the eye without a need for any invasive procedure. An IOL of the invention has an optical chamber having at least a flexible region that is deformable under influence of a fluid. The IOL further include a reservoir for storing an optical fluid in fluid communication with the optical chamber, and a valve that regulates the fluid communication between the reservoir and the optical chamber. The lens can also include a pump that is actuated by an external energy source to transfer the optical fluid between the reservoir and the optical chamber to change the amount of fluid in the optical chamber, thereby modifying the focusing performance of the IOL.

The present invention relates generally to intraocular lenses, and more particularly to intraocular lenses whose focusing performance can be adjusted externally after implantation in an individual""s eye, without a need for any invasive procedure.
The lens and the cornea of the human eye provide a combined refractive power of approximately 60 diopters (D), with the cornea providing about 40 D of the power and the lens providing about 20 D of the refractive power. Certain diseases of the eye, such as cataracts, cause the lens to become progressively opaque. The opacity typically worsens over time, and can ultimately result in blindness. It is typically necessary to surgically remove the opaque lens to allow an unobstructed transmission of light to the retina. The removal of the lens, however, deprives the eye from the substantial refractive power that the lens provides.
When the natural lens is removed from the eye, an intraocular lens (IOL) can be implanted in the eye to assist the eye in focusing light onto the retina. Intraocular lenses typically provide one or more fixed focusing performances. Typically, the needed refractive correction(s) is (are) determined before implantation of the IOL in the eye. Such pre-operative predictions of the needed corrective power are sometimes not sufficiently accurate. Furthermore, once implanted, an IOL can shift position within the eye, thereby causing a loss of focus. Hence, an individual having an implanted IOL may require additional corrective devices, such as glasses, to acquire the desired visual acuity.
Accordingly, it is object of the present invention to provide an intraocular lens whose focusing performance can be modified in situ.
It is another object of the invention to provide an intraocular lens whose focusing performance can be externally modified after implantation in the eye.
It is yet another object of the invention to provide an intraocular lens whose focusing performance can be adjusted over a selected range.
The present invention attains the above and other objects by providing an intraocular lens whose focusing performance can be adjusted over a selected range after implantation in a patient""s eye without a need for an invasive procedure. In particular, the focusing performance of an IOL according to the invention can be modified by application of energy, such as magnetic or electric energy, supplied from an external source to the IOL. An intraocular lens according to the teachings of the invention includes an optical chamber deformable under influence of pressure from a fluid. The IOL further includes a reservoir, in fluid communication with the optical chamber, for storing an optical fluid. A valve regulates the fluid communication between the reservoir and the optical chamber.
As used herein, the term xe2x80x9copticxe2x80x9d or xe2x80x9coptical bodyxe2x80x9d is intended to encompass the component(s) within the intraocular lens of the present invention that cumulatively enable the intraocular lens to focus the light. The optic can include an optical chamber and optical fluid within such chamber, as well as one or more physical lens structures, if desired. The term xe2x80x9cintraocular lensxe2x80x9d, as used herein, encompasses all of the above described optical elements and other structures such as haptics useful for attaching the IOL to the eye as well as other structures elaborated below.
The IOL can further include a pump capable of being actuated by an energy source external to the eye to cause a flow of a selected volume of the optical fluid between the reservoir and the optical chamber. A flow of the optical fluid into and/or out of the optical chamber selectively varies an amount of fluid in the optical chamber. The change in the amount of fluid in optical chamber can vary a pressure exerted on the flexible portion(s) of the optical chamber to cause a change in radius of curvature of the flexible portion(s) and/or vary a distance between optical surfaces of the optical chamber. Such changes in the optical chamber can lead to a change in the focusing performance of the IOL.
The external energy source can include, but is not limited to, a magnetic field generator, an electric field generator, or a source of photons, such as a laser. In one preferred embodiment, an oscillatory magnetic field is employed for actuating the pump. In another embodiment, a rotating magnetic field is employed for activating the pump.
In general, the index of refraction of the optical fluid useful in the present invention can have any value. In most implementations, however, the index of refraction of the optical fluid is preferably selected to be greater than approximately 1.337. One preferred embodiment of the invention employs silicone with an index of refraction of about 1.4 as the optical fluid.
In many implementations, the IOL can include an optical body having two optical elements, at least one of which has a flexible convex region. These elements form an optical chamber therebetween. In such an embodiment, pumping a volume of the optical fluid into the chamber increases the hydrostatic pressure within the optical chamber and hence causes a decrease in the radius of curvature of the flexible region of the chamber. Such a decrease in the radius of curvature, in combination with the focusing performance of the fluid, leads to an increase in the focusing performance of the intraocular lens.
The IOL device can also include one or more haptics to allow fixation of the lens within the eye. The haptics can also include the reservoir of fluid for use in modifying the shape of the optical chamber.
One embodiment of the present invention provides an intraocular lens that employs a gear-pump. Such an intraocular lens includes an optical body having at least an optical chamber with at least a flexible region deformable in response to an applied pressure. A reservoir, which is in fluid communication with the optical chamber through a valve positioned between the reservoir and the optical chamber, stores a selected volume of an optical fluid. The gear pump is configured to be actuated by an energy source positioned external to the eye to cause the optical fluid to move, through the valve, between the optical chamber and the reservoir.
The gear pump can include a pair of inter-locking gears formed, for example, of silicone rubber. At least one of the gears is selected to be magnetically rotatable, for example, by implanting a permanent magnet in the silicone rubber. An external magnetic field generator can be utilized to apply a rotating magnetic field to the magnetic gear to cause a rotation thereof. The rotation of the magnetic gear in turn causes a rotation of the other gear, i.e., the gear engaged with the magnetic gear, in an opposed direction. The combined rotation of the gears controls the flow of the optical fluid between the reservoir and the optical chamber of the lens.
Another preferred embodiment of the invention employs a peristaltic pump for providing fluid communication between an optical chamber and a reservoir of an optical fluid. The peristaltic pump can also include a valve for regulating the flow of the optical fluid between the reservoir and the optical chamber. A magnetic field, such as an external rotating magnetic field, actuates the peristaltic pump according to the invention by inducing a propagating deformation, e.g., constriction, therein, which causes a flow of the optical fluid between the reservoir and the optical chamber. Thus, by actuating the pump, the clinician (or the subject) can calibrate or tune the focusing performance of the IOL to a desired value.
A peristaltic pump according to the teachings of the invention can have a tubular structure that is formed, for example, of a resilient material such as silicone rubber, or another polymeric elastomer. A plurality of magnetic particles, such as ferrite, magnetite, nickel cobalt, neodymium, boron, samarium, iron or compounds or alloys of such materials, are distributed within the wall of the tubular structure such that a rotating magnetic field can be applied to the tubular structure to induce a propagating constriction within the tubular structure. The propagating constriction causes the optical fluid within the tubular structure to flow from one end of the structure to the other, thereby inducing the fluid flow between the reservoir and the optical chamber.
Another embodiment of an intraocular lens according to the teachings of the present invention utilizes a diaphragm pump to transfer an optical fluid between an optical chamber, formed in the optical body, and a reservoir for storing the optical fluid. The diaphragm pump can be actuated by an energy source positioned external to the eye. For example, the diaphragm pump can be magnetically and/or electrically actuated.
The diaphragm pump can include a housing having an inlet opening and outlet opening, and further can include a flexible diaphragm disposed in mechanical communication with the housing. The diaphragm can be formed of a material such as Silicon (Si), Titanium, Stainless Steel, and can be selected to have at least one resonant vibrational frequency. Alternatively, the diaphragm can be formed of elastomeric materials such as poly(dimethylsiloxane) (PDMS). Application of an oscillatory magnetic field having an oscillation frequency which is substantially similar to the resonant vibrational frequency of the diaphragm induces a large amplitude oscillation in the diaphragm, and thereby causes a flow of the fluid between the inlet and the outlet openings.
In yet another embodiment of the invention, the intraocular lens can employ a peristaltic micro-pump utilizing a ferro-fluid material. The IOL can again include an optical body having a base portion and a cover portion that form an optical chamber therebetween. At least one of the cover or the base portions has a flexible region that is deformable in response to an applied pressure. The base portion includes a reservoir for storing an optical fluid, and further has a channel for providing fluid communication between the reservoir and the optical chamber by providing a flow path for the optical fluid. The cover portion has a channel for storing a ferro-fluid material. The channels of the base portion and the cover portion are preferably substantially aligned. A flexible membrane disposed between the channels of the base and the cover portions isolates the ferro-fluid from the optical fluid. The ferro-fluid material can be externally actuated, for example by an external magnetic energy source, to provide a propagating pressure on the flexible membrane. The propagating pressure in turn produces a propagating deformation of the membrane to cause transfer of a selected volume of the optical fluid between the reservoir and the optical chamber. Ferro-fluid materials suitable for use in the intraocular lens of the invention can include oil-based ferrofluids such as silicone oil or petroleum distillate suspension of nanoparticles of magnetite (Fe3O4), Iron, Cobalt, Iron nitride (Fe3N) in which the nanoparticles are typically coated with an ultra-thin layer of surfactant to keep the particles suspended.
In another aspect, the invention provides an intraocular lens that has an optical body having at least an optical chamber and at least a flexible region that is deformable under influence of a fluid. Further, the IOL includes a reservoir for storing a selected volume of an optical fluid. The reservoir is in fluid communication with the optical chamber through a valve which regulates the flow of the optical fluid between the reservoir and the optical chamber. The IOL includes at least one magnet positioned between the reservoir and the optical chamber and pivoted about a rotation axis at an end thereof. A magnetic field supplied by an external magnetic energy source can actuate the magnet to cause it to rotate about its pivot point, thereby forcing the flow of the fluid in a selected direction, for example, from the reservoir to the optical chamber. The IOL can also include a second magnet positioned along a vector directed from one pole of the first magnet to its other pole such that the opposite poles of the first and second magnets are proximate of each other. The magnets can be actuated by an external magnetic source to rotate in opposite directions, albeit about the same rotational axis, to cause a flow of the optical fluid through the valve between the reservoir and the optical chamber.
Another intraocular lens according to the teachings of the invention employs a micro-pump that utilizes at least one ball formed of a magnetic material. Such magnetic material is preferably selected to be soft and can include, for example, silicon steel alloys (2.5%-6% Si and Fe in balance) or iron-cobalt alloys such as, Fexe2x80x94Coxe2x80x94Vxe2x80x94Nb alloys, e.g., Carpenter Hiperco alloy. Such an IOL includes an optical body having a base portion and a cover portion that form an optical chamber therebetween. The base portion has at least a flexible region and further has a reservoir which is in fluid communication with the optical chamber. Further, the cover portion has a channel that includes a surface having at least a flexible portion in contact with at least a portion of the fluid. A valve positioned between the reservoir and the optical chamber regulates the fluid communication between the reservoir and the optical chamber. The ball is positioned in the channel of the cover portion and is actuated by an external magnetic source to move within the channel such that it produces a deformation of the flexible membrane. This deformation, produced in the vicinity of the ball, in turn causes a flow of the fluid through the channel between the reservoir and the optical chamber.
Although the invention is described in terms of discrete xe2x80x9cbasexe2x80x9d and xe2x80x9ccoverxe2x80x9d portions, it should be clear that an IOL of the invention can be constructed as a unitary structure having two surfaces corresponding to the base and cover portions described above. Moreover, even when two components are formed in manufacturing of the IOL, the construction process can be such that the xe2x80x9cbasexe2x80x9d and xe2x80x9ccoverxe2x80x9d components are completely fused so as to form an essentially unitary structure.
A further embodiment of an IOL of the invention can employ the Faraday effect to actuate a piezo-electric element which in turn actuates a diaphragm pump. In particular, the IOL includes an optical body having an optical chamber and at least a flexible region that is deformable in response to an applied pressure. The optical body further includes a reservoir for storing an optical fluid. The piezo-electric element can be actuated by energy, such as a time-varying magnetic flux, provided by an external source, to cause the diaphragm pump to transfer a selected volume of the optical fluid between the reservoir and the optical chamber.
The piezo-electrically driven diaphragm pump can include a housing having inlet and outlet openings (which can be one-way valves), a flexible membrane that is in mechanical communication with the housing, and a piezo-electric element in contact with the diaphragm. A periodic modulation of the stress in the piezo-electric element, induced, for example, by an oscillatory flux, can result in a mechanical oscillation of the diaphragm. Such an oscillation of the diaphragm forces a fluid within the diaphragm housing to flow between the inlet and the outlet openings of the diaphragm pump.
An intraocular lens according to another aspect of the invention can include a vapor-operated pump. The vapor-operated pump can include housing having a reservoir of a selected volume of a fluid, e.g., water, in contact with a flexible membrane. A resistive element, such as a resistor, energized by an external energy source can be employed to periodically turn the fluid into vapor, thereby providing a periodic pressure change against the flexible membrane. This periodic pressure change in turn causes a periodic deflection of the diaphragm that provides a pumping action for transferring fluid through the housing of the pump between an input port and an output port (which can be one-way valves).
In another aspect of the invention, a pump for transferring the optical fluid between the reservoir and the optical chamber employs reverse electrophoresis.


The present invention is directed to a backlight device using light emitting units (7) in which a large number of light emitting diodes (12) are mounted, which comprises a reflection plate (16) for reflecting rays of light which have been emitted from a light emitting unit (11), wherein the reflection plate (16) is composed of a bottom surface reflection plate (16a) for reflecting rays of light emitted from the light emitting units (7) from the bottom surface direction, side surface reflection plates (16b) to (16e) for reflecting rays of light emitted from the light emitting units (7) from respective forward and backward, and left and right side surface directions, and corner reflection plates (16f) to (16i) in which the bottom surface reflection plate (16a) and the side surface reflection plates (16b) to (16e) are connected to cover the respective corner portions, and serves to permit rays of light incident onto a display panel (1) to be uniform to realize uniformity of brightness of the entire surface thereof.

Hitherto, since Liquid Crystal Display apparatuses can realize large-sized display screen, light weight, thin structure and/or low power consumption, etc. as compared to Cathode-Ray Tube (CRT), they are used in Television Image Receiver and/or display apparatus for various display purposes along with, e.g., self-light emitting type Plasma Display Panel (PDP), etc. In the liquid crystal display apparatus, liquid crystals are included between two transparent bases (substrates) of various sizes to apply voltage across the transparent electrodes to vary orientation of liquid crystal molecules to change light transmission factor to optically display a predetermined image, etc.
In the liquid crystal display apparatuses, since the liquid crystal itself is not light emitting body, there is provided a backlight unit functioning as a light source, e.g., at the rear face portion of the liquid crystal panel. The backlight unit comprises, e.g., primary light source, light guide plate, reflection film, lens sheet and/or diffusion film, etc. and serves to deliver display light over the entire surface of the liquid crystal panel. In the backlight unit, Cold Cathode Fluorescent Lamp (CCLF) adapted so that mercury or xenon is included within fluorescent tube is used as primary light source. However, it is necessary to solve the problems that light emitting luminance that the cold cathode fluorescent lamp has is low, life time is short and/or low luminance region exists at the cathode side so that uniformity ratio, etc. is bad.
Meanwhile, in liquid crystal display apparatuses of the large size, there is generally provided an Area Litconfiguration Backlight unit in which plural elongated cold cathode fluorescent lamps are disposed at the rear face of the diffusion plate to deliver display light to the liquid crystal panel. Also in such area litconfiguration backlight unit, it is necessary to solve the problems resulting from the above-described cold cathode fluorescent lamp. Particularly, in the case where the area litconfiguration backlight unit is applied to such a large sized television image receiver above 40 inches, the problems of realization of high luminance and realization of high uniformity ratio become more conspicuous.
On the other hand, in the area litconfiguration backlight units, in place of the above-described cold cathode florescent lamp, attention is drawn to backlight of the Light Emitting Diode (hereinafter referred to as LED as occasion may demand) area light type in which a large number of red, green and blue LEDs of light three primary colors are two-dimensionally arranged in the state positioned at the rear face side of the diffusion film to obtain white light. Such LED backlight unit permits reduction of cost with realization of reduction of cost of LED, and permits display of high luminance on large-sized liquid crystal panel by low power consumption.
Moreover, the LED backlight unit is caused to be of the configuration in which a large number of LEDs are mounted on wiring board to diffuse rays of light which have been emitted from the LEDs by diffusion plate to emit the rays of light thus obtained to the liquid crystal panel. Further, in order to efficiently guide light, to the diffusion plate, rays of light which have been emitted from the LEDs disposed at the edge portion of the LED backlight unit, there is provided a reflection plate. Since the reflection plate permits rays of light which have been emitted from the LEDs to be efficiently emitted to the liquid crystal panel, the reflection plate is composed of a bottom surface reflection plate, and forward and backward, and left and right side surface reflection plates.
Meanwhile, in the LED backlight unit, as shown in FIG. 1, respective corner portions where the bottom surface reflection plate and the forward and backward, and left and right side surface reflection plates are connected to each other are furthest apart from LEDs 20A to 20D disposed in the vicinity of these corner portions. In this case, FIG. 2 shows the LEDs 20A to 20D arranged in the vicinity of respective corner portions in an enlarged manner. Since the LEDs 20A to 20D are arranged in this way, in the case where rays of light which have been emitted from the LEDs 20A to 20D arranged in the vicinity of respective corner portions of the LED backlight unit are reflected by the reflection plate, luminance would be lowered as compared to reflected light from LEDs arranged at places except for the portions in the vicinity of the corner portions. When luminance of reflected light is lowered in this way, the corner portion of the liquid crystal panel becomes dark.


An image-based biomarker is generated using image features obtained through object-oriented image analysis of medical images. The values of a first subset of image features are measured and weighted. The weighted values of the image features are summed to calculate the magnitude of a first image-based biomarker. The magnitude of the biomarker for each patient is correlated with a clinical endpoint, such as a survival time, that was observed for the patient whose medical images were analyzed. The correlation is displayed on a graphical user interface as a scatter plot. A second subset of image features is selected that belong to a second image-based biomarker such that the magnitudes of the second image-based biomarker for the patients better correlate with the clinical endpoints observed for those patients. The second biomarker can then be used to predict the clinical endpoint of other patients whose clinical endpoints have not yet been observed.

Systems for detecting and analyzing target patterns in digital imagery have a wide variety of uses. Such systems can be used to detect geographical objects, military targets or weather patterns from satellite images. Radar or sonar shadows of airplanes, ships, submarines and schools of fish can also be detected and analyzed. Much effort has been expended to develop systems for detecting and analyzing anatomical regions in radiological images. For example, systems for analyzing computed tomography (CT) images are used for the computer-aided detection (CAD) of cancerous regions in human lungs.
One of the more difficult tasks of detecting patterns in medical images involves detecting cancerous mass lesions and micro-calcifications in X-ray images of breasts (also called mammograms). Early detection of these cancerous regions in the breast increases the chance of survival of women with breast cancer. The X-ray images are digitized, and the pixel data is analyzed. Detecting cancerous regions in breasts is made more difficult, however, by the similar appearance of pixels associated with benign and malignant lesions and micro-calcifications.
Systems for computer-assisted interpretation of mammograms are now widely used to assist in the early detection of breast cancer. Such systems include ImageChecker by R2 Technologies of Sunnyvale, Calif.; Second Look by CADx Systems of Beavercreek, Ohio and MammoReader by iCAD of Hudson, N.H. These systems are designed to provide very high detection rates of cancerous regions at the expense of "detecting" a significant number of regions that are not cancerous. As the probability threshold of missing a cancerous region is lowered, the rate of incorrectly designating cancerous regions increases. Thus, although current systems have achieved a high degree of sensitivity, there remains a tradeoff between the probability threshold for detected objects and the false positive detection rate. Systems employing computer-aided detection (CAD) of early breast cancer can, therefore, be improved by decreasing the false positive detection rate while maintaining the detection of nearly all cancerous regions.
Current CAD schemes for analyzing mammograms to detect breast cancer involve rules-based selection of abnormal regions. The rules are based on pixel filtering and thresholding and the dimensions and orientation of the target region. For example, pixel data from a mammogram is filtered according to brightness or intensity, and pixels with a similar brightness are associated together as an object. A gradient histogram is used to indicate the statistical distribution of brightness among all pixels of the mammogram. The histogram is then used to define thresholds for the brightness of pixels that are associated together. In addition to filtering and thresholding, the distance of one pixel from another pixel may be used to determine whether pixels are associated together. For example, the spatial orientation and the ratio of the dimensions of an area of brightness may be used to determine whether the area is cancerous. Once the CAD scheme has been developed, however, the process of detecting abnormal regions is static. Although the threshold and filtering variables and the target dimensions can be adjusted, the process in which the rules are applied does not change once the CAD scheme begins analyzing a particular digital image.
An improved CAD scheme is sought for locating specified image structures in a digital image that decreases the false positive detection rate while detecting substantially all of the target objects in the digital image. Such an improved CAD scheme is desired in which the process itself adapts to the characteristics of the digital image in which the target objects are located. Moreover, such an improved CAD scheme would detect an object in a digital image by employing processes in addition to associating pixels with an object based on filtering and thresholding pixels and on the dimensions of the object.

Context driven image mining to generate image-based biomarkers


Power reduction in transmitters is very important. One method to realize reduction is to make use of switching power amplifiers (PA) that have a better efficiency. Switching PA concepts are only possible in combination with suitable modulation methods like pulse width modulation (PWM) and out-phasing concepts. However, PWM and out-phasing concepts rely on accurate phase control and duty cycle of the signals. Digitally generation of signals of variable duty cycles and phase is proposed without sacrificing their accuracy. Accordingly, a out-phasing power amplifier arrangement is disclosed, where the generation of the out-phasing angle (θ) and duty cycles (d1 and d2) are controlled by a set of n-bit digital input words (D1, D2, D3, D4). The baseband phase information (φ(t)) is phase modulated back to radio frequency and used as the clock signal of digital circuitry for phase and duty cycle generation after being frequency multiplied by 2n-1. The resolution of the out-phasing angle and of the duty cycle is 2π/2n and 2π/2n-1 equivalently. The resolution of the phase information φ is dependent on the PM realization.

Mobile, in particular wireless communication is broadly used in several fields of applications, e.g. in the home, public or office area, as well as for any kind of communication, e.g. speech, data, and/or multi-media communication. Basically, such applications are confronted with two major problems.
As a matter of fact, available bandwidth for transmitting information is limited due to the general shortage of available spectrum. In this regard, it is well known to modulate both the amplitude and the phase of the carrier to reduce required bandwidth. For instance, systems, in which the amplitude and the phase are modulated, i.e. which process wide-band complex envelope signals, are EDGE, UMTS (WCDMA), HSxPA, WiMAX (OFDM) and 3G-LTE (OFDM). However, amplifying amplitude modulated carriers without distortion in the transmitter output stage imposes significant linearity constraints on the output stage amplifier.
Further, power efficiency of mobile transmitters is important, since mobile terminals in wireless communication are typical portable and as such, usually battery powered. In mobile terminals, the output stage of the transmitter unit is usually the largest power consumer of the whole device. Consequently, any improvement in this stage with respect to power efficiency is appreciated. Known efficient power amplifiers topologies or circuit arrangements are, for instance, class-C and class-E radio frequency (RF) amplifiers in which the active output amplification devices conduct current only at the time, e.g. in case of transistors, when the collector-emitter voltage is at its lowest value. Unfortunately, class-C and class-E amplifiers are very nonlinear and thus, introduce substantial distortion of the amplitude modulation.
Linear Amplification using Nonlinear Components (LINC) is a well-known concept for high efficient linear power amplification of RF signals. Detailed information may, for instance, be gathered from S. C. Crips, "Advanced Techniques in RF Power Amplifiers Design", Artech House 2002, or from D. C. Cox in "Linear Amplification with Nonlinear Components", IEEE Transactions on Communications, December 1974, pp. 1942-1945.
WO 01/45205 discloses transmission of multiple radio channel frequency signals modulated with respective information modulation from a common antenna at multiple radio frequencies. Multiple modulators are provided, a respective one of which corresponds to a respective one of the radio channel frequencies. Each modulator generates at least one constant amplitude, phase modulated drive signal at the corresponding radio channel frequency from the respective information modulation, such that the at least one constant amplitude, phase modulated drive signal corresponds to the information modulation for the corresponding radio frequency. At least one saturated power amplifier is provided for each of the at least one constant amplitude, phase modulated drive signals. A respective saturated power amplifier is responsive to the corresponding constant amplitude, phase modulated drive signal, to produce a corresponding amplified output signal at an output thereof. A coupling network connects the outputs of the saturated power amplifiers in series, to produce a combined signal that is applied to the common antenna, such that the common antenna radiates the radio channel frequency signals that are modulated with the respective information modulation. In some embodiments, at least two constant amplitude phase modulated drive signals are provided at the corresponding radio channel frequency, such that the at least two constant amplitude, phase modulated drive signals correspond to the information modulation for the corresponding radio frequency.
The LINC concept, also known as out-phasing, is illustrated by means of the simplified out-phasing power amplifier (PA) 100 shown in FIG. 1. Accordingly, an amplitude (A(t)) and phase (φ(t)) modulated RF signal Sin(t), represented by equation (1), is split by means of a signal component separation unit 102 in two RF signals S1(t), represented by equation (2), and S2(t), represented by equation (3), each being phase modulated by the baseband phase information φ(t) and an out-phasing angle θ(t) that is based on the baseband amplitude information A(t), according to equation (4). The most important aspect is the fact that both RF signals S1(t) and S2(t) have constant amplitude.Sin(t)=A(t)sin(ωt+φ(t))  (1)S1(t)=½ sin(ωt+φ(t)+θ(t))  (2)S2(t)=½ sin(ωt+φ(t)−θ(t))  (3)θ(t)=arcos(A(t))  (4)
Then, the signals S1(t) and S2(t) with constant amplitudes can be separately amplified by means of efficient nonlinear saturated power amplifiers RF PA1 and RF PA2 in amplification branches 110, 120. After amplification, the output RF signal can be reconstructed by means of a signal component combiner unit 104. The output signal of the combiner unit equals the sum (or difference) of the two input signals S1(t) and S2(t) as depicted by equation (5).Sout=S′1(t)+S′2(t)=G cos(θ(t))sin(ωt+φ(t))=G A(t)sin(ωt+φ(t))  (5),where G represents the gain of the amplification stages, i.e. the power amplifiers RF PA1 and RF PA2.
Ideally voltage sources are to be combined so that the average current in the amplification devices can vary as function of the out-phasing angle θ(t). However, if ideal class-A, class-B or class-C operation is applied, the amplification devices act as current sources and the DC current does not vary with the out-phasing angle, meaning that the efficiency drops linearly with output power, i.e. class-A like. However, in overdriven or saturated class-A, class-B or class-C operation modes, the amplification devices act more as voltage sources. That is, approximately independent of input drive and output current and the DC current is able to vary with the out-phasing angle. Ideally the efficiency will drop according to the square root of the output power, i.e. class-B like. So effectively there is no gain in power efficiency compared to a linear class-B PA design.
Power efficiency of a LINC amplifier depends strongly upon the type of power combiner used at the output. The efficiency of the combiner is reduced by the reactive part of the impedance. One combining technique that circumvents such losses is the well known Chireix combining technique as described in H. Chireix, "High power out phasing modulation", Proceedings of the Institute of Radio Engineers (Proc. IRE), vol. 23, no. 11, pp. 1370-1392, November 1935. Accordingly, the reactive part of the effective load impedance can be cancelled by the use of compensating reactances. However, in practice it is difficult to improve the efficiency for a wide range of output power levels by implementing reactive cancellation, e.g. by using a so called RF Micro-Electromechanical System (MEMS) switches for tuning the compensating reactance as function of output power in discrete steps.
Another way to optimize the efficiency is to use switching-mode PAs, e.g. operated in class D, E, DE, or F mode, in an out-phasing configuration. In a class-DE out-phasing power amplifier with variable duty cycle the duty cycle can be used on each out-phasing path to compensate for the losses generated by the combining network, i.e. instead of the afore-mentioned Chireix component. However, this technique relies on accurate phase and duty cycle generation as well as control of the driving signals. Importantly, this offers very desirable capabilities for software-defined-radio (SDR) applications, where the duty cycle could be used in a digital calibration and/or pre-distortion routine during start-up of the radio for efficient and linear operation of the transmitter.
As mentioned above reduction of power consumption in transmitter circuits, in particular in the power amplifier circuitry therein, is very important. One method to realize desired reduction is use switching power amplifiers (PA) having better efficiency. However, switching PA concepts are only feasible in combination with suitable modulation methods like pulse width modulation (PWM) and out-phasing concepts, which in turn rely on accurate phase control and the duty cycle of the signals. Accordingly, one of the problems in the connection with switch-mode out-phasing PA concept is the generation of the required phase and duty cycle modulated signals with suitable accuracy.

Variable duty cycle generation for out-phasing and PWM power amplifiers


Embodiments for a poultry feed device are provided. The device includes at least one baffle having an outer hood cover, an inner hood cover, and an outer shield. In some embodiments, the device is capable of connecting to a bucket, allowing poultry to access feed through the device.

Currently there are a number of solutions for poultry feed devices. Some of these solutions include narrow cylindrical tubes with a rain cover over a feed tray at the bottom of the tubes. Some of these tubes can be set on the ground while others require the support of a wall, fence, or gate.
However, during the use of the above-mentioned poultry feed devices, poultry are often able to contaminate their feed with feces and often waste their feed by spilling it out of the devices.
Due to all of the existing shortcoming in presently available poultry feed devices, there is a need for a device that solves the present problems in the prior art.


There is provided a compound of formula III, and a process for preparing a compound of formula V comprising converting a compound of formula III to the compound V, wherein X is fluoro, chloro, bromo or iodo.

Gefitinib is an anilinoquinazoline which is useful in the treatment of a certain type of lung cancer (non-small cell lung cancer or NSCLC) that has not responded to chemotherapy. The chemical name for gefitinib is 4-(3′-chloro-4′-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline. Its structural formula is:

The earliest known synthesis of gefitinib was first disclosed in the patent application WO 96/33980. The synthetic method employed is depicted in the following reaction scheme 1.

The process involves selective demethylation of 6,7-dimethoxy quinazoline-4-one using methanesutfonic acid and L-methionine to get its 6-hydroxyl derivative, which is protected by acetylation. The acetoxy compound is chlorinated and condensed with chloro-fluoroaniline. Hydrolysis of the acetoxy compound followed by etherification with 3-morpholinopropyl chloride gives crude gefitinib which is purified by column chromatography. The process suffers from many disadvantages as it involves several protection and deprotection steps. The selective demethylation using methionine results in isomeric impurities and has to be purified or else the impurity carries over to subsequent steps in the preparation of gefitinib making it more difficult to isolate a pure product. The process also leads to formation of an N-alkylated impurity at the final stage which must be separated by column chromatography to obtain gefitinib.
Several other approaches are also described in the literature to make gefitinib.
WO 2004/024703 discloses a process for the preparation of gefitinib starting from 3-hydroxy-4-methoxy benzonitrile which involves condensation of 3-hydroxy-4-methoxy benzonitrile with morpholino propyl chloride, nitration, reduction with sodium dithionite to amino compound, hydrolysis of nitrile to amide, cyclisation in the presence of formamide to obtain quinazoline, chlorination with phosphorous oxychloride and finally condensation with chloro-fluoro aniline to obtain gefitinib. The process involves multiple steps and hence is time consuming.
WO 2005/023783 discloses a process for the manufacture of gefitinib starting from 2-amino-4-methoxy-5-(3-morpholinopropoxy)benzonitrile. The process involves a rearrangement reaction of 3-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)3,4-dihydroqunazoline-4-imine. The process is not feasible industrially, as the basic raw material is not readily available on a commercial scale and involves the use of excess 3-chloro-4-fluoroaniline which is expensive. A further draw back of the process is in the isomerization of the 4-imine compound which requires anhydrous conditions at high temperature for a longer duration of 96 hours. All the problems associated with this prior art process are overcome by the novel process of the present invention.
WO2005/070909 discloses a process for the preparation of gefitinib starting from isovanillin as depicted in scheme 2

The WO' 909 process has disadvantages as it forms cis-trans geometrical isomers of the oxime, which have different reactivities. Furthermore, the process uses a large excess of acetic anhydride to convert the oxime to the nitrile at higher temperature.
The patent applications 901/CHE/2006 and 903/CHE/2006 disclose another route for preparing gefitinib starting from isovanillin. The process involves formation of a formamido compound [N′-[2-cyano-4-{3-(4-morpholinyl)propoxy}phenyl]-N,N-dimethyl formamide], which is unstable and may result in undesired impurities in the final condensation with 3-chloro-4-fluoro aniline, thereby making the process less feasible on an industrial scale.
The processes disclosed in the prior art are cumbersome. Therefore, there exists a need for a more economical and efficient method of making gefitinib which is suitable for industrial scale-up.
The process of the present invention avoids use of reagents such as sodium dithionite, acetic anhydride and allows substantial reduction in the number of problems associated with these reagents.

Process for the preparation of gefitinib

Abstract: There is also provided a process for preparing a compound of formula XI comprising converting a compound of formula X to the compound XI.

Abstract: The compounds V and XI so prepared may be used in a process for preparing gefitinib.