Two stage hemofiltration that generates replacement fluid

The present invention relates to a system for two-stage blood dialysis of a patient. In one embodiment, the system comprises a first filtration device for receiving the blood from the patient and for producing a first filtrate and processed blood. The system further comprises a second filtration device for receiving the first filtrate and producing replacement fluid and waste product. At least one of the first and second filtration devices preferably comprises a Taylor vortex-enhanced blood filtration device.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Preferred aspects of the present invention relate to multistep filtrations wherein successive filtrations remove filtrates of various specifications. Preferred embodiments of the present invention are particularly useful to regenerate fluid lost during blood dialysis.

2. Description of the Related Art

Traditionally, dialysis is the maintenance therapy used to treat kidney disease. There are two common approaches. One is peritoneal dialysis, wherein the process is done internally to the patient, in the patient's pericardium. Peritoneal dialysis uses the patient's abdominal lining as a blood filter. The abdominal cavity is filled with dialysate, thereby creating a concentration gradient between the bloodstream and the dialysate. Toxins diffuse from the patient's blood stream into the dialysate, which must be exchanged periodically with fresh dialysate.

The second approach is by filtration dialysis. Filtration dialysis encompasses two main filtration techniques: hemodialysis and hemofiltration. Both operate extracorporeally by removing the patient's blood, treating the blood to remove toxins, and returning the processed blood to the patient. Yet, each process functions by a different physical separation technique.

Hemodialysis effects removal of toxins from blood by diffusion. The patient's blood flows past one side of a membrane while dialysate flows past the other side. The membrane selectively allows for the flux of small molecules. Due to the concentration gradient between the blood and the dialysate, small molecule toxins diffuse into the dialysate. At the same time, nutrients, such as electrolytes and other chemicals, present in the dialysate diffuse into the blood. The processed blood is then returned to the patient.

Hemofiltration effects removal of toxins from blood by convection. The patient's blood is passed through a filter that is permeable to plasma water and, generally, molecules smaller than 20,000 Daltons. The resulting plasma water filtrate, called “blood-waste,” contains water, the toxic blood components, and “small desirable molecules,” including small molecule nutrients and electrolytes. Since the processed blood lacks vital components lost through filtration, and since its volume is substantially reduced, a replacement fluid must be added to the processed blood before its reintroduction to the patient. Depending on the hemofiltration needs, the replacement fluid can be added pre- or post-hemofiltration.

In addition to these two blood purification techniques, methods combining hemodialysis and hemofiltration, known as hemodiafiltration, have been used. Hemodiafiltration effects removal of toxins from blood by both diffusion and convection. As in hemofiltration, blood volume and nutrients/electrolytes must be replaced with replacement fluid in hemodiafiltration procedures.

Generally, replacement fluid is engineered to mimic healthy plasma water with respect to pH, electrolyte and nutrient concentration. However, the replacement fluid may also be adjusted to correct for abnormalities in the individual patient. Biologically compatible buffers, such as citrate, lactate, acetate and bicarbonate, often serve as the base for replacement fluids. The buffers may then be supplemented with electrolytes, such as chloride, sodium, calcium, magnesium, potassium, and phosphate, and nutrients, such as glucose and dextrose, as required by the patient.

Disadvantages of these blood processing methods include the difficulties and costs associated with the production of a large amount of replacement fluid that is free of contaminants harmful to the patient. In addition, hemodialysis, hemofiltration and hemodiafiltration create a substantial amount of medical waste that is costly to dispose of. Consequently, there exists a need to recycle the waste from these systems to generate bio-compatible, low cost replacement fluid or dialysate. Thereby, the need for the production of large volumes of foreign dialysate or replacement fluid may be eliminated. Filtration of the patient's blood-waste generated during blood dialysis meets these needs.

Another problem faced by those using well-known methods of blood dialysis is filter clogging, described as “concentration polarization.” As a result of the selective permeability properties of a filter, filtered material that cannot pass through the filter often becomes concentrated on the surface of the filter. This phenomenon is clearly illustrated by the case of a “dead-end” filter, such as a coffee filter. During the course of the filtration process, the filtered material (coffee grounds) building up on the filter creates flow resistance to the filtrate, the fluid (coffee), which can pass through the filter. Consequently, filtrate flux is reduced, and filtration performance diminishes.

Various solutions to the problem of concentration polarization have been suggested. These include: increasing the fluid velocity and/or pressure (see e.g., Merin et al., (1980)J. Food Proc. Pres.4(3):183-198); creating turbulence in the feed channels (Blatt et al.,Membrane Science and Technology, Plenum Press, New York, 1970, pp. 47-97); pulsing the feed flow over the filter (Kennedy et al., (1974)Chem. Eng. Sci.29:1927-1931); designing flow paths to create tangential flow and/or Dean vortices (Chung et al., (1993)J. Memb. Sci.81:151-162); and using rotating filtration to create Taylor vortices (see e.g., Lee and Lueptow (2001)J. Memb. Sci.192:129-143 and U.S. Pat. Nos. 5,194,145, 4,675,106, 4,753,729, 4,816,151, 5,034,135, 4,740,331, 4,670,176, and 5,738,792, all of which are incorporated herein in their entirety by reference thereto). In U.S. Pat. No. 5,034,135, Fischel discloses creating Taylor vorticity to facilitate blood fractionation. Fischel also describes variations in the width of the gap between a rotary spinner and a cylindrical housing, but does not teach variation in this width about a circumferential cross-section.

Taylor vortices are induced in the gap between coaxially arranged cylindrical members when the inner member is rotated relative to the outer member. Taylor-Couette filtration devices generate strong vorticity as a result of centrifugal flow instability (“Taylor instability”), which serves to mix the filtered material concentrated along the filter back into the fluid to be processed. Typically, a cylindrical filter is rotated within a stationary outer housing. It has been observed that membrane fouling due to concentration polarization is very slow compared to dead-end or tangential filtration. Indeed, filtration performance may be improved by approximately one hundred fold.

The use of Taylor vortices in rotating filtration devices has been applied to the separation of plasma from whole blood (See, e.g., U.S. Pat. No. 5,034,135). For this application, the separator had to be inexpensive and disposable for one-time patient use. Further, these separators only had to operate for relatively short periods of time (about 45 minutes). Moreover, the separator was sized to accept the flow rate of blood that could reliably be collected from a donor (about 200 ml/minute). This technology provided a significant improvement to the blood processing industry. The advantages and improved filtration performance seen with rotating filtration systems (Taylor vortices) have not been explored in other areas of commercial fluid separation—including kidney dialysis

Consequently, an improved blood dialysis system may be configured to significantly reduce the artificial replacement fluids necessary. In addition, this improved blood dialysis system may produce Taylor vortices to alleviate the problem of concentration polarization so prevalent with known methods of filtration.

SUMMARY OF THE INVENTION

In one embodiment, the present invention relates to a system for two-stage blood dialysis of a patient. The system comprises a first filtration device for receiving the blood from the patient and producing a first filtrate and processed blood. The system further comprises a second filtration device for receiving the first filtrate and producing replacement fluid and waste product. At least one of the first and second filtration devices preferably comprises a Taylor vortex-enhanced blood filtration device.

In another embodiment, the present invention relates to another system for two-stage blood dialysis of a patient. The system comprises a dialysis device for receiving the blood from the patient and dialysate and producing waste dialysate and processed blood. The system further comprises a filtration device for receiving the waste dialysate and producing recycled dialysate and waste product.

In another embodiment, a method for performing hemodialysis on a patient may be implemented in accordance with the present invention. A first filtration device configured to create Taylor vorticity is provided, and a second filtration device is also provided. Blood is introduced from the patient into the first filtration device, and a first filtrate from the first filtration device is introduced into the second filtration device. A replacement fluid may then be obtained from the second filtration device.

In another embodiment, a second method for performing hemodialysis on a patient may be implemented in accordance with the present invention. A first filtration device is provided, and a second filtration device configured to create Taylor vorticity is also provided. Blood is introduced from the patient into the first filtration device, and a first filtrate from the first filtration device is introduced into the second filtration device. A replacement fluid may then be obtained from the second filtration device.

In another embodiment, another method for performing hemodialysis on a patient may be implemented in accordance with the present invention. A dialysis device and a filtration device are provided. Blood is introduced from the patient into the dialysis device, and waste dialysate from the dialysis device is introduced into the filtration device. A recycled dialysate may then be obtained from the filtration device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Traditionally, blood dialysis procedures are single stage. In other words, the blood is removed from the patient, processed through a single filtration device to remove waste products, and returned to the patient. Unfortunately, blood is a heterogeneous fluid with molecules that are both smaller and larger than these waste products, which are generally in the range of 300-6,000 Daltons. As a result, filtration devices that remove the waste products from blood often inadvertently remove many of those smaller molecules, e.g. water and electrolytes, in the process. These smaller molecules must then be replaced prior to reintroduction of the blood to the patient.

In typical machines, blood is pumped from the patient at 300-450 mL/min. Approximately half of this flow is filtered from the blood and disposed of as blood-waste. In a 3 hour procedure, between 20 and 30 liters of replacement fluid must therefore be added to the blood flow in order to keep the patient's blood volume constant. Of course, the majority of the filtrate in such a procedure comprises water and other small, desirable molecules.

One embodiment of the present invention contemplates using a multi-stage filtration process to recapture much of this desirable filtrate and combine it with the processed blood in order to improve the blood volume returning to the patient without using excessive volumes of artificial replacement fluid. In one embodiment, a two-stage filtration process is employed. In the first stage, a filtration device, like that in the prior art, is used that is permeable to water, small nutrient molecules and waste products. In the second stage, blood-waste emerging from this first stage filtration device is sent through a second filtration device that filters the larger waste product molecules. The plasma water filtrate emerging from the second filtration device can then be used as clean, bio-compatible replacement fluid to increase the blood volume returning to the patient. Of course, in other embodiments, more stages may be necessary to filter out particular waste products from other, similarly sized molecules.

A variety of filtration devices may be used to perform either the first or second stages of one embodiment of the present invention.FIG. 1shows a cross section of one possible filtration device10to be used in the present invention. In this filtration device, a single rotor creates Taylor vorticity. In the illustrated embodiment, the filtration device10is used to perform hemodialysis, filtering molecules of a certain size (including waste products) from blood. In other embodiments, the device10may be used, more generally, to transfer mass from one fluid. In still other embodiments, the device10may be used to transfer heat from one fluid. As would be well known to those of skill in the art, the invention should not be limited to medical applications.

In one embodiment, the filtration device10comprises a cylindrical case12housing a cylindrical rotor14. A gap16exists between the case12and the rotor14, and, in a preferred embodiment, the rotor14is disposed coaxially within the cylindrical case12. In other embodiments, different geometries and configurations may be chosen for the case and rotor, to accommodate other fluids and other means of generating Taylor vorticity.

In the illustrated embodiment, the cylindrical, circumferential walls of the rotor14are at least partially composed of a filtration membrane18, and partially define a rotor interior20. The rotor interior20is further defined by the top and bottom walls of the rotor14, which may or may not comprise filtration membrane. As illustrated inFIG. 1, the filtration membrane18may be used for the first stage of a two-stage dialysis method. The filtration membrane acts as a dialysis membrane, porous to water, electrolytes, small nutrient molecules and the small to medium-sized molecules that make up waste products present in blood. In a typical application, the dialysis membrane18is porous up to a mass of approximately 10,000 Daltons. In another application, the dialysis membrane18may be more or less porous, in the range of 6,000 to 20,000 Daltons. In another embodiment, the filtration membrane may be used for the second stage of the two-stage dialysis method. The filtration membrane might then be permeable for molecules up to a mass of approximately 300 Daltons. Thus, plasma water, electrolytes and small nutrient molecules would flow through as filtrate into the rotor interior20, and the heavier waste products would be filtered out. In other embodiments, varying degrees of filtration and/or heat transfer may be facilitated by the use of different filtration membranes. For example, in a heat transfer application, the filtration membrane may comprise an impermeable structure, which nevertheless is an effective transferor of heat.

In the illustrated embodiment, the cylindrical case12has three fluid access ports22,24,26; two22,24leading to and from the gap16between the case12and rotor14, and one26leading from the rotor interior20. In other embodiments, different fluid access configurations may be provided. For example, in one embodiment, only one fluid access port leads to the gap between the case and rotor, and two ports may lead to the rotor interior.

In one embodiment, mounted in the axis A of the cylindrical case12are two pivot pins30,32, one on either end. These pivot pins30,32define the axis of rotation A for the rotor14and facilitate the free rotation of this rotor14. As illustrated, the bottom pivot pin32may be hollow, allowing fluid transport passage through the case12and rotor14. Of course, in other embodiments, the top pivot pin30may also be hollow to accommodate another fluid access port. Other means of facilitating rotation may be provided, including, e.g., ball-bearing assemblies and other means well known to those of skill in the art.

In one embodiment of the invention, the rotor14can rotate freely within the cylindrical case12. In order to control this rotation, a spinner magnet34may be mounted internally to the rotor14, and an external rotating magnetic field (not shown) may be configured to interact with this spinner magnet34. By modulating the external magnetic field, the magnet34and, in turn, the rotor14can be made to spin in different directions and at varying speeds. In a preferred embodiment of the invention, the rotor14can be spun at a speed sufficient to create Taylor vorticity within a fluid in the gap16between the rotor14and case12. By creating Taylor vorticity in this gap16, filtration performance can be dramatically improved. Other means of spinning the rotor14in order to create Taylor vorticity may be used in keeping with this invention, as is known to those of skill in the art. For example, in one embodiment, a motor may be attached to at least one of the pivot pins, e.g. the top pivot pin30, attached to the rotor14.

In one embodiment, the rotating magnetic fields that control the rotor14can be produced by a series of magnetic coils that surround the filtration device10at its top. These electrical coil assemblies can be formed in half arch (“C” sections) that can be closed around the device10, although other configurations are possible.

The illustrated size of the device10is considered adequate for hemodialysis, although in other applications, larger or smaller filtration devices may be utilized to suit the particular fluids being processed.

In a hemodialysis application, the gap16between the rotor14and inside wall of the case12is selected to provide adequate Taylor vorticity in the blood. This gap16depends on the diameter and the RPM of the rotor14, which parameters can be modified by one of skill in the art. With a centrifugal speed in the range of about 2000-5000 RPM and a rotor diameter of about 0.1 to 10 inches, the width adequate to generate Taylor vortices may be in the range of about 0.003 to about 0.3 inches. More preferably, a gap16having a width of about 0.03 inches should provide adequate vorticity for a rotor14of about 1 inch in diameter spun at about 2,400 RPM. In a preferred embodiment of the filtration device10, the rotor has a diameter of approximately 2 inches and is slightly longer than 6 inches.

FIGS. 2-4illustrate some further structural features of different embodiments of the hemodialysis device described above for use in the two-stage filtration process. In particular, different geometries and configurations of the housing and rotor are shown, which may be implemented to attain various advantages. InFIG. 2, the embodiment described above is shown. As can be more clearly seen in this Figure, the rotor14is cylindrical and disposed coaxially within the cylindrical case12. Thus, the gap16is of constant width about the circumference of the device10. In this relatively simple embodiment, calibrating the appropriate speed of the rotor14is more easily accomplished, and the Taylor vortices are fairly constant in strength about the entire filtration membrane18.

InFIG. 3, another configuration of the case12and rotor14is shown. In this embodiment, the case12and rotor14have individual cross-sections similar to those inFIG. 2, but are no longer aligned coaxially. As shown inFIG. 3, the gap16therefore varies in width about the circumference of the case12. Since the Taylor number, reflecting the strength of resulting vortices, is directly proportional to the width of the gap, the sections of rotor14farther from the wall of the case12experience greater Taylor vorticity than those sections nearer to the wall. As the rotor14passes these wider gap locations, residual concentration polarization and any clogging of the filter membrane18will be “blown” off by the stronger vortices, opening up blinded zones in the membrane18. As a result, once per revolution, the longitudinally extending sections of the membrane18will be “cleaned” by passing the widened portions of the gap16, and the efficiency of the device10may be improved. In addition, where the width of the gap16decreases, the shear forces in the gap increase, and this varying shear force may also tend to increase mass transport across the membrane18. Thus, once per revolution, we can increase shear and decrease vorticity at any point on the membrane18on rotor14.

InFIG. 4, another configuration of the case12and rotor14is shown that will similarly create a non-constant width gap. In this configuration, the case12and rotor14are configured similarly to those inFIG. 2, but the case12further has a bulge42incorporated into its wall. The gap16therefore varies in width about the circumference of the case12, widening at the site of the bulge42, producing the advantages discussed above with reference toFIG. 3. The abrupt shift between wide and narrow widths in this embodiment may introduce further vortex characteristics that may facilitate dialysis. In other embodiments, the case12and rotor14may have other cross-sectional geometries, resulting in a variable width gap16.

Returning toFIG. 1, one method of implementing the hemodialysis device10may be discussed with reference to the Figure. Arrows36,38and40show the input and output of the flows into and out of the device10. In the illustrated embodiment, blood from a patient flows through the gap16between the rotor14and the case12, while water, small nutrient molecules, electrolytes and waste products are filtered into the rotor interior20. Due to the concentration gradient between the blood and the plasma water that initially crosses the membrane18, certain waste products will preferentially flow through the dialysis membrane18into the plasma water, thereby dialyzing the blood. The rotor14spins at a speed sufficient to create Taylor vortices in the blood and prevents concentration polarization in the blood near the dialysis membrane18. In this way, one embodiment of the present invention enables use of a smaller, more biocompatible hemodialysis device10.

In further detail, a blood inlet port22is located at the top of the cylindrical case12and a blood outlet port24is located at the bottom. This allows blood to flow from top to bottom simply using gravitational energy, and pressure from the blood influx. The device10is preferably designed such that in the time it takes a certain quantity of blood to travel from the top of the hemodialysis device10to the bottom, the desired amount of waste by-product has been extracted. A water and waste by-product outlet port26is located at the bottom of the rotor14. In a preferred embodiment, this solution flows out of the device10for further filtering as described in further detail below.

In another embodiment, a dialysis fluid may be used to facilitate hemodialysis. Another fluid access port may be added to the top of the device10to allow dialysis fluid to enter the device. As is described in detail with reference toFIG. 6, waste products diffuse into the dialysis fluid and are carried away from the device by the dialysate flow. Other modifications may also be made in keeping with the present invention.

FIG. 5shows a cross section of another possible embodiment for use with the present invention, in which a dual rotor device creates Taylor vorticity. This illustrated device may preferably be used in a two-stage blood dialysis system, such as that described in detail with reference toFIG. 8. In the illustrated embodiment, the filtration device110is used to perform hemodialysis, filtering undesirable waste products from blood into a dialysis fluid, or “dialysate.” In other embodiments, the device110may be used, more generally, to transfer mass from one fluid to another. In still other embodiments, the device110may be used to transfer heat from one fluid to another. As would be well known to those of skill in the art, the invention should not be limited to medical applications.

In one embodiment, the filtration device110comprises a cylindrical case112housing a cylindrical outer rotor114. A first gap116exists between the case112and the outer rotor114through which blood flows, and, in a preferred embodiment, the outer rotor114is disposed coaxially within the cylindrical case112. In other embodiments, different geometries and configurations may be chosen for the case and rotor, as discussed above with reference toFIGS. 2-4.

In the illustrated embodiment, the cylindrical, circumferential walls of the outer rotor114are at least partially composed of a filtration membrane118, and partially define an outer rotor interior120. The outer rotor interior120is further defined by the top and bottom walls of the outer rotor114, which may or may not comprise filtration membrane. As illustrated inFIG. 5, the filtration membrane118is a dialysis membrane. This dialysis membrane118preferably facilitates the diffusion of molecules smaller than approximately 10,000 Daltons, and the device110may thereby function as the first-stage device in the two-stage blood dialysis system illustrated inFIG. 8. In other embodiments, varying degrees of filtration and/or heat transfer may be facilitated by the use of different filtration membranes. For example, in a heat transfer application, the filtration membrane may comprise an impermeable structure, which nevertheless is an effective transferor of heat.

In one embodiment, mounted in the axis A of the cylindrical case112are two pivot pins130,132, one on either end. These pivot pins130,132define the axis of rotation A for the outer rotor114, and facilitate the free rotation of this rotor114. As illustrated, the pivot pins130,132may also be hollow, providing fluid transport passages through the case112and outer rotor114. In other embodiments, other means of facilitating rotation may be provided, including, e.g., ball-bearing assemblies and other means well known to those of skill in the art.

In one embodiment of the invention, the outer rotor114can rotate freely within the cylindrical case112. In order to control this rotation, a spinner magnet134may be mounted internally to the outer rotor114, and an external rotating magnetic field (not shown) may be configured to interact with this spinner magnet134. By modulating the external magnetic field, the magnet134and, in turn, the outer rotor114can be made to spin in different directions and at varying speeds. In a preferred embodiment of the invention, the outer rotor114can be spun at a speed sufficient to create Taylor vorticity within a fluid in the first gap116between the outer rotor114and case112. By creating Taylor vorticity in this first gap116, filtration performance can be dramatically improved. Other means of spinning the outer rotor114in order to create Taylor vorticity may be used in keeping with this invention, as is known to those of skill in the art. For example, in one embodiment, a motor may be attached to at least one of the pivot pins, e.g. upper pivot pin130, attached to the outer rotor114.

Inside the outer rotor114, an inner rotor144, also supported by the upper and lower pivot pins130,132, may be mounted coaxially, with a second gap146created between the two rotors114,144. Although the inner rotor144may partially comprise another filtration membrane, in a preferred embodiment, the inner rotor is relatively impermeable, simply defining the second gap between the two rotors114,144. As described in further detail above with respect to the outer rotor and case, the inner rotor144may also have differing cross-sectional geometries, and may be mis-aligned to accommodate other fluids and other means of generating Taylor vorticity. In these alternative embodiments, the inner rotor144may be supported by structures other than those supporting the outer rotor114, and may spin about a different axis.

In a preferred embodiment, the inner rotor144rotates freely within both the outer rotor114and cylindrical case112. In order to control this rotation, a second spinner magnet148may be mounted internally to the inner rotor144, and a second external rotating magnetic field (not shown) may be configured to interact with this second spinner magnet148. In the illustrated embodiment, the second spinner magnet148for the inner rotor144is located at the top of the device110, and the spinner magnet134for the outer rotor114is located at the bottom of the device110. Thus, two separate and independent magnetic fields can control the rotation of the two rotors114,144. As described in further detail above, the second spinner magnet148mounted to the inner rotor144may be controlled similarly to the one mounted to the outer rotor114. In a preferred embodiment, the inner rotor144can be spun at a speed sufficient to create Taylor vorticity within a fluid in the second gap146between the inner and outer rotors. In a further preferred embodiment, the inner rotor144is spun in a direction opposite the outer rotor114to create even more powerful Taylor vortices. By creating Taylor vorticity in this second gap146, filtration performance can be further improved, as concentration polarization is prevented on the side of the filtration membrane118facing the inner rotor144. Other means of spinning the inner rotor144in order to create Taylor vorticity may be used, as is known to those of skill in the art. For example, in one embodiment, a motor may be attached to at least one of the pivot pins, e.g. lower pivot pin132, attached to the inner rotor144.

In one embodiment, the rotating magnetic fields that control the two rotors can be produced by a series of magnetic coils that surround the filtration device110at its top and bottom. Since pre-connected tubing (not shown) enters and exits the device110on axis A in the illustrated embodiment, these electrical coil assemblies can be formed in half arch (“C” sections) that can be closed around the device110.

The illustrated size of the device110is considered adequate for hemodialysis, although in other applications, larger or smaller filtration devices may be utilized to suit the particular fluids being processed.

In a hemodialysis application, the first gap116between the outer rotor114and inside wall of the case112is selected to provide adequate Taylor vorticity in the blood. This first gap116depends on the diameter and the RPM of the outer rotor114, which parameters can be modified by one of skill in the art. With a centrifugal speed in the range of about 1000-5000 RPM and an outer rotor diameter of about 0.1 to 10 inches, the width adequate to generate Taylor vortices may be in the range of about 0.003 to about 0.3 inches. More preferably, a first gap116having a width of about 0.03 inches should provide adequate vorticity for an outer rotor114of about 1 inch in diameter spun at about 2,400 RPM.

In the illustrated embodiment, the second gap146between the inner and outer rotors is selected to provide adequate Taylor vorticity in the dialysate. This second gap146depends on the diameters and the RPM difference between the inner and outer rotors. With a centrifugal speed in the range of about 1000-5000 RPM and an inner rotor diameter of about 0.1 to 10 inches, the width adequate to generate Taylor vortices between the inner rotor144and outer rotor114may be in the range of about 0.003 to about 0.3 inches. Preferably, a second gap146having a width of about 0.03 inches should create adequate vorticity for an inner rotor diameter of about 0.8 inches spun at about 3,600 RPM. This preferred set of parameters would give a rotating speed of the inner rotor144relative to the outer rotor114of about 1,200 RPM. Alternatively, by spinning the inner rotor144in the opposite direction of the outer rotor114, powerful Taylor vorticity can be created in the dialysate.

For the various potential applications, the dimensions and speeds of the inner and outer rotors and casing may be dramatically different. For example, in certain industrial applications, the filtration device110may be designed on a much larger-scale in order to accommodate larger flows and liquids of varying viscosity. Optimizing the ranges of gap and rotor sizes, as well as centrifugal speed and rotor direction can be done by one of skill in the art based on the teaching herein.

In the illustrated embodiment, the cylindrical case has four fluid access ports122,124,126,128. A first inlet port122is located at the top of the cylindrical case112, and a first outlet port124is located at the bottom. In a hemodialysis application, this allows blood to flow from top to bottom through the first gap116simply using gravitational energy, and pressure from the blood influx. The device110is preferably designed such that in the time it takes a certain quantity of blood to travel from the top of the hemodialysis device110to the bottom, the desired amount of waste by-product has been extracted. A second inlet port126is located at the bottom of the outer rotor114, and a second outlet port128is located at the top of the outer rotor114. In the hemodialysis application, the dialysis fluid flows through these ports from the bottom of the device110to the top through the second gap146between the inner and outer rotors. In this preferred embodiment, the fluid paths are designed to take advantage of counter-current mass transfer, meaning that the paths of blood and dialysate are opposite. Fresh dialysate is exposed through the dialysis membrane118with mostly dialyzed blood, where the concentration gradient is the lowest. As is well known to those of skill in the art, however, other numbers and configurations of fluid access ports may be used in keeping with the present invention.

Since the first inlet and outlet ports122,124are on the outer diameter of the case112, there is no need for high pressure on that flow path. This being the case, in the illustrated embodiment, blood will not be forced to the center of rotation of the outer rotor114, thus fluid seals are not necessary there to prevent blood from entering the inner rotor144. Fluid seals can be added if higher fluid pressures are employed in hemodialysis or other applications, or if fluids for filtering enter the inner rotor144for any reason.

In a preferred embodiment, the second inlet port126for dialysate is configured so that the dialysate passes through the lower pivot pin132and is then directed into the second gap146between the inner and outer rotors, and not downward into the first gap116between the outer rotor114and case112. A fluid seal150at the top pivot pin130is included in the illustrated embodiment to prevent migration of dialysate into the first gap116between the outer rotor114and case112. This seal150can be any conventional polymer lip seal. As is well known to those of skill in the art, other seals may be implemented. In an alternative embodiment, another fluid seal is included at the bottom pivot pin132.

In one method of practicing the present invention, blood is exposed to the dialysis membrane118with Taylor vorticity resulting in a minimal concentration polarization layer in the first gap116between the outer rotor114and case112, maximizing the ability to remove low molecular weight waste products from the patient's blood. In the process of passing through the filtration device110, dialysate is also exposed to Taylor vorticity, resulting in a minimal concentration polarization layer near the interior of the dialysis membrane118, maximizing the ability to mix the low molecular weight waste products into the dialysate flow. In a preferred embodiment, the waste dialysate emerging from the device110may then be directed through another filtration device to produce recycled, clean dialysate.

In connection withFIG. 6, an exemplary method of performing hemodialysis will be described using the device described inFIG. 5. Within the device110, the inner and outer rotors are spinning in opposite directions at speeds sufficient to create Taylor vortices in fluids between the outer rotor114and case112, and between the inner rotor144and outer rotor114. Blood is collected from the patient at a particular flow rate136, and enters the hemodialysis device110through the blood inlet port122, located at the top of the device110. Dialysis fluid also enters the hemodialysis device140, but from the bottom, through a second, dialysate inlet port126. The two fluids are subjected to the forces from the rotors, and Taylor vortices form within them. Thus, concentration polarization is largely alleviated at the dialysis membrane118of the outer rotor114, and a more constant flow of waste products travels through the membrane118into the dialysate. The dialysate travels through the hemodialysis device110, within the second gap146between the outer and inner rotors, and exits the top through a dialysate outlet port128, while the processed blood exits through the blood outlet port124at the bottom of the device110and is returned to the patient.

In other embodiments, other Taylor vortex-enhanced filtration devices may be used, as further discussed in the co-pending U.S. patent application Ser. No. 10/797,510, which application is herein incorporated by reference in its entirety.

One problem with many of the above described methods of hemodialysis is that the dialysis membrane may be porous to water as well as waste products. Thus, large volumes of plasma water accompany waste products traveling through the dialysis membrane, and the flow of processed blood exiting through the blood outlet port is dramatically reduced from the blood entering the hemodialysis device. This problem is especially acute with respect to the filtration device10illustrated inFIG. 1. In one embodiment, a sterile replacement fluid may be added to the processed, dialyzed blood at a junction prior to return to the patient. However, this embodiment risks patient exposure to contaminated replacement fluid, and increases the costs of hemodialysis by the cost of the replacement fluid.

FIGS. 7A and 7Bare schematic illustrations of alternate embodiments of two-stage blood dialysis systems according to the present invention, wherein replacement fluid is generated from the blood-waste emerging from a first stage filtration device, reducing the need for artificial replacement fluid. The illustrated embodiments differ in the ordering of steps by which this goal is accomplished but share many operative features. Therefore, the components of these two systems will be discussed together, and the differences will be highlighted, as necessary, in the following discussion. The directions of the flows of various fluids flowing through the systems are illustrated by arrows.

A patient is represented by the box200farthest to the left. In a typical implementation, the patient200may have a kidney disease that is producing uremic metabolic abnormalities. It is believed that this is due to the fact that intermediate molecular weight molecules (300-6,000 Daltons), removed by healthy kidneys, are producing a morbid toxicity in these patients. In order to alleviate this accumulated toxicity, such a patient200typically undergoes periodic dialysis procedures, which remove these intermediate weight molecules. In other embodiments, it may be understood by those of skill in the art that the patient200may have another disease in which dangerous or harmful substances are present in the patient's blood. In still other embodiments, the source of the fluid that will be filtered need not be a patient. The process may be used in an industrial setting, for example, in which the fluid is some heterogeneous mixture from which intermediate sized molecules must be extracted.

The device used for the first stage of this two-stage blood dialysis system may be described as a blood filtration device210. As described above, such a device210generally produces filtrates of molecules smaller than a certain size. As is well-known to those of skill in the art, the filtration membrane used in the device210can have a wide variety of characteristics and can be chosen to filter any of a number of different sized particles. In one embodiment, the blood filtration device210is configured to filter out those molecules having a weight of 10,000 Daltons or less. In this embodiment, the filtrate will preferably include those intermediate weight molecules that are toxic to the patient200.

The device used for the second stage of this two-stage blood dialysis system may be described as an ultrafiltration device220, so called because it is permeable to smaller molecules. In a preferred embodiment, the purpose of the ultrafiltration device220is to filter out the intermediate weight, toxic molecules from a heterogeneous solution, leaving only water and other small desirable molecules. In the preferred embodiment, the filtration membrane used in the ultrafiltration device220is chosen to allow molecules having a weight less than approximately 300 Daltons to pass, thereby separating the potentially toxic waste products from the rest of the solution. In other embodiments, the filtration membrane may only allow molecules having a weight less than approximately 200 Daltons to pass, preventing other, questionably toxic molecules from emerging as filtrate.

The same or different types of filtration devices may be used for the blood filtration device210and ultrafiltration device220. They may comprise, for example, conventional hollow fiber dialysis membrane cartridges, or other filtration devices well known to those of skill in the art. In a preferred embodiment, the devices are Taylor vortex-enhanced filtration devices that function similarly to the filtration device10described above with reference toFIG. 1. As described above, these filtration devices may have any combination of a variety of sizes, shapes and speeds for their respective rotors and housings, in order to accommodate the different viscosities and flow rates of the processed fluids.

A waste bag230is used to collect the undesirable waste products produced by this two-stage blood dialysis system. In one embodiment, this waste bag230should collect many of the same waste products that would normally be collected by a healthy kidney. Of course, the waste bag230may represent any of a number of means for collecting and/or disposing of waste and need not be a physical receptacle of any particular shape or size. Often, the waste bags230must be collected as hazardous waste for careful disposal according to applicable laws and regulations. Due to the unique features of the present invention, the volume of the waste products generated by the two-stage blood dialysis system may be far less than that generated by a typical single-stage dialysis procedure.

Supplemental replacement fluid sources240are also shown inFIGS. 7A and 7B, although they are shown at different locations in the two systems. Although much of the replacement fluid necessary to keep the patient's blood volume constant may be generated from the patient's own blood-waste, there may remain a need for relatively small amounts of artificial replacement fluid during the procedure. Even if the two-stage filtration system functioned perfectly, the volume represented by the intermediate-weight waste molecules should typically be replaced in order to keep the patient's blood volume constant. In one embodiment, it is estimated that approximately three liters of artificial replacement fluid must be added to the patient's blood flow every three hours, as approximately three liters of waste products are removed over the same time frame. This would represent a significant improvement over the 20-30 liters needed during a typical procedure, as described above.

The supplemental, artificial replacement fluid may be generated in a number of ways, but must be sterile, pyrogen-free and generally at body temperature. In one embodiment, artificial replacement fluid may be produced from common tap water as shown in “Successful Production of Sterile Pyrogen-Free Electrolyte Solution by Ultrafiltration,”Kidney International,14, 522-25, 1978, a paper by Lee Henderson and Erminia Beans, which is hereby incorporated by reference in its entirety. In other embodiments, such fluid may be produced by other methods well known to those of skill in the art.

InFIG. 7A, an optional component of a two-stage blood dialysis system is shown: an anticoagulant source250. This anticoagulant source250may comprise a source for heparin, for example, that is mixed with blood to prevent the blood from coagulating extracorporeally. In other embodiments, other means for facilitating filtration, and for preventing clumping or other undesirable fluid characteristics may be employed. For example, water may be added to other heterogeneous solutions to facilitate the production of vortices in the filtration devices210,220.

Using the two-stage blood dialysis system illustrated inFIG. 7A, a method of performing blood dialysis according to the present invention may now be discussed in further detail. The first step in the procedure is drawing blood from the patient, illustrated by the arrow255extending from the patient200to the blood dialysis filtration device210. Conventionally, blood is drawn from the patient200via an IV tube connected to a patient's artery in the patient's arm. Of course, other means of drawing blood from a patient are well-known to those of skill in the art. As discussed above, a typical rate of blood flow from the patient is 300-450 mL/min. In order to keep the patient's blood volume relatively constant, therefore, the fluid returning to the patient, arrow265, must flow at a similar rate. Conventionally, the fluid returning to the patient200is returned through an IV tube connected to the patient's vein.

In an optional second step, the blood flowing from the patient200is mixed with an anticoagulant from an anticoagulant source250. In this way, performance of the blood dialysis system may be improved.

The blood that is flowing from the patient200is then passed through the blood dialysis filtration device210. The filtration device210may filter the blood in a number of ways well known to those of skill in the art. In a preferred embodiment, the filtration device210works similarly to the device10described in detail above. In this implementation, the blood flows into the gap16between the case12and the rotor14through the inlet port22. The filtration membrane18is designed to allow molecules with a molecular weight less than approximately 10,000 Daltons to pass into the rotor interior20. The blood flowing from the patient200has a number of constituents, including: water, electrolytes, small nutrient molecules, waste products, high molecular weight molecules (e.g. proteins, etc.) and blood cells and other cells of various types. The first four of the above-listed constituents comprise blood-waste and can pass through the filtration membrane18into the rotor interior20. Thus the rotor interior fills with water, electrolytes and small nutrient molecules, and waste products.

Meanwhile, the rotor14spins rapidly enough to create Taylor vortices in the blood flowing through the gap16between the rotor14and housing12. These Taylor vortices mix the blood in this gap16and thereby alleviate the problem of concentration polarization on the outside portion of the filtration membrane18.

The filtration device210has two outlet ports,24and26. The first outlet port24communicates with the gap16between the rotor14and housing12. If the blood-waste were not recycled, the blood constituents that were too large to pass through the filtration membrane18would pass out of the blood filtration device210through the outlet port24. In a typical implementation, the flow rate from this outlet port24would be roughly half the flow rate going into the inlet port22. Thus, roughly half of the patient's blood comprises water, small desirable molecules, and waste products, and the other half comprises larger molecules and cells which pass out through outlet port24. These larger components would be represented by the arrow265leading back to the patient200.

However, since the water and small desirable molecules are recycled back into the two stage system as replacement fluid, as shown by the arrow275, the blood filtration device210is unable to filter the incoming fluid completely, and the arrow265representing the processed blood and replacement fluid returning to the patient comprises a volume at least roughly equivalent to the blood flow255coming from the patient200. The return flow265thereby comprises both larger components and replacement fluid without undesirable waste products. Further details of this process are discussed below.

The second outlet port26, which is in communication with the rotor interior20, conducts a flow285, roughly half that of the blood flow255from the patient, comprising water, small desirable molecules, and waste products. This flow of blood-waste285enters the ultrafiltration device220.

As described above, the ultrafiltration device220may function similarly to the filtration device10. The filtration membrane18of the ultrafiltration device220is configured such that water and small desirable molecules enter the rotor interior20of the ultrafiltration device220. The intermediate weight waste products are filtered out and pass from the ultrafiltration device220to the waste bags230, as represented by the arrow285. The filtrate, meanwhile, now comprises a clean, warm, bio-compatible replacement fluid that can be used to increase the volume of blood that is returning to the patient.

In the embodiment shown inFIG. 7A, this patient-generated replacement fluid flow275is recycled to the beginning of the two-stage filtration system, where a T-junction mixes the replacement fluid flow275and the flow from the patient255. The T-junction may be any of a number of devices that mix two fluid inputs and have one fluid output, as is well known to those of skill in the art. In one embodiment, the T-junction simply comprises T-shaped sections of tubing. The amount of fluid entering the blood dialysis device210is thereby increased, and the flow265back to the patient200is also increased. Since there may be a reduction in flow due to the loss of waste products, a small amount of artificial, supplemental replacement fluid240may also be introduced. According to a preferred embodiment of the present invention, the flow265returning to the patient200approximates the flow255exiting the patient200, and the patient's blood volume is kept relatively constant.

In a preferred embodiment, the replacement fluid can be supplemented with a variety of additives. Typical additives include biologically compatible buffers, such as bicarbonate, lactate, citrate, and acetate. Other components, such as chloride, sodium, calcium, magnesium, potassium, phosphate, dextrose, and glucose, or any other molecule required by the particular patient, may also be added to the replacement fluid.

The implementation illustrated inFIG. 7Bis very similar to the one described above with respect toFIG. 7A. The sole difference lies in the location of the T-junction, at which the patient-generated replacement fluid flow275reenters the system. InFIG. 7B, this flow275is combined with the flow of processed blood returning to the patient200. Thus, the return flow265is increased to approximate the extraction flow255, immediately before reintroduction to the patient. In a preferred embodiment, flow meters may be placed at various points in the two-stage systems ofFIGS. 7A and 7Bin order to monitor fluid flows, and to provide feedback regarding the need for supplemental artificial fluid, for example. As is well-known to those of skill in the art, a variety of flow meters may be used, provided that they are sterile and configured for use in a hospital environment.

In both of these Figures, the blood dialysis device210can utilize hemofiltration or hemodiafiltration, including continuous veno-venous hemofiltration and continuous arterio-venous hemofiltration.

AlthoughFIGS. 7A and 7Bdescribe continuous processes, it is to be understood that batch processes are embraced. Batch processes include processing portions of blood removed from patients. The blood can then be processed to selectively remove components from the generated replacement fluid. The processed blood can be combined with the replacement fluid and returned to the patient.

In another embodiment, dialysate can be recycled in a two-stage blood dialysis system. Typically, dialysate is disposed of after a single run through a dialysis device, such as filtration device110, once it has been contaminated by waste products. As a result, prior art dialysis devices suffer from many of the same inefficiencies discussed above with respect to filtration devices; large volumes of replacement dialysate are necessary, and large volumes of waste are generated. Instead, according to one embodiment of the present invention, the dialysate containing the intermediate weight waste products can be sent through a second filtration device, such as one of filtration devices10or110, in order to separate the waste products from the dialysate. The recycled dialysate emerging as filtrate from this second filtration device can then be used in further dialysis procedures.

FIG. 8is a schematic illustration of such a two-stage blood dialysis system, wherein clean, recycled dialysate is generated from waste dialysate, reducing the need for large volumes of replacement dialysis fluid. As above, the directions of the flows of various fluids flowing through the system are illustrated by arrows.

A patient is represented by the box300farthest to the left. In a typical implementation, the patient300has characteristics similar to those discussed above with respect to patient200. Alternatively, the two-stage system may be used in an industrial setting, in which the filtered fluid is some heterogeneous mixture from which intermediate sized molecules must be extracted.

The device comprising the first stage of this two-stage blood dialysis system is hemodialysis device310. As is well-known to those of skill in the art, the filtration membrane used in the device310can have a wide variety of characteristics and can be chosen to filter any of a number of differently sized particles. In one embodiment, the hemodialysis device310is configured to allow only those molecules having a weight of 10,000 Daltons or less to diffuse across the membrane.

In general, a hemodialysis device, as discussed above, has two liquids running therethrough, one on either side of a filtration membrane. Since aqueous solutions are present on both sides of the membrane, the volumes of the liquids stay roughly the same, but the molecules therein tend to equilibrate across the membrane, as long as they can diffuse through. Thus, dialysate, having a relatively high concentration of electrolytes, salts, and other small desirable molecules, may be sent along one side of the filtration membrane, and the patient's blood, having a high concentration of waste by-products, may be sent along the other side of the filtration membrane. The two solutions will move towards equilibrium with respect to the molecules that can diffuse across the membrane, and the result will typically be a solution of dialysate and waste products, and processed blood with additional small desirable molecules.

The device used for the second stage of this two-stage blood dialysis system may be described as an ultrafiltration device320, so called because it is permeable to smaller molecules. In a preferred embodiment, the purpose of the ultrafiltration device320is to filter out the intermediate weight, toxic molecules from a heterogeneous solution, leaving only the dialysate and other small desirable molecules. In the preferred embodiment, the filtration membrane used in the ultrafiltration device320is chosen to allow molecules having a weight less than approximately 300 Daltons to pass, thereby separating the potentially toxic molecules from the rest of the solution. In other embodiments, the filtration membrane may only allow molecules having a weight less than approximately 200 Daltons to pass, preventing other, possibly toxic molecules from emerging as filtrate.

The same or different types of filtration devices may be used for the hemodialysis device310and ultrafiltration device320. As is well-known to those of skill in the art, a number of possible hemodialysis devices and filtration devices may be used. In a preferred embodiment, the hemodialysis device310is a Taylor vortex-enhanced filtration device that functions similarly to the filtration device110described above with reference toFIGS. 5 and 6. The ultrafiltration device320is preferably a Taylor vortex-enhanced filtration device similar to the filtration device10described above. As described above, these filtration devices may have any combination of a variety of sizes, shapes and speeds for their respective rotors and housings, in order to accommodate the different viscosities and flow rates of the processed fluids.

A waste bag330is used to collect the undesirable waste products produced by this two-stage blood dialysis system. In one embodiment, this waste bag330should collect many of the same waste products that would normally be collected by a healthy kidney. Of course, the waste bag330may represent any of a number of means for collecting and/or disposing of waste and need not be a physical receptacle of any particular shape or size. Often, the waste bags330must be collected as hazardous waste for careful disposal according to applicable laws and regulations. Due to the unique features of the present invention, the volume of the waste products generated by the two-stage blood dialysis system may be far less than that generated by a typical single-stage hemodialysis procedure.

Dialysate source350is shown with dialysate flow355entering the hemodialysis device310. In one embodiment, the dialysate flow355entering the hemodialysis device310is roughly equivalent to the blood flow365from the patient. Thus, the processed blood flow375back to the patient300is not substantially reduced in comparison to the flow from the patient. As discussed above, the dialysate flowing through the device310will travel along the other side of a filtration membrane from the blood flowing through the device310. In order to encourage the diffusion of waste products and prevent blood contamination, the dialysate should be sterile, pyrogen-free and generally at body temperature.

In a preferred embodiment, the dialysate is supplemented with a variety of additives. Typical additives include biologically desirable components, such as chloride, sodium, calcium, magnesium, potassium, phosphate, dextrose, and glucose, or any other molecule required by the particular patient. These smaller molecules can diffuse across the filtration membrane into the processed blood returning to the patient.

Using the two-stage blood dialysis system illustrated inFIG. 8, a method of performing blood dialysis according to the present invention may now be discussed in further detail. The first step in the procedure is drawing blood from the patient, illustrated by the arrow365extending from the patient300to the hemodialysis device310. Conventionally, blood is drawn from the patient300via an IV tube connected to a patient's artery in the patient's arm. Of course, other means of drawing blood from a patient are well-known to those of skill in the art. As discussed above, a typical rate of blood flow from the patient is 300-450 mL/min. In order to keep the patient's blood volume relatively constant, therefore, the fluid returning to the patient, arrow375, should flow at a similar rate. Conventionally, the fluid returning to the patient300is returned through an IV tube connected to the patient's vein.

The blood that is flowing from the patient300is then passed through the hemodialysis device310. The hemodialysis device310may dialyze the blood in a number of ways well known to those of skill in the art. In a preferred embodiment, the hemodialysis device310works similarly to the device110described in detail above. In this implementation, the blood flows into the first gap116through the inlet port122. Dialysate flows into the second gap146through the inlet port126.

The filtration membrane118, separating the second gap146from the first gap116, is designed to allow molecules with a molecular weight less than approximately 10,000 Daltons to pass in either direction. The blood flowing from the patient300has a number of constituents, including: water, electrolytes, small nutrient molecules, waste products, high molecular weight molecules (e.g. proteins, etc.) and blood cells and other cells of various types. The dialysis fluid flowing from the dialysate source350includes water and other small desirable molecules that might supplement the patient's processed blood. Thus, as the dialysate and blood flow in opposite directions through the hemodialysis device310, the blood accumulates the small desirable molecules diffusing from the dialysate, and the dialysate accumulates the waste products diffusing from the blood.

Meanwhile, the rotors144,114spin rapidly in order to create Taylor vortices in both the blood flowing through the first gap116, and in the dialysate flowing through the second gap146. These Taylor vortices mix the fluids in both gaps and thereby alleviate the problems of concentration polarization on the outside and inside of the filtration membrane118.

The filtration device310has two outlet ports,124and128. The first outlet port124communicates with the first gap116. Because very little water diffuses across the filtration membrane118(since the dialysate and blood have relatively equivalent flows), in a typical implementation, the flow rate from this outlet port124is roughly equal to the flow rate into the inlet port122. If there are small discrepancies, they can be rectified using supplemental replacement fluid or by removing a small quantity of the processed blood before return to the patient.

The second outlet port128, which is in communication with the second gap146, conducts the flow of waste dialysate385. This waste dialysate385enters the ultrafiltration device320.

As described above, the ultrafiltration device320may function similarly to the filtration device10. The filtration membrane18of the ultrafiltration device320is configured such that the dialysate substrate and small desirable molecules enter the rotor interior20of the ultrafiltration device320. The intermediate weight waste products are filtered out and pass from the ultrafiltration device320to the waste bags330. The filtrate, meanwhile, now comprises a clean, warm, bio-compatible dialysate that can be used once again to diffuse waste products from the patient's blood.

Since the concentration of small desirable molecules in the dialysate has been depleted by diffusion into the patient's processed blood, these molecules may be supplemented from a small desirable molecule source390. In a preferred embodiment, the system may detect the flow of dialysate and add appropriate amounts of concentrated liquid to the recycled dialysate through a T-junction.

In the embodiment shown inFIG. 8, the recycled dialysate395is introduced at the beginning of the two-stage filtration system, where a T-junction combines the recycled dialysate395and the new dialysate flow355. Ideally, very little unused dialysate will be needed once the system has gone through a complete cycle.

In variations of the embodiments illustrated inFIGS. 1-8, this invention can be applied to a vast number of other applications. In a general sense, embodiments of this invention can be useful in any application where filters lose performance due to clogging or concentration polarization, and where replacement fluid is desirable. These applications include: removal of salt from water, processing sea water for human consumption, processing sea water for agricultural uses, reprocessing waste water for agricultural uses, reprocessing waste water for human consumption, concentrating sugar or other desired components from sap from plants, such as sugar cane sap or maple sap, concentrating latex from the sap of rubber plants, removing impurities from water for industrial applications, such as needed in the pharmaceutical or electronic industries, recycling cooking oil, recycling motor oil or lubricating oils, and producing sterile water for intravenous injection.

Further, where molecular exclusion or sieving membranes are employed, the device can be used for large scale cell and biotechnology separation applications, such as purifying cell supernatants and/or lysates from cellular material in a bioprocessor or fermentor.

The various materials, methods and techniques described above provide a number of ways to carry out the invention. Of course, it is to be understood that not necessarily all objectives or advantages described may be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the components of the system may be made and the methods may be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as may be taught or suggested herein.

Although the present invention has been described in terms of certain preferred embodiments, other embodiments of the invention including variations in dimensions, configuration and materials will be apparent to those of skill in the art in view of the disclosure herein. In addition, all features discussed in connection with any one embodiment herein can be readily adapted for use in other embodiments herein. The use of different terms or reference numerals for similar features in different embodiments does not imply differences other than those which may be expressly set forth. Accordingly, the present invention is intended to be described solely by reference to the appended claims, and not limited to the preferred embodiments disclosed herein.