US 8,328,024 B2Grant
Buoy suspension fractionation system
Issue Date:2012-12-11
•22 Claims
•15 Drawing Sheets
Abstract
A separator that uses centrifugation to fractionate a suspension such as blood comprises a separation container and a buoy. The buoy is carried in the separation container and has a tuned density that is configured to reach an equilibrium position in a suspension. The guide surface is carried on the buoy upper surface and is inclined to an accumulation position near a buoy perimeter. The buoy suspension fractionation system can be used in a method of isolating a fraction from a suspension, and in a method for re-suspending particulates for withdrawal.
Metadata
Assignees
- Hanuman, LLC
- Biomet Biologics, LLC
Inventors
- Michael D. Leach
- Randel Dorian
- Jacy C. Hoeppner
Application Information
Application Number:US 13/198,038
Filing Date:2011-08-04
Priority Date:2007-04-12
Art Unit:1777
Classifications
IPC:
B01D21/26B01D45/12B04B5/02B04B7/00
Patent Drawings (15 sheets)
Description
Cross-Reference to Related Applications
[0001] This application is a continuation of U.S. patent application Ser. No. 12/101,586, filed Apr. 11, 2008, which claims the benefit of U.S. Provisional Application No. 60/911,407, filed on Apr. 12, 2007. The disclosures of the above applications are incorporated herein by reference.
Field
[0002] The present teachings relate to a separator that uses density differences to fractionate a suspension such as blood.
Background
[0003] Clinicians have identified a wide range of therapeutic and laboratory applications for autologous isolated fractions, such as platelet concentrate, platelet-poor-plasma, and stromal cells, of suspensions such as blood, bone marrow aspirate, and adipose tissue. Clinicians generally prefer to draw and fractionate the autologous suspension at the point-of-care. Point-of-care fractionation can reduce the need for multiple appointments to draw and fractionate the autologous suspension which can be costly and inconvenient. Additionally, point-of-care preparation reduces potential degradation of the autologous suspension that can begin once the autologous suspension is removed from a patient. Point-of-care fractionation systems should be easy to operate to reduce the need to provide clinicians with extensive instruction, quick so the therapeutic fraction can be isolated and administered during a single patient visit, efficient to effectively isolate the fraction to a desired concentration, and reproducible to operate over wide variations in suspension characteristics. An example of a buoy based suspension fractionation system is shown in Biomet Biologics, Inc. international brochure entitled “Gravitational Platelet Separation System Accelerating the Body's Natural Healing Process.” 2006
Summary
[0004] A buoy suspension fractionation system comprises a separation container and a buoy. The separation container defines a volume enclosed by a container wall, a container bottom, a container top and an access port to access the volume. The buoy is carried in the separation container and has a tuned density that is configured to reach an equilibrium position in a suspension. The buoy comprises a buoy upper surface and a buoy sidewall defining a height, a transverse dimension, and a perimeter. The buoy further comprises a guide surface and a collection space above the buoy upper surface. The guide surface is carried on the buoy upper surface and is inclined to an accumulation position near the buoy perimeter. The buoy suspension fractionation system can be used in a method of isolating a fraction from a suspension, and in a method for isolating a fraction and re-suspending isolated particulates for withdrawal.
Brief Description of the Drawings
[0005] The present teachings will become more fully understood from the detailed description and the accompanying drawings, wherein:
[0006] FIG. 1 is an environmental view of a fractionation device including a suspension fractionated during the centrifuge process;
[0007] FIG. 2 is an environmental view of a suspension being added to a fractionation device;
[0008] FIG. 3 is an environmental view of a centrifuge;
[0009] FIG. 4 is an environmental view of a first fraction being removed from the fractionation device;
[0010] FIG. 5 is an environmental view of the fractionation device being agitated to re-suspend a portion in a second fraction;
[0011] FIG. 6 is an environmental view of the second fraction being removed from the fractionation device;
[0012] FIG. 7 is an environmental view of a therapeutic application of the second fraction;
[0013] FIG. 8 is an environmental view of a separation container and a buoy;
[0014] FIG. 9A is a plan view of a buoy according to various embodiments;
[0015] FIG. 9A1 is a plan view of a buoy at a selected transverse plane;
[0016] FIG. 9A2 is a plan view of a buoy at a selected transverse plane;
[0017] FIG. 9B is a cross-sectional view of the buoy of FIG. 2A ;
[0018] FIG. 10 is a perspective view of a buoy, according to various embodiments;
[0019] FIG. 11A is a perspective view of a buoy, according to various embodiments;
[0020] FIG. 11B is a perspective view of a buoy in a closed position, according to various embodiments;
[0021] FIG. 12 is a perspective view of a buoy, according to various embodiments;
[0022] FIG. 13 is a perspective view of a buoy, according to various embodiments;
[0023] FIG. 14 is a plan view of a buoy, according to various embodiments;
[0024] FIG. 15 is a plan view of a buoy, according to various embodiments;
[0025] FIG. 16 is a plan view of a buoy, according to various embodiments;
[0026] FIG. 17 is a plan view of a buoy, according to various embodiments;
[0027] FIG. 18 is a plan view of a buoy, according to various embodiments;
[0028] FIG. 19 is an environmental view of a selected component being withdrawn from a separation device according to various embodiments; and
[0029] FIG. 20 is a kit according to various embodiments, for separation and extraction of a selected component of a suspension.
Detailed Description of Various Embodiments
[0030] FIG. 1 shows a buoy suspension fractionation system 10, according to various embodiments that can be used in a clinical or laboratory environment to isolate fractions from a suspension or multi-component material removed from a patient or a preparation of extracted or excised material from a patient. The suspension can include a sample of blood, bone marrow aspirate, cerebrospinal fluid, adipose tissue, and the isolated fractions can include platelets, platelet poor plasma, platelet rich plasma and stromal cells. The isolated fractions can each have equilibrium point or positions within the separation container that are achieved when separation has occurred. For example, a buffy coat of whole blood may have an equilibrium position above that of the red blood cells when a sample of whole blood is separated.
[0031] Isolated fractions can be used in a variety of clinical applications, animal applications, and laboratory applications. Some of the clinical applications include peripheral vascular disease, orthopedic surgery, plastic surgery, oral surgery, cardio-thoracic surgery, brain and neural procedures, and wound healing. Laboratory applications include isolating, creating or synthesizing therapeutic materials or materials for analysis from fractions produced by the fractionation system.
[0032] Although the fractionation system 10 can be used allogeneically, such as with pooled blood, the fractionation system 10 can be used autologously to reduce risks of potential incompatibility and contamination with pathogenic diseases. Also, other autologous materials can be used including cerebrospinal fluid, cerebrospinal fluid can be obtained via a spinal tap or other appropriate collection procedure. A general description of a fractionation system is provided in a Biomet Biologics, Inc. international brochure “Gravitation Platelet Separation System Accelerating the Body's Natural Healing Process” (2006) and a description of a therapeutic procedure using platelet concentrate is shown in a Biomet Biologics, Inc. international brochure “Shoulder Recovery with the GPS® Platelet Concentration System” (2004), incorporated herein by reference.
[0033] FIGS. 2-7 show exemplary fractionation system operational steps for a clinical therapeutic application embodiment. The operational steps begin in FIG. 2 by inputting autologous (although pooled blood can be used) whole blood into the fractionation system 10, via an access port 22. The fractionation system 10 is placed into a centrifuge 23 in FIG. 3 and spun about five minutes to about twenty minutes at a rate of about 320 rpm to about 5000 rpm (this speed may produce a selected gravity that may be approximately 7.17×g to about 1750×g (times greater than the normal force of gravity)). The first fraction or top fraction 308 (FIG. 1 ), which can be platelet-poor-plasma according to various embodiments including from a whole blood sample, is shown being removed in FIG. 4 . The fractionation system 10 is agitated in FIG. 5 to re-suspend at least a portion of a second fraction 310, which can be platelet-rich-plasma or platelet concentrate, according to various embodiments including from whole blood fractionation. The second fraction is removed from the fractionation system 10 in FIG. 6 . Finally, the second fraction is applied as part of a therapy, such as shown in FIG. 7 to treat elbow tendonitis. The second fraction can be injected into a selected portion of an elbow 29 to treat tendonitis.
[0034] It will be understood that the buoy 30 can be altered depending upon the material placed in the container 12. For example, if neural stem cells are to be separated from cerebrospinal fluid then the buoy 30 can have a density to allow collection of the neural stem cells in the collection area 52 of the system 12. The collected neural stem cells can also be applied for therapeutic reasons or used in laboratory study, isolation, culture, etc.
[0035] Returning reference to FIG. 1 and with additional reference to FIGS. 8-9B , the suspension fractionation system 10 comprises a separation container 12 and a buoy 30. The separation container 12 can be a separation tube having a container wall 16, a container bottom 18, and a container top 20 enclosing a volume 21 that can be accessed by one or more access ports 22, 26, 27, and a container vent 31. The container 12 may be formed of any appropriate material, such as the Cryolite Med® 2 material sold by Cyro Industries Evonik Degussa Corp. The container 12 can be about 50 mm to about 150 mm in height, including about 102 mm in height. The container 12 can have an internal diameter of about 20 mm to about 40 mm, including about 25 mm to about 35 mm and define a volume of about 30 ml to about 100 ml, including about 30 ml to about 60 ml. The separation container 12 can have any appropriate shape, such as an oval, provided the buoy 30 is shaped to conform to the separation container 12. Though not particularly illustrated, the separation container 12 can also have more than one compartment, such as a separation tube and an area to transfer tube contents away from the separation tube 12. For example, a separate compartment can be formed to house the assembly of the buoy 30 and isolator 32 separate from another area.
[0036] The various ports 22, 26 and 27 can be provided to allow access to any appropriate compartment of the container 12. The access ports 22, 26, 27 can be any means that allow communication from outside the separation container 12 to the separation container volume 21 such as a Luer lock port, a septum, a valve, or other opening. The container vent 31 allows movement of air between the inside and outside the separation container 12 to equalize pressure when suspension in introduced into or withdrawn from the separation container 12. The container vent 31 can include a vent filter 31a to serve as a sterile barrier to allow air to enter the separation container 12 while preventing undesired materials from entering the separation container 12.
[0037] When the separation container 12 is at rest, a buoy perimeter 30a and the container wall 16 can be dimensioned to form an interference fit to hold the buoy 30 at a position in the separation container 12. When the separation container 12 is centrifuged, the buoy perimeter 30a and the container wall 16 have clearance allowing the buoy 30 to move within the separation container 12 and a material to pass between the buoy perimeter 30a and the container wall 16. For example, the container 12 can compress axially to increase its internal diameter. Alternatively, the buoy 30 could have an opening (e.g. FIG. 16 ), such as a centrally or internally located opening 176 or a peripheral channel 168a (FIG. 13 ) running the height of the buoy, which would allow a material to move through the buoy.
[0038] The buoy 30 is carried in the separation container 12 and has a tuned density that is configured to reach a selected equilibrium position in a suspension. The buoy can have its density tuned in the range from about 1.0 g/cc to about 1.10 g/cc, such as about 1.06 g/cc. The buoy 30, according to various embodiments, can be formed to include the tuned density and can be formed of one or more materials to achieve the tuned density.
[0039] For example, the density of about 1.06 g/cc can position the buoy 30, or a selected part of the buoy 30 including the collection area 52, at an equilibrium position of a buffy coat of a separated whole blood sample. In a further example, the density can also be tuned so that the collection area 52 is near an equilibrium position, such as where neural stem cells collect in a selected suspension. Regardless of the density of the buoy 30, it can be selected to position the buoy 30 at an equilibrium position of a selected material.
[0040] As illustrated in FIG. 1 , the collection area 52 is positioned within the container 12 after a separation procedure has occurred. The collection area, defined relative to the buoy 30, is positioned at the equilibrium position of the separated or isolated fraction 310 in the container. The equilibrium position of a selected fraction can be defined as its position within the container relative to other fractions in the container of a separated sample or material. The equilibrium position can also be defined relative to the axis X of the buoy 30 or the container 12. The equilibrium position, however, may depend upon the amount of the sample of the amount of a selected fraction within a sample. According to the illustration in FIG. 1 , the equilibrium position of the fraction 308 is above or nearer the top 20 of the container 12 than the equilibrium position of the fraction 310. Thus, the buoy 30 can be tuned, such as including a selected density or specific gravity, to position the collection area 52 relative to an equilibrium position of any selected fraction.
[0041] The buoy comprises a buoy upper surface 48 and a buoy sidewall 38, 40 defining a height H1, H2, a transverse dimension at planes A1, A2, and a perimeter 30a, discussed further herein. The buoy further comprises a guide surface 42. In some embodiments, the buoy can further comprise a collection port 50 and a precision collection region 44. The collection port 50 communicates with the access port 27 and communicates with a collection space 52 above the buoy upper surface 42 and can be located near the buoy perimeter 30a. In some embodiments, the collection port 50 is not carried on the buoy, but rather the collection port is a withdraw device such as a syringe that is inserted through an access port or top of the tube 12.
[0042] With reference to FIG. 9A , the buoy 30 has a first height dimension H1, a second height dimension H2, a maximum width or transverse cross sectional area W1 at plane A1, a second width or transverse cross sectional area W2 at plane A2, a guide surface angle ∝, and precision collection area 44 including a surface 46 defining a precision collection region angle β. The height of the buoy 30, according to various embodiments, can be defined relative to a central axis X, which can also be a longitudinal axis X of the container 12. The sidewalls of the buoy 30 and the container 12 can also be substantially parallel to the axis X. Although certain dimensions are shown in FIG. 9A , the buoy perimeter could be shaped differently provided the perimeter conforms to the separation container 12.
[0043] The guide surface 42 is carried on and/or defined by the buoy upper surface 48 and is inclined to an accumulation position at or near the buoy perimeter. The guide surface 42 serves as a guide means for conveying particles down an incline toward an equilibrium interface or collection region. The guide surface 42 can be inclined relative to the buoy sidewall 38 height for a distance of more than one-half the buoy transverse dimension or width W1, such as about two-thirds the buoy transverse dimension, and in various embodiments the guide surface can be inclined relative to the buoy sidewall 38 substantially throughout a length of the guide surface 42.
[0044] The guide surface 42 can be substantially planar and can have an average angle in the range from the minimum for particulates to move down the guide surface, regarding blood platelets, for example, about 10 degrees to about 60 degrees. For example, angle α can be about 5 degrees to about 89 degrees, or greater, including about 30 degrees to about 89 degrees. Angle α can, exemplary, be exactly or about 60 degrees in various embodiments. In some embodiments, the guide surface can include contours defined in the guide surface with multiple angles such as shown in FIGS. 10 and 12 . For example, in FIG. 10 , a buoy 80, according to various embodiments, can include two guide surface contour walls 96, 98 to assist in defining a guide surface 100. The two walls 96, 98 can define a trough that extends a selected distance across the guide surface 100, such as more than two thirds. The trough can define an area of the guide surface that is lower than the surrounding area. A contoured precision collection region 92 can also be defined that communicates with a port 94. In FIG. 12 , a buoy 140 can include a guide surface 152 that includes two inclined sides 154, 156 angled towards a selected region, such as a center of the guide surface 152. The entire guide surface can also be inclined towards a collection port 158, in an amount as discussed above.
[0045] In various embodiments, as exemplary illustrated in FIGS. 9A , 9A1, and 9A2 the different buoy transverse cross-sectional areas W1, W2 can be defined at various planes, such as A1, A2, etc. As illustrated, various transverse cross-sectional areas can be defined by the buoy 30 due to the angled top wall 42. The transverse cross-sectional areas defined at the various planes A1, A2 can be positioned at selected locations based upon characteristics of the buoy 30, such as density. The height H2, angle α, etc. The width dimension can be 1 inch to about 2 inches including about 1.347 inches (about 25 mm to about 51 mm, including about 34.21 mm) for W2. The dimension of W1 can depend upon the selected location of plane A1. These dimensions can achieve various areas depending upon the geometry of the buoy 30. Nevertheless, the area at plane A2 can be substantially similar to an area at a transverse plane within the container 12.
[0046] In use, the substantially maximum transverse cross-sectional area W1 of the buoy 30 can be positioned at a selected location. As illustrated in FIG. 9A1, the maximum cross-sectional area is at plane A1. The plane A1 can be positioned at or near a selected equilibrium interface, in use. The position of the plane A1 is selected by selecting a density of the buoy 30 and the known or estimated density of the material into which the buoy 30 is positioned. The buoy's maximum transverse cross-sectional area near the intended or selected interface results in a substantially maximum change in displacement of the relative volume of a fraction below the equilibrium interface and substantially maximum change in displacement of a fraction above the equilibrium interface relative to change in the axial orientation of the buoy relative to the interface. This can improve fractionation isolation by ensuring that the maximum transverse cross-section displaces a maximum amount of area within the container 12 at the selected interface. For example, more than 90% of a whole blood's platelets can be isolated.
[0047] Thus, in applications involving suspensions, such as whole blood, which may be variable in composition between samples, sample density variation will result in minimal variation in the axial orientation of the buoy relative to a selected equilibrium interface. The minimal variation in axial location of the buoy 30 in the container 12 is based at least in part on the maximum displacement of a material in the container at the maximum transverse cross-section of the buoy 30. In other words, for each small variation of axial location of the buoy 30, a maximum displacement occurs. In selected uses, the buoy's maximum cross-sectional plane A1 is provided at a selected location and the minimal axial variation helps to ensure the plane A1 is properly placed.
[0048] Additionally, at or near the buoy's maximum transverse cross-sectional area, the cross-sectional area of the fractionated material is near minimal. Simply, within the container 12 at a selected position if a maximum transverse cross-section of the buoy 30 is at a selected position, then a relatively minimal amount of other material can be present at the same location. In combination, the minimization of cross-sectional area of fractionated material and minimization of variation of axial orientation of the buoy in relation to an equilibrium interface results in minimization of variability of fractionated material volume near the interface.
[0049] The precision collection region 44, 92 (FIGS. 9A , 9B, and 10) can be interposed between the guide surface and the accumulation position at or near the buoy perimeter. The precision collection region 44, 92 serves as a precision collection structure for collecting a precise, high yield and/or pure amount of a selected fraction. The precision collection region 44, 92 can be raised or lowered in relation to the buoy perimeter to vary the fraction in the collection region without the need to make substantial changes to other buoy design features. In other words, the dimension H1 can be changed. Generally, the height H2 can be about 2.5 mm to about 5.1 mm. The height H1 will generally be constrained by the height H2 and the angle α. According to various embodiments, the precision collection region 44 is shown in FIG. 9A formed at an angle β in relation to the sidewall 40. The angle β can be any appropriate angle such as about 10 degrees to about 60 degrees, including about 45 degrees. According to various embodiments, the precisions collection region 92 can be contoured, FIG. 10 .
[0050] According to various embodiments, an isolator 32, is coupled to the buoy 30. The combination of the isolator and buoy, according to various embodiments, can also be referred to as a separation assembly member. Exemplary isolators 82, 122, 170, 180, 190 are illustrated coupled to exemplary buoys 80, 120, 140, 160, 182, 192. The isolator 32, for example, provides a means for creating the collection compartment 52 and comprises one or more spacers 58, 60 to position the isolator 32 apart from the buoy 30 to create the collection compartment 52. A withdraw port 70 can be carried on the isolator 32 communicating with the withdraw port 27 and the collection port 50. The spacer 58, 60 can also serve as a conduit 68 between the collection port 50 and a withdraw or withdraw port 27. The withdraw port 27 serves as a structure for withdrawing the isolated or second fraction 310 from the collection compartment 52.
[0051] The isolator 32 can be configured from a material with a lower density than the buoy 30, such as a density of about 1.0 g/cc or less. A volume of the isolator 32 can be substantially less than a volume of the buoy 30. The isolator 32 can be configured so the isolator volume and the buoy volume combined below a selected equilibrium interface are greater than the isolator volume and the buoy volume combined above the equilibrium interface. As discussed above, an equilibrium interface can include a position relative to the platelet concentrate or buffy coat from a centrifuged whole blood sample, such as at or just below the platelet concentrate or buffy coat. By configuring the isolator 32 and buoy 30 with more volume below the equilibrium interface than above the equilibrium interface, the buoy 30 operates in a more repeatable manner even between a wide range in variations in compositions such as whole blood where the variability in density of a more dense fraction (e.g. red blood cells) is less than the variability in density of a less dense fraction (e.g. plasma). For example, the make up of a whole blood sample from one patient to the next can be markedly different.
[0052] Between individual patients, the density of the red blood cell or erythrocyte fraction of a whole blood sample can generally vary less than the density of a plasma or serum portion of a whole blood sample. Therefore, positioning a greater volume of the isolator and buoy within the denser fraction can assist in having highly repeatable and highly efficient collection or separation of a whole blood sample. The height H2 can be varied or selected to ensure a maximum or selected volume of the isolator and buoy are positioned within the denser fraction of the whole blood sample.
[0053] According to various embodiments, the isolator may include various features. An isolator 122 can be configured to move relative to a buoy 120, as illustrated in FIGS. 11A and 11B . The isolator 122 can move along a column or spacer 132 in the direction of arrow 123 during extraction of a selected fraction. The isolator 32, 82 can also be substantially uniformly thick or vary in thickness 122, 180, 190.
[0054] An isolator 170 can include collection openings 174 (FIG. 13 ). The isolator 32 can also include a collection vent 67 (FIG. 9A ), which can also include a collection valve, a collection passage, or a collection vent tube or passage 203. The collection openings 174 can reduce the distance particles, such as platelets which are fragile and adherent, travel to reach a guide surface 162 and reduce the time that particles are in contact with surfaces. Various types of collection openings can be used.
[0055] The collection openings 174 can be sized to permit selected particles to pass yet sufficiently small so suspension fluid tension maintains adequate isolation of the collection compartment. The collection openings can also include various valves such as a duck bill or flapper bill which can open under certain conditions and close under others. A collection valve can be interconnected with any appropriate portion such as with a collection port 70 or passage 68.
[0056] The collection vent passage 67 through the isolator 32 equalizes pressure when fluid is withdrawn from the collection area 52. The spacer 58 can serve as a conduit for the collection vent passage 67, the collection port 50, or both. The collection valve communicates with the collection vent passage 67 to control collection vent passage 67 operation and close the collection vent passage 67 during re-suspension agitation. The collection vent tube 203 communicates with the collection vent passage 67 and air. The air can be the air above the collection area 52 (i.e. a portion of the suspension above the isolator 32 has been removed) or through an opening 205 in the container wall and generally through a sterile barrier (e.g. a sterile foam filter). The collection vent tube 203 allows removal of fractionated suspension in the collection compartment without the need to remove the fraction, such as plasma, above the isolator 32. Although, without a collection vent tube 203, the fraction above the isolator could be removed and the collection area could be vented to the area above the isolator.
[0057] Various embodiments further comprise a mechanical agitator 130 carried in a collection compartment 128 (for example FIGS. 11A and 11B ).
[0058] The isolator 122 is moveable relative to the buoy 120. The isolator 122 can be in an open position after centrifugation of the separation container. During removal of material from the collection compartment through the collection port 134, the isolator 122 can move in the direction indicated by arrow 123 toward the buoy 120 to decrease or close the volume of the collection compartment 128.
[0059] The buoy 30 can also be formed in a plurality of selectable sizes, having different dimensions, such as those illustrated in FIG. 9A . The axial dimensions of the buoy 30 can be selected to achieve an appropriate displacement of the suspension in the container 12, especially after fractionation has occurred. Angle α, defined between the outer edge 38 and the surface 42 can be any selected angle. For example, angle α can be about 30 degrees to about 89 degrees, including about 60 degrees. The angle α can generally be created to be as small as possible to allow a steep angle of the surface 42 towards the inlet port 50 that will not damage the material being collected within the collection space 52. As discussed above, the height H2 can be selected to determine or select the amount of the buoy 30 positioned within a selected fraction, such as a dense fraction, of a sample separated within the separation system. Height H2 can be about 0.1 inches to about 0.2 inches, including about 0.18 inches (about 2.5 mm to about 5.1 mm, including about 4.57 mm). An exemplary height H2 is 0.1795 inches (4.559 mm), depending upon selected applications, the size of the separation system, and other selected factors. Nevertheless, the height H1 is generally defined by the height H2 and the angle α. Height H1 can be about 0.8 inches to about 1.2 inches, including about 1 inch (about 20 mm to about 30 mm, including about 25 mm). An exemplary height H1 can include 1.0 inches (25 mm). The positioning of the collection area 52, including the inlet port 50, can be based upon the height H2 and how the buoy 30 interacts with the material into which it is positioned, via the height H2.
[0060] A buoy 182, as illustrated in FIG. 17 , can include an isolator 180 positioned relative thereto. The isolator 180 can include a center placed substantially over a center of the buoy 182. The center of the buoy 182 and the isolator 182 can both be defined by peaks or apexes 184 and 186, respectively.
[0061] A buoy 192, as illustrated in FIG. 18 , can also be positioned relative to an isolator 190. The buoy 192 can include an apex 194 near a center of the buoy 192 and the guide surface extending from an edge of the buoy 192 to a second edge of the buoy 192. The isolator 190 can also include an apex 196 generally near its center. The isolator 190 can also include a surface 198 that extends from one edge of the isolator to another edge of the isolator 190.
[0062] The isolators 180, 190 can act substantially similar to the isolator 32, discussed above. The isolator 180, 190 can define an angle between an apex or the withdrawal port 70 and an outer edge of the isolators 180, 190. The upper surface of the isolators can include an angle to assist in directing a selected material, such as a platelet fraction of whole blood sample, to the collection area or surface 42 of the buoys 182, 192. Generally, the isolators 180, 190 can include a height or volume to substantially minimize the volume of the isolator 180, 190 relative to the buoys 182, 192. As discussed above, this can assist in positioning the buoys 182, 192 relative to a dense (e.g. red blood cell) fraction of a whole blood sample. The angle of the isolators 180, 190 and the height of the isolators 180, 190 can be selected to provide for a minimal distance of travel or least disturbance of a selected collected fraction of a material, such as a whole blood sample.
[0063] As discussed above, the buoy suspension fractionation system 10 can be used in a method of isolating a fraction from a suspension. The separation container 12 can be centrifuged for a period that is appropriate for the suspension. The buoy 30 in the separation container 12 is allowed to reach an equilibrium position within the formed fractions. Typically, the buoy moves from the separation container bottom to an equilibrium position within and/or between the fractions. In some embodiments, the buoy 30 is configured with the transverse dimension cross-sectional area of the buoy near the equilibrium interface to be substantially the buoy's maximum transverse cross-sectional area A1, as illustrated in FIG. 1 . As discussed above, the design of the buoy can be determined to position a maximum cross sectional area of the buoy within a selected fraction, such as the red blood cell fraction, of a whole blood sample. The positioning of the buoy can be based upon the density of the buoy which is determined from the density of a selected fraction, such as a red blood cell fraction. Therefore, the buoy can be created or formed to include a density to substantially position it within a red blood cell fraction, for example, of a sample to be separated. For example, the buoy can have a density of about 1.010 g/cc to about 1.1 g/cc. Exemplary densities include about 1.058 g/cc to about 1.070 g/cc, including about 1.064 g/cc. Such a buoy design effects a substantially maximum change in displacement of a volume of fractionated suspension below an equilibrium interface and effects a substantially maximum change in displacement of a volume of fractionated suspension above the equilibrium interface relative to the axial displacement of the buoy resulting in more precisely controlling the selected fraction isolation. As discussed above, the buoy, according to various embodiments, has a maximum cross section at a selected region. Positioning a maximum cross section within a selected fraction or area of a sample will maximum displacement of the sample relative to the buoy do to the maximum cross section of the buoy. In other words, by positioning the biggest portion of the buoy within a selected sample the biggest portion of the sample is displaced because of the displacement of the buoy.
[0064] Particulates are concentrated using a guide surface 42, 90, 138, 152, 162 of the buoy that is inclined to an accumulation position near a perimeter of the buoy. The guide surface can be inclined relative to the buoy sidewall substantially throughout a length of the guide surface. The guide surface can be defined by or positioned near the top wall of the buoy.
[0065] The particulates are conveyed along the guide surface of the buoy to a collection space. The particulates can be conveyed along a substantially planar path to the collection space. According to various embodiments, however, the guide surface can also include multiple angles 42, 44 and 152, 154 and/or contours 96, 98. The particulates can be selected from the group consisting of platelets, stromal cells, white blood cells, or the like.
[0066] A desired fraction is withdrawn from the collection space through an access port. In some embodiments, the desired fraction can be withdrawn from the collection space by tipping the separation container and pouring the desired fraction out through an access port or out through the container top. This is especially true when only the buoy 30′, 30″, 30′″ is present (FIGS. 14 , 15, and 16).
[0067] In some embodiments, the method of isolating a fraction can further comprise isolating an isolated fraction in a collection compartment between the guide surface of the buoy 30, 80, 120, 140, 160, 180, 190 and an isolator 32, 82, 122, 142, 162, 182, 192 coupled to the buoy and withdrawing the isolated fraction through a withdraw port through the isolator.
[0068] The buoy suspension fractionation system can be used in a method of isolating and re-suspending particulates for withdrawal. The method begins by filling a separation container through an access port with a suspension. The separation container has a buoy with a tuned density and the suspension can contact the buoy.
[0069] The separation container can be centrifuged to cause the suspension to separate into fractions of varying densities. Centrifugation can occur for a period that is appropriate for the suspension, such as about five to about thirty minutes.
[0070] The buoy in the separation container is allowed to reach equilibrium within the fluid between two or more fractions. Typically the buoy moves from the separation container bottom to equilibrium within the fractions. In some embodiments, particulates can be concentrated using a guide surface of the buoy. The guide surface can be inclined to an accumulation position 44, 92 near a buoy perimeter location. According to various embodiments, the guide surface can be inclined relative to a buoy sidewall substantially throughout the length of the guide surface. The particulates can be conveyed along the guide surface of the buoy to a collection port. The particulates can be platelets, stromal cells, white blood cells, or the like.
[0071] A fraction is isolated in a collection compartment between the guide surface of the buoy and an isolator coupled to the buoy. In some embodiments, there can be a fraction 308 located above the isolator that can be withdrawn prior to withdrawing a first increment of the second fraction 310. In other embodiments, the collection vent tube 203 can eliminate the need to withdraw the fraction 308 located above the isolator prior to withdrawing the first increment of the second fraction 310.
[0072] Particulates within the isolated fraction can be re-suspended within the collection compartment by moving an agitator 130, 316 (FIGS. 11A and 19 ) in the separation container 12 to agitate the isolated fraction to create a more uniform particulate distribution within the isolated fraction. In some embodiments, the agitator is an air bubble 316 that is created by withdrawing the first increment of the isolated fraction 310 from a collection compartment allowing air to enter the collection compartment through the collection vent 58. In other embodiments, the agitator 130 is a mechanical agitator placed in the collection compartment.
[0073] The re-suspended isolated fraction can be withdrawn from the collection compartment.
[0074] For illustration and for efficiency of use of the system, the various components can be included in a kit 320, illustrated in FIG. 20 . The kit 320 includes the fractionation system 10 and a counterweight container 322 if required for centrifuge balance. The kit 320 can also include various syringes 302, 312, and 314 for extraction and application of the fractions and samples. The kit 320 can also include bandages 3226, tape 330, a tourniquet 328, and various additive materials. The kit 320 can include a container 332 for transport and sterilization.
[0075] Thus, embodiments of a buoy suspension fractionation system are disclosed. One skilled in the art will appreciate that the teachings can be practiced with embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation, and the invention is only limited by the claims that follow.
Claims
What is claimed is:
1. A buoy fractionation system, comprising:
a first buoy portion having a first apex on a first guide surface of the first buoy portion;
a second buoy portion having a second apex on a second guide surface of the second buoy portion;
a third buoy portion interconnecting the first buoy portion and the second buoy portion;
a collection surface defined by the second guide surface of the second buoy portion proximal to a center of rotation;
an inlet port defined through the collection surface and in communication with a buoy withdrawal passage operable to allow withdrawal of a material from near the second guide surface;
a withdrawal port; and
a withdrawal passage formed through the third buoy portion and connected to the withdrawal port;
wherein the first buoy portion is positioned a distance apart from the second buoy portion.
2. A buoy fractionation system, comprising:
a first buoy portion having a first apex on a first guide surface of the first buoy portion;
a second buoy portion having a second apex on a second guide surface of the second buoy portion;
a third buoy portion interconnecting the first buoy portion and the second buoy portion;
a withdrawal port;
a withdrawal passage formed through the third buoy portion and connected to the withdrawal port;
a buoy withdrawal passage defined through at least a portion of the second buoy portion and in communication with the withdrawal port through the withdrawal passage;
a collection surface defined by the second guide surface of the second buoy portion proximal to a center of rotation; and
an inlet port defined through the collection surface and in communication with the buoy withdrawal passage;
wherein the first buoy portion is positioned a distance apart from the second buoy portion.
3. The buoy fractionation system of claim 1, further comprising:
a separation container in which the first buoy portion, the second buoy portion, and the third buoy portion are positioned;
wherein the first buoy portion and the second buoy portion are each fixed to the third buoy portion and at the distance apart from one another;
wherein a volume is defined between the first buoy portion and the second buoy portion within the separation container.
4. The buoy fractionation system of claim 1, wherein the first buoy portion has a first volume less than a second volume of the second buoy portion.
5. The buoy fractionation system of claim 1, wherein the first buoy portion has a first height substantially smaller than a second height of the second buoy portion to provide for a minimal distance of travel or least disturbance of a selected collected fraction that is collected between the first buoy portion and the second buoy portion.
6. The buoy fractionation system of claim 1, wherein the first buoy portion has the first guide surface that is proximal a center of rotation and tapers out distally;
wherein the second buoy portion has the second guide surface that is proximal the center of rotation and tapers out distally.
7. A buoy fractionation system, comprising:
a first buoy portion having a first apex on a first surface of the first buoy portion, wherein the first surface substantially defines a first cone having a slanted base; and
a second buoy portion having a second apex on a second surface of the second buoy portion, wherein the second surface substantially defines a second cone having a slanted base;
a withdrawal port;
a withdrawal passage formed through the third buoy portion and connected to the withdrawal port;
a buoy withdrawal passage defined through at least a portion of the second buoy portion and in communication with the withdrawal port through the withdrawal passage;
a collection surface defined by the second surface of the second buoy portion proximal to a center of rotation of the buoy fractionation system; and
an inlet port defined through the collection surface and in communication with the buoy withdrawal passage;
wherein the first buoy portion is spaced a distance apart from the second buoy portion.
8. The buoy fractionation system of claim 7, wherein the first surface is asymmetrically inclined from the first apex to each of the first edge and the second edge.
9. The buoy fractionation system of claim 8, wherein the asymmetrical incline of the first surface from the first apex to each of the first edge and the second edge includes a steeper incline towards the first edge than towards the second edge.
10. The buoy fractionation system of claim 7, wherein the second surface is asymmetrically inclined from the second apex to each of the first buoy sidewall and the second buoy sidewall.
11. The buoy fractionation system of claim 10, wherein the asymmetrical incline of the second surface from the second apex to each of the first buoy sidewall and the second buoy sidewall includes a steeper incline towards the first buoy sidewall than towards the second buoy sidewall.
12. The buoy fractionation system of claim 10, wherein the second apex is near a center of the second buoy portion.
13. The buoy fractionation system of claim 12, wherein the first apex is near a center of the first buoy portion.
14. The buoy fractionation system of claim 13, wherein the first apex is axially aligned with the second apex.
15. The buoy fractionation system of claim 14, further comprising:
a third buoy portion interconnecting the first buoy portion and the second buoy portion.
16. The buoy fractionation system of claim 15, wherein the third buoy portion interconnects the first buoy portion and the second buoy portion aligned with the first apex and second apex.
17. The buoy fractionation system of claim 7, further comprising:
a separation container in which the first buoy portion, the second buoy portion, and the third buoy portion are positioned;
wherein the first buoy portion and the second buoy portion are each fixed to the third buoy portion and at the spaced apart distance from one another;
wherein a volume is defined between the first buoy portion and the second buoy portion within the separation container based at least on the first buoy portion and the second buoy portion spaced the distance apart from one another.
18. The buoy fractionation system of claim 7, wherein the first buoy portion has a first surface that is proximal a center of rotation that is conical and tapers outward from the first apex distally;
wherein the second buoy portion has a second surface that is proximal the center of rotation that is conical and tapers outward from the second apex distally.
19. A method for separating a material with a buoy fractionation system, comprising:
placing a material in a container having a buoy assembly including,
a first buoy portion having a first apex on a first surface of the first buoy portion, wherein the first surface substantially defines a first cone having a slanted base,
a second buoy portion having a second apex on a second surface of the second buoy portion, wherein the second surface substantially defines a second cone having a slanted base, wherein the second buoy portion is spaced a distance apart from the first buoy portion,
a third buoy portion interconnecting the first buoy portion and the second buoy portion,
a withdrawal port,
a withdrawal passage formed through the third buoy portion and connected to the withdrawal port,
a buoy withdrawal passage defined through at least a portion of the second buoy portion and in communication with the withdrawal port through the withdrawal passage,
a collection surface defined by the second surface of the second buoy portion proximal to a center of rotation, and
an inlet port defined through the collection surface and in communication with the buoy withdrawal passage; and
applying a centrifugal force to the material relative to the first buoy portion wherein at least a selected portion of material travels a minimal distance relative to the first buoy portion and the second buoy portion due to a first height of the first buoy portion being substantially smaller than a second height of the second buoy portion, wherein at least the selected portion travels the minimal distance to a volume between the first buoy portion and the second buoy portion.
20. The method of claim 19, further comprising:
withdrawing at least the selected portion from between the first buoy portion and the second buoy portion through the withdrawal port near the first apex that is in fluid communication with the withdrawal passage formed through the third buoy portion and the inlet port from the volume between the first buoy portion and the second buoy portion.
21. The method of claim 20, wherein withdrawing at least the selected portion from between the first buoy portion and the second buoy portion further comprises withdrawing through the buoy withdrawal passage defined through at least a portion of the second buoy portion that is in communication with the withdrawal port through the withdrawal passage and the inlet port that is defined through a collection surface in the second buoy portion.
22. The method of claim 21, further comprising:
placing a separation container containing the first buoy portion, the second buoy portion, and the third buoy portion in a centrifuge device;
wherein applying a centrifugal force includes operating the centrifuge device with the separation container placed therein.
Patent Citations (551)
| Patent | Date | Inventor | Cited By |
|---|---|---|---|
| US280820(A) | 1883-07-01 | Hickson et al. | Applicant |
| US593333(A) | 1897-11-01 | Park | Applicant |
| US1468313(A) | 1923-09-01 | Lux | Applicant |
| US1593814(A) | 1926-07-01 | Vogel | Applicant |
| US2722257(A) | 1955-11-01 | Lockhart | Applicant |
| US3013557(A) | 1961-12-01 | Pallotta | Applicant |
| US3159159(A) | 1964-12-01 | Cohen | Applicant |
| US3409165(A) | 1968-11-01 | Creith | Applicant |
| US3441143(A) | 1969-04-01 | Kudlaty | Applicant |
| US3453364(A) | 1969-07-01 | Flodin et al. | Applicant |
| US3469369(A) | 1969-09-01 | Helmke | Applicant |
| US3508653(A) | 1970-04-01 | Coleman | Applicant |
| US3545671(A) | 1970-12-01 | Ross | Applicant |
| US3583627(A) | 1971-06-01 | Wilson | Applicant |
| US3596652(A) | 1971-08-01 | Winkelman | Applicant |
| US3654925(A) | 1972-04-01 | Holderith | Applicant |
| US3706305(A) | 1972-12-01 | Berger et al. | Applicant |
| US3706306(A) | 1972-12-01 | Berger et al. | Applicant |
| US3723244(A) | 1973-03-01 | Breillatt, Jr. | Applicant |
| US3779383(A) | 1973-12-01 | Ayres | Applicant |
| US3785549(A) | 1974-01-01 | Latham, Jr. | Applicant |
| US3814248(A) | 1974-06-01 | Lawhead | Applicant |
| US3849072(A) | 1974-11-01 | Ayres | Applicant |
| US3850369(A) | 1974-11-01 | Bull et al. | Applicant |
| US3879295(A) | 1975-04-01 | Glover et al. | Applicant |
| US3887466(A) | 1975-06-01 | Ayres | Applicant |
| US3894952(A) | 1975-07-01 | Ayres | Applicant |
| US3896733(A) | 1975-07-01 | Rosenberg | Applicant |
| US3897337(A) | 1975-07-01 | Ayres | Applicant |
| US3897343(A) | 1975-07-01 | Ayres | Applicant |
| US3909419(A) | 1975-09-01 | Ayres | Applicant |
| US3929646(A) | 1975-12-01 | Adler | Applicant |
| US3931010(A) | 1976-01-01 | Ayres et al. | Applicant |
| US3931018(A) | 1976-01-01 | North, Jr. | Applicant |
| US3935113(A) | 1976-01-01 | Ayres | Applicant |
| US3937211(A) | 1976-02-01 | Merten | Applicant |
| US3941699(A) | 1976-03-01 | Ayres | Applicant |
| US3945928(A) | 1976-03-01 | Ayres | Applicant |
| US3951801(A) | 1976-04-01 | Ayres | Applicant |
| US3957654(A) | 1976-05-01 | Ayres | Applicant |
| US3962085(A) | 1976-06-01 | Liston et al. | Applicant |
| US3965889(A) | 1976-06-01 | Sachs | Applicant |
| US3972812(A) | 1976-08-01 | Gresl, Jr. | Applicant |
| US3982691(A) | 1976-09-01 | Schlutz | Applicant |
| US4001122(A) | 1977-01-01 | Griffin | Applicant |
| US4020831(A) | 1977-05-01 | Adler | Applicant |
| US4046699(A) | 1977-09-01 | Zine, Jr. | Applicant |
| US4055501(A) | 1977-10-01 | Cornell | Applicant |
| US4059108(A) | 1977-11-01 | Latham, Jr. | Applicant |
| US4066549(A) | 1978-01-01 | Oeser et al. | Applicant |
| US4077396(A) | 1978-03-01 | Wardlaw et al. | Applicant |
| US4088582(A) | 1978-05-01 | Murty et al. | Applicant |
| US4146172(A) | 1979-03-01 | Cullis et al. | Applicant |
| US4152270(A) | 1979-05-01 | Cornell | Applicant |
| US4154690(A) | 1979-05-01 | Ballies et al. | Applicant |
| US4159896(A) | 1979-07-01 | Levine et al. | Applicant |
| US4187979(A) | 1980-02-01 | Cullis et al. | Applicant |
| US4203840(A) | 1980-05-01 | Stoeppler et al. | Applicant |
| US4204537(A) | 1980-05-01 | Latham, Jr. | Applicant |
| US4225580(A) | 1980-09-01 | Rothman et al. | Applicant |
| US4269718(A) | 1981-05-01 | Persidsky | Applicant |
| US4294707(A) | 1981-10-01 | Ikeda et al. | Applicant |
| US4298598(A) | 1981-11-01 | Schwarz et al. | Applicant |
| US4300717(A) | 1981-11-01 | Latham, Jr. | Applicant |
| US4303193(A) | 1981-12-01 | Latham, Jr. | Applicant |
| US4314823(A) | 1982-02-01 | Rich, Jr. et al. | Applicant |
| US4322298(A) | 1982-03-01 | Persidsky | Applicant |
| US4362567(A) | 1982-12-01 | Schwarz et al. | Applicant |
| US4364832(A) | 1982-12-01 | Ballies | Applicant |
| US4377572(A) | 1983-03-01 | Schwarz et al. | Applicant |
| US4379849(A) | 1983-04-01 | Heimreid | Applicant |
| US4411794(A) | 1983-10-01 | Schwinn et al. | Applicant |
| US4414976(A) | 1983-11-01 | Schwarz et al. | Applicant |
| US4416654(A) | 1983-11-01 | Schoendorfer et al. | Applicant |
| US4417981(A) | 1983-11-01 | Nugent | Applicant |
| US4424132(A) | 1984-01-01 | Iriguchi et al. | Applicant |
| US4427650(A) | 1984-01-01 | Stroetmann et al. | Applicant |
| US4427651(A) | 1984-01-01 | Stroetmann et al. | Applicant |
| US4442655(A) | 1984-04-01 | Stroetmann et al. | Applicant |
| US4443345(A) | 1984-04-01 | Wells | Applicant |
| US4446021(A) | 1984-05-01 | Aufderhaar et al. | Applicant |
| US4453927(A) | 1984-06-01 | Sinko | Applicant |
| US4453939(A) | 1984-06-01 | Zimmerman et al. | Applicant |
| US4464167(A) | 1984-08-01 | Schoendorfer et al. | Applicant |
| US4511662(A) | 1985-04-01 | Baran et al. | Applicant |
| US4537767(A) | 1985-08-01 | Rothman et al. | Applicant |
| USRE32089(E) | 1986-03-01 | Blatt et al. | Applicant |
| US4577514(A) | 1986-03-01 | Bradley et al. | Applicant |
| US4610656(A) | 1986-09-01 | Mortensen | Applicant |
| US4617009(A) | 1986-10-01 | Ohlin et al. | Applicant |
| US4627879(A) | 1986-12-01 | Rose et al. | Applicant |
| US4631055(A) | 1986-12-01 | Redl et al. | Applicant |
| US4632761(A) | 1986-12-01 | Bowers et al. | Applicant |
| US4639316(A) | 1987-01-01 | Eldegheidy | Applicant |
| US4650678(A) | 1987-03-01 | Fuhge et al. | Applicant |
| US4655211(A) | 1987-04-01 | Sakamoto et al. | Applicant |
| US4672969(A) | 1987-06-01 | Dew | Applicant |
| US4675117(A) | 1987-06-01 | Neumann et al. | Applicant |
| US4680025(A) | 1987-07-01 | Kruger et al. | Applicant |
| US4714457(A) | 1987-12-01 | Alterbaum | Applicant |
| US4735616(A) | 1988-04-01 | Eibl et al. | Applicant |
| US4735726(A) | 1988-04-01 | Duggins | Applicant |
| US4755300(A) | 1988-07-01 | Fischel et al. | Applicant |
| US4755301(A) | 1988-07-01 | Bowers | Applicant |
| US4770779(A) | 1988-09-01 | Ichikawa et al. | Applicant |
| US4776964(A) | 1988-10-01 | Schoendorfer et al. | Applicant |
| US4818291(A) | 1989-04-01 | Iwatsuki et al. | Applicant |
| US4818386(A) | 1989-04-01 | Burns | Applicant |
| US4828710(A) | 1989-05-01 | Itoh et al. | Applicant |
| US4832851(A) | 1989-05-01 | Bowers et al. | Applicant |
| US4844818(A) | 1989-07-01 | Smith | Applicant |
| US4846835(A) | 1989-07-01 | Grande | Applicant |
| US4850952(A) | 1989-07-01 | Figdor et al. | Applicant |
| US4853137(A) | 1989-08-01 | Ersson et al. | Applicant |
| US4871462(A) | 1989-10-01 | Fischel et al. | Applicant |
| US4874368(A) | 1989-10-01 | Miller et al. | Applicant |
| US4877520(A) | 1989-10-01 | Burns | Applicant |
| US4879031(A) | 1989-11-01 | Panzani et al. | Applicant |
| US4902281(A) | 1990-02-01 | Avoy | Applicant |
| US4909251(A) | 1990-03-01 | Seelich et al. | Applicant |
| US4915847(A) | 1990-04-01 | Dillon et al. | Applicant |
| US4917801(A) | 1990-04-01 | Luderer et al. | Applicant |
| US4928603(A) | 1990-05-01 | Rose et al. | Applicant |
| US4929242(A) | 1990-05-01 | Desecki et al. | Applicant |
| US4939081(A) | 1990-07-01 | Figdor et al. | Applicant |
| US4943273(A) | 1990-07-01 | Pages et al. | Applicant |
| US4946601(A) | 1990-08-01 | Fiehler | Applicant |
| US4957637(A) | 1990-09-01 | Cornell | Applicant |
| US4957638(A) | 1990-09-01 | Smith | Applicant |
| US4983157(A) | 1991-01-01 | Pober et al. | Applicant |
| US4983158(A) | 1991-01-01 | Headley | Applicant |
| US4985153(A) | 1991-01-01 | Kuroda et al. | Applicant |
| US5000970(A) | 1991-03-01 | Shanbhag et al. | Applicant |
| US5002571(A) | 1991-03-01 | O'Donnell, Jr. et al. | Applicant |
| US5019243(A) | 1991-05-01 | McEwen et al. | Applicant |
| US5024613(A) | 1991-06-01 | Vasconcellos et al. | Applicant |
| US5030215(A) | 1991-07-01 | Morse et al. | Applicant |
| US5030341(A) | 1991-07-01 | McEwen et al. | Applicant |
| US5039401(A) | 1991-08-01 | Columbus et al. | Applicant |
| US5045048(A) | 1991-09-01 | Kaleskas et al. | Applicant |
| US5047004(A) | 1991-09-01 | Wells | Applicant |
| US5053127(A) | 1991-10-01 | Schoendorfer et al. | Applicant |
| US5053134(A) | 1991-10-01 | Luderer et al. | Applicant |
| US5071570(A) | 1991-12-01 | Shiraki et al. | Applicant |
| US5080262(A) | 1992-01-01 | Herold et al. | Applicant |
| US5086784(A) | 1992-02-01 | Levine et al. | Applicant |
| US5100564(A) | 1992-03-01 | Pall et al. | Applicant |
| US5104375(A) | 1992-04-01 | Wolf et al. | Applicant |
| US5112484(A) | 1992-05-01 | Zuk, Jr. | Applicant |
| US5112490(A) | 1992-05-01 | Turpen | Applicant |
| US5131907(A) | 1992-07-01 | Williams et al. | Applicant |
| US5137832(A) | 1992-08-01 | Levine et al. | Applicant |
| US5141645(A) | 1992-08-01 | Shiraki et al. | Applicant |
| US5147290(A) | 1992-09-01 | Jonsson et al. | Applicant |
| US5152905(A) | 1992-10-01 | Pall et al. | Applicant |
| US5156613(A) | 1992-10-01 | Sawyer | Applicant |
| US5165938(A) | 1992-11-01 | Knighton | Applicant |
| US5171456(A) | 1992-12-01 | Hwang et al. | Applicant |
| US5173295(A) | 1992-12-01 | Wehling et al. | Applicant |
| US5178602(A) | 1993-01-01 | Wells | Applicant |
| US5185001(A) | 1993-02-01 | Galanakis | Applicant |
| US5190057(A) | 1993-03-01 | Sarfarazi | Applicant |
| US5190759(A) | 1993-03-01 | Lindblad et al. | Applicant |
| US5197985(A) | 1993-03-01 | Caplan et al. | Applicant |
| US5203825(A) | 1993-04-01 | Haynes et al. | Applicant |
| US5204537(A) | 1993-04-01 | Bennet et al. | Applicant |
| US5206023(A) | 1993-04-01 | Hunziker et al. | Applicant |
| US5207638(A) | 1993-05-01 | Choksi et al. | Applicant |
| US5217426(A) | 1993-06-01 | Bacehowski et al. | Applicant |
| US5217627(A) | 1993-06-01 | Pall et al. | Applicant |
| US5219328(A) | 1993-06-01 | Morse et al. | Applicant |
| US5226877(A) | 1993-07-01 | Epstein | Applicant |
| US5226914(A) | 1993-07-01 | Caplan et al. | Applicant |
| US5234608(A) | 1993-08-01 | Duff | Applicant |
| US5236604(A) | 1993-08-01 | Fiehler | Applicant |
| US5251786(A) | 1993-10-01 | Sarrine | Applicant |
| US5258126(A) | 1993-11-01 | Pall et al. | Applicant |
| US5260420(A) | 1993-11-01 | Burnouf-Radosevich et al. | Applicant |
| US5269927(A) | 1993-12-01 | Fiehler | Applicant |
| US5271852(A) | 1993-12-01 | Luoma, II | Applicant |
| US5279825(A) | 1994-01-01 | Wehling et al. | Applicant |
| US5281342(A) | 1994-01-01 | Biesel et al. | Applicant |
| US5290552(A) | 1994-03-01 | Sierra et al. | Applicant |
| US5290918(A) | 1994-03-01 | Bui-Khac et al. | Applicant |
| US5298171(A) | 1994-03-01 | Biesel et al. | Applicant |
| US5304372(A) | 1994-04-01 | Michalski et al. | Applicant |
| US5316674(A) | 1994-05-01 | Pall et al. | Applicant |
| US5318524(A) | 1994-06-01 | Morse et al. | Applicant |
| US5318782(A) | 1994-06-01 | Weis-Fogh et al. | Applicant |
| US5321126(A) | 1994-06-01 | van Dommelen et al. | Applicant |
| US5322620(A) | 1994-06-01 | Brown et al. | Applicant |
| US5330974(A) | 1994-07-01 | Pines et al. | Applicant |
| US5344752(A) | 1994-09-01 | Murphy | Applicant |
| US5354483(A) | 1994-10-01 | Furse | Applicant |
| US5370802(A) | 1994-12-01 | Brown | Applicant |
| US5372945(A) | 1994-12-01 | Alchas et al. | Applicant |
| US5376263(A) | 1994-12-01 | Fischel | Applicant |
| US5387187(A) | 1995-02-01 | Fell et al. | Applicant |
| US5393674(A) | 1995-02-01 | Levine et al. | Applicant |
| US5395923(A) | 1995-03-01 | Bui-Khac et al. | Applicant |
| US5403272(A) | 1995-04-01 | Deniega et al. | Applicant |
| US5405607(A) | 1995-04-01 | Epstein | Applicant |
| US5409833(A) | 1995-04-01 | Hu et al. | Applicant |
| US5411885(A) | 1995-05-01 | Marx | Applicant |
| US5417650(A) | 1995-05-01 | Gordon | Applicant |
| US5420250(A) | 1995-05-01 | Lontz | Applicant |
| US5443481(A) | 1995-08-01 | Lee | Applicant |
| US5454958(A) | 1995-10-01 | Fiehler | Applicant |
| US5456693(A) | 1995-10-01 | Conston et al. | Applicant |
| US5456885(A) | 1995-10-01 | Coleman et al. | Applicant |
| US5474687(A) | 1995-12-01 | Van Vlasselaer | Applicant |
| US5486359(A) | 1996-01-01 | Caplan et al. | Applicant |
| US5494578(A) | 1996-02-01 | Brown et al. | Applicant |
| US5494592(A) | 1996-02-01 | Latham, Jr. et al. | Applicant |
| US5501371(A) | 1996-03-01 | Schwartz-Feldman | Applicant |
| US5505685(A) | 1996-04-01 | Antwiler | Applicant |
| US5510102(A) | 1996-04-01 | Cochrum | Applicant |
| US5520885(A) | 1996-05-01 | Coelho et al. | Applicant |
| US5525477(A) | 1996-06-01 | Hassouna | Applicant |
| US5533518(A) | 1996-07-01 | Vogler | Applicant |
| US5560830(A) | 1996-10-01 | Coleman et al. | Applicant |
| US5575778(A) | 1996-11-01 | Hardt et al. | Applicant |
| US5577513(A) | 1996-11-01 | Van Vlasselaer | Applicant |
| US5585007(A) | 1996-12-01 | Antanavich et al. | Applicant |
| US5588958(A) | 1996-12-01 | Cunningham et al. | Applicant |
| US5589462(A) | 1996-12-01 | Patat et al. | Applicant |
| US5601727(A) | 1997-02-01 | Bormann et al. | Applicant |
| US5603845(A) | 1997-02-01 | Holm | Applicant |
| US5607579(A) | 1997-03-01 | Latham, Jr. et al. | Applicant |
| US5614106(A) | 1997-03-01 | Payrat et al. | Applicant |
| US5618663(A) | 1997-04-01 | Delmas et al. | Applicant |
| US5632895(A) | 1997-05-01 | Tsukagoshi et al. | Applicant |
| US5632905(A) | 1997-05-01 | Haynes | Applicant |
| US5641414(A) | 1997-06-01 | Brown | Applicant |
| US5641622(A) | 1997-06-01 | Lake et al. | Applicant |
| US5643192(A) | 1997-07-01 | Hirsh et al. | Applicant |
| US5645540(A) | 1997-07-01 | Henniges et al. | Applicant |
| US5646004(A) | 1997-07-01 | Van Vlasselaer | Applicant |
| US5648223(A) | 1997-07-01 | Van Vlasselaer | Applicant |
| US5649903(A) | 1997-07-01 | Deniega et al. | Applicant |
| US5663051(A) | 1997-09-01 | Vlasselaer | Applicant |
| US5674173(A) | 1997-10-01 | Hlavinka et al. | Applicant |
| US5707331(A) | 1998-01-01 | Wells et al. | Applicant |
| US5707647(A) | 1998-01-01 | Dunn et al. | Applicant |
| US5707876(A) | 1998-01-01 | Levine | Applicant |
| US5716616(A) | 1998-02-01 | Prockop et al. | Applicant |
| US5723331(A) | 1998-03-01 | Tubo et al. | Applicant |
| US5724988(A) | 1998-03-01 | Dennehey et al. | Applicant |
| US5733466(A) | 1998-03-01 | Benebo et al. | Applicant |
| US5733545(A) | 1998-03-01 | Hood, III | Applicant |
| US5736033(A) | 1998-04-01 | Coleman et al. | Applicant |
| US5738784(A) | 1998-04-01 | Holm et al. | Applicant |
| US5738796(A) | 1998-04-01 | Bormann et al. | Applicant |
| US5750025(A) | 1998-05-01 | Holmes et al. | Applicant |
| US5750658(A) | 1998-05-01 | Coelho et al. | Applicant |
| US5762798(A) | 1998-06-01 | Wenthold et al. | Applicant |
| US5785700(A) | 1998-07-01 | Olson | Applicant |
| US5786217(A) | 1998-07-01 | Tubo et al. | Applicant |
| US5788662(A) | 1998-08-01 | Antanavich et al. | Applicant |
| US5792344(A) | 1998-08-01 | Holm | Applicant |
| US5795489(A) | 1998-08-01 | Holm et al. | Applicant |
| US5795571(A) | 1998-08-01 | Cederholm-Williams et al. | Applicant |
| US5795751(A) | 1998-08-01 | Apel | Applicant |
| US5811094(A) | 1998-09-01 | Caplan et al. | Applicant |
| US5811151(A) | 1998-09-01 | Hendriks et al. | Applicant |
| US5817519(A) | 1998-10-01 | Zelmanovic et al. | Applicant |
| US5823986(A) | 1998-10-01 | Peterson | Applicant |
| US5824084(A) | 1998-10-01 | Muschler | Applicant |
| US5830359(A) | 1998-11-01 | Knight et al. | Applicant |
| US5833866(A) | 1998-11-01 | Brown | Applicant |
| US5834418(A) | 1998-11-01 | Brazeau et al. | Applicant |
| US5837150(A) | 1998-11-01 | Langley et al. | Applicant |
| US5840502(A) | 1998-11-01 | Van Vlasselaer | Applicant |
| US5860937(A) | 1999-01-01 | Cohen | Applicant |
| US5863892(A) | 1999-01-01 | Stern et al. | Applicant |
| US5865785(A) | 1999-02-01 | Bischof | Applicant |
| US5885239(A) | 1999-03-01 | Headley et al. | Applicant |
| US5889584(A) | 1999-03-01 | Wardlaw | Applicant |
| US5895346(A) | 1999-04-01 | Wells et al. | Applicant |
| US5899874(A) | 1999-05-01 | Jonsson et al. | Applicant |
| US5900245(A) | 1999-05-01 | Sawhney et al. | Applicant |
| US5906934(A) | 1999-05-01 | Grande et al. | Applicant |
| US5916557(A) | 1999-06-01 | Berlowitz-Tarrant et al. | Applicant |
| US5916743(A) | 1999-06-01 | Lake et al. | Applicant |
| US5918622(A) | 1999-07-01 | Perez et al. | Applicant |
| US5924972(A) | 1999-07-01 | Turvaville et al. | Applicant |
| US5934803(A) | 1999-08-01 | Hutter | Applicant |
| US5938621(A) | 1999-08-01 | Kelly et al. | Applicant |
| US5955032(A) | 1999-09-01 | Kelly et al. | Applicant |
| US5955436(A) | 1999-09-01 | Kunkle, Jr. | Applicant |
| US5958250(A) | 1999-09-01 | Brown et al. | Applicant |
| US5958253(A) | 1999-09-01 | Holm et al. | Applicant |
| US5980734(A) | 1999-11-01 | Itoh | Applicant |
| US5985315(A) | 1999-11-01 | Patat et al. | Applicant |
| US6007811(A) | 1999-12-01 | Sawyer et al. | Applicant |
| US6010627(A) | 2000-01-01 | Hood, III | Applicant |
| US6020196(A) | 2000-02-01 | Hu et al. | Applicant |
| US6022306(A) | 2000-02-01 | Dumont et al. | Applicant |
| US6025201(A) | 2000-02-01 | Zelmanovic et al. | Applicant |
| US6027655(A) | 2000-02-01 | Holm | Applicant |
| US6049026(A) | 2000-04-01 | Muschler | Applicant |
| US6051146(A) | 2000-04-01 | Green et al. | Applicant |
| US6051147(A) | 2000-04-01 | Bischof | Applicant |
| US6053856(A) | 2000-04-01 | Hlavinka | Applicant |
| US6054122(A) | 2000-04-01 | MacPhee et al. | Applicant |
| US6063297(A) | 2000-05-01 | Antanavich et al. | Applicant |
| US6063624(A) | 2000-05-01 | Kandler et al. | Applicant |
| US6071421(A) | 2000-06-01 | Brown | Applicant |
| US6071422(A) | 2000-06-01 | Hlavinka et al. | Applicant |
| US6071423(A) | 2000-06-01 | Brown et al. | Applicant |
| US6090793(A) | 2000-07-01 | Zimmermann et al. | Applicant |
| US6096309(A) | 2000-08-01 | Prior et al. | Applicant |
| US6117425(A) | 2000-09-01 | MacPhee et al. | Applicant |
| US6123655(A) | 2000-09-01 | Fell et al. | Applicant |
| US6150163(A) | 2000-11-01 | McPherson et al. | Applicant |
| US6153113(A) | 2000-11-01 | Goodrich et al. | Applicant |
| US6183737(B1) | 2001-02-01 | Zaleske et al. | Applicant |
| US6196987(B1) | 2001-03-01 | Holmes et al. | Applicant |
| US6197325(B1) | 2001-03-01 | MacPhee et al. | Applicant |
| US6200287(B1) | 2001-03-01 | Keller et al. | Applicant |
| US6200606(B1) | 2001-03-01 | Peterson et al. | Applicant |
| US6214338(B1) | 2001-04-01 | Antanavich et al. | Applicant |
| US6221315(B1) | 2001-04-01 | Giesler et al. | Applicant |
| US6245900(B1) | 2001-06-01 | Yamasaki et al. | Applicant |
| US6264890(B1) | 2001-07-01 | Boehringer et al. | Applicant |
| US6274090(B1) | 2001-08-01 | Coelho et al. | Applicant |
| US6277961(B1) | 2001-08-01 | Hock et al. | Applicant |
| US6280400(B1) | 2001-08-01 | Niermann | Applicant |
| US6296602(B1) | 2001-10-01 | Headley | Applicant |
| US6316247(B1) | 2001-11-01 | Katz et al. | Applicant |
| US6322785(B1) | 2001-11-01 | Landesberg et al. | Applicant |
| US6327491(B1) | 2001-12-01 | Franklin et al. | Applicant |
| US6328765(B1) | 2001-12-01 | Hardwick et al. | Applicant |
| US6342157(B1) | 2002-01-01 | Hood, III | Applicant |
| US6351659(B1) | 2002-02-01 | Vilsmeier | Applicant |
| US6355239(B1) | 2002-03-01 | Bruder et al. | Applicant |
| US6368298(B1) | 2002-04-01 | Beretta et al. | Applicant |
| US6368498(B1) | 2002-04-01 | Guilmette | Applicant |
| US6398972(B1) | 2002-06-01 | Blasetti et al. | Applicant |
| US6406671(B1) | 2002-06-01 | DiCesare et al. | Applicant |
| US6409528(B1) | 2002-06-01 | Bodnar | Examiner |
| US6410344(B1) | 2002-06-01 | Chung et al. | Applicant |
| US6417004(B1) | 2002-07-01 | Brady et al. | Applicant |
| US6440444(B2) | 2002-08-01 | Boyce et al. | Applicant |
| US6444228(B1) | 2002-09-01 | Baugh et al. | Applicant |
| US6464624(B2) | 2002-10-01 | Pages | Applicant |
| US6471069(B2) | 2002-10-01 | Lin et al. | Applicant |
| US6472162(B1) | 2002-10-01 | Coelho et al. | Applicant |
| US6508778(B1) | 2003-01-01 | Verkaart et al. | Applicant |
| US6516953(B1) | 2003-02-01 | DiCesare et al. | Applicant |
| US6523698(B1) | 2003-02-01 | Dennehey et al. | Applicant |
| US6544162(B1) | 2003-04-01 | Landin et al. | Applicant |
| US6544727(B1) | 2003-04-01 | Hei | Applicant |
| US6558341(B1) | 2003-05-01 | Swisher | Applicant |
| US6596180(B2) | 2003-07-01 | Baugh et al. | Applicant |
| US6623959(B2) | 2003-09-01 | Harris | Applicant |
| US6629919(B2) | 2003-10-01 | Egozy et al. | Applicant |
| US6638503(B2) | 2003-10-01 | Chitte et al. | Applicant |
| US6676629(B2) | 2004-01-01 | Andrew et al. | Applicant |
| US6719901(B2) | 2004-04-01 | Dolecek et al. | Applicant |
| US6733471(B1) | 2004-05-01 | Ericson et al. | Applicant |
| US6758978(B1) | 2004-07-01 | Bedell | Applicant |
| US6777231(B1) | 2004-08-01 | Katz et al. | Applicant |
| US6803022(B2) | 2004-10-01 | DiCesare et al. | Applicant |
| US6811777(B2) | 2004-11-01 | Mishra | Applicant |
| US6830762(B2) | 2004-12-01 | Baugh et al. | Applicant |
| US6835353(B2) | 2004-12-01 | Smith et al. | Applicant |
| US6835377(B2) | 2004-12-01 | Goldberg et al. | Applicant |
| USRE38730(E) | 2005-04-01 | Wells et al. | Applicant |
| US6899813(B2) | 2005-05-01 | Dolecek et al. | Applicant |
| US6905612(B2) | 2005-06-01 | Dorian et al. | Applicant |
| US6911202(B2) | 2005-06-01 | Amir et al. | Applicant |
| USRE38757(E) | 2005-07-01 | Wells et al. | Applicant |
| US7011644(B1) | 2006-03-01 | Andrew et al. | Applicant |
| US7077273(B2) | 2006-07-01 | Ellsworth et al. | Applicant |
| US7077827(B2) | 2006-07-01 | Greenfield | Applicant |
| US7155288(B2) | 2006-12-01 | Soykan et al. | Applicant |
| US7179391(B2) | 2007-02-01 | Leach et al. | Applicant |
| US7195606(B2) | 2007-03-01 | Ballin | Applicant |
| US7223346(B2) | 2007-05-01 | Dorian et al. | Applicant |
| US7273886(B2) | 2007-09-01 | Olivero et al. | Applicant |
| US7354515(B2) | 2008-04-01 | Coull et al. | Applicant |
| US7374678(B2) | 2008-05-01 | Leach et al. | Applicant |
| US7411006(B2) | 2008-08-01 | Shanbrom | Applicant |
| US7470371(B2) | 2008-12-01 | Dorian et al. | Applicant |
| US7531355(B2) | 2009-05-01 | Rodriguez et al. | Applicant |
| US7553413(B2) | 2009-06-01 | Dorian et al. | Applicant |
| US7845499(B2) | 2010-12-01 | Higgins et al. | Applicant |
| US7914689(B2) | 2011-03-01 | Higgins et al. | Applicant |
| US8048321(B2) | 2011-11-01 | Leach et al. | Applicant |
| US8062534(B2) | 2011-11-01 | Higgins et al. | Applicant |
| US2001/0009757(A1) | 2001-07-01 | Bischof et al. | Applicant |
| US2002/0035820(A1) | 2002-03-01 | Farris | Applicant |
| US2002/0076400(A1) | 2002-06-01 | Katz et al. | Applicant |
| US2002/0082220(A1) | 2002-06-01 | Hoemann et al. | Applicant |
| US2002/0090711(A1) | 2002-07-01 | Karlsson | Applicant |
| US2002/0104808(A1) | 2002-08-01 | Blasetti et al. | Applicant |
| US2002/0114775(A1) | 2002-08-01 | Pathak | Applicant |
| US2002/0161449(A1) | 2002-10-01 | Muschler | Applicant |
| US2002/0169408(A1) | 2002-11-01 | Beretta et al. | Applicant |
| US2002/0172666(A1) | 2002-11-01 | Sacchi et al. | Applicant |
| US2002/0182664(A1) | 2002-12-01 | Dolecek et al. | Applicant |
| US2002/0192632(A1) | 2002-12-01 | Hei et al. | Applicant |
| US2003/0033021(A1) | 2003-02-01 | Plouhar et al. | Applicant |
| US2003/0033022(A1) | 2003-02-01 | Plouhar et al. | Applicant |
| US2003/0050709(A1) | 2003-03-01 | Noth et al. | Applicant |
| US2003/0050710(A1) | 2003-03-01 | Petersen et al. | Applicant |
| US2003/0082152(A1) | 2003-05-01 | Hedrick et al. | Applicant |
| US2003/0185803(A1) | 2003-10-01 | Kadiyala et al. | Applicant |
| US2003/0191429(A1) | 2003-10-01 | Andrew et al. | Applicant |
| US2003/0205538(A1) | 2003-11-01 | Dorian et al. | Applicant |
| US2004/0013575(A1) | 2004-01-01 | Stevens et al. | Applicant |
| US2004/0120942(A1) | 2004-06-01 | McGinnis et al. | Applicant |
| US2004/0171146(A1) | 2004-09-01 | Katz et al. | Applicant |
| US2004/0182395(A1) | 2004-09-01 | Brookman | Applicant |
| US2004/0182788(A1) | 2004-09-01 | Dorian et al. | Applicant |
| US2004/0182795(A1) | 2004-09-01 | Dorian et al. | Applicant |
| US2004/0251217(A1) | 2004-12-01 | Leach et al. | Applicant |
| US2005/0076396(A1) | 2005-04-01 | Katz et al. | Applicant |
| US2005/0084961(A1) | 2005-04-01 | Hedrick et al. | Applicant |
| US2005/0084962(A1) | 2005-04-01 | Simon | Applicant |
| US2005/0109716(A1) | 2005-05-01 | Leach et al. | Examiner |
| US2005/0130301(A1) | 2005-06-01 | McKay et al. | Applicant |
| US2005/0153441(A1) | 2005-07-01 | Hedrick et al. | Applicant |
| US2005/0153442(A1) | 2005-07-01 | Katz et al. | Applicant |
| US2005/0186120(A1) | 2005-08-01 | Dorian et al. | Applicant |
| US2005/0196393(A1) | 2005-09-01 | Shanbrom | Applicant |
| US2005/0196874(A1) | 2005-09-01 | Dorian et al. | Applicant |
| US2005/0247715(A1) | 2005-11-01 | Ellsworth et al. | Applicant |
| US2005/0260174(A1) | 2005-11-01 | Fraser et al. | Applicant |
| US2005/0260175(A1) | 2005-11-01 | Hedrick et al. | Applicant |
| US2005/0282275(A1) | 2005-12-01 | Katz et al. | Applicant |
| US2006/0051865(A1) | 2006-03-01 | Higgins et al. | Applicant |
| US2006/0057693(A1) | 2006-03-01 | Simon | Applicant |
| US2006/0083720(A1) | 2006-04-01 | Fraser et al. | Applicant |
| US2006/0140923(A1) | 2006-06-01 | Evangelista et al. | Applicant |
| US2006/0151384(A1) | 2006-07-01 | Ellsworth et al. | Examiner |
| US2006/0175242(A1) | 2006-08-01 | Dorian et al. | Applicant |
| US2006/0175244(A1) | 2006-08-01 | Dorian et al. | Applicant |
| US2006/0178610(A1) | 2006-08-01 | Nowakowski | Applicant |
| US2006/0196885(A1) | 2006-09-01 | Leach et al. | Applicant |
| US2006/0243676(A1) | 2006-11-01 | Swift et al. | Applicant |
| US2006/0273049(A1) | 2006-12-01 | Leach et al. | Applicant |
| US2006/0273050(A1) | 2006-12-01 | Higgins et al. | Applicant |
| US2006/0278588(A1) | 2006-12-01 | Woodell-May | Applicant |
| US2007/0034579(A1) | 2007-02-01 | Dorian et al. | Applicant |
| US2007/0036768(A1) | 2007-02-01 | Fraser et al. | Applicant |
| US2007/0075016(A1) | 2007-04-01 | Leach | Applicant |
| US2007/0208321(A1) | 2007-09-01 | Leach et al. | Applicant |
| US2008/0011684(A1) | 2008-01-01 | Dorian et al. | Applicant |
| US2008/0164204(A1) | 2008-07-01 | Hatamian et al. | Applicant |
| US2008/0173593(A1) | 2008-07-01 | Coull et al. | Applicant |
| US2008/0193424(A1) | 2008-08-01 | McKale et al. | Applicant |
| US2008/0210645(A1) | 2008-09-01 | Coull et al. | Applicant |
| US2008/0217263(A1) | 2008-09-01 | Higgins et al. | Applicant |
| US2008/0217264(A1) | 2008-09-01 | Leach et al. | Applicant |
| US2008/0217265(A1) | 2008-09-01 | Leach et al. | Applicant |
| US2008/0268064(A1) | 2008-10-01 | Woodell-May | Applicant |
| US2008/0269762(A1) | 2008-10-01 | Simon et al. | Applicant |
| US2008/0283474(A1) | 2008-11-01 | Leach et al. | Applicant |
| US2008/0306431(A1) | 2008-12-01 | Yoo | Applicant |
| US2009/0014391(A1) | 2009-01-01 | Leach et al. | Applicant |
| US2009/0018313(A1) | 2009-01-01 | Shanbrom | Applicant |
| US2009/0101599(A1) | 2009-04-01 | Dorian et al. | Applicant |
| US2009/0192528(A1) | 2009-07-01 | Higgins et al. | Applicant |
| US2009/0220482(A1) | 2009-09-01 | Higgins et al. | Applicant |
| US2009/0221075(A1) | 2009-09-01 | Dorian et al. | Applicant |
| US2009/0236297(A1) | 2009-09-01 | Dorian et al. | Applicant |
| US2009/0250413(A1) | 2009-10-01 | Hoeppner | Applicant |
| US2009/0253566(A1) | 2009-10-01 | Chavarria | Applicant |
| US2010/0055087(A1) | 2010-03-01 | Higgins et al. | Applicant |
| US2010/0140182(A1) | 2010-06-01 | Chapman et al. | Applicant |
| US2010/0206798(A1) | 2010-08-01 | Dorian et al. | Applicant |
| US2010/0256595(A1) | 2010-10-01 | Leach et al. | Applicant |
| US2010/0323870(A1) | 2010-12-01 | Leach et al. | Applicant |
| US2010/0324450(A1) | 2010-12-01 | Leach et al. | Applicant |
| US2011/0014705(A1) | 2011-01-01 | Leach et al. | Applicant |
| US2011/0020196(A1) | 2011-01-01 | Grippi et al. | Applicant |
| US2011/0021334(A1) | 2011-01-01 | Leach et al. | Applicant |
| US2011/0036786(A1) | 2011-02-01 | Ellsworth | Applicant |
| US2011/0056893(A1) | 2011-03-01 | Leach et al. | Applicant |
| US2011/0065183(A1) | 2011-03-01 | Dorian et al. | Applicant |
| US2011/0077596(A1) | 2011-03-01 | Higgins et al. | Applicant |
| US2011/0168193(A1) | 2011-07-01 | Leach et al. | Applicant |
| US2011/0192804(A1) | 2011-08-01 | Landrigan et al. | Applicant |
| US2011/0251041(A1) | 2011-10-01 | Chavarria et al. | Applicant |
| US2012/0015796(A1) | 2012-01-01 | Leach et al. | Applicant |
| AU696278 | 1999-01-01 | Applicant | |
| BR9103724 | 1993-03-01 | Applicant | |
| CA1321138 | 1993-08-01 | Applicant | |
| CA2182862 | 1996-06-01 | Applicant | |
| CA2448415(A1) | 2002-12-01 | Applicant | |
| CN1074709 | 1993-07-01 | Applicant | |
| DE56103 | 1860-10-01 | Applicant | |
| DE1443359 | 1968-11-01 | Applicant | |
| DE4202667 | 1993-05-01 | Applicant | |
| EP90997 | 1983-10-01 | Applicant | |
| EP102773 | 1984-03-01 | Applicant | |
| EP109374 | 1984-05-01 | Applicant | |
| EP142339 | 1985-05-01 | Applicant | |
| EP244834(A2) | 1987-11-01 | Applicant | |
| EP253198 | 1988-01-01 | Applicant | |
| EP295771 | 1988-12-01 | Applicant | |
| EP417818 | 1991-03-01 | Applicant | |
| EP534178 | 1993-03-01 | Applicant | |
| EP534178 | 1993-03-01 | Applicant | |
| EP592242 | 1994-04-01 | Applicant | |
| EP1005910 | 2000-06-01 | Applicant | |
| EP1006360(A2) | 2000-06-01 | Applicant | |
| EP1289618 | 2003-03-01 | Applicant | |
| EP1406492(B1) | 2004-04-01 | Applicant | |
| EP1427279(A1) | 2004-06-01 | Applicant | |
| EP1467746(A2) | 2004-10-01 | Applicant | |
| EP1509326 | 2005-03-01 | Applicant | |
| EP1670315(A2) | 2006-06-01 | Applicant | |
| EP1716901 | 2006-11-01 | Applicant | |
| GB854715 | 1960-11-01 | Applicant | |
| JP60-053845 | 1985-03-01 | Applicant | |
| JP60250014(A) | 1985-12-01 | Applicant | |
| JP2036872 | 1990-02-01 | Applicant | |
| JP2071747 | 1990-03-01 | Applicant | |
| JP2129224 | 2000-10-01 | Applicant | |
| WO-8400905 | 1984-03-01 | Applicant | |
| WO-8802259 | 1988-04-01 | Applicant | |
| WO-9010031 | 1990-09-01 | Applicant | |
| WO-9222312 | 1992-12-01 | Applicant | |
| WO-9305067 | 1993-03-01 | Applicant | |
| WO-9308904 | 1993-05-01 | Applicant | |
| WO-9407548 | 1994-04-01 | Applicant | |
| WO-9617871 | 1996-06-01 | Applicant | |
| WO-9917871(A1) | 1996-06-01 | Applicant | |
| WO-9848938(A1) | 1998-11-01 | Applicant | |
| WO-0061256 | 2000-10-01 | Applicant | |
| WO-0074713(A1) | 2000-12-01 | Applicant | |
| WO-0103756 | 2001-01-01 | Applicant | |
| WO-0183068 | 2001-11-01 | Applicant | |
| WO-0238610(A1) | 2002-05-01 | Applicant | |
| WO-02060925(A1) | 2002-08-01 | Applicant | |
| WO-02098566(A2) | 2002-12-01 | Applicant | |
| WO-03015800 | 2003-02-01 | Applicant | |
| WO-03024215(A1) | 2003-03-01 | Applicant | |
| WO-03053362(A2) | 2003-07-01 | Applicant | |
| WO-03088905 | 2003-10-01 | Applicant | |
| WO-03092894 | 2003-11-01 | Applicant | |
| WO-03099412(A1) | 2003-12-01 | Applicant | |
| WO-2004009207 | 2004-01-01 | Applicant | |
| WO-2004104553 | 2004-12-01 | Applicant | |
| WO-2005034843(A2) | 2005-04-01 | Applicant | |
| WO-2007127834(A2) | 2007-11-01 | Applicant | |
| WO-2007142908(A1) | 2007-12-01 | Applicant | |
| WO-2009021257(A1) | 2009-02-01 | Applicant |
Non-Patent Literature (158)
- “Caps for Corning® and Costar® Plastic Labware,” Technical Bulletin. (Dec. 2008) Corning, Incorporated.Applicant
- “Cell Isolation Techniques, Methods and Materials, Working with Enzymes,” (2004) (9 pages) Worthington Biochemical Corp.Applicant
- “Cell Isolation Theory, Tissue Types,” (2004) (5 pages) Worthington Biochemical Corp.Applicant
- “Centrifuge Tubes” CORNING Costar brochure. 1996/1997 Catalog pp. 76-77.Applicant
- “Clotalyst® Autologous Clotting Factor” brochure. (Aug. 15, 2008) Biomet Biologics.Applicant
- “Clotalyst® Autologous Clotting Factor. Would you like to have an autologous thrombin for rapid clotting and haemostasis?” Brochure. Biomet Biologics (Aug. 15, 2008).Applicant
- “Corning® 15 and 50 mL Centrifuge Tubes,” Life Sciences. (Jun. 2005) Corning Incorporated.Applicant
- “Cytori Celution Cell Concentrate Device,” Exhibit 14, 510(k) Summary, FDA approval K060482 (Sep. 28, 2006).Applicant
- “Frequently Asked Questions, 1. Kits, 2. Engzymes,” (2003) 3 pages Worthington Biochemical Corp.Applicant
- “Letter CryoSeal FS System. Vaccines, Blood & Biologics,” letter. (Jul. 26, 2007) FDA U.S. Food and Drug Administation. http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/ucm091631.htm (Web accessed Aug. 12, 2011).Applicant
- “MarrowStim™ Concentration Kit Peripheral Arterial Disease (PAD) Study” brochure. Web. Jul. 2, 2009 http://www.biomet.com/patients/clinical—recruitment—padstudy.cfm.Applicant
- “MarrowStim™ Concentration System,” brochure. Biomet Biologics Jun. 15, 2008.Applicant
- “Plasmax® Plasma Concentration System” brochure. (Jun. 15, 2008) Biomet® Biologics.Applicant
- “Prosys PRP Kit,” brochure Tozai Holdings, Inc. http://tozaiholdings.en.ec21.com/Prosys—PRP—Kit--5467051—5467061.html Printed from Web Aug. 24, 2011.Applicant
- “Prosys PRP Kit,” Tozai Holdings, Inc. EC21 Global B2B Marketplace http://www.ec21.com/product-details/Prosys-PRP-Kit--5467061.html Printed from Web Jul. 18, 2011.Applicant
- “ThermoGenesis Corp. to Supply Autologous Thrombin Kits to Biomet, Inc.,” PR Newslink: http:/tinyurl.com/4h3up. (Apr. 5, 2005) http://www.noblood.org/press-releases/2128-thermogenesis-corp-supply-autologous-thrombin-kits-biomet-inc [web accessed Sep. 27, 2011].Applicant
- “Trypsinizing cells.” Baits Cookbook, Web. Apr. 14, 2010. http://pingu.salk.edu/˜sefton/Hyper—protocols/trypsin.html.Applicant
- Anesthesiology, vol. 81, No. 4, pp. 1074-1077, Oct. 1994, Hiromasa Mitsuhata, M.D., et al., “An Anaphylactic Reaction to Topical Fibrin Glue”.Applicant
- Ann Thorac Surg, vol. 53, pp. 530-531, 1992, Mehmet C. Oz, M.D., et al., “Autologous Fibrin Glue From Intraoperatively Collected Platelet-Rich Plasma”.Applicant
- Ann Thorac Surg, vol. 56, pp. 387-389, 1993, Robert L. Quigley, M.D., et al., “Intraoperative Procurement of Autologous Fibrin Glue”.Applicant
- Badiavas, et al., “Treatment of Chronic Wounds With Bone Marrow-Derived Cells,” (Reprinted) Arch Dermatol. 139:510-516 (Apr. 2003).Applicant
- Bang, N.U., et al., “Plasma Protein Requirements for Human Platelet Aggregation” Ann. N.Y. Acad Sci, 201:280-299 (1972).Applicant
- Berguer, R., R. L. Staerkel, E. E. Moore, F. A. Moore, W. B. Galloway, and M. B. Mockus. “Warning: fatal reaction to the use of fibrin glue in deep hepatic wounds. Case reports.” J Trauma 31:3 (1991): 408-11.Applicant
- Berruyer, M., J. Amiral, P. Ffrench, J. Belleville, O. Bastien, J. Clerc, A. Kassir, S. Estanove, and M. Dechavanne. “Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors,” J Thorac Cardiovasc Surg 105: 5 (1993): 892-7.Applicant
- BioCUE™ Platelet Concentration System, Dec. 2010. (2 pages).Applicant
- Biopolymers, vol. 27, pp. 763-774, 1988, Gerald Marx, “Mechanism of Fibrin Coagulation Based on Selective, Cation-Driven, Protofibral Association”.Applicant
- Boomgaard, et al., “Pooled Platelet Concentrates Prepared by the Platelet-Rich-Plasma Method and Filtered with Three Different Filters and Stored for 8 Days.” Vox Sanq, vol. 68: 82-89, Feb. 1995.Applicant
- Brodke, et al., “Bone Grafts Prepared with Selective Cell Retention Technology Heal Canine Segmental Defects as Effectively as Autograft”, SCR-Enriched Bone Crafts Heal Canine Segmental Defects, Journal of Orthopaedic Research (May 2006) pp. 857-866.Applicant
- Casali, B., F. Rodeghiero, A. Tosetto, B. Palmieri, R. Immovilli, C. Ghedini, and P. Rivasi. “Fibrin glue from single-donation autologous plasmapheresis.” Transfusion 32:7 (1992): 641-3.Applicant
- CLOTALYST™ Automatic Clotting Factor, Would you like to have an autologous thrombin for rapid clotting and haemostasis?, brochure, Biomet Biologics, Inc., Feb. 2007 (12 pages).Applicant
- Collier, B.S. et al., “The pH Dependence of Quantitative Ristocetin-induced Platelet Aggregation: Theoretical and Practical Implications—A New Device for Maintenance of Platelet-Rich Plasma pH”, Hematology Service, Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Md. 20014, Blood, vol. 47, No. 5 (May 1976).Applicant
- Connolly, “Injectable Bone Marrow Preparations to Stimulate Osteogenic Repair,” Clinical Orthopaedics and Related Research 313:8-18 (Apr. 1995).Applicant
- Connolly, John, M.D., et al. “Development of an Osteogenic Bone-Marrow Preparation.” The Journal of Bone and Joint Surgery, Incorporated. vol. 71-A, No. 5 (Jun. 1989) pp. 684-691.Applicant
- Dallari, et al., “In Vivo Study on the Healing of Bone Defects Treated with Bone Marrow Stromal Cells, Platelet-Rich Plasma, and Freeze-Dried Bone Allografts, Alone and in Combination,” Healing of Bone Defects, Journal of Orthopaedic Research (May 2006) pp. 877-888.Applicant
- De Ugarte, et al., “Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow,” Cells Tissues Organs 174:101-109 (2003).Applicant
- De Ugarte, et al., “Differential Expression of Stem Cell Mobilization-Associated Molecules on Multi-Lineage Cells from Adipose Tissue and Bone Marrow,” Immunology Letters 89:267-270 (2003).Applicant
- DelRossi, A. J., A. C. Cernaianu, R. A.Vertrees, C. J. Wacker, S. J. Fuller, J. Cilley Jr., and W. A. Baldino. “Platelet-rich plasma reduces postoperative blood loss after cardiopulmonary bypass.” J Thorac Cardiovasc Surg 100:2 (Aug. 1990): 281-6.Applicant
- DePalma, L., et al., “The preparation of fibrinogen concentrate for use as fibrin glue by four different methods.” Transfusion (1993) vol. 33, No. 9; pp. 717-720.Applicant
- DeUgarte, M.D., Daniel A., et al., “Future of Fat as Raw Material for Tissue Regeneration,” (Feb. 2003) pp. 215-219, Lippincott Williams & Wilkins, Inc.Applicant
- DiMuzio, Paul et al., “Development of a Tissue-Engineered Bypass Graft Seeded with Stem Cells,” Vasucular, vol. 14, No. 6, (2006) pp. 338-342, BC Decker, Inc.Applicant
- Drug Intelligence and Clinical Pharmacy, vol. 22, pp. 946-952, Dec. 1988, Dennis F. Thompson, et al., “Fibrin Glue: A Review of Its Preparation, Efficacy, and Adverse Effects as a Topical Hemostat”.Applicant
- Edlich, Richard F., George T. Rodeheaver, and John G. Thacker. “Surgical Devices in Wound Healing Management.” In Wound Healing: Biochemical & Clinical Aspects,ed. I. Kelman Cohen, Robert F. Diegelmann, and William J. Lindblad. 581-600. 1st ed., Vol. Philadelphia: W.B. Saunders Company, 1992.Applicant
- Eppley, et al., “Platelet Quantification and Growth Factor Analysis from Platelet-Rich Plasma: Implications for Wound Healing,” Plastic and Reconstructive Surgery, 114(6):1502-1508 (Nov. 2004).Applicant
- Epstein, G. H., R. A. Weisman, S. Zwillenberg, and A. D. Schreiber. “A new autologous fibrinogen-based adhesive for otologic surgery.” Ann Otol Rhinol Laryngol 95 (May 25-26, 1985) 40-5.Applicant
- Fibrostik™ Plasma Concentrator, Attention Operating Surgeon, Cell Factor Technologies, Inc., Jul. 2003.Applicant
- First clinical results: Kuderma, H. and Helene Matras. “Die klinische Anwendung der Klebung van Nervenanastomosen mit Gerinnungssubstanzen bei der Rekonstruction verletzter peripherer Nerven.” Wein Klin Wochenschr 87 (Aug. 15, 1975): 495-501.Applicant
- Floryan, K. et al. “Home Study Program: Intraoperative Use of Autologous Platelet-Rich and Platelet-Poor Plasma for Orthopedic Surgery Patients” vol. 80, No. 4 (Oct. 2004) p. 667-674.Applicant
- Frasier, John K., et al., “Plasticity of human adipose stem cells toward endothelial cells and cardiomyocytes,” Nature Clinical Practice Cardiovascular Medicine, vol. 3, Supplement 1 (Mar. 2006) pp. S33-S37.Applicant
- Friesen, M.D., Robert, et al. “Blood Conservation During Pediatric Cardiac Surgery: Ultrafiltration of the Extracorporeal Circuit Volume After Cardiopulmonary Bypass.” ANESTH. ANALG 1993: 77-702-7.Applicant
- Galois, et al., “Cartilage Tissue Engineering: State-of-the-Art and Future Approaches,” Pathol Biol (Paris), 53(10), Dec. 2005.Applicant
- Gibble, J. W. and P. M. Ness. “Fibrin glue: the perfect operative sealant?” Transfusion 30(1990): 741-7.Applicant
- Gimble, Jeffrey M., “Adipose-Derived Stem Cells for Regenerative Medicine,” Circulation Research (May 11, 2007) pp. 1249-1260, American Heart Association, Inc.Applicant
- Gomillion, Cheryl T., et al., “Stem cells and adipose tissue engineering,” Biomaterials 27, Science Direct (2006) pp. 6052-6063, Elsevier.Applicant
- GPS® III System, GPS® III Platelet Separation System, Leadership through Technology, brochure, Jul. 2007 (8 sheets).Applicant
- GPS® System, “GPS® Platelet Concentrate System,” Cell Factor Technologies, Inc., Biomet Orthopaedics, Inc., (Feb. 29, 2004) (9 pages).Applicant
- GPS® System, “Shoulder Recovery with the GPS® Platelet Concentrate System, Rotator Cuff Surgical Techniques,” brochure, Cell Factor Technologies, Inc., Biomet Orthopaedics, Inc., (2004) 6 pages.Applicant
- GPS® System, “Shoulder Recovery with the GPS® Platelet Concentrate System, Rotator Cuff Surgical Techniques,” Cell Factor Technologies, Inc., Biomet Orthopaedics, Inc., (2004) 3 pages, http://www.cellfactortech.com/global—products.cfm, printed Sep. 16, 2005.Applicant
- GPS® II System, Gravitational Platelet Separation System, “Accelerating the Body's Natural Healing Process,” Biomet Biologics (Jul. 15, 2006) 16 pages.Applicant
- GPS® II System, Gravitational Platelet Separation System, “Accelerating the Body's Natural Healing Process,” Cell Factor Technologies, Inc., Biomet Europe (2005) 16 pages, http://www.cellfactortech.com/global—products.cfm, printed Sep. 16, 2005.Applicant
- GPS® II System, Gravitational Platelet Separation System, “User Manual,” Cell Factor Technologies, Inc., Biomet Europe [date unknown] 13 pages, http://www.cellfactortech.com/global—products.cfm, printed Sep. 16, 2005.Applicant
- Grove, et al., “Plasticity of Bone Marrow-Derived Stem Cells,” Stem Cells: Concise Review, Jan. 22, 2004.Applicant
- Guilak, Frank, et al., “Adipose-derived adult stem cells for cartilage tissue engineering,” Biorheology 41 (2004) pp. 389-399, IOS Press.Applicant
- Harris, E.L.V. Concentration of the Extract. In. Protein Purification Methods: A Practical Approach Harris, E.L.V.; Angel, S.; Editors. (1989) Publisher: (IRL Press, Oxford, UK), pp. 67-69.Applicant
- Hartman, A. R., D. K. Galanakis, M. P. Honig, F. C. Seifert, and C. E. Anagnostopoulos. “Autologous whole plasma fibrin gel. Intraoperative procurement.” Arch Surg 127 (Mar. 1992): 357-9.Applicant
- Harvest SmartPrep PRP-20 Procedure Pack, “Instructions for Use” (date unknown).Applicant
- Harvest Technologies brochure, SmartPrep2 (2002).Applicant
- Hattori, et al., “Osteogenic Potential of Human Adipose Tissue-Derived Stromal Cells as an Alternative Stem Cell Source,” Cells Tissues Organs (2004) 178:2-12 Karger.Applicant
- Haynesworth, S.E. et al. “Mitogenic Stimulation of Human Mesenchymal Stem Cells by Platelet Releasate Suggests a Mechanism for Enhancement of Bone Repair by Platelet Concentrate” 48th Annual Meeting of the Orthopaedic Research Society Poster No. 0462 (2002).Applicant
- Hennis, H. L., W. C. Stewart, and E. K. Jeter. “Infectious disease risks of fibrin glue [letter].” Ophthalmic Surg 23 (Sep. 1992): 640.Applicant
- Hernigou, et al., “Percutaneous Autologous Bone-Marrow Grafting for Nonunions. Influence of the Number and Concentration of Progenitor Cells,” Journal of Bone & Joint Surgery, 87-A(7):1430-1437 (Jul. 2005).Applicant
- Hom, D., et al. “Promoting Healing with Recombinant Human Platelet-Derived Growth Factor-BB in a Previously Irradiated Problem Wound.” The Laryngoscope, vol. 113 (pp. 1566-1671) Sep. 2003.Applicant
- Hood, Andrew G., et al., “Perioperative Autologous Sequestration III: A New Physiologic Glue with Wound Healing Properties,” (Jan. 1993) vol. 14 pp. 126-129.Applicant
- International Preliminary Examination Report and Written Opinion issued Aug. 31, 2010 for PCT/US2009/035564 claiming benefit of U.S. Appl. No. 61/078,178, filed Jul. 3, 2008, which priority is also claimed of said provisional case by U.S. Appl. No. 12/395,085, filed Feb. 27, 2009.Applicant
- International Preliminary Report on Patentability and Written Opinion mailed Oct. 13, 2011 for PCT/US2010/029957 which claims benefit of U.S. Appl. No. 12/417,789, filed Apr. 3, 2009.Applicant
- International Preliminary Report on Patentability completed Aug. 13, 2009 for PCT/US2008/004687 claiming benefit of U.S. Appl. No. 60/911,407, filed Apr. 12, 2007.Applicant
- International Preliminary Report on Patentability mailed Jan. 26, 2012 for PCT/US2010/041942 claiming benefit of U.S. Appl. No. 12/504,413, filed Jul. 16, 2009.Applicant
- International Search Report and Written Opinion mailed Aug. 9, 2011 for PCT/US2011/031954 claiming benefit of U.S. Appl. No. 12/758,127, filed Apr. 12, 2010.Applicant
- International Search Report and Written Opinion mailed Jul. 2, 2008 for International Application No. PCT/US2008/004687 which claims priority to U.S. Appl. No. 60/911,407, filed Apr. 12, 2007.Applicant
- International Search Report and Written Opinion mailed Jul. 3, 2009 for PCT/US2009/035564 claiming benefit of U.S. Appl. No. 61/078,178, filed Jul. 3, 2008.Applicant
- International Search Report and Written Opinion mailed Jul. 30, 2010 for PCT/US2010/029957 which claims benefit of U.S. Appl. No. 12/417,789, filed Apr. 3, 2009.Applicant
- International Search Report and Written Opinion mailed Nov. 7, 2011 for PCT/US2011/045290 claiming benefit of U.S. Appl. No. 12/846,944, filed Jul. 30, 2010.Applicant
- International Search Report and Written Opinion mailed Oct. 8, 2010 for PCT/US2010/041942 claiming benefit of U.S. Appl. No. 12/504,413, filed Jul. 16, 2009.Applicant
- International Search Report for International Application No. PCT/US/0316506 mailed Oct. 13, 2003 which claims benefit of U.S. Appl. No. 60/383,013, filed May 24, 2002.Applicant
- International Search Report for International Application No. PCT/US2007/012587 mailed Nov. 6, 2007 which claims benefit of U.S. Appl. No. 11/441,276, filed May 25, 2006.Applicant
- lshida, et al., “Platelet-Rich Plasma With Biodegradable Gelatin Hydrogel Promotes Rabbit Meniscal Tissue Regeneration,” 52nd Annual Meeting of the Orthopaedic Research Society Paper No. 1035, 1 page (2006).Applicant
- Jackson, C. M. and Y. Nemerson. “Blood coagulation.” Annu Rev Biochem 49 (1980): 765-811)Applicant
- Jayadev, Suprya. “Trypsinization of Adherent Cells.” Aug. 8, 1991. Web. Apr. 14, 2010 http://www.duke.edu/web/ceramide/protocols/0005.html.Applicant
- Johnstone, et al., “Autologous Mesenchymal Progenitor Cells in Articular Cartilage Repair”, Clinical Orthopaedics and Related Research 367S:S156-S162 (Oct. 1999).Applicant
- Jorgensen, et al., “Stem Cells for Repair of Cartilage and Bone: The Next Challenge in Osteoarthritis and Rheumatoid Arthritis,” Annals of Rheumatic Diseases, Aug. 2000.Applicant
- Journal of Oral Maxillofacial Surgery, vol. 43, pp. 605-611, Helene Matras, M.D., “Fibrin Seal: The State of the Art” (1985).Applicant
- Karpatkin, S., “Heterogeneity of Human Platelets. VI., Correlation of Platelet Function with Platelet Volume”, Blood, vol. 51, No. 2 (Feb. 1978).Applicant
- Kjaergard, H. K,, U. S. Weis-Fogh, H. Sorensen, J. Thiis, and I. Rygg. “A simple method of preparation o£ autologous fibrin glue by means of ethanol.” Surg Gynecol Obstet 175 (1992): 72-3.Applicant
- Kjaergard, H. K., Fogh Us Weis, and J. J. Thiis. “Preparation of autologous fibrin glue from pericardial blood.” Ann Thorac Sur 55 (1993): 543-4.Applicant
- Kumar, Vijay et al. “Stability of Human Thrombin Produced From 11 ml of Plasma Using the Thrombin Processing Device,” Journal of American Society of Extra-Corporeal Technology. JECT: Mar. 2005:37; 390-395.Applicant
- Kumar, Vijay et al. “Whole Blood Thrombin: Development of a Process for Intra-Operative Production of Human Thrombin.” Journal of American Society of Extra-Corporeal Technology. JECT: Apr. 2007; 39:18-23.Applicant
- Kumar, Vijay et al., “Autologous Thrombin: Intraoperative Production From Whole Blood.” Journal of American Society of Extra-Corporeal Technology. JECT: Apr. 2008; 40:94-98.Applicant
- Laryngoscope vol. 99, pp. 974-976, Sep. 1989, Kyosti Laitakari, M.D., et al., “Autologous and Homologous Fibrinogen Sealants: Adhesive Strength”.Applicant
- Laryngoscope, vol. 95, pp. 1074-1076, Sep. 1985, Karl H. Siedentop, M.D., et al., “Autologous Fibrin Tissue Adhesive”.Applicant
- Laryngoscope, vol. 96, pp. 1062-1064, Oct. 1986, Karl H. Siedentop, M.D., et al., “Extended Experimental and Preliminary Surgical Findings with Autologous Fibrin Tissue Adhesive Made from Patient's Own Blood”.Applicant
- Lasher, Lisa, M.D., “My Experience with PRP,” PowerPoint presentation, http://www.cellfactortech.com/global—products.cfm, printed Sep. 16, 2005.Applicant
- Lendeckel, Stefan, et al., “Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report,” Journal of Cranio-Maxillofacial Surgery (2004) European Association for Cranio-Maxillofacial Surgery.Applicant
- Lerner, R. and N. S. Binur. “Current status of surgical adhesives.” J Surg Res 48 (Feb. 1990): 165-81.Applicant
- Longas, Maria O., “An Improved Method for the Purification of Human Fibrinogen.” J. Biochem (1980) vol. 11, pp. 559-564.Applicant
- Lu, et al., “Bone Marrow Mesenchymal Stem Cells: Progress in Bone/Cartilage Defect Repair,” 19(1), Jan. 2002.Applicant
- Marrowstim Concentration System, Biomet Biologics, Inc., 20 pages (REV Feb. 15, 2008).Applicant
- Marx, Gerard, et al., “Heat Denaturation of Fibrinogen to Develop a Biomedical Matrix.” Journal of Biomedical Materials Research Part B: Applied Biomaterials (Apr. 2007) pp. 49-57.Applicant
- Masri, Marwan A., et al. “Isolation of Human Fibrinogen of High Purity and in High Yield Using Polyethylene Glycol 1000.” Thromb Haemostas (Struttgart) (1983) vol. 49 (2); pp. 116-119.Applicant
- Matras, Helene, H. P. Dinges, H. Lassmann, and B. Mamoli. “Zur nahtlosen interfaszikularen Nerventransplantation im Tierexperiment.” Wein Med Woschtr 122:37 (1972): 517-523.Applicant
- Minntech® Filtration Technologies Group, “Hemocor HPH® Hemoconcentrator,” Minntech Corporation (2004); http://www.minntech.com/ftg/products/hph/index.html, printed Jul. 15, 2004 (2 pages).Applicant
- Minntech® Filtration Technologies Group, “Medical Applications: Blood Filtration” Minntech Corporation (2004); http://www.minntech.com/ftg/industries/medical/blood—filter.html, printed Jul. 15, 2004 (1 page).Applicant
- Minntech® Filtration Technologies Group, “Renaflo® II Hemofilter,” Minntech Corporation (2004); http://www.minntech.com/ftg/products/renaflo/index.html, printed Jul. 15, 2004 (2 pages).Applicant
- Molnar, Amy, “Stem Cells from Muscles Can Repair Cartilage, Study Finds Genetically Engineered Muscle-Derived Stem Cells Improved Cartilage Repair in Rats”, American College of Rheumatology, (2005).Applicant
- Moretz, W., Jr., J Shea Jr., J. R. Emmett, and J Shea. “A simple autologous fibrinogen glue for otologic surgery.” Otolaryngol Head Neck Surg 95 (Jul. 1986): 122-4.Applicant
- Nakagami, Hironori, et al., “Novel Autologous Cell Tehrapy in Ischemic Limb Disease Through Growth Factor Secretion by Cultured Adipose Tissue-Derived Stromal Cells,” Angiogenesis by Adipose Tissue-Derived Cells, (Dec. 2005) pp. 2542-2547, American Heart Association, Inc.Applicant
- Nathan, Suresh,, et al., “Cell-Based Therapy in the Repair of Osteochondral Defects: A Novel Use for Adipose Tissue,” Tissue Engineering, vol. 9, No. 4 (2003) pp. 733-744 Mary Ann Liebert, Inc.Applicant
- Nilsson, et al., “Bone Repair Induced by Bone Morphogenetic Protein in Ulnar Defects in Dogs,” The Journal of Bone and Joint Surgery, vol. 68 B., No. 4, Aug. 1986.Applicant
- Notice of Allowance mailed Mar. 24, 2011 for U.S. Appl. No. 12/101,586.Applicant
- Notice of Allowance mailed May 27, 2010 for U.S. Appl. No. 12/101,594, filed Apr. 11, 2008.Applicant
- Notice of Allowance mailed Oct. 18, 2011 for U.S. Appl. No. 12/897,401.Applicant
- Office Action (Final) mailed Mar. 18, 2010 for U.S. Appl. No. 12/101,594, filed Apr. 11, 2008.Applicant
- Office Action mailed Feb. 3, 2011 for U.S. Appl. No. 12/101,586, filed Apr. 14, 2008.Applicant
- Office Action mailed Nov. 16, 2010 for U.S. Appl. No. 12/897,401 claiming benefit of U.S. Appl. No. 12/101,594, filed Apr. 11, 2008.Applicant
- Office Action mailed Oct. 16, 2009 for U.S. Appl. No. 12/101,594, filed Apr. 11, 2008.Applicant
- Office Action mailed Sep. 20, 2010 for U.S. Appl. No. 12/101,586, filed Apr. 14, 2008.Applicant
- Orphardt, Charles E., “Denaturation of Proteins,” Virtual Chembook, Elmhurst College (2003) 3 pages. http://www.elmhurst.edu/˜chm/vchembook/568denaturation.html (web accessed Mar. 9, 2011).Applicant
- Otolaryngologic Clinics of North America, vol. 27, No. 1, pp. 203-209, Feb. 1994, Dean M. Toriumi, M.D., et al., “Surgical Tissue Adhesives in Otolaryngology—Head and Neck Surgery”.Applicant
- Parker, Anna M., et al., Adipose-derived stem cells for the regeneration of damaged tissues, Expert Opinion, Cell- & Tissue-based Therapy, Expert Opin. Biol. Ther. (2006) pp. 567-578 Informa UK Ltd.Applicant
- Planat-Bénard, V., et al., “Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells,” Adipose-Derived Cell Cardiomyocyte (Feb. 6, 2004) pp. 223-229 American Heart Association, Inc.Applicant
- Ponticiello, Michael S., “A Rapid Technique for the Isolation and Concentration of Stem Cells from Human Bone Marrow”, Cell Factor Technologies, Inc. (2006) 2 pages.Applicant
- Rangappa, Sunil, M.D., “Transformation of Adult Mesenchymal Stem Cells Isolated From the Fatty Tissue Into Cardiomyocytes,” Adult Stem Cells Transformed into Cardiomyoctyes, (2003) pp. 775-779 Ann Thorac Surg.Applicant
- Rigotti, M.D., et al, “Clinical Treatment of Radiotherapy Tissue Damage by Lipoaspirate Transplant: A Healing Process Mediated by Adipose-Derived Adult Stem Cells,” Plastic and Reconstructive Surgery, Breast, PRS Journal vol. 119, No. 5, Stem Cell Therapy for Angiogenesis, (Apr. 15, 2007) pp. 1409-1422.Applicant
- Rubin, M.D., et al, “Clinical Treatment of Radiotherapy Tissue Damage by Lipoaspirate Transplant: A Healing Process Mediated by Adipose-Derived Adult Stem Cells,” Plastic and Reconstructive Surgery, Discussion vol. 119, No. 5, Stem Cell Therapy for Angiogenesis, (Apr. 15, 2007) pp. 1423-1424.Applicant
- Sanal, M. “Does fibrin glue cause foreign body reactions? [letter].” Eur J Pediatr Surg 3.(1992): 190 (1 page).Applicant
- Sanal, M., H. Dogruyol, A. Gurpinar, and O. Yerci. “Does fibrin glue cause foreign body reactions?” Eu r J Pediatr Surg 2 (1992): 285-6.Applicant
- Schmidt, K.G., et al., “Labelling of Human and Rabbit Platelets with Indium-Oxine Complex”, 23:97-106 (1979).Applicant
- Schmidt, K.G., et al., “Preparation of Platelet Suspensions from Whole Blood in Buffer”, Scand. J. Hoemato, 23:88-96 (1979).Applicant
- Schäffler, Andreas, et al., “Concise Review: Adipose Tissue-Derived Stromal Cells—Basic and Clinical Implications for Novel Cell-Based Therapies,” Tissue-Specific Stem Cells, Stem Cells® (Apr. 10, 2007) pp. 818-827 AlphaMed Press.Applicant
- Semple, Elizabeth, PhD, et al. “Quality of Thrombin Produced From the Patient's Own Plasma Using the TPD™, a New Thrombin-Processing Device.” Journal of American Society of Extra-Corporeal Technology. JECT: 2005; 37:196-200.Applicant
- Sierra, D. H. “Fibrin sealant adhesive systems: a review of their chemistry, material properties and clinical applications.” J Biomater Appl 7 (Apr. 1993): 309-52.Applicant
- Sigma-Aldrich® Alkaline Phosphatase (Procedure No. 85), drug fact sheet, (2003) pp. 1-2, Sigma-Aldrich, Inc.Applicant
- Silver, Frederick H., et al., “REVIEW Preparation and use of fibrin glue in surgery.” Biomaterials 16 (1995) pp. 891-903.Applicant
- Solem, Jan Otto, et al., “Hemoconcentration by Ultrafiltration During Open-Heart Surgery,” Scand J Thor Cardiovasc Surg 22:271-274, 1988.Applicant
- Sutton, Robin G., et al. “Comparison of Three Blood-Processing Techniques During and After Cardiopulmonary Bypass.” Ann Thorac Surg (1993) vol. 56; pp. 941-943.Applicant
- Swift, Mathew J., et al., “Characterization of Growth Factors in Platelet Rich Plasma,” 1-Cell Factor Technologies, http://www.cellfactortech.com/global—products.cfm, printed Sep. 16, 2005.Applicant
- Symphony II Platelet Concentrate System/PCS brochure; “Increasing bone graft bioactivity through reproducible concentrations of natural growth factors,” DePuy (Jan. 2003).Applicant
- Takahashi, Kazutoshi et al., “Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,” Cell, (Nov. 30, 2007) pp. 1-12, Elsevier Inc.Applicant
- The American Journal of Surgery, vol. 168, pp. 120-122, Aug. 1994, Roy L. Tawes, Jr., M.D., et al., “Autologous Fibrin Glue: The Last Step in Operative Hemostatis”.Applicant
- The American Surgeon, vol. 55, pp. 166-168, Mar. 1989, William D. Spotnitz, M.D., et al., “Successful Use of Fibrin Glue During 2 Years of Surgery at a University Medical Center”.Applicant
- The Sports Medicine Center, “Knee Cartilage Implantation”, Carticel™, “Autologous Cultured Chondrocyte Implantation”, http://www.orthoassociates.com/carticel.htm (printed Apr. 6, 2006).Applicant
- The Stone Clinic, “Platelet Rich Plasma (PRP)”, web site printed May 2006.Applicant
- Weis-Fogh, U. S. “Fibrinogen prepared from small blood samples for autologous use in a tissue adhesive system.” Eur Surg Res 20 (1988): 381-9.Applicant
- Weisman, MD., Robert A., “Biochemical Characterization of Autologous Fibrinogen Adhesive,” Laryngoscope 97: Oct. 1987; pp. 1186-1190.Applicant
- Wiseman, David M., David T. Rovee, and Oscar M. Alverez. “Wound Dressings: Design and Use.” In Wound Healing: Biochemical & Clinical Aspects,ed. I. Kelman Cohen, Robert F. Diegelmann, and William J. Lindblad. 562-580. 1st ed., vol. Philadelphia: W. B. Saunders Company, 1992.Applicant
- Woodell-May, et al., “Producing Accurate Platelet Counts for Platelet Rich Plasma: Validation of a Hematology Analyzer and Preparation Techniques for Counting,” Scientific Foundation, Journal of Carniofacial Surgery 16(5):749-756 (Sep. 2005).Applicant
- Written Opinion of the International Preliminary Examining Authority mailed Mar. 17, 2009 for International Application No. PCT/US2008/004687 which claims priority to U.S. Appl. No. 60/911,407, filed Apr. 12, 2007.Applicant
- Yoon, Eulsik, M.D., Ph.D., et al., “In Vivo Osteogenic Potential of Human Adipose-Derived Stem Cells/Poly Lactide-Co-Glycolic Acid Constructs for Bone Regneration in a Rat Critical-Sized Calvarial Defect Model,” Tissue Engineering, vol. 13, No. 3 (2007) pp. 619-627 Mary Ann Liebert, Inc.Applicant
- Zhang, Duan-zhen, et al., “Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction,” Chinese Medical Journal, vol. 120, No. 4 (2007) pp. 300-307 General Hospital of Shenyang Military Region, Shenyang, China.Applicant
- Zuk, Patricia A., Ph.D., “Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies,” Tissue Engineering, vol. 7, No. 2, (2001) pp. 211-228 Mary Ann Liebert, Inc.Applicant