US3647070A - Method and apparatus for the provision of fluid interface barriers - Google Patents

Method and apparatus for the provision of fluid interface barriers Download PDF

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US3647070A
US3647070A US47495A US3647070DA US3647070A US 3647070 A US3647070 A US 3647070A US 47495 A US47495 A US 47495A US 3647070D A US3647070D A US 3647070DA US 3647070 A US3647070 A US 3647070A
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barrier
interface
plasma
blood
container
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Stanford L Adler
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Bayer Corp
Technicon Corp
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Technicon Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/49Blood
    • G01N33/491Blood by separating the blood components

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  • ABSTRACT New and improved method and apparatus for the provision of a satisfactory physical and chemical barrier at a fluid interface in the nature of that which occurs at the interface of the separated plasma and packed cells layers in centrifuged blood samples are provided, and are embodied by barrier means which are of greater specific gravity than said blood plasma layer but lesser specific gravity than said blood cells layer and are operable, upon insertion into a centrifuged blood sample container, to sink through said blood plasma layer substantially to said interface and to be wetted and expanded by said blood plasma to expand into firm contact with each other and with the walls of said container to automatically form said barrier at said interface.
  • a'result it may be understood to be standard laboratory procedure, following the suitable centrifugation of each of said blood samples to separate the blood sample plasma or serum and blood sample cells into contiguous layers.(it being the plasma or serum which is to be analyzed), to manually decant or otherwise remove the plasma or serum from the packed cells portion of a centrifuged blood sample prior to the analysis thereof to prevent unwanted'changes in some of the blood sampleconstituents of said plasma or serum for which said automated analysis is to be effected.
  • such constituents may, for example, include serum potassium, glucose, and certain blood enzymes, and that said unwanted changes therein would occur as a result of ionic or other contaminant diffusion from said cells to said plasma or serum layer at the interface thereof.
  • barrier devices are known: in the prior art which may be inserted or added to the container of a blood sample which has been separated by centrifugation into a plasma or serum layer and a packed cells layer, it may be understood that such devices will not, in general, be found to provide both the requisite satisfactory physical and chemical separation that is required in order to enable the respective plasma and packed cells layers to remain in the same container, to render loss of identification of the former impossible, while substantially preventing adverse effects upon the subsequent auto- OBJECTS OF THE INVENTION It is, accordingly, an object of this invention to provide new and improved method and apparatus for the satisfactory physical and chemical separation between separated fluid layers of differing densities within the same container.
  • Another object of this invention is the provision of apparatus as above which are automatically and accurately operable upon the insertion thereof into said separated fluid layers within said container.
  • Another object of this invention is the provision of apparatus as above which are of particularly low cost.
  • Another object of this invention is the provision of method and apparatus as above which are particularly adapted for use in conjunction with automated fluid processing and testing equipment.
  • a further-object-of' this invention isthe provision of method and apparatus as above which are particularly adapted for use inpmviding for the satisfactory physicaland chemical separation in the same container between the respective plasma or serum and packed cells layers of centrifuged blood samples.
  • .thenew and improved method and apparatus of the invention comprise .the addition of barrier means to the .tubelike container of a centrifuged blood sample which has-been separated into aplasma or serum layer and a more dense ,packed cells'layer.
  • Said barrier means may, for example take granular, ellipsoidal, disclike or spherical form, and maybe made from areadily wettable and expandable materialin the nature of a nonionic hydrophilic polymer, or a synthetic, sponge.
  • the specific gravity of said barrier means is predetermined to be greater than that of said plasma and less than that of said packed cells.
  • said-barrier means Upon additionto the centrifuged blood sample, said-barrier means will 'sin'k through said plasma .layer for suspension in the same at the plasma/packed cells interface, will be wetted by said plasma and expanded for adhesiveand cohesive-formation of a barrier at said'interfacein said container to physically and chemically separate said plasma and packed cells layers and prevent cellular diffusion from the latter to the former.
  • said barrier means comprise sleeve and stopper means which are operatively associated with'said centrifuged blood container andare automaticallyoperable upon appropriate insertion thereinto to form the desired physical and chemical barrier between said plasma and packed cells layers.
  • FIG. 1 is a perspectiveview of a first form of barrier means constructed in accordance withthe teachings of this invention
  • FIGS. 2 and 3 illustrate the application of the barrier means of FIG. lato a centrifuged blood sample
  • FIG. 4 is a perspective view of a second form of barrier means constructed in accordance with the teachings of this in- -vention
  • FIGS. 5 and 6 illustrate the application of the barrier means of F IG. 4 to a centrifuged blood sample
  • FIG. 7 is a perspective view of another form of barrier device constructed inaccordance with the teachings of this invention.
  • FIG. 8 is a perspective view of still another form of barrier means constructed in accordance-with the teachings of this invention.
  • FIG.9 is a cross-sectional view of automatic, barrier means dispensing means
  • FIG. 10 illustrates the barrier means dispensing means of FIG.'9 in operativerelationship with-blood sample processing equipment
  • FIGS. 11 :through 14 illustrate another form of the barrier means of the invention.
  • FIG..:15 illustrates a modification of the form of the barrier means of the invention of FIGS. 11 through 14.
  • a form of the new and improved plasma/cells barrier means of the invention is indicated generally'at l0'and comprises a plurality of granules 12 of a suitable material in the nature of a nonionic, hydrophylic polymer, or othermaterial, that would function in a similar manner inthe presence of a plasma liquid.
  • the granules 12 may, for example, be formed from the nonionic, hydrophylic polymers identified as polyhydroxyethylmethacrylate, or polyacrylamide hydrogel, and, as such, would of course have a substantial affinity for water and would be expandable in all directions upon the wetting thereof by a plasma or serum liquid.
  • the specific gravity of the granules 12 is controlled in the formation thereof to insure that the same will be denser than blood plasma or serum, but less dense than the packed blood cells so that said granules will float substantially at the interface of separated plasma and cells.
  • a suitable blood sample container or tube which may, for example, take the form of a Vacutainer, is indicated at 14 and includes therein a blood sample which has been separated by appropriate centrifugation into a packed cell layer 18 and a plasma or serum layer 16 having an interface 20, the introduction as illustrated of a plurality of the granules 12 into the centrifuged blood sample container 14 will result in the said granules sinking through the less dense plasma layer 16 to float at or assume the depicted position thereof in said plasma layer substantially at the interface of the same and the more dense packed cells layer 18.
  • the wetting of the granules 12 by the plasma liquid will, of course, soon commence the expansion of the former substantially in all directions with the result that the said granules will expand into firm cohesive and adhesive contact with each other and with the inner wall surface of the tube 14 to ultimately form a substantially integral plug 22 as depicted in FIG. 3 at the plasma/cells interface 20.
  • the length of time required for the information of plug 22 will be dependent, in part, upon the compacting pressure utilized in the formation of the granules 12 and may, for example, be arranged to occur within three to ten minutes as desired.
  • the plug 22 will be effective to prevent ionic and/or other cellular contaminant diffusion between the packed cells layer 18 and the plasma or serum layer 16 to thus prevent changes that might otherwise occur in some of the blood constituents, such as serum potassium, glucose and certain enzymes, for which subsequent quantitative analyses may be performed on said plasma or serum layer. Accordingly is believed made clear that the actual physical and chemical separation provided by the plug 22 between the plasma or serum layer 16 and the packed cells layer 18 will, under normal use and environmental conditions, be the substantial equivalent of that which would be provided by independent tubes or containers therefor.
  • the same may be seen to take the shape of a disc 24 which may, for example, be made from the same nonionic, hydrophilic polymeric materials referred to hereinabove with regard to the granules 12 of FIG. 1.
  • the specific gravity of the disc 24 is again controlled in the formation thereof as through variation in the amount of compacting pressure utilized in disc formation to provide a disc which is more dense than the plasma or serum and less dense than the packed cells.
  • something in the range, for example, of 500 to 10,000 p.s.i. compacting pressure has proven particularly suitable in providing a disc 24 of lesser density than the packed cells layer 18 but of greater density than the plasma or serum layer 16.
  • the wetting of the disc 24 by the plasma liquid will result in the expansion of the disc polymer as described into firm cohesion, and into firm adhesive contact with the inner wall surface of the tube 14, to the relative size and position of the disc 24 as depicted in FIG. 6 to form the desired physical and chemical plasma/cells barrier.
  • the plug or barrier formed by the expanded disc 24 will actually exert physical pressure against the inner wall surface of the blood sample container 14 and will be effective to maintain the desired plasma/cells separation despite reasonable container vibration and/or turning over of the latter.
  • FIG. 7 Another form of the plasma/cells barrier means of the invention is illustrated in FIG. 7 and may be seen to take the form of an elipsodial member 28 which may again, for example, be made from the nonionic, hydrophilic polymeric materials discussed hereinabove and will, of course, function in the nature of the disc 24 of FIG. 4 to provide the desired physical and chemical barrier between the plasma or serum layer 16 and the packed cells layer 18. More specifically, it is believed clear that the elipsoid 28 would be so dimensioned that the diameter D (FIG. 7) thereof would be somewhat less than the internal diameter of the blood sample container or tube 14 whereby the elipsoid 28 may be oriented as depicted in FIG.
  • FIG. 8 Another form of the plasma/cell barrier means of the invention is indicated at 30 in FIG. 8 and, as depicted therein, may be seen to again take the shape of a disc which, in this instance, is preferably made from a compressed synthetic sponge material in the nature of an insoluble cellulose sponge material which is compacted under suitable pressure to provide for the desired density thereof relative to the respective plasma or serum and cells layers as discussed hereinabove, and which may, in addition, be coated with one or more layers of a solution of the nonionic, hydrophilic polymeric materials referred to hereinabove to delay the wetting thereof by the plasma liquid.
  • the use of a number of coatings of such polymeric materials of the disc 30 as may be applied, for example, by the clipping of the said disc in a solution of said polymeric materials, will function to provide for a time delay to delay the wetting and attendant expansion of the synthetic sponge material until the disc 30 has assumed the proper level in the blood sample container 14 just above the plasma/cells interface 20 in the manner clearly illustrated for the disc 24 in FIGS. 5 and 6.
  • the function of the synthetic sponge material disc 30 is, of course, quite analogous to that of the nonionic, hydrophillic polymeric material disc 24 of FIG. 2 in that the wetting of the former by the plasma liquid will, of course, effect the expansion thereof against the inner wall surfaces of the tube 14 to thus provide the desired physical and chemical plasma/cells separation.
  • Automatic dispensing apparatus for the automatic dispensing of discs in the nature of 24 or 30 into Vacutainers or other containers 14 which contain centrifuged blood sampics including a plasma or serum layer 16 and a packed cells layer 18, are indicated generally at 31 in FIG. 9 and, as depicted therein, may be seen to comprise a generally elongated, cylindrical container 32 having a base plate 34 and within which are stacked as shown a plurality of said discs as here indicated at 36.
  • a disc dispensing slot is indicated-at 37 and is formed as shown at the lower extremity of the disc container 32.
  • a leafspring is indicated at 38 and is affixedas indicated to the disc container 32 by attachment means40.
  • a slot 42 is provided in the container 32 adjacent the lower extremity thereof and the adjacent end 44 of the leafspring 38 is extendable therethrough as shown.
  • a cam is indicated at 46 and is drivingly rotatable about an axis 48. The cam 46 and leafspring 38 are cooperatively associated as depicted in such manner that each rotation of the former will be effective to move the latter from the position thereof depicted in solid lines to the position thereof depicted in dashed lines within the container and enable the return thereof to the former position.
  • a cap 50 is provided for the container 32, and a coilspring 52 is operatively associated therewith and with plunger means 54 to maintain a substantial downward pressure of the stack of discs 36.
  • the disc dispenser 31 and tube 14 are preferably arranged in such manner that the disc 36a will enter the said plasma layer substantially edge-first to thus substantially prevent or inhibit such entrapment of air.
  • FIG. 10 An application of the automatic disc dispenser 31 to the insertion of a barrier disc in each of a plurality of tubes 14 as are supported in a generally circular array thereof on the blood sample tray of a sample tray centrifuge is depicted in FIG. 10, and as seen therein, comprises said sample tray as indicated at 56 which is rotatable at high speed from drive motor 58 through drive shaft 60.
  • the sample tray 56 would be rotated by drive motor 58 at high speed while the respective blood sample containers 14 would be allowed to pivot radially outwardly from the respective upper portions thereof as well known to those skilled in this art to effect the centrifuging of the respective blood samples contained therein.
  • the disc dispenser means 31 would be operatively positioned relative thereto as shown and operated, through rotation of cam 46 in synchronism with the indexing of the sample tray 56 through each individual blood sample tube position thereof, to automatically dispense a barrier disc as again illustrated by disc 36a into each of said blood sample tubes to effect the provision of a satisfactory physical and chemical barrier between the respective, separated plasma or serum and packed cells layers as are now contained in each of said tubes.
  • the sample tray 56 may, if desired, be readily and conveniently operatively positioned on automated blood sample supply, treatment and analysis means of the nature disclosed, for example, in saidU.S. Pat. No. 3,241,432, for the subsequent, automated quantitative analysis of the separated plasma or serum portion of each of said blood samples with regard to'a plurality of constituents thereof.
  • the new and improved plasma/cells barrier means of the invention provides a satisfactory physical and chemical barrierbetween the respective separated plasma and packed cells layers of each of said blood samples to thus prevent changes inthe former as might otherwise occur to inhibit the accurate quantitative analysis thereof while, at the same time, rendering substantially impossible any loss of identification of a said blood sample by insuring that the respective separated plasma and packed cells layers thereof are maintained in the same tube.
  • loss or mixup in blood sample identification insofar as confusion of the separated plasma and packed cells from the same blood sample is concerned, are rendered substantially impossible.
  • a further form of the new 'and improved plasma/cells barrier means of the invention is indicated generally at 62 in FIGS. 11 through 14- and, as best seen in FIGS. 11 and 12, comprises a container assembly 63 including a Vacutainer or like tube 64 having a sleeve 66 insertable thereinto as shown in generally fluidtight manner as providedby annual stop 68 and generally wedge-shaped soft plastic sealing ring 70.
  • the sleeve 66 terminates as shown in a generally truncated cone-shaped end portion 72 having an opening 74 formed centrally thereofand screw threads 76 formed on the exterior surface thereof.
  • a sample sleeve cap 78 (FIG. 11) is provided, as is asleeve cap 80 (FIG. 12) which includes a glass or plastic rod 82 extending therefrom as shown and terminating in a plug or stopper 84 which is effective to substantially plug the opening 72 as illustrated in FIG. 42.
  • An end portion cap 86 which is screw threaded as indicated at 88, is also provided and is effective to screw over the sleeve end portion 72 to seal the same as illustrated in FIG. 13.
  • the container assembly 63 which may, for example, contain a suitable anticoagulant, is filled with a whole blood sample and mixed, following which the cap 78 is removed.
  • the said container assembly is then centrifuged to result in the separation of said blood sample into a plasma or serum layer and a packed cells layer 92 having an interface 94, and it may be understood that the distance between the upper end of sleeve opening 74 and the bottom of container 64 is predetermined, in accordance with the largest anticipated volume of the packed cells after configuration, to insure that said interface94 falls as shown below the upper end of the opening 74.
  • Knowledge that the volume of packed cells will rarely, if ever, exceed 60 percent of the total blood sample volume will, of course, be a principal factor in such distance determination.
  • cap 80 containing rod 82 and stopper 84 is inserted as shown into sleeve 66 with resultant substantial sealing of the opening 74 by stopper 84 and attendant containment of plasma or serum, only, from plasma or serum layer 90' in the now completed sleeve assembly.
  • said plasma-containing completed sleeve assembly is removed from the tube 64 in obvious manner and thethreaded cover 86 is attached as illustrated in FIG. 13 to the sleeve end portion 72 to insure a leakproof blood plasma or serum container for plasma shipment if desired.
  • sleeve 66 and tube 64 Of particular significance with regard to the sleeve 66 and tube 64 is the face that the same originate as the same container assembly 63 and would be so marked by appropriate blood sample identification information formed on each prior to separation thereof, whereby loss of identification, for example, of the separated plasma or serum layer removed therefrom as described is, of course, rendered impossible.
  • cap 80 including rod 82 and stopper 84 may be eliminated and far simpler sleeve-opening closure means substituted therefor. More specifically, such sleeve-opening closure means may be seen to take the form of a simple metal or plastic ball 94 of suitable density which, when dropped into the plasma or serum layer 90, will sink therethrough to occupy and close the sleeve opening 74 and substantially prevent the flow of said plasma or serum layer therefrom upon removal as described of the sleeve 66 from the tube 64. More sturdy closure of the opening 74 may, of course, be readily effected by attachment as described of the threaded cover 86 to the lower end of the sleeve 66.
  • a method of effecting the substantial physical and chemical separation of the respective blood plasma and blood cell layers of a blood sample, which resulted from the centrifugation thereof, by the formation of a physical and chemical barrier in the blood sample container substantially at the interface of said blood plasma and blood cell layer comprising the steps of, inserting barrier means into said blood sample container and through said blood plasma layer, so as to be located substantially at said interface, structuring said barrier means to pass freely through said blood plasma layer and to be ineffective to form said barrier when initially positioned at said interface, and forming said barrier means of a material having a greater specific gravity than said blood plasma layer but a lesser specific gravity than said blood cell layer, so as to sink through said blood plasma layer to said interface, said material forming said barrier means characterized as being expandable when wetted, so as to expand into firm contact with the walls of said container to define said barrier at said interface.
  • barrier means for insertion into said blood sample container, said barrier means being structured to pass freely through said blood plasma layer, so as to be located substantially at said interface and to be ineffective to define a barrier when initially located at said interface, said barrier means comprising a material having a greater specific gravity than said blood plasma layer and a lesser specific gravity than said blood cell layer, so as to sink through said blood plasma layer to said interface, said material characterized as being expandable when wetted, so as to expand into firm contact with the walls of said container to define said barrier at said interface.
  • said barrier means comprises granules of said expandable material, said granules, when wetted, expanding into firm contact with eachother and with the walls of said container to define said barrier at said interface.
  • said barrier means is formed of a single body of said material, said 'body, when wetted, expanding into firm contact the walls of said container to define said barrier at said interface.
  • said material is an nonionic, hydrophylic polymeric material selected from the group consisting of polyhydroxyethylmethacrylate and polyacrylamide hydrogel.
  • said material is an insoluble cellulose spongelike material having one or more coatings of a nonionic, hydrophylic polymeric material applied thereto to delay the wetting and separation thereof until said body is located substantially at said interface.

Abstract

New and improved method and apparatus for the provision of a satisfactory physical and chemical barrier at a fluid interface in the nature of that which occurs at the interface of the separated plasma and packed cells layers in centrifuged blood samples are provided, and are embodied by barrier means which are of greater specific gravity than said blood plasma layer but lesser specific gravity than said blood cells layer and are operable, upon insertion into a centrifuged blood sample container, to sink through said blood plasma layer substantially to said interface and to be wetted and expanded by said blood plasma to expand into firm contact with each other and with the walls of said container to automatically form said barrier at said interface.

Description

United States Patent Adler [54] METHOD AND APPARATUS FOR THE PROVISION OF FLUID INTERFACE BARRIERS [72] Inventor: Stanford L. Adler, Monsey, NY.
[73] Assignee: Technicon Corporation, Tarrytown, NY.
[22] Filedz June 11, 1970 [21] Appl. No.: 47,495,
[52] US. Cl ..2l0/83, 210/361, 210/516, 210/518 [51] Int. Cl ..B0ld 21/26 [58] FieldofSearch ..210/78, 83, 361,362
[56] References Cited UNITED STATES PATENTS 3,437,266 4/1969 Patterson ..210/361 X 3,508,653 4/1970 Coleman ..210/83 1 Mar. 7, 1972 2,858,940 11/1958 Calvert; ..210/5l6 3,499,531 3/1970 Feasel ..210/114 Primary ExaminerJohn Adee Attorney-S. P. Tedesco and Stephen E. Rockwell [57] ABSTRACT New and improved method and apparatus for the provision of a satisfactory physical and chemical barrier at a fluid interface in the nature of that which occurs at the interface of the separated plasma and packed cells layers in centrifuged blood samples are provided, and are embodied by barrier means which are of greater specific gravity than said blood plasma layer but lesser specific gravity than said blood cells layer and are operable, upon insertion into a centrifuged blood sample container, to sink through said blood plasma layer substantially to said interface and to be wetted and expanded by said blood plasma to expand into firm contact with each other and with the walls of said container to automatically form said barrier at said interface.
7 Claims, 15 Drawing Figures METHOD AND APPARATUS FOR THEPROVISION OF FLUID INTERFACE BARRIERS BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to new and improved method and apparatus for theprovision of asatisfactory physical and chemical barrier at a fluid interface in the nature of that which occurs at the interface of the separated plasma or serum and packed cells layers in centrifuged blood samples.
2. Description of the Prior Art In the automatic analysis of-blood samples through the use of improved versions of automated analysis apparatus in the nature of those described in US. Pat. No. 3,241,432, issued Mar. 22, 1966, to Dr. Leonard P. Skeggs, et al. and assigned to the assignee hereof, and marketed for example as the SMA 12/60 Auto-Analyzer by said assignee, it may be understood that a not insubstantial period of time may'elapse between the removal of the blood sample tobe analyzed from the patient in question and the automated processing and analysis of said blood sample by said analysis apparatus. As a'result, it may be understood to be standard laboratory procedure, following the suitable centrifugation of each of said blood samples to separate the blood sample plasma or serum and blood sample cells into contiguous layers.(it being the plasma or serum which is to be analyzed), to manually decant or otherwise remove the plasma or serum from the packed cells portion of a centrifuged blood sample prior to the analysis thereof to prevent unwanted'changes in some of the blood sampleconstituents of said plasma or serum for which said automated analysis is to be effected. More specifically, it may be understood that such constituents may, for example, include serum potassium, glucose, and certain blood enzymes, and that said unwanted changes therein would occur as a result of ionic or other contaminant diffusion from said cells to said plasma or serum layer at the interface thereof.
The significant disadvantages of this manual plasma/cells separation technique insofar'as the tediousness and time consuming nature thereof are believed readily apparent. Of even more significant disadvantage, however, is the fact that the same gives rise to the basically unacceptable risk of the loss of blood sample identification that can occur as a result of the transfer of a portion (here the separated plasma or serum) of a blood sample from the original container bearing the blood sample identification information to another container, and the necessity for accurate transcription of 'thebloodsample identification information along to said other container. Thus, and although barrier devices are known: in the prior art which may be inserted or added to the container of a blood sample which has been separated by centrifugation into a plasma or serum layer and a packed cells layer, it may be understood that such devices will not, in general, be found to provide both the requisite satisfactory physical and chemical separation that is required in order to enable the respective plasma and packed cells layers to remain in the same container, to render loss of identification of the former impossible, while substantially preventing adverse effects upon the subsequent auto- OBJECTS OF THE INVENTION It is, accordingly, an object of this invention to provide new and improved method and apparatus for the satisfactory physical and chemical separation between separated fluid layers of differing densities within the same container.
Another object of this invention is the provision of apparatus as above which are automatically and accurately operable upon the insertion thereof into said separated fluid layers within said container.
Another object of this invention is the provision of apparatus as above which are of particularly low cost.
Another object of this invention is the provision of method and apparatus as above which are particularly adapted for use in conjunction with automated fluid processing and testing equipment.
A further-object-of' this inventionisthe provision of method and apparatus as above which are particularly adapted for use inpmviding for the satisfactory physicaland chemical separation in the same container between the respective plasma or serum and packed cells layers of centrifuged blood samples.
SUMMARYOF THE DISCLOSURE As disclosed herein, .thenew and improved method and apparatus of the invention comprise .the addition of barrier means to the .tubelike container of a centrifuged blood sample which has-been separated into aplasma or serum layer and a more dense ,packed cells'layer. Said barrier means may, for example take granular, ellipsoidal, disclike or spherical form, and maybe made from areadily wettable and expandable materialin the nature of a nonionic hydrophilic polymer, or a synthetic, sponge. The specific gravity of said barrier means is predetermined to be greater than that of said plasma and less than that of said packed cells. Upon additionto the centrifuged blood sample, said-barrier means will 'sin'k through said plasma .layer for suspension in the same at the plasma/packed cells interface, will be wetted by said plasma and expanded for adhesiveand cohesive-formation of a barrier at said'interfacein said container to physically and chemically separate said plasma and packed cells layers and prevent cellular diffusion from the latter to the former. In other disclosed forms, said barrier means comprise sleeve and stopper means which are operatively associated with'said centrifuged blood container andare automaticallyoperable upon appropriate insertion thereinto to form the desired physical and chemical barrier between said plasma and packed cells layers.
'DESCRIPTION'OF THE'DRAWINGS Theaboveand other objects and significant advantages of this invention are believed made clear by the following detailed description thereof taken in conjunction with the accompanying drawings wherein:
FIG. 1 is a perspectiveview of a first form of barrier means constructed in accordance withthe teachings of this invention;
FIGS. 2 and 3 illustrate the application of the barrier means of FIG. lato a centrifuged blood sample;
FIG. 4 isa perspective view of a second form of barrier means constructed in accordance with the teachings of this in- -vention;
FIGS. 5 and 6 illustrate the application of the barrier means of F IG. 4 to a centrifuged blood sample;
FIG. 7 is a perspective view of another form of barrier device constructed inaccordance with the teachings of this invention;
FIG. 8 is a perspective view of still another form of barrier means constructed in accordance-with the teachings of this invention;
FIG.9 is a cross-sectional view of automatic, barrier means dispensing means;
FIG. 10 illustrates the barrier means dispensing means of FIG.'9 in operativerelationship with-blood sample processing equipment;
FIGS. 11 :through 14 illustrate another form of the barrier means of the invention; and
FIG..:15 illustrates a modification of the form of the barrier means of the invention of FIGS. 11 through 14.
DETAILED DESCRIPTION OF THE INVENTION Referring'now to FIG. 1, a form of the new and improved plasma/cells barrier means of the invention is indicated generally'at l0'and comprises a plurality of granules 12 of a suitable material in the nature of a nonionic, hydrophylic polymer, or othermaterial, that would function in a similar manner inthe presence of a plasma liquid. More specifically, the granules 12 may, for example, be formed from the nonionic, hydrophylic polymers identified as polyhydroxyethylmethacrylate, or polyacrylamide hydrogel, and, as such, would of course have a substantial affinity for water and would be expandable in all directions upon the wetting thereof by a plasma or serum liquid.
For use in accordance with the teachings of this invention in providing for a satisfactory barrier between the separated plasma or serum and packed cells portions of a blood sample as illustrated in FIGS. 2 and 3, it may be understood that the specific gravity of the granules 12 is controlled in the formation thereof to insure that the same will be denser than blood plasma or serum, but less dense than the packed blood cells so that said granules will float substantially at the interface of separated plasma and cells.
More specifically, and as best seen in FIG. 2 wherein a suitable blood sample container or tube which may, for example, take the form of a Vacutainer, is indicated at 14 and includes therein a blood sample which has been separated by appropriate centrifugation into a packed cell layer 18 and a plasma or serum layer 16 having an interface 20, the introduction as illustrated of a plurality of the granules 12 into the centrifuged blood sample container 14 will result in the said granules sinking through the less dense plasma layer 16 to float at or assume the depicted position thereof in said plasma layer substantially at the interface of the same and the more dense packed cells layer 18. As this occurs, it may be understood that the wetting of the granules 12 by the plasma liquid will, of course, soon commence the expansion of the former substantially in all directions with the result that the said granules will expand into firm cohesive and adhesive contact with each other and with the inner wall surface of the tube 14 to ultimately form a substantially integral plug 22 as depicted in FIG. 3 at the plasma/cells interface 20. The length of time required for the information of plug 22 will be dependent, in part, upon the compacting pressure utilized in the formation of the granules 12 and may, for example, be arranged to occur within three to ten minutes as desired.
The extent of this expansion of the granules 12 will be sufficient to actually give rise to an outwardly directed physical pressure on said inner wall surface of the tube 14, whereby may be understood that the thusly formed plug or barrier 22 will provide a firm and not readily displaceable physical barrier between the plasma layer 16 and packed cells 18, which barrier will be capable of withstanding substantial vibration without fracture, and will be of sufficient strength to enable the turning over of the tube 14 without packed cells spillage or runoff into said plasma layer.
In addition to providing for an excellent physical barrier between the plasma layer 16 and the packed cells layer 18, it may be understood that the plug 22 will be effective to prevent ionic and/or other cellular contaminant diffusion between the packed cells layer 18 and the plasma or serum layer 16 to thus prevent changes that might otherwise occur in some of the blood constituents, such as serum potassium, glucose and certain enzymes, for which subsequent quantitative analyses may be performed on said plasma or serum layer. Accordingly is believed made clear that the actual physical and chemical separation provided by the plug 22 between the plasma or serum layer 16 and the packed cells layer 18 will, under normal use and environmental conditions, be the substantial equivalent of that which would be provided by independent tubes or containers therefor.
Referring now to the form of the plasma/cell barrier means of the invention as depicted in FIG. 4, the same may be seen to take the shape of a disc 24 which may, for example, be made from the same nonionic, hydrophilic polymeric materials referred to hereinabove with regard to the granules 12 of FIG. 1. The specific gravity of the disc 24 is again controlled in the formation thereof as through variation in the amount of compacting pressure utilized in disc formation to provide a disc which is more dense than the plasma or serum and less dense than the packed cells. In this regard, it may be understood that something in the range, for example, of 500 to 10,000 p.s.i. compacting pressure has proven particularly suitable in providing a disc 24 of lesser density than the packed cells layer 18 but of greater density than the plasma or serum layer 16.
For use in accordance with the teachings of this invention in providing for a satisfactory chemical and physical barrier between the respective separated plasma or serum and packed cells layers 16 and 18 of a Vacutainer or like tube 14 containing an appropriately centrifuged blood sample as depicted in FIGS. 5 and 6, it may be understood that the disc 24 would initially be dimensioned so that the same would fit with suitable clearance as indicated at 26 within the tube 14, whereby is believed made clear that insertion of said disc thereinto will, of course, result in said disc sinking through the plasma layer 16 and coming to rest substantially in the latter at the plasma/cells interface 20 substantially as depicted in FIG. 5.
Following this, it may be understood that the wetting of the disc 24 by the plasma liquid will result in the expansion of the disc polymer as described into firm cohesion, and into firm adhesive contact with the inner wall surface of the tube 14, to the relative size and position of the disc 24 as depicted in FIG. 6 to form the desired physical and chemical plasma/cells barrier. Again, as discussed hereinabove with regard to the granules 12, it may be understood that the plug or barrier formed by the expanded disc 24 will actually exert physical pressure against the inner wall surface of the blood sample container 14 and will be effective to maintain the desired plasma/cells separation despite reasonable container vibration and/or turning over of the latter.
Another form of the plasma/cells barrier means of the invention is illustrated in FIG. 7 and may be seen to take the form of an elipsodial member 28 which may again, for example, be made from the nonionic, hydrophilic polymeric materials discussed hereinabove and will, of course, function in the nature of the disc 24 of FIG. 4 to provide the desired physical and chemical barrier between the plasma or serum layer 16 and the packed cells layer 18. More specifically, it is believed clear that the elipsoid 28 would be so dimensioned that the diameter D (FIG. 7) thereof would be somewhat less than the internal diameter of the blood sample container or tube 14 whereby the elipsoid 28 may be oriented as depicted in FIG. 7 and inserted with clearance into the tube 14, in the manner of the disc 24 as depicted in FIG. 5, sink through the plasma layer 16 substantially to the plasma/cell interface 20, and expand through the wetting thereof by the plasma liquid into firm surface contact with the inner wall surface of the tube 14 to form the desired physical and chemical plasma/cells barrier.
Another form of the plasma/cell barrier means of the invention is indicated at 30 in FIG. 8 and, as depicted therein, may be seen to again take the shape of a disc which, in this instance, is preferably made from a compressed synthetic sponge material in the nature of an insoluble cellulose sponge material which is compacted under suitable pressure to provide for the desired density thereof relative to the respective plasma or serum and cells layers as discussed hereinabove, and which may, in addition, be coated with one or more layers of a solution of the nonionic, hydrophilic polymeric materials referred to hereinabove to delay the wetting thereof by the plasma liquid. More specifically, it may be understood that the use of a number of coatings of such polymeric materials of the disc 30 as may be applied, for example, by the clipping of the said disc in a solution of said polymeric materials, will function to provide for a time delay to delay the wetting and attendant expansion of the synthetic sponge material until the disc 30 has assumed the proper level in the blood sample container 14 just above the plasma/cells interface 20 in the manner clearly illustrated for the disc 24 in FIGS. 5 and 6. The function of the synthetic sponge material disc 30 is, of course, quite analogous to that of the nonionic, hydrophillic polymeric material disc 24 of FIG. 2 in that the wetting of the former by the plasma liquid will, of course, effect the expansion thereof against the inner wall surfaces of the tube 14 to thus provide the desired physical and chemical plasma/cells separation.
Automatic dispensing apparatus for the automatic dispensing of discs in the nature of 24 or 30 into Vacutainers or other containers 14 which contain centrifuged blood sampics including a plasma or serum layer 16 and a packed cells layer 18, are indicated generally at 31 in FIG. 9 and, as depicted therein, may be seen to comprise a generally elongated, cylindrical container 32 having a base plate 34 and within which are stacked as shown a plurality of said discs as here indicated at 36. A disc dispensing slot is indicated-at 37 and is formed as shown at the lower extremity of the disc container 32.
A leafspring is indicated at 38 and is affixedas indicated to the disc container 32 by attachment means40. A slot 42 is provided in the container 32 adjacent the lower extremity thereof and the adjacent end 44 of the leafspring 38 is extendable therethrough as shown. A cam is indicated at 46 and is drivingly rotatable about an axis 48. The cam 46 and leafspring 38 are cooperatively associated as depicted in such manner that each rotation of the former will be effective to move the latter from the position thereof depicted in solid lines to the position thereof depicted in dashed lines within the container and enable the return thereof to the former position. A cap 50 is provided for the container 32, and a coilspring 52 is operatively associated therewith and with plunger means 54 to maintain a substantial downward pressure of the stack of discs 36.
With the respective components of the plasma/cells barrier means dispenser 31 arranged and operative as described, and a container 14 of a centrifuged blood sample arranged relative thereto as shown, it is believed clear that each complete, driven rotation of the cam 46 will be effective to dispense one of the discs 36 from the container 42, under the action of the end 44 of leafspring 38 thereon, into the adjacent container 14 of a centrifuged blood sample in the manner and along the general trajectory as indicated by the just-dispensed barrier disc 36a and the dashed lines drawn therewith. For purposes of preventing entrapment of air by the said disc as the same enters the plasma layer 16 in the tube 14, it may be understood that the disc dispenser 31 and tube 14 are preferably arranged in such manner that the disc 36a will enter the said plasma layer substantially edge-first to thus substantially prevent or inhibit such entrapment of air.
Following such dispensing of the disc 36a in the manner described, it is believed clear that the same will, of course, sink through the plasma layer 16 to the desired position thereof just at the plasma/packed cells interface 20 and, after the expiration of the predetermined period of wetting time, will expand into firm contact with the inner surface wall of the tube 14 to thus provide the desired physical andchemical barrier as described in detail hereinabove.
An application of the automatic disc dispenser 31 to the insertion of a barrier disc in each of a plurality of tubes 14 as are supported in a generally circular array thereof on the blood sample tray of a sample tray centrifuge is depicted in FIG. 10, and as seen therein, comprises said sample tray as indicated at 56 which is rotatable at high speed from drive motor 58 through drive shaft 60. For centrifugation of the respective blood samples which are contained in the tubes 14, it may be understood that the sample tray 56 would be rotated by drive motor 58 at high speed while the respective blood sample containers 14 would be allowed to pivot radially outwardly from the respective upper portions thereof as well known to those skilled in this art to effect the centrifuging of the respective blood samples contained therein.
Following this, and after the sample tray 56 has come to a halt, the disc dispenser means 31 would be operatively positioned relative thereto as shown and operated, through rotation of cam 46 in synchronism with the indexing of the sample tray 56 through each individual blood sample tube position thereof, to automatically dispense a barrier disc as again illustrated by disc 36a into each of said blood sample tubes to effect the provision of a satisfactory physical and chemical barrier between the respective, separated plasma or serum and packed cells layers as are now contained in each of said tubes. Subsequently, the sample tray 56 may, if desired, be readily and conveniently operatively positioned on automated blood sample supply, treatment and analysis means of the nature disclosed, for example, in saidU.S. Pat. No. 3,241,432, for the subsequent, automated quantitative analysis of the separated plasma or serum portion of each of said blood samples with regard to'a plurality of constituents thereof.
Of particularly significant advantage here, however, is the fact that the new and improved plasma/cells barrier means of the invention provides a satisfactory physical and chemical barrierbetween the respective separated plasma and packed cells layers of each of said blood samples to thus prevent changes inthe former as might otherwise occur to inhibit the accurate quantitative analysis thereof while, at the same time, rendering substantially impossible any loss of identification of a said blood sample by insuring that the respective separated plasma and packed cells layers thereof are maintained in the same tube. Thus, loss or mixup in blood sample identification insofar as confusion of the separated plasma and packed cells from the same blood sample is concerned, are rendered substantially impossible.
A further form of the new 'and improved plasma/cells barrier means of the invention is indicated generally at 62 in FIGS. 11 through 14- and, as best seen in FIGS. 11 and 12, comprises a container assembly 63 including a Vacutainer or like tube 64 having a sleeve 66 insertable thereinto as shown in generally fluidtight manner as providedby annual stop 68 and generally wedge-shaped soft plastic sealing ring 70.
The sleeve 66 terminates as shown in a generally truncated cone-shaped end portion 72 having an opening 74 formed centrally thereofand screw threads 76 formed on the exterior surface thereof. A sample sleeve cap 78 (FIG. 11) is provided, as is asleeve cap 80 (FIG. 12) which includes a glass or plastic rod 82 extending therefrom as shown and terminating in a plug or stopper 84 which is effective to substantially plug the opening 72 as illustrated in FIG. 42. An end portion cap 86, which is screw threaded as indicated at 88, is also provided and is effective to screw over the sleeve end portion 72 to seal the same as illustrated in FIG. 13.
In use, the container assembly 63 which may, for example, contain a suitable anticoagulant, is filled with a whole blood sample and mixed, following which the cap 78 is removed. The said container assembly is then centrifuged to result in the separation of said blood sample into a plasma or serum layer and a packed cells layer 92 having an interface 94, and it may be understood that the distance between the upper end of sleeve opening 74 and the bottom of container 64 is predetermined, in accordance with the largest anticipated volume of the packed cells after configuration, to insure that said interface94 falls as shown below the upper end of the opening 74. Knowledge that the volume of packed cells will rarely, if ever, exceed 60 percent of the total blood sample volume will, of course, be a principal factor in such distance determination.
Following this blood sample centrifugation, cap 80 containing rod 82 and stopper 84 is inserted as shown into sleeve 66 with resultant substantial sealing of the opening 74 by stopper 84 and attendant containment of plasma or serum, only, from plasma or serum layer 90' in the now completed sleeve assembly. Subsequently, said plasma-containing completed sleeve assembly is removed from the tube 64 in obvious manner and thethreaded cover 86 is attached as illustrated in FIG. 13 to the sleeve end portion 72 to insure a leakproof blood plasma or serum container for plasma shipment if desired. Removal of the cap 80 from the covered sleeve 66 will, at this point, of course render the latter suitable for direct use as the blood plasma container on the sample tray of automated blood analysis apparatus as-discussed above. If desired, the now distinct packed cells layer 92 remaining as shown in FIG. 14 may be stored through the simple utilization of the cap 17 as illustrated in said FIG.
Of particular significance with regard to the sleeve 66 and tube 64 is the face that the same originate as the same container assembly 63 and would be so marked by appropriate blood sample identification information formed on each prior to separation thereof, whereby loss of identification, for example, of the separated plasma or serum layer removed therefrom as described is, of course, rendered impossible.
Referring now to FIG. 15, it may be seen that cap 80 including rod 82 and stopper 84 may be eliminated and far simpler sleeve-opening closure means substituted therefor. More specifically, such sleeve-opening closure means may be seen to take the form of a simple metal or plastic ball 94 of suitable density which, when dropped into the plasma or serum layer 90, will sink therethrough to occupy and close the sleeve opening 74 and substantially prevent the flow of said plasma or serum layer therefrom upon removal as described of the sleeve 66 from the tube 64. More sturdy closure of the opening 74 may, of course, be readily effected by attachment as described of the threaded cover 86 to the lower end of the sleeve 66.
Although disclosed hereinabove by way of illustration as directed to the provision of a satisfactory physical and chemical barrier between the respective separated plasma or serum and packed cells layers of centrifuged blood samples as an adjunct to the automated analysis of the latter, it is believed clear that the method and apparatus of the invention would be equally applicable to the provision of such barrier in a wide variety of fluids having one or more relative sharp density gradients.
While I have shown and described the preferred embodiment of my invention, it will be understood that the invention may be embodied otherwise than as herein specifically illustrated or described, and that certain changes in the form and arrangement of parts and in the specific manner of practicing the invention may be made without departing from the underlying idea or principles of this invention within the scope of the appended claims.
What is claimed is:
1. In a method of effecting the substantial physical and chemical separation of the respective blood plasma and blood cell layers of a blood sample, which resulted from the centrifugation thereof, by the formation of a physical and chemical barrier in the blood sample container substantially at the interface of said blood plasma and blood cell layer, comprising the steps of, inserting barrier means into said blood sample container and through said blood plasma layer, so as to be located substantially at said interface, structuring said barrier means to pass freely through said blood plasma layer and to be ineffective to form said barrier when initially positioned at said interface, and forming said barrier means of a material having a greater specific gravity than said blood plasma layer but a lesser specific gravity than said blood cell layer, so as to sink through said blood plasma layer to said interface, said material forming said barrier means characterized as being expandable when wetted, so as to expand into firm contact with the walls of said container to define said barrier at said interface.
2. The method of claim 1, further comprising the steps of, forming said barrier means of granules of said expandable material, which upon being wetted expand into firm contact with each other and said walls of said container to define said barrier at said interface.
3. In an apparatus for effecting the substantial physical and chemical separation of the respective blood plasma and blood cell layers of a blood sample, which result from the centrifugation thereof, by the formation of a physical and chemical barrier'in the blood sample container substantially at the interface of said blood plasma and blood cell layers, comprising barrier means for insertion into said blood sample container, said barrier means being structured to pass freely through said blood plasma layer, so as to be located substantially at said interface and to be ineffective to define a barrier when initially located at said interface, said barrier means comprising a material having a greater specific gravity than said blood plasma layer and a lesser specific gravity than said blood cell layer, so as to sink through said blood plasma layer to said interface, said material characterized as being expandable when wetted, so as to expand into firm contact with the walls of said container to define said barrier at said interface.
4. ln apparatus as in claim 3 wherein, said barrier means comprises granules of said expandable material, said granules, when wetted, expanding into firm contact with eachother and with the walls of said container to define said barrier at said interface.
5. In apparatus as in claim 3 wherein said barrier means is formed of a single body of said material, said 'body, when wetted, expanding into firm contact the walls of said container to define said barrier at said interface.
6. In an apparatus as in claim 3 wherein, said material is an nonionic, hydrophylic polymeric material selected from the group consisting of polyhydroxyethylmethacrylate and polyacrylamide hydrogel.
7. ln apparatus as in claim 3, wherein said material is an insoluble cellulose spongelike material having one or more coatings of a nonionic, hydrophylic polymeric material applied thereto to delay the wetting and separation thereof until said body is located substantially at said interface.

Claims (6)

  1. 2. The method of claim 1, further comprising the steps of, forming said barrier means of granules of said expandable material, which upon being wetted expand into firm contact with each other and said walls of said container to define said barrier at said interface.
  2. 3. In an apparatus for effecting the substantial physical and chemical separation of the respective blood plasma and blood cell layers of a blood sample, which result from the centrifugation thereof, by the formation of a physical and chemical barrier in the blood sample container substantially at the interface of said blood plasma and blood cell layers, comprising barrier means for insertion into said blood sample container, said barrier means being structured to pass freely through said blood plasma layer, so as to be located substantially at said interface and to be ineffective to define a barrier when initially located at said interface, said barrier means comprising a material having a greater specific gravity than said blood plasma layer and a lesser specific gravity than said blood cell layer, so as to sink through said blood plasma layer to said interface, said material characterized as being expandable when wetted, so as to expand into firm contact with the walls of said container to define said barrier at said interface.
  3. 4. In apparatus as in claim 3 wherein, said barrier means comprises granules of said expandable material, said granules, when wetted, expanding into firm contact with each other and with the walls of said container to define said barrier at said interface.
  4. 5. In apparatus as in claim 3 wherein said barrier means is formed of a single body of said material, said body, when wetted, expanding into firm contact the walls of said container to define said barrier at said interface.
  5. 6. In an apparatus as in claim 3 wherein, said material is an nonionic, hydrophylic polymeric material selected from the group consisting of polyhydroxyethylmethacrylate and polyacrylamide hydrogel.
  6. 7. In apparatus as in claim 3, wherein said material is an insoluble cellulose spongelike material having one or more coatings of a nonionic, hydrophylic polymeric material applied thereto to delay the wetting and separation thereof until said body is located substantially at said interface.
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Cited By (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3780935A (en) * 1972-07-10 1973-12-25 Lukacs & Jacoby Ass Serum separating method
US3786985A (en) * 1973-01-05 1974-01-22 Hoffmann La Roche Blood collection container
US3799342A (en) * 1970-07-27 1974-03-26 Medical Res & Dev Inc Method of using a serum separator
DE2359670A1 (en) * 1972-12-11 1974-06-12 Corning Glass Works ARRANGEMENT FOR KEEPING LIQUID PHASES SEPARATE
JPS5040198A (en) * 1973-08-10 1975-04-12
US3879295A (en) * 1973-08-17 1975-04-22 Eastman Kodak Co Vacutainer with positive separation barrier
JPS5056294A (en) * 1973-09-14 1975-05-16
US3886928A (en) * 1970-03-07 1975-06-03 Sarstedt W Device for the extraction of blood
US3897337A (en) * 1974-02-27 1975-07-29 Becton Dickinson Co Plasma separator assembly having interface-seeking piston with centrifugal valve
US3909419A (en) * 1974-02-27 1975-09-30 Becton Dickinson Co Plasma separator with squeezed sealant
US3919085A (en) * 1974-02-27 1975-11-11 Becton Dickinson Co Plasma separator assembly
US3920557A (en) * 1974-02-27 1975-11-18 Becton Dickinson Co Serum/plasma separator--beads-plus-adhesive type
US3935113A (en) * 1974-02-27 1976-01-27 Becton, Dickinson And Company Serum/plasma separator with centrifugal valve
US3972812A (en) * 1975-05-08 1976-08-03 Becton, Dickinson And Company Blood serum separation filter disc
US4021352A (en) * 1974-03-30 1977-05-03 Walter Sarstedt Kunststoff-Spritzgusswerk Filter device for separating blood fractions
US4027660A (en) * 1976-04-02 1977-06-07 Wardlaw Stephen C Material layer volume determination
US4052320A (en) * 1975-08-29 1977-10-04 Eastman Kodak Company Telescoping serum separator and dispenser
US4140631A (en) * 1976-09-29 1979-02-20 Nippon Paint Co., Ltd. Sealant for separation of serum or plasma, and its use
US4162979A (en) * 1976-11-22 1979-07-31 Boehringer Mannheim Gmbh Device for the chemical and/or physical treatment of liquids
US4180465A (en) * 1975-12-19 1979-12-25 Sherwood Medical Industries Inc. Fluid collection device with phase separation means
US4315892A (en) * 1980-07-18 1982-02-16 Sherwood Medical Industries, Inc. Fluid collection device having phase partitioning means
US4369117A (en) * 1980-05-12 1983-01-18 American Hospital Supply Corporation Serum separating method and apparatus
US4477574A (en) * 1980-12-23 1984-10-16 Ab Tesi Method of time-marking sedimentation processes
DE3419823A1 (en) * 1984-05-26 1985-11-28 Gesellschaft für Strahlen- und Umweltforschung mbH, 8000 München Process and device for the preliminary purification and concentration of particles from cells
US4824560A (en) * 1985-04-18 1989-04-25 Assaf Pharmaceutical Industries Ltd. Separation of materials from a liquid dispersion by sedimentation
WO1996018897A1 (en) * 1994-12-13 1996-06-20 Coleman Charles M Separator float for blood collection tubes
US5736033A (en) * 1995-12-13 1998-04-07 Coleman; Charles M. Separator float for blood collection tubes with water swellable material
US6376210B1 (en) 1999-07-06 2002-04-23 General Atomics Methods and compositions for assaying analytes
US20020057996A1 (en) * 2000-04-10 2002-05-16 Bass Leland L. Centrifuge tube assembly
US20030092684A1 (en) * 1999-04-27 2003-05-15 Fredeking Terry M. Compositions and methods for treating hemorrhagic virus infections and other disorders
US6610504B1 (en) 2000-04-10 2003-08-26 General Atomics Methods of determining SAM-dependent methyltransferase activity using a mutant SAH hydrolase
US20030215389A1 (en) * 2000-10-02 2003-11-20 Anthony Montgomery Methods for detecting vasculopathies and tumors
US20040014083A1 (en) * 2000-02-25 2004-01-22 Chong-Sheng Yuan Detection of heteroduplex polynucleotides using mutant nucleic acid repair enzymes with attenuated catalytic activity
US20050244912A1 (en) * 2004-04-30 2005-11-03 Chong-Sheng Yuan Methods for assaying inhibitors of S-adenosylhomocysteine (SAH) hydrolase and S-adenosylmethionine (SAM)-dependent methyltransferase
US20060175244A1 (en) * 2005-02-07 2006-08-10 Hanuman Llc Apparatus and method for preparing platelet rich plasma and concentrates thereof
US7192729B2 (en) 1999-07-06 2007-03-20 General Atomics Methods for assaying homocysteine
US20070187341A1 (en) * 2005-08-10 2007-08-16 The Regents Of The University Of California Photopolymer serum separator
US20080011684A1 (en) * 2005-02-07 2008-01-17 Dorian Randel E Apparatus and method for preparing platelet rich plasma and concentrates thereof
US20080132874A1 (en) * 2005-08-10 2008-06-05 The Regents Of The University Of California Collection tubes appratus, systems, and methods
US20090129973A1 (en) * 2005-08-10 2009-05-21 The Regents Of The University Of California Collection Tubes Apparatus, Systems and Methods
US20090139937A1 (en) * 2005-08-10 2009-06-04 The Regents Of The University Of California Polymers for Use in Centrifugal Separation of Liquids
US20090221075A1 (en) * 2008-02-29 2009-09-03 Biomet Manufacturing Corp. System And Process For Separating A Material
US20090289014A1 (en) * 2008-05-23 2009-11-26 Biomet Biologics, Llc Blood Separating Device
US7708152B2 (en) 2005-02-07 2010-05-04 Hanuman Llc Method and apparatus for preparing platelet rich plasma and concentrates thereof
US20100160135A1 (en) * 2008-07-21 2010-06-24 Becton, Dickinson And Company Density Phase Separation Device
US20100288694A1 (en) * 2009-05-15 2010-11-18 Becton, Dickinson And Company Density Phase Separation Device
US20110014705A1 (en) * 2009-07-16 2011-01-20 Biomet Biologics, Llc Method and apparatus for separating biological materials
US20110056893A1 (en) * 2002-05-24 2011-03-10 Biomet Biologics, LLC. Apparatus and Method for Separating and Concentrating Fluids Containing Multiple Components
US8187475B2 (en) 2009-03-06 2012-05-29 Biomet Biologics, Llc Method and apparatus for producing autologous thrombin
US8394342B2 (en) 2008-07-21 2013-03-12 Becton, Dickinson And Company Density phase separation device
US8950586B2 (en) 2002-05-03 2015-02-10 Hanuman Llc Methods and apparatus for isolating platelets from blood
US8992862B2 (en) 2009-04-03 2015-03-31 Biomet Biologics, Llc All-in-one means of separating blood components
US9114334B2 (en) 2002-05-24 2015-08-25 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9138664B2 (en) 2007-04-12 2015-09-22 Biomet Biologics, Llc Buoy fractionation system
US9239276B2 (en) 2011-04-19 2016-01-19 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9333445B2 (en) 2008-07-21 2016-05-10 Becton, Dickinson And Company Density phase separation device
US9393576B2 (en) 2000-04-28 2016-07-19 Harvest Technologies Corporation Blood components separator disk
US9533090B2 (en) 2010-04-12 2017-01-03 Biomet Biologics, Llc Method and apparatus for separating a material
US9556243B2 (en) 2013-03-15 2017-01-31 Biomet Biologies, LLC Methods for making cytokine compositions from tissues using non-centrifugal methods
US9642956B2 (en) 2012-08-27 2017-05-09 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9649579B2 (en) 2007-04-12 2017-05-16 Hanuman Llc Buoy suspension fractionation system
US9669405B2 (en) 2012-10-22 2017-06-06 The Regents Of The University Of California Sterilizable photopolymer serum separator
US9682373B2 (en) 1999-12-03 2017-06-20 Becton, Dickinson And Company Device for separating components of a fluid sample
US9694359B2 (en) 2014-11-13 2017-07-04 Becton, Dickinson And Company Mechanical separator for a biological fluid
US9701728B2 (en) 2008-02-27 2017-07-11 Biomet Biologics, Llc Methods and compositions for delivering interleukin-1 receptor antagonist
US9713810B2 (en) 2015-03-30 2017-07-25 Biomet Biologics, Llc Cell washing plunger using centrifugal force
US9757721B2 (en) 2015-05-11 2017-09-12 Biomet Biologics, Llc Cell washing plunger using centrifugal force
US9895418B2 (en) 2013-03-15 2018-02-20 Biomet Biologics, Llc Treatment of peripheral vascular disease using protein solutions
US9897589B2 (en) 2002-05-24 2018-02-20 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9950035B2 (en) 2013-03-15 2018-04-24 Biomet Biologics, Llc Methods and non-immunogenic compositions for treating inflammatory disorders
US10143725B2 (en) 2013-03-15 2018-12-04 Biomet Biologics, Llc Treatment of pain using protein solutions
US10576130B2 (en) 2013-03-15 2020-03-03 Biomet Manufacturing, Llc Treatment of collagen defects using protein solutions
US11957733B2 (en) 2019-10-28 2024-04-16 Biomet Manufacturing, Llc Treatment of collagen defects using protein solutions

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858940A (en) * 1957-10-03 1958-11-04 George W Calvert Device for removing cream from milk in bottles
US3437266A (en) * 1967-07-03 1969-04-08 Sondell Research & Dev Co Centrifugal separation enhancement
US3499531A (en) * 1969-06-25 1970-03-10 Ind Service Co Inc Cyclonic separation devices
US3508653A (en) * 1967-11-17 1970-04-28 Charles M Coleman Method and apparatus for fluid handling and separation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858940A (en) * 1957-10-03 1958-11-04 George W Calvert Device for removing cream from milk in bottles
US3437266A (en) * 1967-07-03 1969-04-08 Sondell Research & Dev Co Centrifugal separation enhancement
US3508653A (en) * 1967-11-17 1970-04-28 Charles M Coleman Method and apparatus for fluid handling and separation
US3499531A (en) * 1969-06-25 1970-03-10 Ind Service Co Inc Cyclonic separation devices

Cited By (144)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3886928A (en) * 1970-03-07 1975-06-03 Sarstedt W Device for the extraction of blood
US3799342A (en) * 1970-07-27 1974-03-26 Medical Res & Dev Inc Method of using a serum separator
US3780935A (en) * 1972-07-10 1973-12-25 Lukacs & Jacoby Ass Serum separating method
JPS5724508B2 (en) * 1972-12-11 1982-05-25
DE2359670A1 (en) * 1972-12-11 1974-06-12 Corning Glass Works ARRANGEMENT FOR KEEPING LIQUID PHASES SEPARATE
JPS4989389A (en) * 1972-12-11 1974-08-27
US3786985A (en) * 1973-01-05 1974-01-22 Hoffmann La Roche Blood collection container
JPS5040198A (en) * 1973-08-10 1975-04-12
JPS542120B2 (en) * 1973-08-10 1979-02-02
US3879295A (en) * 1973-08-17 1975-04-22 Eastman Kodak Co Vacutainer with positive separation barrier
JPS5056294A (en) * 1973-09-14 1975-05-16
US3920557A (en) * 1974-02-27 1975-11-18 Becton Dickinson Co Serum/plasma separator--beads-plus-adhesive type
US3909419A (en) * 1974-02-27 1975-09-30 Becton Dickinson Co Plasma separator with squeezed sealant
US3935113A (en) * 1974-02-27 1976-01-27 Becton, Dickinson And Company Serum/plasma separator with centrifugal valve
US3897337A (en) * 1974-02-27 1975-07-29 Becton Dickinson Co Plasma separator assembly having interface-seeking piston with centrifugal valve
US3919085A (en) * 1974-02-27 1975-11-11 Becton Dickinson Co Plasma separator assembly
US4021352A (en) * 1974-03-30 1977-05-03 Walter Sarstedt Kunststoff-Spritzgusswerk Filter device for separating blood fractions
US3972812A (en) * 1975-05-08 1976-08-03 Becton, Dickinson And Company Blood serum separation filter disc
US4052320A (en) * 1975-08-29 1977-10-04 Eastman Kodak Company Telescoping serum separator and dispenser
US4180465A (en) * 1975-12-19 1979-12-25 Sherwood Medical Industries Inc. Fluid collection device with phase separation means
DE2714763A1 (en) * 1976-04-02 1977-10-06 Wardlaw Stephen C METHOD AND DEVICE FOR DETERMINING THE VOLUME OF A MATERIAL LAYER
US4077396A (en) * 1976-04-02 1978-03-07 Wardlaw Stephen C Material layer volume determination
US4027660A (en) * 1976-04-02 1977-06-07 Wardlaw Stephen C Material layer volume determination
US4140631A (en) * 1976-09-29 1979-02-20 Nippon Paint Co., Ltd. Sealant for separation of serum or plasma, and its use
US4162979A (en) * 1976-11-22 1979-07-31 Boehringer Mannheim Gmbh Device for the chemical and/or physical treatment of liquids
US4369117A (en) * 1980-05-12 1983-01-18 American Hospital Supply Corporation Serum separating method and apparatus
US4315892A (en) * 1980-07-18 1982-02-16 Sherwood Medical Industries, Inc. Fluid collection device having phase partitioning means
US4477574A (en) * 1980-12-23 1984-10-16 Ab Tesi Method of time-marking sedimentation processes
DE3419823A1 (en) * 1984-05-26 1985-11-28 Gesellschaft für Strahlen- und Umweltforschung mbH, 8000 München Process and device for the preliminary purification and concentration of particles from cells
US4824560A (en) * 1985-04-18 1989-04-25 Assaf Pharmaceutical Industries Ltd. Separation of materials from a liquid dispersion by sedimentation
WO1996018897A1 (en) * 1994-12-13 1996-06-20 Coleman Charles M Separator float for blood collection tubes
US5560830A (en) * 1994-12-13 1996-10-01 Coleman; Charles M. Separator float and tubular body for blood collection and separation and method of use thereof
US5736033A (en) * 1995-12-13 1998-04-07 Coleman; Charles M. Separator float for blood collection tubes with water swellable material
US20030092684A1 (en) * 1999-04-27 2003-05-15 Fredeking Terry M. Compositions and methods for treating hemorrhagic virus infections and other disorders
US6376210B1 (en) 1999-07-06 2002-04-23 General Atomics Methods and compositions for assaying analytes
US7192729B2 (en) 1999-07-06 2007-03-20 General Atomics Methods for assaying homocysteine
US9682373B2 (en) 1999-12-03 2017-06-20 Becton, Dickinson And Company Device for separating components of a fluid sample
US20040014083A1 (en) * 2000-02-25 2004-01-22 Chong-Sheng Yuan Detection of heteroduplex polynucleotides using mutant nucleic acid repair enzymes with attenuated catalytic activity
US6610504B1 (en) 2000-04-10 2003-08-26 General Atomics Methods of determining SAM-dependent methyltransferase activity using a mutant SAH hydrolase
US20020057996A1 (en) * 2000-04-10 2002-05-16 Bass Leland L. Centrifuge tube assembly
US9393576B2 (en) 2000-04-28 2016-07-19 Harvest Technologies Corporation Blood components separator disk
US9393575B2 (en) 2000-04-28 2016-07-19 Harvest Technologies Corporation Blood components separator disk
US9656274B2 (en) 2000-04-28 2017-05-23 Harvest Technologies Corporation Blood components separator disk
US7070939B2 (en) 2000-10-02 2006-07-04 The Scripps Research Institute Methods for detecting vasculopathies and tumors
US20060211038A1 (en) * 2000-10-02 2006-09-21 Anthony Montgomery Methods for detecting vasculopathies and tumors
US20030215389A1 (en) * 2000-10-02 2003-11-20 Anthony Montgomery Methods for detecting vasculopathies and tumors
US8950586B2 (en) 2002-05-03 2015-02-10 Hanuman Llc Methods and apparatus for isolating platelets from blood
US10183042B2 (en) 2002-05-24 2019-01-22 Biomet Manufacturing, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9897589B2 (en) 2002-05-24 2018-02-20 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US10393728B2 (en) 2002-05-24 2019-08-27 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US20110056893A1 (en) * 2002-05-24 2011-03-10 Biomet Biologics, LLC. Apparatus and Method for Separating and Concentrating Fluids Containing Multiple Components
US9114334B2 (en) 2002-05-24 2015-08-25 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US8808551B2 (en) 2002-05-24 2014-08-19 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US7384760B2 (en) 2004-04-30 2008-06-10 General Atomics Methods for assaying inhibitors of S-adenosylhomocysteine (SAH) hydrolase and S-adenosylmethionine (SAM)-dependent methyltransferase
US20050244912A1 (en) * 2004-04-30 2005-11-03 Chong-Sheng Yuan Methods for assaying inhibitors of S-adenosylhomocysteine (SAH) hydrolase and S-adenosylmethionine (SAM)-dependent methyltransferase
US8133389B2 (en) 2005-02-07 2012-03-13 Hanuman, Llc Method and apparatus for preparing platelet rich plasma and concentrates thereof
US7708152B2 (en) 2005-02-07 2010-05-04 Hanuman Llc Method and apparatus for preparing platelet rich plasma and concentrates thereof
US20080011684A1 (en) * 2005-02-07 2008-01-17 Dorian Randel E Apparatus and method for preparing platelet rich plasma and concentrates thereof
US20100206798A1 (en) * 2005-02-07 2010-08-19 Hanuman Llc Method And Apparatus For Preparing Platelet Rich Plasma And Concentrates Thereof
US8105495B2 (en) 2005-02-07 2012-01-31 Hanuman, Llc Method for preparing platelet rich plasma and concentrates thereof
US7824559B2 (en) 2005-02-07 2010-11-02 Hanumann, LLC Apparatus and method for preparing platelet rich plasma and concentrates thereof
US8096422B2 (en) 2005-02-07 2012-01-17 Hanuman Llc Apparatus and method for preparing platelet rich plasma and concentrates thereof
US7987995B2 (en) 2005-02-07 2011-08-02 Hanuman, Llc Method and apparatus for preparing platelet rich plasma and concentrates thereof
US7866485B2 (en) 2005-02-07 2011-01-11 Hanuman, Llc Apparatus and method for preparing platelet rich plasma and concentrates thereof
US20060175244A1 (en) * 2005-02-07 2006-08-10 Hanuman Llc Apparatus and method for preparing platelet rich plasma and concentrates thereof
US20110042296A1 (en) * 2005-02-07 2011-02-24 Hanuman Llc Apparatus and method for preparing platelet rich plasma and concentrates thereof
US8318077B2 (en) * 2005-08-10 2012-11-27 The Regents Of The University Of California Collection tubes apparatus, systems, and methods
US9586203B2 (en) 2005-08-10 2017-03-07 The Regents Of The University Of California Collection tubes apparatus, systems, and methods
US20100108619A1 (en) * 2005-08-10 2010-05-06 The Regents Of The University Of California Photopolymer serum separator
US20070187341A1 (en) * 2005-08-10 2007-08-16 The Regents Of The University Of California Photopolymer serum separator
US7674388B2 (en) 2005-08-10 2010-03-09 The Regents Of The University Of California Photopolymer serum separator
US7780861B2 (en) 2005-08-10 2010-08-24 The Regents Of University Of California Photopolymer serum separator
US8936162B2 (en) 2005-08-10 2015-01-20 The Regents Of The University Of California Collection tubes apparatus, systems and methods
US8151996B2 (en) 2005-08-10 2012-04-10 The Regents Of The University Of California Photopolymer serum separator
US7673758B2 (en) 2005-08-10 2010-03-09 The Regents Of The University Of California Collection tubes apparatus, systems, and methods
US20080132874A1 (en) * 2005-08-10 2008-06-05 The Regents Of The University Of California Collection tubes appratus, systems, and methods
US20100314335A1 (en) * 2005-08-10 2010-12-16 The Regents Of The University Of California Photopolymer serum separator
US9248447B2 (en) 2005-08-10 2016-02-02 The Regents Of The University Of California Polymers for use in centrifugal separation of liquids
US20090139937A1 (en) * 2005-08-10 2009-06-04 The Regents Of The University Of California Polymers for Use in Centrifugal Separation of Liquids
US20090129973A1 (en) * 2005-08-10 2009-05-21 The Regents Of The University Of California Collection Tubes Apparatus, Systems and Methods
US8580183B2 (en) 2005-08-10 2013-11-12 The Regents Of The University Of California Collection tubes apparatus, systems, and methods
US7971730B2 (en) 2005-08-10 2011-07-05 The Regents Of The University Of California Collection tubes apparatus, systems and methods
US9649579B2 (en) 2007-04-12 2017-05-16 Hanuman Llc Buoy suspension fractionation system
US9138664B2 (en) 2007-04-12 2015-09-22 Biomet Biologics, Llc Buoy fractionation system
US8206638B2 (en) 2007-11-01 2012-06-26 The Regents Of The University Of California Collection tubes apparatus, systems, and methods
US20100117269A1 (en) * 2007-11-01 2010-05-13 The Regents Of The University Of California Collection tubes appratus, systems, and methods
US11725031B2 (en) 2008-02-27 2023-08-15 Biomet Manufacturing, Llc Methods and compositions for delivering interleukin-1 receptor antagonist
US10400017B2 (en) 2008-02-27 2019-09-03 Biomet Biologics, Llc Methods and compositions for delivering interleukin-1 receptor antagonist
US9701728B2 (en) 2008-02-27 2017-07-11 Biomet Biologics, Llc Methods and compositions for delivering interleukin-1 receptor antagonist
US20090221075A1 (en) * 2008-02-29 2009-09-03 Biomet Manufacturing Corp. System And Process For Separating A Material
US8801586B2 (en) * 2008-02-29 2014-08-12 Biomet Biologics, Llc System and process for separating a material
US8337711B2 (en) 2008-02-29 2012-12-25 Biomet Biologics, Llc System and process for separating a material
US20130196425A1 (en) * 2008-02-29 2013-08-01 Biomet Biologics, Llc System and Process for Separating a Material
US9719063B2 (en) 2008-02-29 2017-08-01 Biomet Biologics, Llc System and process for separating a material
US8012077B2 (en) 2008-05-23 2011-09-06 Biomet Biologics, Llc Blood separating device
US20090289014A1 (en) * 2008-05-23 2009-11-26 Biomet Biologics, Llc Blood Separating Device
US9714890B2 (en) 2008-07-21 2017-07-25 Becton, Dickinson And Company Density phase separation device
US9700886B2 (en) 2008-07-21 2017-07-11 Becton, Dickinson And Company Density phase separation device
US9339741B2 (en) 2008-07-21 2016-05-17 Becton, Dickinson And Company Density phase separation device
US9933344B2 (en) 2008-07-21 2018-04-03 Becton, Dickinson And Company Density phase separation device
US10350591B2 (en) 2008-07-21 2019-07-16 Becton, Dickinson And Company Density phase separation device
US20100160135A1 (en) * 2008-07-21 2010-06-24 Becton, Dickinson And Company Density Phase Separation Device
US9452427B2 (en) 2008-07-21 2016-09-27 Becton, Dickinson And Company Density phase separation device
US8747781B2 (en) 2008-07-21 2014-06-10 Becton, Dickinson And Company Density phase separation device
US8394342B2 (en) 2008-07-21 2013-03-12 Becton, Dickinson And Company Density phase separation device
US9333445B2 (en) 2008-07-21 2016-05-10 Becton, Dickinson And Company Density phase separation device
EP2866030A1 (en) 2008-12-09 2015-04-29 The Regents of The University of California Polymers for use in centrifugal separation of liquids
US8783470B2 (en) 2009-03-06 2014-07-22 Biomet Biologics, Llc Method and apparatus for producing autologous thrombin
US8187475B2 (en) 2009-03-06 2012-05-29 Biomet Biologics, Llc Method and apparatus for producing autologous thrombin
US8992862B2 (en) 2009-04-03 2015-03-31 Biomet Biologics, Llc All-in-one means of separating blood components
US10343157B2 (en) 2009-05-15 2019-07-09 Becton, Dickinson And Company Density phase separation device
US10413898B2 (en) 2009-05-15 2019-09-17 Becton, Dickinson And Company Density phase separation device
US11786895B2 (en) 2009-05-15 2023-10-17 Becton, Dickinson And Company Density phase separation device
US9079123B2 (en) 2009-05-15 2015-07-14 Becton, Dickinson And Company Density phase separation device
US11351535B2 (en) 2009-05-15 2022-06-07 Becton, Dickinson And Company Density phase separation device
US10807088B2 (en) 2009-05-15 2020-10-20 Becton, Dickinson And Company Density phase separation device
US10456782B2 (en) 2009-05-15 2019-10-29 Becton, Dickinson And Company Density phase separation device
US9731290B2 (en) 2009-05-15 2017-08-15 Becton, Dickinson And Company Density phase separation device
US20100288694A1 (en) * 2009-05-15 2010-11-18 Becton, Dickinson And Company Density Phase Separation Device
US9802189B2 (en) 2009-05-15 2017-10-31 Becton, Dickinson And Company Density phase separation device
US10376879B2 (en) 2009-05-15 2019-08-13 Becton, Dickinson And Company Density phase separation device
US8794452B2 (en) 2009-05-15 2014-08-05 Becton, Dickinson And Company Density phase separation device
US9919308B2 (en) 2009-05-15 2018-03-20 Becton, Dickinson And Company Density phase separation device
US9919307B2 (en) 2009-05-15 2018-03-20 Becton, Dickinson And Company Density phase separation device
US9919309B2 (en) 2009-05-15 2018-03-20 Becton, Dickinson And Company Density phase separation device
US9364828B2 (en) 2009-05-15 2016-06-14 Becton, Dickinson And Company Density phase separation device
US8998000B2 (en) 2009-05-15 2015-04-07 Becton, Dickinson And Company Density phase separation device
US20110014705A1 (en) * 2009-07-16 2011-01-20 Biomet Biologics, Llc Method and apparatus for separating biological materials
US9011800B2 (en) 2009-07-16 2015-04-21 Biomet Biologics, Llc Method and apparatus for separating biological materials
US9533090B2 (en) 2010-04-12 2017-01-03 Biomet Biologics, Llc Method and apparatus for separating a material
US9239276B2 (en) 2011-04-19 2016-01-19 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9642956B2 (en) 2012-08-27 2017-05-09 Biomet Biologics, Llc Apparatus and method for separating and concentrating fluids containing multiple components
US9669405B2 (en) 2012-10-22 2017-06-06 The Regents Of The University Of California Sterilizable photopolymer serum separator
US10208095B2 (en) 2013-03-15 2019-02-19 Biomet Manufacturing, Llc Methods for making cytokine compositions from tissues using non-centrifugal methods
US9950035B2 (en) 2013-03-15 2018-04-24 Biomet Biologics, Llc Methods and non-immunogenic compositions for treating inflammatory disorders
US9895418B2 (en) 2013-03-15 2018-02-20 Biomet Biologics, Llc Treatment of peripheral vascular disease using protein solutions
US9556243B2 (en) 2013-03-15 2017-01-31 Biomet Biologies, LLC Methods for making cytokine compositions from tissues using non-centrifugal methods
US10143725B2 (en) 2013-03-15 2018-12-04 Biomet Biologics, Llc Treatment of pain using protein solutions
US10441634B2 (en) 2013-03-15 2019-10-15 Biomet Biologics, Llc Treatment of peripheral vascular disease using protein solutions
US10576130B2 (en) 2013-03-15 2020-03-03 Biomet Manufacturing, Llc Treatment of collagen defects using protein solutions
US9694359B2 (en) 2014-11-13 2017-07-04 Becton, Dickinson And Company Mechanical separator for a biological fluid
US9713810B2 (en) 2015-03-30 2017-07-25 Biomet Biologics, Llc Cell washing plunger using centrifugal force
US9757721B2 (en) 2015-05-11 2017-09-12 Biomet Biologics, Llc Cell washing plunger using centrifugal force
US11957733B2 (en) 2019-10-28 2024-04-16 Biomet Manufacturing, Llc Treatment of collagen defects using protein solutions

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