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Method of using a serum separator

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US3799342A
US3799342A US26570772A US3799342A US 3799342 A US3799342 A US 3799342A US 26570772 A US26570772 A US 26570772A US 3799342 A US3799342 A US 3799342A
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Prior art keywords
tube
collection
serum
plug
separator
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D Greenspan
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MEDICAL RES AND DEV Inc
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MEDICAL RES AND DEV Inc
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5021Test tubes specially adapted for centrifugation purposes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D33/00Filters with filtering elements which move during the filtering operation
    • B01D33/01Filters with filtering elements which move during the filtering operation with translationally moving filtering elements, e.g. pistons
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons

Abstract

The method of isolating serum or plasma from the formed elements of blood comprising steps of effecting precipitation of the formed blood elements to the bottom of a container, inserting a plug into the container, said plug having normally closed valve means which are openable when pressure within the container is greater than atmospheric pressure. A handle for manipulating the plug functions as a container to collect and remove serum or plasma. In a second embodiment, the handle is removably attached to the plug so that the plug can be left in place in the container to maintain isolation between the serum or plasma and the formed blood elements. In a third embodiment, the plug is provided with a container for collecting and storing the serum or plasma. A similar plug inside the container is used to effect an additional filtration step.

Description

United States Patent 91 Greenspan METHOD OF USING A SERUM SEPARATOR [75] Inventor: Donald J. Greenspan, Riverside,

[73] Assignee: U.S. Medical Research &

Development, Inc., Riverside, NJ.

[22] Filed: June 23', 1972 [21] Appl. No.: 265,707

Related US. Application Data [63] Continuation-impart of Ser. No. 58,557, July 7,

1970, Pat. No. 3,661,265.

[52] U.S. Cl 210/73, 210/83, 210/117, 210/359,- 210/D1G. 23 [51] Int. Cl B01d 21/26, BOld 33/00 [58] Field of Search. 210/73, 83, 117, 136, 416, 210/359, DIG. 23, 42

Farr 2l0/DIG. 23

[ 1 Mar. 26, 1974 Primary Examiner-John Adee Attorney, Agent, or Firm-Woodcock, Washburn, Kurtz & Mackiewicz [57] ABSTRACT The method of isolating serum or plasma from the formed elements of blood comprising steps of effecting precipitation of the formed blood elements to the bottom of a container, inserting a plug into the container, said plug having normally closed valve means which are openable when pressure within the container is greater than atmospheric pressure, A handle for manipulating the plug functions as a container to collect and remove serum or plasma. In a second embodiment, the handle is removably attached to the plug so that the plug can be left in place in the container to maintain isolation between the serum or plasma and the formed blood elements. In a third embodiment, the plug is provided with a container for collecting and storing the serum or plasma. A similar plug inside the container is used to effect an additional filtration step.

30 Claims, 11 Drawing Figures PAIENIEUmaswm 3399.342

' SHEET 2 0F 3 FIG. 7

METHOD OF USING A SERUM SEPARATOR This invention is a continuation-in-part of my copending application, Ser. No. 58,557, filed July 7, 1970 entitled Serum Separator and Method of Use, now US. Pat. No. 3,661,265.

BACKGROUND OF THE INVENTION Ordinarily, separation of the formed elements (white cells, red cells and platelets) of blood from the serum is accomplished by the use of a centrifuge. In my copending application, Ser. No. 847,469, filed Aug. 4, I969, there is described a method of chemically separating serum or plasma from the formed elements of blood by adding a positively charged polymer and a lectin to the blood in a collection tube.

With either method, a short time after the formed elements are precipitated, the red blood cells begin to liberate potassium and other contaminants which may interfere with the tests performed on the serum. or plasma. Consequently, it is desirable to isolate the serum or plasma from the formed elements promptly after mechanical or chemical precipitation. With chemical separation methods, smallamounts of red cells and fibrin may be left in suspension, and it therefore it also desirable in the case of chemical separation to remove all of the residual suspended matter from the serum or plasma. I

In the past, attempts have been made to isolate centrifugally separated serum from the formed elements by the use of a pick-up device consisting of a first tube fitted at the lower end with a rubber element adapted to engage and slide along the walls ofa collection tube. The pick-up device has a second tube which passes through an opening in the rubber element to a point near theupper end of the first tube, and the second tube has a downwardlyv facing opening which delivers serum into the first tube as the pick-up device is pushed into the collection tube. The device is inserted into thecollection tube, fills with serum, and is then removed from the collection tube. The serum retained in the devicecanthen be tested.

A problem with the use 'of the device just described is that it cannot be used to transport the separated serum or plasmato the laboratory for testing from the point at which the blood sample is taken. Consequently, the collected serum must be transferred to a suitable container in a time consuming and error prone procedure. This problem becomes serious where blood tests are being performed for a large number of persons.

If the pick-up device just described were used in conjunction with a chemical separation method where the presence of suspended debris in the serum or plasma is likely, the debris would pass into the first tube of the pick-up device through the second tube.

" SUMMARY OF THE INVENTION In accordance with this invention, the serum separator includes a plug consisting of a disc having one way valve openings associated with a fibrous filter disc which prevents suspended debris and formed elements from passing through the plug. The plug thus maintains may be used for transporting serum or plasma to the laboratory for testing.

In accordance with a second embodiment of the invention, a separation plug is left in the blood collection tube, and maintains the formed. elements and the serum or plasma isolated from each other. In this case, the collection tube itself can be used for transporting the serum or plasma to the laboratory.

In accordance with a third embodiment of the invention. a separation plug is provided with a container for collecting serum or plasma. The container has its own internal separation plug similar to the one to which it is attached. The internal separation plug is used to effect a second filtration prior to testing of the serum or plasma.

BRIEF DESCRIPTION OF THE DRAWINGS FIG; 1 is a vertical section of a blood collection tube showing a first embodiment of the serum separator as it is being inserted into the collection tube.

FIG. 2 is a top plan view of the plug at the lower end of the serum separator show in FIG. 1.

FIG. 3 is a bottom plan view of the plug at the lower end of the serum separator shown in FIG. 1.

FIG. 4 and 4A are a vertical sections taken along Line 44 of FIG. 2 looking in the direction of the arrows.

FIG. 5 is a vertical section of the closure shown at the upper end of the serum separator in FIG. 1.

FIG. 6 is a sectional view showing, in detail, a perforation in the plug of FIG. 4 in the condition which exists when the serum separator is being inserted into the collection tube.

FIG. 7 is an exploded view of a second embodiment of the invention showing a removable handle, a perforated plug and a fibrous filter disc in a separated condition.

FIG. 8 is an elevation of a blood collection tube showing the perforated plug and fibrous filter disc in place maintaining separation between formed elements in the lower part I of the collection tube and serum or plasma in the upper part of the collection tube. V

FIG. 9 is a vertical section of a blood collection tube showing the third embodiment of the invention.

FIG. 10 is a top plan view of the serum container of the third embodiment of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION The first embodiment of the invention, by which serum or plasma is removed from the collection tube in a separate container, .is illustrated in FIGS. 1 through 6.

The collection tube 10 is preferably a tube of a well known type used for drawing blood from a patients vein by means of a vacuum. A serum separator 12 is shown partially inserted into the tube 10. The separator 12 consists of a tube 14 which is sufficiently long that when the lower end is near the bottom of collection tube 10, its upper end protrudes beyond the opening at the upper end 16 of the collection tube.

A plug 18 is fitted into the opening at the lower end of the separator tube 14, the fit being sufficiently tight so that the plug will not pull out of the separator tube in normal usage. Retaining means such as inwardly extending ridges (not shown) in the collection tube may be provided if desired, but are not necessary.

The details of the plug 18 are illustrated in FIGS. 2, 3 and 4. The plug comprises a disc 20 and an integral upstanding short tube 22, both preferably consisting of rubber or a synthetic polymer such as polyvinylchloride. Various other resilient materials may be used so long as they exhibit sufficient resiliency to provide an adequate seal between the edge 24 of the disc and collection tube and to allow the one way valves 26 to operate properly.

Valves 26, as shown in detail in FIG. 6, consist of flaps 28 which are formed in the rubber and are adapted to close off the holes 30 which extend part way through the rubber disc 20. The valves may be formed in the rubber disc by first producing the holes 30, and then producing V-shaped slits 25 (FIG. 2) from the top of the disc. The slits 25 meet the upper ends of the holes 30 and communicate therewith to permit the passage of air or liquid as hereinafter more fully set forth.

The upstanding tube 22 fits into the lower end of the separator tube 14. The edge 24 is tapered to allow the plug to deform easily as it is moved into the collection tube I0. At the upper end of the separator tube 14 there is provided a closure 32 which also is preferably made of rubber or a synthetic polymer. The closure 32 consists of a disc 34 having an integral tube 36 extending into the upper end of separator tube 14. The closure 32, as shown in FIG. 5, has one way valves 38 which are similarly formed to those in the plug 18.

Underneath the plug 18 is fastened a disc 40 of sufficient diameter to cover all of the holes 30. The disc 40 preferably consists of compacted polypropylene fibers, but may also be made up of fibers of other polyolefins or of fibers of other substances which do not react with blood. The disc 40 is adhered to the underside of the rubber member 20 by a suitable cement, and is arranged with respect to the holes 30 so that all fluid which passes upwardly through the holes 30 must have first passed through the filter disc 40.

In operation of the device just described, blood is first collected in the tube by a conventional collection method. Following collection, the formed elements are precipitated either mechanically by the use ofa centrifuge, or chemically by the addition of chemical substances. With a centrifuge, fibrin is separated out with the formed blood elements, leaving serum. With chemical separation, ordinarily only the formed blood elements will separate out, leaving plasma rather than serum. This may be satisfactory, but if it is desired to obtain serum, a suitable clotting agent such as thrombin may be used to precipitate out fibrin so that serum rather plasma is left over.

After the formed blood elements are precipitated so that they collect at the bottom of the collection tube 10 at 42, the separator 12 is inserted into the collection tube as shown in FIG. 1. The serum or plasma 44 passes through filter disc 40 and through the one way valves 26 into the interior of the tube 14. The air which is displaced passes through the filter disc 40 and through the one way valves 38 which are provided in the closure 32. The separator is moved downwardly to a point just above the interface between the formed blood elements and the serum or plasma and is then withdrawn from the collection tube. As the separator is withdrawn, air is drawn between the edge 24 of the plug and the interior wall '11 of the collection tube 10 into the lower part of the collection tube. The serum or plasma which is retained within the tube 14 cannot pass through the valves 26 in the opposite direction and consequently remains within the separation tube 14. The separation tube itself may then be marked for identification and sent to a laboratory for testing in conventional manner. The separator 12 is suitable for shipping in styrofoam containers.

An alternative device is shown in FIG. 7 wherein a plug is illustrated which comprises a resilient element 46 and a fibrous filter disc 48. The element 46 and the disc 48 are normally cemented together. The element 46 is made of resilient rubber or rubber-like material such as polyvinylchloride and the disc 48 is preferably made from olefin fibers or other fibers such as nylon, which do not react with blood. The disc 46 is provided with a plurality of one way valves 50 which are identical to the one way valves shown in FIG. 6. These valves are arranged in the element 46 so that any blood which passes through them must first have passed through disc 48.

Retainers 52 are attached to the top surface 54 of the element 46 for removably securing the handle 60. The retainers have overhanging parts 56 which are adapted to rotatively receive the tabs 58 which are attached at the lower end of a tubular plastic or paper handle 60. The handle 60 is attached to the plug 45 which consists of the element 46 and filter disc 48, by twisting the handle 60 in a clockwise direction (looking downwardly) so that tabs 58 are held between overhanging parts 56 of retainers 52 and the top surface 54. The entire assembly in FIG. 7 can then be inserted into a col-' lection tube 62 (FIG. 8) in which formed blood elements have been precipitated out of the serum or plasma 64 and the tube 62 can be detached from the plug 45 by counter-clockwise rotation when the plug is in place as shown in FIG. 8. The collection tube 62 can then be closed by a cap 65 and sent to the laboratory for testing of the serum or plasma 64. The serum or plasma 64 remains isolated from the formed blood elements 66 at the bottom of the tube by the plug 45. The one way valves 50 remain closed and the potassium (not shown) which is liberated by the red cells cannot contaminate the serum or plasma 64.

FIG. 9 shows a collection tube 66 in which there is located a separation plug 68 which consists of a rubber disc 70 attached to a fibrous filter disc 72. The disc 70 has one way valves 74 similar to those previously described. The disc 70 is also provided with an integral upstanding short tube 76 which has an outwardly extending lip 78 attached thereto to engage the inwardly extending lip 80 of a container 82. A secure and liquid tight seal is provided between the inwardly extending lip 80 and the lip 78 by fitting tightly into the groove 84 between the lip 78 and the upper part of disc 70. The container 82 has a cylindrical inner wall 86 and a top closure 88 which has a relatively narrow central opening 90. The top closure 88, as more clearly shown in FIG. 10, has retianers 92 similar to those indicated at 52 in FIG. 7. These retainers are adapted to engage tabs 94 on the handle 96 which is simialr to the handle 60 in FIG. 7. The handle 96 is.detachable from the container 82 by virtue of the removable engagement of the tabs 94 underneath the overhanging parts of the retainers 92.

position within the container 82. pushed downwardly into the collection tube'66, as

Within the container 82 there is provided a second plug 98 which consists of a rubber element 100 and an attached fibrous filter disc 102 which is fabricated similarly to disc 72. The element 100 has a pair of peripheral ridges 101 and 103 which are in sealing engagement with the inner wall 86, but which allow relatively easy axial sliding of the plug 98 within the container v82, so that the pressure required to cause the plug 98 to slide is less than that required to open the one way valves 74. The disc 100 is also provided with openings 105 in the form of one way valves 107 which permit the flow of liquid upwardly through the plug 98 as it is moved downwardly within the container 82. These one way valves 107, like the one way valves 26, 50 in the other embodiments are arranged so that any liquid which flows through the one way valves 107 must first have passed through the fibrous filter disc 102.

In operation, the contianer 82 is first attached to the handle 96 and the plug 98 is in the lowermost possible The assembly is shown in FIG. 9. As the plasma or serum 106 passes through the one way valve openings 74, it begins to fill the space 108 underneath the plug'98 and within the container 82. The'plug98 moves upwardly with respect to the container'82 as the container is pushed downwardly into the collection tube 66. When the ridge comes into register with the mark 104, the assembly is pulled out of the collection tube 66, the handle 96 is removed and the container82, now containing serum or plasma can be packed in a sytrofoam container, for example, (not shown) and shipped to a laboratory for testingpAt the laboratory, the plasma or serum 106 inthe container 82 can be subjected to a second filtration to remove any residual debris by pushing the plug 98 downwardly with a suitable implement which is inserted through the opening90. The serum or plasma, 'now above the plug 98,.can be poured through the opening 90 into any suitable container for testing in conventional manner.

Various modifications can be made to the three embodiments disclosed. The valves in the plugs, for example, can take various forms andneed not consist of holes communicating with V-shaped slits. Any similar valve which 'opens under the influence of a differential pressure may be used. Valves-which permit flow in one direction, but which prohibit flow in the other direction are not absolutely necessary for the operation of the invention. In the embodiment shown in FIG. 1, for example, even if the valves in the plug 'l8'were not one way valves, the one way valves in the closure 32 would prevent serum or plasma from escaping from the separator tube 14 when'it is withdrawn. A closure having no valves at all could be substituted for the closure 32, but it would have to be removed when the separator was inserted into the collection tube. Various other modifications to the invention can be made. The valves may be used in any number or placed in any position .along the separator to assure its proper functioning.

One or more check valves can be located at the edge the lower part'of the collection tube when the serum separator 12 is withdrawn. Valves 25 inverted from the orientation shown in FIG. 4 are suitable. See FIG. 4A.

I claim:

1. A method of isolating serum or plasma from formed elements of the blood in a collection tube having a closed end andan open end comprising the steps of:

precipitating the formed elements of the blood to separate the serum or plasma;

causing the precipitated formed elements to rest at the closed end of the collection tube with the serum or plasma positioned closer to the open end;

inserting into the open end a first resilient plug including at least one passageway extending therethrough having a constriction therein;

establishing a seal between the walls of said tube and said first resilient plug;

pushing said first resilient plug into said collection tube through the serum or plasma towards said closed end while maintaining said seal;

forcing said constriction in said passageway open so as to permit the flow of serum or plasma from one side of said first resilient plug adjacent said closed end to the other side of said first resilient plug adjacent said open end in response to the pressure differential on said one side and said other side as said first resilient plug is pushed through the serum or plasma; and

biasing said constriction in said passageway closed when said plug is stationary within said tube in' response to the resiliency of the plug so as to substantially isolate said blood cells on said one side from said serum or plasma on said other side.

2. The methodof claim 1 including the additional step of placing a second plug in the open end of the collection tube to close the said open end and to seal the plasma or serum in the collection tube in the space defined between the first plug and the second plug.

3. The method of claim 1 wherein said first resilient plug is pushed into said collection tube with an elongated handle engaging said other side of said plug radially outwardly of the area of communication of said passageway with said other side.

-4. The method of claim 3 and the additional step of removing the handle from thefirst plug after the first plug is pushed to the a position-wherein it approaches the formed elements of the blood.

5. The method of claim 1 including the additional step of filtering said serum or plasma while forcing said constriction open.

*6. The method of claim 1 and the additional step of flowing the serum or plasma through saidpassageway into a separator tube sealed to said other side of said plug. 1

7. The method of claim 6 and the additional step of employing the separator tube to'push the first plug into 'the collection tube.

"8. The method of claim 7 and the additional step of placing a second plug in the open end of the separator tube and to seal the plasma or serum in the separator tube in the space defined between the first plug and the second plug.

9. The method of claim "8 including the additional step of removing the separator tube with the plasma or serum therein while permitting air between the collection tube and the separator tube to pass from said other side to said one side of said first plug without allowing plasma or serum or air to flow through said passageway and employing the collection tube with the first and second plugs as a shipping contianer.

10. A method of isolating serum or plasma from formed elements of blood stored in a collection tube comprising the steps of:

precipitating the formed elements of the blood to separate serum or plasma therefrom;

causing the precipitated formed elements to be positioned closer to the closed end of the collection tube with the serum or plasma positioned closer to the open end of the collection tube;

inserting into the open end of the collection tube a separator tube having a resilient plug forming a closed end thereof;

creating a seal between the walls of the collection tube and a flange extending radially outwardly from the resilient plug and forming an air space between the walls of the collection tube and the separator tube above the resilient plug when the separator tube is inserted into the collection tube; pushing the separator tube into the collection tube such that the plug moves through the serum or plasma toward the closed end of the collection tube while maintaining a seal between the walls of the collection tube and the flange of the plug; forcing open a constriction in a serum passageway extending through the plug open so as to permit a substantial flow of serum or plasma through the serum passageway into the separator tube in response to movement of the plugs through the serum or plasma while said seal between the flange and the walls of the collection tube prevent a substantial flow of fluid into the space between the walls of the collection tube and the separator tube;

resiliently biasing the constriction in the passageway closed when the separator tube is stationary within the collection tube; moving the separator tube toward the open end of the collection tube; and

maintaining the constriction in the passageway substantially closed so as to prevent a substantial flow of serum or plasma through the passageway from the separator tube into the collection tube during withdrawal of the separator tube from the collection tube while permitting a substantial flow of air from the space between the walls of the collection tube and the separator tube into the space beneath the resilient plug and above the formed elements of the blood.

ll. The method of claim 10 including the step of opening a constriction in an air passageway leading from the space between the walls of the collection tube and the separator tube to the space beneath the resilient plug and above the formed elements of the blood in response to withdrawal of the separator tube from the collection tube so as to permit the flow of air through the air passageway.

12. The method of claim 11 wherein the constriction in the air passageway remains substantially closed during the insertion of the separator tube into the collection tube.

13. The method of claim 10 including the step of breaking the seal between the flange and the walls of the collection tube in response to withdrawal of the separator tube from the collection tube to permit the flow of air between the flange and the walls of the collection tube.

14. The method of claim 10 including the step ofdeflecting the serum or plasma flowing through the constriction from an axial flow path.

15. The method of claim 10 including the step of filtering serum or plasma flowing through the passageway.

16. Apparatus for isolating serum or plasma from formed elements of blood comprising:

a collection tube for storing a sample of blood wherein the formed elements have been precipitated toward the closed end of the tube and the serum or plasma is located closer to the open end of the tube; and

a separator tube having a hollow interior and a closed end for storing serum or plasma, said separator tube being inserted into said collection tube so as to leave an air space between the walls of said collection tube and said separator tube, said closed end comprising serum valve means betweenthe interior of the separator tube and the space between the closed end of the collection tube and the closed end of the separator tube, said serum valve means opening when said separator tube is moved through said serum to allow serum to flow into said interior of said separator tube and closing when said separator tube is withdrawn from said collection tube, said closed end of said separator tube further comprising air valve means between said air space and the space between the said closed end of separator tube and said closed end of said collection tube, said air valve means remaining closed when said separator tube means is inserted into said collection tube so as to substantially prevent the flow of serum or plasma to said air space, said air valve means opening when said separator tube is withdrawn from said collection tube so as to permit the flow of air into the space between said closed end of said separator tube and said closed end of said collection tube.

17. The apparatus of claim 16 wherein said separator tube comprises a hollow tubular member and said closed end comprises a resilient plug attached to one end of said closed member, said serum valve comprising a serum passageway communicating between the interior of said hollow member and the space between said resilient plug and said closed end of said collection tube and a constriction in said serum passageway opening in response to insertion of said resilient plug into said collection tube, said constriction being resiliently biased closed when said resilient plug is stationary within or withdrawn from said collection tube.

18. The apparatus of claim 17 wherein said resilient plug comprises a substantially cylindrical surface of substantial length resiliently engaging the interior of the walls of said hollow tubular member, said serum passageway comprising a first portion substantially coaxial with said cylindrical portion and having an overall length substantially equal to a substantial portion of the overall length of said cylindrical portion, said passageway further comprising another portion of lesser cross-sectional area, said constriction being located at the end of said portion of lesser cross-sectional area.

19. The apparatus of claim 18 including means associated with said constriction for at least partially radially deflecting the flow of serum passing through said constriction.

20. The apparatus of claim 19 wherein said means for at least partially radially deflecting the flow of fluid through said constriction comprises a sealing surface of said constriction which extends axially and radially outwardly.

21. The apparatus of claim 17 including filter means in the path of flow of said serum through said passageway.

22. The apparatus of claim 21 wherein said filter means is of smaller diameter than said collection tube.

23. The apparatus of claim 17 wherein said resilient plug comprises a radially outwardly extending flange for sealingly engaging the walls of said collection tube.

24. The apparatus of claim 17 wherein said air valve means comprises a flange extending radially outwardly from said hollow tubular member, said flange forming a seal with the walls of said collection tube when said separator tube is inserted into said collection tube so as to prevent flow of plasma or serum between said flange and said walls of said collection tube, said seal being broken when said. separator tube is removed from said collection tube so as to permit the flow of air into the space between the resilient plug and the closed end of the collection tube when said separator tube is moved toward the open end of said collection tube.

25. The apparatus of claim 24 wherein said flange adjacent said walls of said collection tube comprises a surface tapering radially inwardly away from the area of sealing engagement between said flange and the walls of the collection tube.

26. The apparatus of claim 24 wherein said resilient plug includes a flange extending radially outwardly toward said collection tube so as to engage the walls of said collection tube, said air valve means including an air valve passageway spaced radially inwardly from the area of sealing engagement between said flange and the walls of said collection tube, said air valve passageway being closed when said separator tube is inserted into said collection tube and being opened when said separator tube is withdrawn from said collection tube.

27. A tube for separating serum of plasma from formed elements of the blood comprising a hollow tubular member and a resilient plug closing the lower end of said tubular member, said resilient plug comprising a flange extending radially outwardly from the tubular member, said resilient plug comprising a passageway therethrough having a one-way serum valve permitting the flow of serum from the lower side of the plug to the upper side of the plug in direct communication with the interior of the hollow tubular member in automatic response to a pressure differential through said passageway wherein the pressure at the end of the passageway in the hollow tubular member is less than the pressure at the opposite end of the passageway, said resilient plug further comprising one-way air valve means permitting the flow of air from the upper side of the flange to the lower side of said plug while preventing the flow of serum from said lower side of said plug to said upper side of said flange.

28. The tube of claim 27 wherein said one-way air valve opens in response to the deformation of said flange.

29. The tube of claim 28 wherein said one-way air valve comprises a passageway through said flange.

30. The tube of claim 28 wherein said one-way air valve comprises a radially inwardly tapering surface.

m- 'j DOVNAYLD J. GREENSPAN M is crtificd thg'c' error appears in the nbovc i dcinflificc'i. patent am? that $ai 1 Letters Patcpt are hereby corrected asshown below:

in THE SPECI I ATION Cc-l'umn l, iine 26 deleie fit" and insert -is Ccglumn 3, line 9,-afte'r. "th"insi't--*-fl.ahge;

v line 14; before adapts-t1" insert -c0ns t rictiohs-i;

line 14 af-ter "h oles5 inSe rt '--0 PaSSQ' Y 'T-F line's 17 End 18, delte "2 5" I l ine 5,5, afteflrath'ei" insert -than- Column 4,1 lifie Change "retianry' :to -re ta"ine:rs-;

lifiel c hange simialilflito Columh 5 lin e bhaihge f'cbntiner" tq -container v EN TH-E CLAIMS I Column 7, line change "c'on tiane;:" to --cohtainer--;

I line" delete. "plugs and ifisert -?l ug----; Calumn 8} line 59 delete ur-face" and 'insert -port ion- (301mm 10. iih'e delete "24" and :L n sert-' l -7-.--"-; v

si ed and "sealed this 10th day f September 1 97M.

MCCOY M. GIBSON, c, MARSHALL DANN Attes'ting Officer Commissioner of Patents

Claims (29)

  1. 2. The method of claim 1 including the additional step of placing a second plug in the open end of the collection tube to close the said open end and to seal the plasma or serum in the collection tube in the space deFined between the first plug and the second plug.
  2. 3. The method of claim 1 wherein said first resilient plug is pushed into said collection tube with an elongated handle engaging said other side of said plug radially outwardly of the area of communication of said passageway with said other side.
  3. 4. The method of claim 3 and the additional step of removing the handle from the first plug after the first plug is pushed to the a position wherein it approaches the formed elements of the blood.
  4. 5. The method of claim 1 including the additional step of filtering said serum or plasma while forcing said constriction open.
  5. 6. The method of claim 1 and the additional step of flowing the serum or plasma through said passageway into a separator tube sealed to said other side of said plug.
  6. 7. The method of claim 6 and the additional step of employing the separator tube to push the first plug into the collection tube.
  7. 8. The method of claim 7 and the additional step of placing a second plug in the open end of the separator tube and to seal the plasma or serum in the separator tube in the space defined between the first plug and the second plug.
  8. 9. The method of claim 8 including the additional step of removing the separator tube with the plasma or serum therein while permitting air between the collection tube and the separator tube to pass from said other side to said one side of said first plug without allowing plasma or serum or air to flow through said passageway and employing the collection tube with the first and second plugs as a shipping contianer.
  9. 10. A method of isolating serum or plasma from formed elements of blood stored in a collection tube comprising the steps of: precipitating the formed elements of the blood to separate serum or plasma therefrom; causing the precipitated formed elements to be positioned closer to the closed end of the collection tube with the serum or plasma positioned closer to the open end of the collection tube; inserting into the open end of the collection tube a separator tube having a resilient plug forming a closed end thereof; creating a seal between the walls of the collection tube and a flange extending radially outwardly from the resilient plug and forming an air space between the walls of the collection tube and the separator tube above the resilient plug when the separator tube is inserted into the collection tube; pushing the separator tube into the collection tube such that the plug moves through the serum or plasma toward the closed end of the collection tube while maintaining a seal between the walls of the collection tube and the flange of the plug; forcing open a constriction in a serum passageway extending through the plug open so as to permit a substantial flow of serum or plasma through the serum passageway into the separator tube in response to movement of the plugs through the serum or plasma while said seal between the flange and the walls of the collection tube prevent a substantial flow of fluid into the space between the walls of the collection tube and the separator tube; resiliently biasing the constriction in the passageway closed when the separator tube is stationary within the collection tube; moving the separator tube toward the open end of the collection tube; and maintaining the constriction in the passageway substantially closed so as to prevent a substantial flow of serum or plasma through the passageway from the separator tube into the collection tube during withdrawal of the separator tube from the collection tube while permitting a substantial flow of air from the space between the walls of the collection tube and the separator tube into the space beneath the resilient plug and above the formed elements of the blood.
  10. 11. The method of claim 10 including the step of opening a constriction in an air passageway leading from the space between the walls of the collection tube and the separator tube to the space beneath the resilient plug and above The formed elements of the blood in response to withdrawal of the separator tube from the collection tube so as to permit the flow of air through the air passageway.
  11. 12. The method of claim 11 wherein the constriction in the air passageway remains substantially closed during the insertion of the separator tube into the collection tube.
  12. 13. The method of claim 10 including the step of breaking the seal between the flange and the walls of the collection tube in response to withdrawal of the separator tube from the collection tube to permit the flow of air between the flange and the walls of the collection tube.
  13. 14. The method of claim 10 including the step of deflecting the serum or plasma flowing through the constriction from an axial flow path.
  14. 15. The method of claim 10 including the step of filtering serum or plasma flowing through the passageway.
  15. 16. Apparatus for isolating serum or plasma from formed elements of blood comprising: a collection tube for storing a sample of blood wherein the formed elements have been precipitated toward the closed end of the tube and the serum or plasma is located closer to the open end of the tube; and a separator tube having a hollow interior and a closed end for storing serum or plasma, said separator tube being inserted into said collection tube so as to leave an air space between the walls of said collection tube and said separator tube, said closed end comprising serum valve means between the interior of the separator tube and the space between the closed end of the collection tube and the closed end of the separator tube, said serum valve means opening when said separator tube is moved through said serum to allow serum to flow into said interior of said separator tube and closing when said separator tube is withdrawn from said collection tube, said closed end of said separator tube further comprising air valve means between said air space and the space between the said closed end of separator tube and said closed end of said collection tube, said air valve means remaining closed when said separator tube means is inserted into said collection tube so as to substantially prevent the flow of serum or plasma to said air space, said air valve means opening when said separator tube is withdrawn from said collection tube so as to permit the flow of air into the space between said closed end of said separator tube and said closed end of said collection tube.
  16. 17. The apparatus of claim 16 wherein said separator tube comprises a hollow tubular member and said closed end comprises a resilient plug attached to one end of said closed member, said serum valve comprising a serum passageway communicating between the interior of said hollow member and the space between said resilient plug and said closed end of said collection tube and a constriction in said serum passageway opening in response to insertion of said resilient plug into said collection tube, said constriction being resiliently biased closed when said resilient plug is stationary within or withdrawn from said collection tube.
  17. 18. The apparatus of claim 17 wherein said resilient plug comprises a substantially cylindrical surface of substantial length resiliently engaging the interior of the walls of said hollow tubular member, said serum passageway comprising a first portion substantially coaxial with said cylindrical portion and having an overall length substantially equal to a substantial portion of the overall length of said cylindrical portion, said passageway further comprising another portion of lesser cross-sectional area, said constriction being located at the end of said portion of lesser cross-sectional area.
  18. 19. The apparatus of claim 18 including means associated with said constriction for at least partially radially deflecting the flow of serum passing through said constriction.
  19. 20. The apparatus of claim 19 wherein said means for at least partially radially deflecting the flow of fluid through said constriction comprises a seaLing surface of said constriction which extends axially and radially outwardly.
  20. 21. The apparatus of claim 17 including filter means in the path of flow of said serum through said passageway.
  21. 22. The apparatus of claim 21 wherein said filter means is of smaller diameter than said collection tube.
  22. 23. The apparatus of claim 17 wherein said resilient plug comprises a radially outwardly extending flange for sealingly engaging the walls of said collection tube.
  23. 24. The apparatus of claim 17 wherein said air valve means comprises a flange extending radially outwardly from said hollow tubular member, said flange forming a seal with the walls of said collection tube when said separator tube is inserted into said collection tube so as to prevent flow of plasma or serum between said flange and said walls of said collection tube, said seal being broken when said separator tube is removed from said collection tube so as to permit the flow of air into the space between the resilient plug and the closed end of the collection tube when said separator tube is moved toward the open end of said collection tube.
  24. 25. The apparatus of claim 24 wherein said flange adjacent said walls of said collection tube comprises a surface tapering radially inwardly away from the area of sealing engagement between said flange and the walls of the collection tube.
  25. 26. The apparatus of claim 24 wherein said resilient plug includes a flange extending radially outwardly toward said collection tube so as to engage the walls of said collection tube, said air valve means including an air valve passageway spaced radially inwardly from the area of sealing engagement between said flange and the walls of said collection tube, said air valve passageway being closed when said separator tube is inserted into said collection tube and being opened when said separator tube is withdrawn from said collection tube.
  26. 27. A tube for separating serum of plasma from formed elements of the blood comprising a hollow tubular member and a resilient plug closing the lower end of said tubular member, said resilient plug comprising a flange extending radially outwardly from the tubular member, said resilient plug comprising a passageway therethrough having a one-way serum valve permitting the flow of serum from the lower side of the plug to the upper side of the plug in direct communication with the interior of the hollow tubular member in automatic response to a pressure differential through said passageway wherein the pressure at the end of the passageway in the hollow tubular member is less than the pressure at the opposite end of the passageway, said resilient plug further comprising one-way air valve means permitting the flow of air from the upper side of the flange to the lower side of said plug while preventing the flow of serum from said lower side of said plug to said upper side of said flange.
  27. 28. The tube of claim 27 wherein said one-way air valve opens in response to the deformation of said flange.
  28. 29. The tube of claim 28 wherein said one-way air valve comprises a passageway through said flange.
  29. 30. The tube of claim 28 wherein said one-way air valve comprises a radially inwardly tapering surface.
US3799342A 1970-07-27 1972-06-23 Method of using a serum separator Expired - Lifetime US3799342A (en)

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US3865731A (en) * 1973-12-21 1975-02-11 Baxter Laboratories Inc Filter skimming device
US3932277A (en) * 1974-03-29 1976-01-13 Bio-Logics Products, Inc. Method and apparatus for separating blood fractions
US3955423A (en) * 1972-09-18 1976-05-11 Marvin Padover Liquid sampling method
US4035294A (en) * 1975-05-23 1977-07-12 Denver Chemical Manufacturing Company Pressure differential filtering device and method
FR2357898A1 (en) * 1975-03-10 1978-02-03 Farr Andrew Apparatus for preparing liquid samples for analysis in automatic analyzers
US4142668A (en) * 1976-10-01 1979-03-06 Lee Jae Y Serum-plasma separator and transfer apparatus
FR2401008A1 (en) * 1977-05-03 1979-03-23 Greenspan Donald Method for manufacturing a valve for separation tube, and this valve
US4189385A (en) * 1977-05-03 1980-02-19 Greenspan Donald J Method and apparatus for separating serum or plasma from the formed elements of the blood
US4197735A (en) * 1978-11-06 1980-04-15 Chase Instruments Corporation Blood sedimentation rate test means
US4202769A (en) * 1977-06-16 1980-05-13 Greenspan Donald J Method for separating serum or plasma from the formed elements of blood
US4209485A (en) * 1977-05-03 1980-06-24 Greenspan Donald J Method of making a valve apparatus
US4411795A (en) * 1980-03-10 1983-10-25 Baxter Travenol Laboratories, Inc. Particle adsorption
US4486315A (en) * 1982-03-11 1984-12-04 Ortho Diagnostic Systems Inc. Immunoassay microparticle washing system and method of use
WO1984004696A1 (en) * 1983-05-31 1984-12-06 Baxter Travenol Lab Particle adsorption
US4517830A (en) * 1982-12-20 1985-05-21 Gunn Damon M Blood viscosity instrument
US4522713A (en) * 1982-11-26 1985-06-11 Sartorius Gmbh Apparatus for static membrane filtration
US4643981A (en) * 1983-11-09 1987-02-17 Akzo N.V. Pressure filtration system
US4832851A (en) * 1987-02-02 1989-05-23 W. R. Grace & Co. Centrifugal force-enhanced filtration of fluids
US5462716A (en) * 1991-11-11 1995-10-31 Holm; Niels E. Container for receiving and separating a fluid, preferably blood plasma, into its ingredients
US5480378A (en) * 1990-05-14 1996-01-02 Weis-Fogh; Ulla Apparatus for preparing a concentrate of coagulation factors from a blood sample
US5552064A (en) * 1993-02-26 1996-09-03 Ortho Diagnostic Systems, Inc. Column agglutination assay and device using biphasic centrifugation
US5603845A (en) * 1993-11-19 1997-02-18 E. R. Squibb & Sons, Inc. Liquid separation apparatus and method
US5733446A (en) * 1994-12-02 1998-03-31 Bristol-Myers Squibb Company Centrifuge with annular filter
US5738784A (en) * 1994-12-02 1998-04-14 E.R. Squibb & Sons, Inc. Device for separating a blood component from blood or plasma
US5830352A (en) * 1994-12-02 1998-11-03 Bristol-Myers Squibb Company Centrifuge reagent delivery system
US6238578B1 (en) 1996-12-09 2001-05-29 Sherwood Services Ag Method for dispensing separator gel in a blood collection tube
US6302919B1 (en) * 1999-07-20 2001-10-16 Brian Chambers Reverse-flow centrifugal filtration method
US20030175167A1 (en) * 2002-03-18 2003-09-18 Arai Takanori Apparatus for separating biological sample and separating method of the same
US20080017577A1 (en) * 2006-07-21 2008-01-24 Becton, Dickinson And Company Membrane-based Double-layer Tube for Sample Collections
US20080091147A1 (en) * 2004-06-23 2008-04-17 Hee Young Lee Syringe Piston Using in Fat Transplantation
US20080095672A1 (en) * 2006-10-18 2008-04-24 Cytyc Corporation Filter for automated slide preparation system
US20110083560A1 (en) * 2008-09-27 2011-04-14 Yiru Chen Portable Multifunctional Coffee Extracting Device and Its Application
US20110168644A1 (en) * 2010-01-13 2011-07-14 OZOlab Systems and methods for personal water filtration
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Cited By (52)

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US3955423A (en) * 1972-09-18 1976-05-11 Marvin Padover Liquid sampling method
US3865731A (en) * 1973-12-21 1975-02-11 Baxter Laboratories Inc Filter skimming device
US3932277A (en) * 1974-03-29 1976-01-13 Bio-Logics Products, Inc. Method and apparatus for separating blood fractions
FR2357898A1 (en) * 1975-03-10 1978-02-03 Farr Andrew Apparatus for preparing liquid samples for analysis in automatic analyzers
US4035294A (en) * 1975-05-23 1977-07-12 Denver Chemical Manufacturing Company Pressure differential filtering device and method
US4142668A (en) * 1976-10-01 1979-03-06 Lee Jae Y Serum-plasma separator and transfer apparatus
FR2401008A1 (en) * 1977-05-03 1979-03-23 Greenspan Donald Method for manufacturing a valve for separation tube, and this valve
US4189385A (en) * 1977-05-03 1980-02-19 Greenspan Donald J Method and apparatus for separating serum or plasma from the formed elements of the blood
US4209485A (en) * 1977-05-03 1980-06-24 Greenspan Donald J Method of making a valve apparatus
US4202769A (en) * 1977-06-16 1980-05-13 Greenspan Donald J Method for separating serum or plasma from the formed elements of blood
WO1980000923A1 (en) * 1978-11-06 1980-05-15 R Munzer Blood sedimentation rate test means
US4197735A (en) * 1978-11-06 1980-04-15 Chase Instruments Corporation Blood sedimentation rate test means
US4411795A (en) * 1980-03-10 1983-10-25 Baxter Travenol Laboratories, Inc. Particle adsorption
US4486315A (en) * 1982-03-11 1984-12-04 Ortho Diagnostic Systems Inc. Immunoassay microparticle washing system and method of use
US4522713A (en) * 1982-11-26 1985-06-11 Sartorius Gmbh Apparatus for static membrane filtration
US4517830A (en) * 1982-12-20 1985-05-21 Gunn Damon M Blood viscosity instrument
WO1984004696A1 (en) * 1983-05-31 1984-12-06 Baxter Travenol Lab Particle adsorption
US4643981A (en) * 1983-11-09 1987-02-17 Akzo N.V. Pressure filtration system
US4832851A (en) * 1987-02-02 1989-05-23 W. R. Grace & Co. Centrifugal force-enhanced filtration of fluids
US5480378A (en) * 1990-05-14 1996-01-02 Weis-Fogh; Ulla Apparatus for preparing a concentrate of coagulation factors from a blood sample
US5462716A (en) * 1991-11-11 1995-10-31 Holm; Niels E. Container for receiving and separating a fluid, preferably blood plasma, into its ingredients
US5746979A (en) * 1991-11-11 1998-05-05 F. R, Squibb & Sons, Inc. Method for receiving and separating a fluid into its ingredients
US5658533A (en) * 1991-11-11 1997-08-19 E.R. Squibb & Sons, Inc. Container for receiving and separating a fluid into its ingredients
US5674458A (en) * 1991-11-11 1997-10-07 E. R. Squibb & Sons, Inc. Container for receiving and separating a fluid into its ingredients
US5552064A (en) * 1993-02-26 1996-09-03 Ortho Diagnostic Systems, Inc. Column agglutination assay and device using biphasic centrifugation
US5650068A (en) * 1993-02-26 1997-07-22 Ortho Diagnostic Systems Inc. Column agglutination assay and device using biphasic centrifugation
US5792344A (en) * 1993-11-19 1998-08-11 Bristol-Myers Squibb Company Liquid separation container for a centrifugal separator
US5858253A (en) * 1993-11-19 1999-01-12 Bristol-Myers Squibb Company Blood separation process
US5741428A (en) * 1993-11-19 1998-04-21 E.R. Squibb & Sons, Inc. Rapid centrifugal process for preparing fibrin monomer solution
US5603845A (en) * 1993-11-19 1997-02-18 E. R. Squibb & Sons, Inc. Liquid separation apparatus and method
US5776336A (en) * 1993-11-19 1998-07-07 Bristol-Myers Squibb Company Annular filter assembly
US5958253A (en) * 1994-12-02 1999-09-28 Bristol-Myers Squibb Company Centrifuge reagent delivery method
US5795489A (en) * 1994-12-02 1998-08-18 Bristol-Myers Squibb Company Centrifugal filtration method
US5824230A (en) * 1994-12-02 1998-10-20 E.R. Squibb & Sons, Inc. Method and device for separating a component such as fibrin I from blood plasma
US5830352A (en) * 1994-12-02 1998-11-03 Bristol-Myers Squibb Company Centrifuge reagent delivery system
US5738784A (en) * 1994-12-02 1998-04-14 E.R. Squibb & Sons, Inc. Device for separating a blood component from blood or plasma
US5935432A (en) * 1994-12-02 1999-08-10 Bristol-Myers Squibb Company Centrifuge reagent delivery system
US5733446A (en) * 1994-12-02 1998-03-31 Bristol-Myers Squibb Company Centrifuge with annular filter
US20010007315A1 (en) * 1995-12-12 2001-07-12 Fiehler William R. Method and apparatus for dispensing separator gel in a blood collection tube
US6238578B1 (en) 1996-12-09 2001-05-29 Sherwood Services Ag Method for dispensing separator gel in a blood collection tube
US6302919B1 (en) * 1999-07-20 2001-10-16 Brian Chambers Reverse-flow centrifugal filtration method
US20030175167A1 (en) * 2002-03-18 2003-09-18 Arai Takanori Apparatus for separating biological sample and separating method of the same
US7323144B2 (en) * 2002-03-18 2008-01-29 Leisure, Inc. Apparatus for separating biological sample and separating method of the same
US20080091147A1 (en) * 2004-06-23 2008-04-17 Hee Young Lee Syringe Piston Using in Fat Transplantation
US7819846B2 (en) * 2004-06-23 2010-10-26 Medikan Co., Ltd. Syringe piston using in fat transplantation
US20080017577A1 (en) * 2006-07-21 2008-01-24 Becton, Dickinson And Company Membrane-based Double-layer Tube for Sample Collections
US20080095672A1 (en) * 2006-10-18 2008-04-24 Cytyc Corporation Filter for automated slide preparation system
US8034307B2 (en) * 2006-10-18 2011-10-11 Cytyc Corporation Filter for automated slide preparation system
US20110083560A1 (en) * 2008-09-27 2011-04-14 Yiru Chen Portable Multifunctional Coffee Extracting Device and Its Application
US20110168644A1 (en) * 2010-01-13 2011-07-14 OZOlab Systems and methods for personal water filtration
US8313644B2 (en) * 2010-01-13 2012-11-20 OZOlab Bottle with an integrated filtration assembly that is manually operated using a plunger
WO2017059835A1 (en) * 2015-10-09 2017-04-13 Scheiter Oliver Method for separating the phases of a liquid mixture and subsequently separating a liquid supernatant, phase separator for the method, and stopper for the phase separator

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