US3882021A

US3882021A - Sealed assembly for separation of blood with anti-red cell barrier

Info

Publication number: US3882021A
Application number: US446365A
Authority: US
Inventors: Waldemar A Ayres
Original assignee: Becton Dickinson and Co
Current assignee: Becton Dickinson and Co
Priority date: 1974-02-27
Filing date: 1974-02-27
Publication date: 1975-05-06
Anticipated expiration: 1992-05-06

Abstract

A self-contained fluid separator assembly capable of separating blood into its component parts of plasma or serum, the light phase, and cellular portion, the heavy phase, is disclosed. The assembly comprises a container having a first open end for receiving blood for subsequent separation, a second open end for removing the separated plasma or serum and a closure sealing each open end of the container, the closures being formed of a self sealing elastomeric material which is penetrable by a cannula. A piston is slidably disposed in the container having its lateral outer surfaces in sealing contact with the inner surfaces of the container. Pressure responsive valve means is provided on the piston which is normally closed when there is a minimum pressure differential on each side of the piston and which automatically opens in response to a substantial pressure differential so that when the container is subjected to centrifugal force the blood separates into its light phase and heavy phase and the valve means automatically opens as the piston moves down through the light phase while retaining sealing engagement with the inner surfaces of the container. A frangible seal means is also provided to seal said piston in a position opposite to the end for receiving blood with means for removing said frangible seal means. The seal insures that the piston is not contaminated with red blood cells prior to separation of the blood specimen. Stop means is formed on the container so that the piston as it moves through the light phase will contact the stop means and stop a predetermined distance from the bottom closure means, the pressure differential is terminated and the valve means automatically shifts from the open position to the closed position to provide an impervious barrier between the separated phases of the blood.

Description

United States Patent [1 1 [111 3,882,021 Ayres [451 May 6, 1975 1 SEALED ASSEMBLY FOR SEPARATION OF serum, the light phase, and cellular portion, the heavy BLOOD WITH ANTI-RED CELL BARRIER [52] US. Cl. 210/136; 210/359; 210/516;

210/D1G. 23 [51] Int. Cl. 801d 33/00 [58] Field of Search 23/230 B, 258.5, 259, 292;

128/2 F, 214 R, 218 M, 272; 210/83, 84, 109, 131, 359, 514-518, DIG. 23, DIG. 24, 97, 136; 233/1 A, 1 R, 26

[56] References Cited UNITED STATES PATENTS 2,305,278 12/1942 Smith 128/218 M 3,508,653 4/1970 Coleman 210/DIG. 23 3,537,605 11/1970 Solowey 128/218 M X 3,586,064 6/1971 Brown et al. 233/26 3,786,985 1/1974 Blaivas 233/26 Primary Examiner-Samih N. Zahama Assistant Examiner-Robert H. Spitzer Attorney, Agent, or Firml(ane, Dalsimer, Kane, Sullivan and Kurucz 5 7] ABSTRACT A self-contained fluid separator assembly capable of separating blood into its component parts of plasma or phase, is disclosed. The assembly comprises a container having a first open end for receiving blood for subsequent separation, a second open end for removing the separated plasma or serum and a closure sealing each open end of the container, the closures being formed of a self sealing elastomeric material which is penetrable by a cannula. A piston is slidably disposed in the container having its lateral outer surfaces in sealing contact with the inner surfaces of the container. Pressure responsive valve means is provided on the piston which is normally closed when there is a minimum pressure differential on each side of the piston and which automatically opens in response to a substantial pressure differential so that when the container is subjected to centrifugal force the blood separates into its light phase and heavy phase and the valve means automatically opens as the piston moves down through the light phase while retaining sealing engagement with the inner surfaces of the container. A frangible seal means is also provided to seal said piston in a position opposite to the end for receiving blood with means for removing said frangible seal means. The seal insures that the piston is not contaminated with red blood cells prior to separation of the blood specimen. Stop means is formed on the container so that the piston as it moves through the light phase will contact the stop means and stop a predetermined distance from the bottom closure means, the pressure differential is terminated and the valve means automatically shifts from the open position to the closed position to provide an impervious barrier between the separated phases of the blood.

6 Claims, 2 Drawing Figures SEALED ASSEMBLY FOR SEPARATION OF BLOOD WITH ANTI-RED CELL BARRIER BACKGROUND OF THE INVENTION 1. Field of the Invention The invention concerns apparatus for the separation and isolation of blood plasma and blood serum from blood mixtures.

2. Brief Description of the Prior Art It is known to separate blood into its component parts by centrifugation, particularly employing a sealed container such as is disclosed in US. Pat. No. 2,460,641. This patent discloses a container having a closure at its open end which is capable of being penetrated by a cannula through which blood passes into the container. Clinical laboratories have heretofore used this device to collect a blood sample for subsequent separation into a light phase, i.e. the serum or plasma and the heavy phase, i.e. the cellular portion. The light phase is then decanted from the cellular portion by any conventional means, for example by the use of a syringe fitted with a cannula, or a pipette, or the like.

As apparatus also heretofore employed for the separation of blood is disclosed in U.S. Pat. No. 3,508,653. This patent discloses a self-contained assembly for separation of body fluid such as blood in which a deformable piston is disposed in the container and is positioned initially adjacent the stopper for closing the container. After the blood to be separated is in the container the assembly is centrifuged. After the blood is separated, incresed centrifugal force is applied to the container, the seal between the inner surface of the container and piston is broken and the piston is deformed, moving down through the light phase with the light phase passing solely around the lateral surfaces of the piston and the inner surfaces of the container. When the piston reaches the interface between the light phase and the heavy phase, the piston movement is re-established between the inner surface of the container and the resilient piston to present a barrier between the two phases.

Disclosed in my U.S. Pat. No. 3,779,383 is a serum plasma separator employing a piston to effect a sealed isolation of separated blood phases. The present invention is an improvement over that device. The piston component of the earlier disclosed invention is subject to contact with blood as it is received into the container member. On occasion, red blood cells may adhere to the piston member during separation of the blood phases. The light phase blood component passes by the piston during piston descent by centrifugation, and may occasionally dislodge a few red blood cells, carrying them up and mixing them with the light phase component.

The present invention obviates the possibility of red blood cells coming in contact with the piston member during filling of the separator assembly and thereby reduces the likelihood that the desired blood plasma or serum will be contaminated with any red blood cells.

Furthermore, those separator devices of the prior art having filter elements associated with the piston are subject to clogging by red blood cells during filling of the separator assembly with blood. This problem is also obviated by the present invention which has a means of preventing the red blood cells from contacting the piston or associated parts thereof.

Other devices known to the art are generally the filtration devices which separate blood into its component phases such as those disclosed in US. Pat. Nos. 3,481,477 and 3,512,940.

SUMMARY OF THE INVENTION The invention comprises: a self-contained fluid separator assembly capable of separating blood into its component parts of plasma and serum and cellular part comprising (a) a container having a first open end which is adapted to receive blood for subsequent separation into a light phase and a heavy phase and a second open end for removing the separated light phase; (b) closures sealing the open ends of the container, the closures being formed of a self-sealing elastomeric material which is penetrable by a cannula; (c) a piston having a specific gravity relatively greater than the cellular portion of the blood and slidably mounted in the container and having means or an outer surface in sealing engagement with an inner surface of the container; (d) pressure responsive valve means associated with said piston, said valve means being normally closed when there is a minimum of pressure differential on different portions of the valve means and which automatically opens in response to a substantial pressure differential so that when said container is subjected to moderate centrifugal force the blood separates into its light phase and heavy phase but the piston stays in the upper portion of the container and subsequently when increased centrifugal force is used the valve means automatically opens with the light phase passing up through the valve means enabling the piston to move down through the light phase while retaining sealing engagement with the inner surfaces of the container; (e) frangible seal means sealing said piston in a position opposite to the first end for receiving blood; (f) means for removing said frangible seal; and (g) mechanical stop means on the container whereby the piston when moving through the light phase will stop a predetermined distance from one of the ends of the container followed by termination of the differential pressure which permits the valve means to automatically shift from an open position to a closed position to provide an impervious barrier between the separated light phase and heavy phase of the blood.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a cross-sectional side elevational view of a separator assembly of the invention illustrating a cannula penetrating one of the closures through which blood is introduced into the container prior to separation.

FIG. 2 is a view similar to FIG. 1 illustrating the separtion of the blood into the light phase and heavy phase with the piston engaging the stop means.

DETAILED DESCRIPTION OF THE INVENTION For a better unerstanding of the invention, a description of the drawings of the illustrative embodiments is had, particularly with respect to the embodiments shown in FIGS. 1 and 2.

Referring to FIG. 1, it is seen that the separator assembly 10 comprises a tubular member or container 12 having mounted in open ends 11 and 15, closures l4 and 16.

Closures

14 and 16 are made of a self-sealing elastomeric material such as rubber which are capable of receiving cannula 18 penetrated therethrough as illustrated in FIG. 1, for conducting blood 5 into the container. When the cannula is removed the closure is resealed with no loss of blood 5 passing through the penetration portion as illustrated in FIG. 2.

Closure 14 is formed having a depending cylindrical body portion and a flanged head portion 22 integrally formed therewith. Body portion 20 has a diameter slightly greater than the internal diameter of the container 12 so that closure 14 when mounted into end 11 provides a pressure fit to seal the end. Head portion 22 is preferably shaped in the form of a hexagon and is slightly greater in diameter than body portion 20 which permits the assembly to be positioned on its side without danger of rolling. An axial recess 24 is provided for easy access through stopper 16 which reduces the force required to penetrate with cannula 18.

Stopper 16 is formed preferably of the same material as stopper 14 but has different configuration and dimensions. Stopper 16 has a cylindrical body portion 28 and in integrally formed head portion 30 having an axial recess 24. Body portion 28 has an annular recess 29 to provide a self-sealing penetrable zone 31 to facilitate insertion of cannula 18 with minimum force while maintaining a sealed closure. As noted above, stopper or closure 14 as well as 16 is inserted into ends 11 and 15 in compression to maintain ends 11 and 15 of container 12 in sealed engagment.

Tubular member or container 12 is formed preferably of glass but a suitable plastic material may be employed. Intermediate ends 11 and 15 of tubular member 12 is an annular groove 32 which forms a stop means 34 as a part of the inner surfaces 13 of container 12. Thus, as piston moves from the initial starting position illustrated in FIG. 1 to the terminal position after the separation of the light phase 5a from the heavy phase 515 as shown in FIG. 2 the piston comes to rest at the stop means 34 formed by annular groove 32 of container 12.

Piston 40 includes a tubular metal insert 52 which is mounted in annular recess 54 of piston 40. Metal insert 52 is preferably made of stainless steel or other rigid, chemically inert material having a specific gravity substantially greater than blood. Piston 40 is formed of elastomeric material and is provided with annnular recess 54 which is dimensioned to receive tubular member 52 in an interference fit so that no air space remains in annular recess 54.

The elastomeric portion of piston 40 comprises an outer wall 48 and spaced therefrom is inner wall 46 which defines annular recess 54. Formed integrally with wall 48 are a plurality of axially spaced sealing rings 50 which contact the inner wall surface 13 of container 12 in sealing engagement. piston 40 when mounted in container 12 will maintain sealing contact with inner wall 13 of container 12 throughout its path of travel within container 12 as hereinafter described. During a centrifuging operation piston 40 is subjected to centrifugal forces which starts to move the piston downwardly which creates a pressure differential on the opposite sides of the top wall portion 44 of piston 40. Top wall portion or diaphragm 44 has a relatively small thickness and lies adjacent stopper 14 in its initial position as seen in FIGv l. Diaphragm 44 is made of a resilient material and is provided with at least one aperture 42 extending therethrough.

Wall portions

46 and 44 of piston 40 define an axial annular recess or throat 80 within piston 40 which leads from the lower surface 82 of piston 40 to apertures 42. As the assembly is being subjected to centrifugal forces the light phase which is separated from the blood will pass into throat and be guided to apertures 42. Also, since the centrifugal forces acting on piston 40 will cause it to slide downwardly and thereby generate a hydrostatic force greater than the force of the light phase being exerted against the top of diaphragm 44 apertures 42 will automatically open and will permit light phase liquid to flow upwardly and thereby enable piston 40 to move from its initial position of FIG. 1 to its final position of FIG. 2 while maintaining sealing engagement with the inner wall 13 of container 12. When piston 40 stops its movement in container 12 and comes to rest on stop means 34, the pressure differential on each side of diaphragm 44 is substantially equalized and valve means 42 automatically shifts from the open position to the closed position even though the assembly is being subjected to centrifugal forces.

As shown in FIG. 1, a filter 60 substantially fills the throat 80. Filter 60 is an optional element employed when it is desired to filter the blood plasma or serum prior to its passage through valve apertures 42. Also as shown in FIG. 1, piston 40 with all of its component and associate structures is isolated from lower portion 85 of container 12 by a frangible seal 88. This seal 88 forms a protective barrier, preventing blood 5 from contacting piston 40 during the assembly blood filling operation. Seal 88 may be any frangible sealant material which is nonreactive with blood. The seal 88 material should also have a specific gravity exceeding the specific gravity of the heavy phase of blood. Illustrative of seal 88 materials are polymeric waxes such as polyethylene polymer waxes of high molecular weight, parrafin, beeswax and the like. Higher specific gravity sealants can be prepared by mixing the above seal materials with dense inert fillers such as glass beads, clays, metallic powders and like filler materials.

Illustrated in FIG. 1 is a seal breaking disc which may be fabricated of any dense material which is nonreactive with blood such as stainless steel or a dense ceramic. The density of disc 90 is such that it has a specific gravity exceeding the specific gravity of the heavy phase blood. Disc 90 is conveniently nested in the lower portion of piston 40 and preferably is held in place by a light interference fit with wall 89 formed by a recess in the lower surface 82 of piston 40.

As illustrated in FIG. 2, piston 40 has completed its travel within container 12 and is stopped from further movement in container 12 by stop means 34 and valve means 42 is closed.

When operating the separator assembly of the invention herein it is preferred that the assembly be evaculated of air so that when cannula 18 penetrates closure 16 blood will automatically fill container 12.

After cannula 18 is withdrawn and container 12 is filled with blood the assembly of the invention is placed in a centrifuge and the blood is separated employing relatively low centrifugal forces which do not activate the seal breaking means or cause the piston 40 to move from its initial position. Thereafter the rotational speed of the centrifuge is increased, whereby the disc 90 breaks loose and falls to the lower end 15 of container 12, breaking seal 88 in its passage. The broken seal fragments 92 also descent to the lower end 15 of container 12 due to their density and only moderate adhesiveness. The higher centrifugal forces also cause the piston to slide and a substantial differential hydrostatic pressure develops on the piston diaphragm 44, the valve means 42 automatically opens and the piston 40 moves downwardly through the light phase 5a with the light phase passing through the throat 80, through the filter 60 and valve means 42. Piston 40 maintains sealing engagement with the inner wall 13 of container 12 during descent to stop 34. The piston 40 completes its movement when it engages stop means 34, this terminates the pressure differential on piston diaphragm 44, automatically closing the valve means 42 while the assembly is still subjected to centrifugal forces. Diaphragm 44 then presents an impervious barrier between the light 5a and heavy 5b phases of the blood 5 when piston 40 is in the position illustrated in FIG. 2. Centrifugal forces are then terminated and the separated blood sample is ready for use in a diagnostic procedure.

What is claimed is:

l. A self-contained fluid separator assembly capable of separating blood into its component phases of light phase plasma or serum and heavy phase cellular portion comprising:

a. a container having a first open end which is adapted to receive blood for subsequent separation into a light phase and a heavy phase and a second open end for removing the separated light phase;

b. closures sealing the open ends of the container, the closures being formed of a self-sealing elastomeric material which is penetrable by a cannula;

c. a piston having a specific gravity relatively greater than the heavy phase portion of the blood and slidably mounted in the container and having means on an outer surface in sealing engagement with an inner surface of the container;

d. pressure responsive valve means associated with said piston, said valve means being normally closed when there is a minimum of pressure difierential on different portions of the valve means and which automatically opens in response to a substantial pressure differential so that when said container is subjected to moderate centrifugal force the blood separates into its light phase and heavy phase but the piston stays in the upper portion of the container, and subsequently when increased centrifugal force is used the valve means automatically opens with the lighht phase passing up through the valve means enabling the piston to move down through the light phase while retaining sealing engagement with the inner surfaces of the container;

. frangible seal means in a position opposite to the first end for receiving blood and between said first end and said piston to isolate said piston from contact with the blood;

f. means for breaking said frangible seal, said seal and said means for breaking said seal being constructed and arranged so that when the centrifugal force reaches a predetermined value, the seal is broken by said seal breaking means; and

g. mechanical stop means on the container whereby the piston when moving through the light phase will stop a predetermined distance from one of the ends of the container followed by termination of the different pressure with permits the valve means to automatically shift from an open position to a closed position to provide an impervious barrier between the separated light phase and heavy phase of the blood.

2. The self-contained fluid separtor of claim 1 wherein said container comprises a tubular body open at each end in which closures formed of elastomeric material are mounted in sealing engagement with the tubular body and a piston is disposed adjacent one of said closures.

3. The self-contained fluid separator of claim 1 wherein the piston includes a rigid tubular sleeve mounted in a generally tubular outer body portion formed of rubber and having a plurality of spaced axial ribs on its outer portion for sealing engagement with the inner walls of the container and a diaphragm forming a wall across one end of the generally tubular rubber sleeve and having at least one aperture formed therein which is normally closed but which automatically opens when subjected to a substantial pressure differential on opposite sides of the diaphragm.

4. The self-contained fluid separator of claim 1 wherein the piston has a tubular metal sleeve mounted in sealing engagement in a complementary annular recess formed in a rubber body portion of said piston, having an interference fit so that substantially no air space is provided between the walls defining the annular recess and the inner and outer walls of the rigid tubular member.

5. The self-contained fluid separator of claim 1 wherein the stop means formed on the container is an annular groove interposed between the ends of the container forming an annular rim on the inner surface of the container so that said piston is prevented from passing the stop means when subjected to centrifugal forces.

6. The self-contained fluid separator of claim 1 wherein the piston includes a filter component located in the path of said light phase passing up through the valve means.

Claims

1. A self-contained fluid separator assembly capable of separating blood into its component phases of light phase plasma or serum and heavy phase cellular portion comprising: a. a container having a first open end which is adapted to receive blood for subsequent separation into a light phase and a heavy phase and a second open end for removing the separated light phase; b. closures sealing the open ends of the container, the closures being formed of a self-sealing elastomeric material which is penetrable by a cannula; c. a piston having a specific gravity relatively greater than the heavy phase portion of the blood and slidably mounted in the container and having means on an outer surface in sealing engagement with an inner surface of the container; d. pressure responsive valve means associated with said piston, said valve means being normally closed when there is a minimum of pressure differential on different portions of the valve means and which automatically opens in response to a substantial pressure differential so that when said container is subjected to moderate centrifugal force the blood separates into its light phase and heavy phase but the piston stays in the upper portion of the container, and subsequently when increased centrifugal force is used the valve means automatically opens with the lighht phase passing up through the valve means enabling the piston to move down through the light phase while retaining sealing engagement with the inner surfaces of the container; e. frangible seal means in a position opposite to the first end for receiving blood and between said first end and said piston to isolate said piston from contact with the blood; f. means for breaking said frangible seal, said seal and said means for breaking said seal being constructed and arranged so that when the centrifugal force reaches a predetermined value, the seal is broken by said seal breaking means; and g. mechanical stop means on the container whereby the piston when moving through the light phase will stop a predetermined distance from one of the ends of the container followed by termination of the different pressure with permits the valve means to automatically shift from an open position to a closed position to provide an impervious barrier between the separated light phase and heavy phase of the blood.