U.S. patent number 3,799,342 [Application Number 05/265,707] was granted by the patent office on 1974-03-26 for method of using a serum separator.
This patent grant is currently assigned to U.S. Medical Research & Development, Inc.. Invention is credited to Donald J. Greenspan.
United States Patent |
3,799,342 |
Greenspan |
March 26, 1974 |
**Please see images for:
( Certificate of Correction ) ** |
METHOD OF USING A SERUM SEPARATOR
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.
Inventors: |
Greenspan; Donald J.
(Riverside, NJ) |
Assignee: |
U.S. Medical Research &
Development, Inc. (Riverside, NJ)
|
Family
ID: |
26737743 |
Appl.
No.: |
05/265,707 |
Filed: |
June 23, 1972 |
Related U.S. Patent Documents
|
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
58557 |
Jul 7, 1970 |
3661265 |
|
|
|
Current U.S.
Class: |
210/780; 422/918;
210/117; 210/359 |
Current CPC
Class: |
B01D
33/01 (20130101); B01L 3/5021 (20130101); B01L
2400/0478 (20130101); B01L 2300/0681 (20130101) |
Current International
Class: |
B01L
3/14 (20060101); B01D 33/01 (20060101); B01D
33/00 (20060101); B01d 021/26 (); B01d
033/00 () |
Field of
Search: |
;210/73,83,117,136,416,359,DIG.23,42 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Adee; John
Attorney, Agent or Firm: Woodcock, Washburn, Kurtz &
Mackiewicz
Parent Case Text
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 U.S. 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, 1969, 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, small
amounts 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.
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 of a
collection tube. The pick-up device has a second tube which passes
through an opening in the rubber element to a point near the upper
end of the first tube, and the second tube has a downwardly 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 the collection tube, fills with serum, and is then removed
from the collection tube. The serum retained in the device can then
be tested.
A problem with the use of the device just described is that it
cannot be used to transport the separated serum or plasma to 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 the separated serum or plasma relatively free of
contaminants.
In accordance with a first embodiment of the invention, there is
provided a separation device which, itself, 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.
Claims
I claim:
1. A method of isolating serum or plasma from formed elements of
the blood in a collection tube having a closed end and an 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 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.
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 the first 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 said passageway into a separator tube
sealed to said other side of said plug.
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.
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.
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 of deflecting 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 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.
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.
Description
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 4--4 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 of the
collection tube and serum or plasma in the upper part of the
collection tube.
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 patient's 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 10. 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 10 by a conventional collection method. Following
collection, the formed elements are precipitated either
mechanically by the use of a 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 collection 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.
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 82, 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.
A mark 104 is provided on the outer surface of container 82 for the
purpose of indicating that a particular volume of serum or plasma
has been collected when a predetermined one of the ridges 101, 103,
for example ridge 101, comes into register with the mark 104.
In operation, the contianer 82 is first attached to the handle 96
and the plug 98 is in the lowermost possible position within the
container 82. The assembly is pushed downwardly into the collection
tube 66, as 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 plug 98
moves upwardly with respect to the container 82 as the container is
pushed downwardly into the collection tube 66. When the ridge 101
comes into register with the mark 104, the assembly is pulled out
of the collection tube 66, the handle 96 is removed and the
container 82, now containing serum or plasma can be packed in a
sytrofoam container, for example, (not shown) and shipped to a
laboratory for testing. At the laboratory, the plasma or serum 106
in the 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 opening 90. 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 and need 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 18 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 24 of the plug 18 to further
facilitate the flow of air into 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.
* * * * *