Note: Descriptions are shown in the official language in which they were submitted.
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FI~LD ~F T~ INVENTION
This invention relates generally to a device for
separating plasma from red cells (erythrocytes) in blood
samples.
BAC~GROUND OF T~E INVE~TIO~
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Various blood analysis techniques require clear
plasma samples free of red cells. Separation of plasma from
red cells can be accomplished by various methods based on
the fact that the red cells are of a higher specific gravity
than the plasma. For example, if a blood sample can be
allowed to stand for two or more days, the red blood cells
will settle to the bottom by gravity. A faster technique is
centri~ugation using an ordinary laboratory centrifuge. In
routine laboratory analysis, a centrifugation step does not
delay the work flow. However, centrifugation does take some
time (20 minutes or so) and may be unacceptable in an
emergency situation, for example in an operating room. Even
in non-emergency situations such as in a doctor's office, it
may be desirable for the doctor himself or an assistant to
be able to quickly obtain a clear plasma sample without
having to send the blood sample to a laboratory.
~ ~ESCRIPTI~N O~ T~ PRIO~ ~RT
; Centrifuge devices comprising a rotor that rotates
at high speed about a vertical axis have been proposed for
clearing blood samples of chylomicrons (fat particles 80 -
500 nm diameter) prior to clinical analysis. Devices of this
type are available from Beckman Instruments, Inc. of
California and are described in United States Patents NosO
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4,142,670 issued Narch 6, 1979 (Ishimaru et ~l.) and 4,177,921issued December 11, 1979 (Nielsen~. Both of these patents have
been assigned to Beckman Instruments, Inc.
The Beckman chylomicron rotor recei~es a disposable
liner in which chylomicron~ are isolated by flotation. The
liner has a cylindrical centre chamber and a doughnut-shaped
outer chamber. The liner is made of a thin and flexible
polyethylene material and flexes subs~antially under
centrifugal force during centrifugation while being constrained
by the rotor. At this time, the chylomicrons float to the
centre of the liner where they are isolated. The serum can
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then be removed from the liner b'y pipette.
- BRIEF D~SCRIPTIO~ OF_THE INV~T ~W
The invention provides a plasma separator comprising
a container which is symmetrical about a normally vertical xis
and is adapted for rotation at high speed about that axis. The
container is self supporting during such rotation and defines
internally a central chamber for receiving a blood sample, an
annular outer chamber, and an annular passageway connec~ing the
chambers and having respective inner and outer ~nds. The
central chamber has a top wall and a lower wall of inverted
conical shape extending about the said axis, the lower wall
~` having an upper end and a circular edge at said upper end, the
circular edge being dispo~ed at the inner end of the
passageway. The passageway extends downwardly and outwardly
from the edge to the outer chamber and the outer chamber is
located at the outer end of the pas~ageway and below the
circular edge. The inverted conical shape of the lower wall
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of the central chamber provides an internal surface of the
cen~ral chambPr which extends up~ardly away from ~he said axi~
to the circular edge at an inclination selected to permit red
blood cells in a blood sample to migrate up the surface,
5 through the annular passageway and into the outer chamber upon
rotation of the chamber at an appropriate high speed, while
plasma is retained in the inner chamber. The container has a
single opening located in its top wall for permitting insertion
, of a blood sample into and removal of plasma from the central
chamber.
The invention also provides a method of separating
plasma from red cells in a blood sarnple. The method involYes
; providing a transparent container having an axis and being
symmetrical about said axis and self-supporting. The container
defines internally a central chamber, an annular outer chambex
and an annular passageway connecting the chambers and having
respective inn~r and outer ends. ~he central chamber has a top
wall and a lower wall of inverted conical shape extending ~bout
the ~iaid axis. ~he lower wall has an upper end and a circular
edge at said upper end, the said circular edge being dispos~d
at the inner end of the passageway and the passa~eway extending
downwardly and outwardly from the edge to the outer chamber.
The outer chamber i9 located at the outer end of the passageway
and below the circular edge. The container has a single
opening located in the top wall for providing access to the
chamber. A blood sample is inserted into the central chamber
through the opening in the top wall, for example by using a
pipette or syringe. By means of a rotating device, the
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container is then rotated about its axis with the axis
vertical, at a speed selected to cause red cells in the blood
~;; sample to migrate up the lower wall, through the annular
- passageway and into the outer chamber, while plasma is retained
5 in the inner chambex. The container is visually monitored and
the rotation is terminated when the plasma in the inner chamber
is seen to be substantially clear. Plasma is removed from the
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~- central chamber through the opening in the top wall of the
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~ ~hamber. In experiments, it has been found that a clear plasma
- 10 sample can be obtained in the order of 30 seconds.
BRIl~F D33SCRIPTIOll!l OF ~D3 DRAWINGS
In order that the invention may be more clearly
understood, reference will now bP made to the accompanying
drawings which illustrate particular preferred embodiments
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of the invention by way of example, and in which:
Fig. 1 is a perspective view from above of a plasma
- separator in accordance with the invention;
Fig. 2 is a vertical sectional view through the
`~ 5 central axis of the separator shown in Fig. 1, with the
separator shown mounted on a device for rotating the
separator;
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'Fig. 3 is a view similar to Fig. 2 illustrating
' removal of a separated plasma sample from the central
chamber of the separator; and,
Fig. 4 is a view similar to Fig. 2 (but without the
rotary device) illustrating an alternative embodiment of the
invention.
DESCRIPTION OF THE P~EFERRED EMB~DIME~TS
i 15 Referring now to the drawings, Fig. 1 shows the
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external appearance of the plasma separator provided by the
invention, as seen from above. In this embodiment, the
separator is made in one piece in a semi-rigid plastic
material, for example by blow-moulding. In an alternative
embodiment, however, the separator could be made in two or
more parts.
The separator itself is generally denoted by
reference numeral 20 and essentially comprises a container
which is symmetrical about a normally vertical axis 22. The
container is designed so that it can be coupled to a device
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that is capable of rotating the container at high speed
about axis 22. In ~ig. 2, part of such a device is shown
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~ supporting the separator. The device comprises a platform 24
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having a recess 26 into which the separator is frictionally
engaged. The plat~orm 24 ls carried by a vertical shaft 28
that is connected to a drive motor (not shown) for rotating
the shaft and with it the separator at high speed. The
S structure surrounding the platform 24 is indicated at 30.
I The container is designed to be self-supporting
; during rotation and, to this end, is made of a semi-rigid
plastic material as noted previously. The container defines
internally a central chamber 32 for receiving a blood
sample, and an annular outer chamber 34 for receiving red
blood cells separated out of the blood sample by rotation of
the container about axis 22. An annular passageway 36
connects the two chambers 32 and 34.
lSThe central chamber 32 has a lower wall 38 of
inverted conical shape extending to a circular edge 40 at an
upper end of wall 38 and at the inner end of passageway 36.
The passageway extends downwardly and outwardly from edge 40
to the outer chamber 34, which chamher is located at the
~1 20 outer end of the passageway and below the circular edge 40.
, The container has a single opening 42 located in a top wall
-' 44 above the central chamber for permitting insertion of a
blood sample into and removable of plasma from the chamber.
In practice, a blood sample will typically be
introduced into the central chamber 32 through opening 42 by
~means of a pipette. Preferably, the central chamber will be
ifilled to the level of edge 40 as indicated by the level
line "1" in Fig. 2. The container will be frictionally
retained in the recess 26 in platform 24 sufficiently
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tightly that the container will stay in place when the
platform is rotated at high speed. At this time, red cells
in the blood sample will tend to migrate up the inclined
inner surface of wall 38 as shown generally at 46b in Fig.
- 5 2, over edge 40 as indicated at 46a and down the passageway
- 36 into chamber 34.
Preferably, the plasma separator will be made of a
transparent or transluscent plastic material so that the
sample can be visually observed during rotation of the
separator. The person operating the device on which the
separator is rotated can then stop rotation when substan-
tially all of the red cells appear to have migrated into the
outer chamber 34.
Fi~. 3 shows the plasma separator after it has been
removed from platform 24 when separation has been completed.
; Clear plasma indicated by reference numeral 48 remains in
the central chamber 32 while thle outer chamber 34 contains
red blood cells indicated at 50. The stem of a pipette is
shown at 52 as having been inserted through opening 42 for
; 20 withdrawing the plasma sample from chamber 32. Normally, the
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red blood cells 50 would not be required for analysis and
~ would be simply discarded. It is anticipated that the
; separator will be disposable so that it can be simply thrown
away aftex the plasma has been removed from chamber 32. On
the other hand, if it is desired to either retrieve the red
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cells or reuse the separator, then the red cells can be
- transferred into the central chamber by appropriately
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~ tipping the separator and the red cells can then be removed
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by pipette.
From a comparison of Figs. 2 and 3 it will be noted
that the walls of the container that define the passageway
36 are shown spaced apart somewhat in Fig. 2 but in contact
in Fig. 3. Thus, the container is designed so that the walls
that define passageway 36 will tend to move apart under
centrifugal force to allow liquid flow through passageway 36
during rotation of the separator, but will close to in
effect isolate the red cells from the plasma sample when the
separator is stationary. Referring specifically to Fig. 2,
the container has a wall 54 at the inner side of passageway
36 that remains relatively stationary under the effects of
centrifugal force due to the bracing effect of the inverted
conical wall 38. The wall 56 at the outer side of passageway
36 on the other hand is designed to be more flexible and to
move away from wall 54 under the effect of centrifugal
force.
Fig. 4 shows an alternative embodiment of the
invention in which primed reference numerals have been used
to denote parts corresponding to parts shown in the previous
views. In this case, the container forming the separator is
; essentially the same as the container shown in the previoùs
; views except in that an outlet for plasma is provided at the
centre of the bottom wall 38 of chamb~r 32. In Fig. 4, the
.25 outlet is denoted by reference numeral 58 and is surrounded
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by a short neck 60 over which is frictionally fitted an
-inverted cap 62 that acts as a collection chamber for the
plasma. In thls embodiment, when the separation of plasma
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from red blood cells has been completed, all that need be
done is to remove the cap 62, containing the plasma. The
step of inserting a pipette to remove the plasma is
; unnecessary. Opening 42' is still provided in the top wall
44 of the container for the purpose of introducing a blood
sample into the container. The sample would be introduced at
a location off axis 22' while the separator is rotating.
Alternatively, cap 62 may be provided with a plug for outlet
58 as indicated in ghost outline at 64 in Fig. 4.
; 10 The device used to rotate the plasma separator need
;~ not be a high quality laboratory-standard centrifuge as is
required in the prior art, although such a device could
undoubtedly be used for this purpose. All that is required
is a drive means that is capable of engaging and rotating
the separator at relatively high speed. It should also be
noted that the separator is self-supporting during rotation
and that it is unnecessary to confine the separator within
some sort of rotor structure as in the prior art.
In summary, the device provided by the invention
provides an extremely simple and inexpensive means for
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~` separating plasma from a blood sample, quickly and
e~ficiently. Numerous other advantages are also provided by
- the device. For example, in terms of safety, no handling of
, the blood sample is required. The separator can be made of a
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plastic material so that there is no glass that might break.
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t the same time, the separator can be made transparent so
that the blood separation action is visible and the separa-
tor can be made relatively inexpensively so that it can be
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; disposable. ~nlike blood separation techniques performed
using a centrifuge, balancing of the rotary device is not a
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concern. Also, aerosoling of the sample is minimized because
the sample is substantially closed by the separator.
Other advantages are that the separator can be used
to "harvest" plasma by adding one blood sample after another
to a large size separator.
The separators can also be made stackable so that
multiple units can be stacked on the same spinner.
It will of course be understood that the preceding
description relates to particula~ preferred embodiments of
the invention only and that the invention is not limited to
these embodiments.
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