Source: http://www.google.com/patents/US5849178?dq=5,832,511
Timestamp: 2014-03-14 01:52:43
Document Index: 232663717

Matched Legal Cases: ['application No. 60', 'art 2', 'art 3', 'art 3', 'arts 2', 'art 2', 'art 2', 'art 3', 'art 2', 'art 3', 'art 2', 'arts 3']

Patent US5849178 - Apparatus for separating a blood component from blood plasma - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsAn apparatus is provided for centrifuging and further automatically handling a container (110) for separating a component, such as fibrin monomer, from blood. The container (110) comprises a cylindrical member (27) and a piston displaceable in said cylindrical member, said piston comprising a tubular...http://www.google.com/patents/US5849178?utm_source=gb-gplus-sharePatent US5849178 - Apparatus for separating a blood component from blood plasmaAdvanced Patent SearchPublication numberUS5849178 APublication typeGrantPublication dateDec 15, 1998Filing dateJan 8, 1998Priority dateJan 8, 1997Fee statusLapsedAlso published asCA2277860A1, CA2277860C, EP0951360A1, EP0951360A4, WO1998030331A1Publication numberUS 5849178 A, US 5849178A, US-A-5849178, US5849178 A, US5849178AInventorsNiels Erik Holm, Glenn A. JorgensenOriginal AssigneeBristol-Myers Squibb CompanyExport CitationBiBTeX, EndNote, RefManPatent Citations (9), Referenced by (26), Classifications (31), Legal Events (7) External Links: USPTO, USPTO Assignment, EspacenetApparatus for separating a blood component from blood plasmaUS 5849178 AAbstract An apparatus is provided for centrifuging and further automatically handling a container (110) for separating a component, such as fibrin monomer, from blood. The container (110) comprises a cylindrical member (27) and a piston displaceable in said cylindrical member, said piston comprising a tubular piston rod (8) extending through a top wall (73). The piston divides the cylindrical member (27) into a first chamber (70) positioned above said piston between said piston and the top wall (73), and a second chamber positioned below said piston. The top wall (73) of the container comprises an extension (90) defining a circumferential slit surrounding the outer side of the piston rod (8), whereby one end of said slit communicates in the axial direction with the first chamber. In addition, the first chamber communicates through a plurality of channels with the second chamber. The apparatus according to the invention comprises a supporting turntable (101) with means for releasably retaining the cylindrical member (27), said supporting turntable being connected to a first activating means (105) for rotating said supporting turntable (101) with the container (110) about the central axis thereof, as well as a rotatably journalled piston activating mechanism (113, 118) adapted to activate the piston (55) by means of a second activating means (115). The apparatus comprises an optical blood cell detector (130) which is adapted to emit a light beam obliquely towards the piston rod (8) through the extension (90) of the top wall (73) and the slit (91), and which comprises a detecting means for observing the intensity of the reflected light beam. The apparatus further comprises a control means (131) for controlling the piston activating mechanism (113, 118) in response to the measurements of the detecting means.
We claim: 1. An apparatus for centrifuging and further automatically handling a container for separating fibrin monomer from blood, where the container comprises a cylindrical member and a piston displaceable in said cylindrical member said piston comprising a tubular piston rod extending through a top wall, and where the piston divides the cylindrical member into a first chamber positioned above said piston between said piston and the top wall, and a second chamber positioned below said piston and where the top wall of the container comprises an extension defining a circumferential slit surrounding an outer side of the piston rod, whereby one end of the slit communicates in an axial direction with the first chamber, and whereby said first chamber communicates through a plurality of channels with the second chamber, and where said apparatus comprises a supporting turntable with means for releasably retaining the cylindrical member, said supporting turntable being connected to a first activating means for rotating said supporting turntable with the container about a central axis thereof, as well as a rotatably journalled piston activating mechanism adapted to activate the piston by means of a second activating mechanism, the apparatus further comprising an optical blood cell detector which is adapted to emit a light beam obliquely towards the piston rod through the extension of the top wall and the slit, a detecting means for measuring the intensity of the reflected light beam, and a control means for controlling the piston activating mechanism in response to the measurements of the detecting means.
This application claims benefit of U.S. provisional application No. 60/034,055, filed Jan. 8, 1997.
FIELD OF THE INVENTION The present invention relates to methods and apparatus for separating blood into plasma and cellular components using a centrifuge. The invention is more particularly concerned with the use of a cylindrical separation container rotated in the centrifuge about its longitudinal axis and optical sensing means to control the content of cellular components within the separated plasma.
BACKGROUND ART WO96/16714 discloses a container for separating a blood component, e.g., fibrin monomer, from blood by a centrifugation about a vertical axis. The first major step in such a process using this type of device is the centrifugal separation of blood into plasma and cellular fractions as described below. This container comprises a first annular chamber defined by an outer cylindrical wall and an inner cylindrical wall, both walls extending coaxially about a common axis, as well as by a top wall and a bottom wall, where the bottom wall is formed by a piston displaceable within the first chamber. The piston is activated by a piston rod, the outer surface of which provides the inner cylindrical wall. The piston rod extends outwardly through the top wall and is surrounded by a neck-like extension of the top wall. A slit, which is preferably annular, is provided between the extension and the piston rod. The container comprises furthermore a second chamber accommodated below the first chamber and communicating with the end of the said slit opposite the first chamber through a first conduit. The second chamber is defined by the outer cylindrical wall, the bottom wall of the first chamber, and by a second bottom wall. In use a blood sample is fed into the first chamber. Then the container is placed in a centrifuge apparatus and subjected to a centrifugation and activation of the piston. As a result, the blood in the first chamber is separated into a plasma fraction and a remaining portion of blood containing red and white blood cells. This second chamber serves as a reaction chamber for receiving plasma from the first chamber through the slit and the first conduit and for converting the fibrinogen content of the plasma into a non-cross-linked fibrin polymer by addition of a suitable enzyme. Centrifugation provides that the non-crosslinked fibrin polymer is separated from the plasma, and that it is deposited on the outer wall of the reaction chamber. When the piston is subsequently actuated, the remaining plasma is removed from the reaction chamber. Therefore, a solvent is added for dissolving the non-cross-linked fibrin polymer. The transferring of the plasma fraction of the blood from the first chamber to the second chamber through the slit and the first conduit must be carefully observed so that nothing of the remaining portion of blood containing the red blood cells is transferred to the second chamber.
BRIEF DESCRIPTION OF THE INVENTION The object of the invention is to provide an apparatus allowing a control of the transfer of plasma to the second chamber in such a manner that the transfer of plasma is stopped as soon as red blood cells are present in the slit.
In satisfaction of the foregoing object there is provided an apparatus which according to the invention comprises an optical blood cell detector which is adapted to emit a light beam obliquely towards the piston rod through the extension of the top wall and the slit, and which comprises a detecting means for observing the intensity of the reflected light beam, and where the apparatus further comprises a control means for controlling the piston activating mechanism in response to the measurements of the detecting means. A continuous observation of the light beams reflected from the piston rod has the effect that the detector immediately registers a drop in the intensity of the reflected light beams, said drop being caused by red blood cells penetrating into the slit. When the detector registers a drop in the intensity, the movement of the piston is immediately stopped through the control means.
BRIEF DESCRIPTION OF THE DRAWING The invention is described in greater detail below with reference to the accompanying drawing, in which
FIG. 1 is an axial sectional view of a prior art container for separating fibrin monomer from blood plasma,
FIG. 3 illustrates a graphing of the path of light beams through an upper extension of the top wall of the container and the adjacent part of the wall of the piston rod as well as the intensity of the reflected beams when seen during the transfer of plasma from a first chamber to a second chamber in the container, and
FIG. 4 shows the same as FIG. 3, but when red blood cells enter a slit surrounding the outer side of the piston rod.
DESCRIPTION OF A PREFERRED EMBODIMENT OF THE PRESENT INVENTION The present invention provides a remarkably accurate apparatus and method for ensuring that a separated plasma sample is substantially free of cellular blood components, e.g., red and/or white blood cells. This can be accomplished during high speed centrifugation, e.g., at rotational speeds over 5000 RPM. The apparatus comprises two chamber in a centrifugal container; a first container for centrifugal separation into plasma and cellular fractions and a second chamber for receiving the plasma fraction. Transfer is preferably accomplished by action of the displacement of a piston in the first chamber to force the plasma fraction only, through a conduit means in proximity to a detecting means comprising a light beam and light sensor arranged to monitor material passing through the conduit means. The conduit means needs to include an outer light transmissive (at least to the detecting light beam) wall and an inner light reflective (at least at the angle of incidence of the detecting light beam) surface. As described below, an extending neck-portion of the centrifugal container is the outer light transmissive wall and the piston shaft is the inner reflective surface. The action of the piston is preferably responsive to the detecting means such that upon detection of a blood cell in the conduit means the piston motion and corresponding plasma transfer from the first to the second chamber is ceased.
The present invention also includes enhanced methods for preparing blood component compositions, e.g., fibrin monomer solutions, free of blood cells.
The present invention is hereafter described with regard to specific preferred apparatus and methods but is understood to be useful in variously modified ways without departing from the scope of the invention.
The container of FIG. 1 is known from the above WO 96/16714 and is built of parts substantially presenting rotation symmetry and implying that the container can be placed in a centrifuge apparatus shown in FIG. 2 so as to be centrifuged about a central axis 1. The container comprises an outer container part 2 and an inner container part 3 being such that they completely fit into each other and everywhere closely abut one another apart from the portion where an axially extending intermediary channel 4 is provided. The channel 4 is provided by a groove shaped in the inner container part 3. The two container parts 2 and 3 comprise their respective bottoms 5 and 6, respectively, said bottoms defining a central opening 7 allowing passage of a piston rod 8. About the opening 7, the two container parts comprise axially extending portions 9 and 10, respectively, which extend closely to the hollow piston rod 8 in a direction away from the interior of the container parts. The outer container part 2 abuts the hollow piston rod along a short radially extending flange 11 provided with a recess 12 receiving a sealing ring 13.
A Luer-coupling 57 is shaped inside the hollow piston rod for receiving a conventional syringe 58 with a piston-acting plug 59 for acting on the content of the syringe 58. The coupling 57 is shaped substantially as a pipe length communicating with a central opening 61 in the piston 55 through a frusto-conical portion 60. The pipe length 57 is provided with a radially inwardly projecting web 62 for directing the fluid leaving the syringe 58 away from an axial path and thereby round the elongated pipe length 46 therebelow inside the capsule 45. The latter pipe length 46 is of such a length and such dimensions that it can sealingly engage the pipe length 57 inside the hollow piston rod 8 when the piston 55 is in its lowermost position near the cover 27. In order to promote the above sealing connecting, the inner side of the pipe length 57 is formed with a gradually decreasing diameter at the end adjacent the piston 55.
The described container comprises a first annular chamber 70 defined inwardly by the hollow piston 8 forming a cylindrical inner wall 71, and outwardly by a cylindrical outer wall 27 formed by the outer container part 2 and the inner container part 3. When in the conventional use position, cf. FIG. 1, the annular chamber 70 is upwardly defined by a top wall 73 formed by the bottoms 5 and 6, respectively, of the outer container part 2 and the inner container part 3. The axially extending portions 9 and 10 of the container part 2 and 3 provide an extension 90 surrounding the piston rod 8. An annular slit 91 is defined between the extension 90 and the piston rod 8, and through this annular slit 90, the annular chamber 70 communicates with the channels 4 and 21 extending into the second chamber 75. Downwardly, the annular chamber 70 is defined by a bottom wall 74 formed by the piston 55. A second chamber 75 is defined below the piston 55, said second chamber outwardly being defined by the same cylindrical outer wall 72 as the first chamber 70. Downwardly, the second chamber 75 is defined by a second bottom wall 76 formed by the outer disk 19 and the inner disk 20. The capsule 45 is centrally accommodated in the interior of the second chamber 75. A third chamber 77 is provided below the said second bottom wall 76, and this third chamber 77 is defined by the partition means 36 and the annular filter unit 42. In addition, this third chamber 77 communicates with the second chamber 75 through the passage formed by the central opening 22 in the outer disk 19 and the inner disk 20. Finally, a fourth chamber 78 is provided below the partition means 36, said fourth chamber 78 being defined downwardly by the wall 32 of the cover 27 and furthermore by portions of the sleeve 28 of the cover 27 and the bottom side of the outer disk 19.
As described above, the container in question is primarily suited for separation of a component, such as fibrin monomer from blood, and for this purpose the second chamber 75, and preferably the upper chamber 80 of the capsule 46, is in advance filled with a suitable enzyme, such as batroxobin.
As is understood from EP-PS No. 592,242, any thrombin-like enzyme can be employed. Such enzymes include thrombin itself or any other material with a similar activity, such as Ancrod, Acutin, Venyyme, Asperase, Botropase, Crotabase, Flavorxobin, Gabonase, and the preferred Batroxobin. Batroxobin can be chemically bound to biotin, which is a synthetic substance allowing the batroxobin to be captured in a conventionally known manner by means of avidin in an avidin-agarose composition. Accordingly, avidin-agarose is found in the lowermost chamber 81 of the capsule. Both the biotin-batroxobin composition and the avidin-agarose composition are relatively easy to fill into the respective chambers 80 and 81 inside the capsule 45 before said capsule is placed inside the device.
When the interface between the plasma and the remaining portion of the blood has been stabilized, i.e. when the separation is complete, a reduction of the volume of the first chamber 70 is initiated by the piston rod 8 and consequently the piston 55 being pulled out. As a result, first a possible inner layer of air passes through the channels 4 and 21 into the second chamber 75, and a further moving of the piston 55 implies that also the plasma passes to the second chamber 75. The movement of the piston 55 is stopped when the entire layer of plasma has been forced into the second chamber 75, i.e. when the interface between the plasma fraction and the remaining portion of the blood has reached the inner wall 71 of the first chamber 70, whereby red blood cells are recognized in the slit 91.
The transfer of plasma from the first chamber 70 to the second chamber 75, cf. FIG. 1, must be carefully observed in such a manner that red blood cells are not transferred to the second chamber in which they risk having a negative effect on the further preparation of fibrin monomer. The said observation is performed by means of an optical blood cell detector diagrammatically shown in FIG. 2 and designated the general reference numeral 130. The detector 130 comprises a light source which is adapted to emit a laser beam towards the piston rod 8 through the extension 90 of the container 110. The laser beam is directed into such an inclining path relative to the surface of the piston rod 8 that it is reflected from said piston rod 8. The detector 130 comprises furthermore a detecting means which is adapted to register the intensity of the reflected beam(s) and consequently of the changes therein, said changes indicating that blood cells are present in the slit 91, cf. FIG. 1, between the extension 90 and the piston rod 8.
In order to adjust the movement of the piston rod 8 in response to the above, the blood cell detector 130 is connected to a control means 131. At a signal from the blood cell detector 130 through a conduit 132, the control means 131 causes an immediate stop of the movement of the piston rod 8 when red blood cells are detected in the slit 91. The movement of the piston rod 8 is stopped at a signal from the control means 131 to the motor 115 through a conduit 133.
The accurate position of the light source and the detecting means of the blood cell detector 130 relative to one another and to the extension 90 of the container 110 is determined in a conventionally known manner by means of a computer-produced model (ray tracing model).
FIGS. 3 and 4 are diagrammatic views of the path of the laser beam. The laser beam transmitted towards the container 110 is designated the general reference numeral 140. It hits the extension 90 of the container 110, and in sequence it subsequently passes through the axially extending portions 9 and 10 of the container parts 3 and 4, respectively, and the wall of the hollow piston rod 8. As a result, the laser beam 140 passes initially through a slit 141 between the axially extending portions 9 and 10 and subsequently through the slit 91 adjacent the piston rod 8. Everywhere, portions of the laser beam 140 are reflected, and especially at the transition from the plastic material to air. A suitable setting of the angle of incidence of the beam relative to the outermost surface of the extension 90 has the effect that the resulting reflection is strongest from the inner side of the piston rod, i.e. after the passage of the slit 91. Portions of the light beam reflected from the slit 91 are refracted several times, but the main beam exits in form of a beam at 142. The intensity of the latter as well as of other reflected beams indicated in the drawing in form of the length of the beam in a direction substantially radially outwards from a circular arc 0. The detecting means is arranged on the location where the strongest reflection exits so as to observe the intensity of said beam. The position of the detecting means in indicated in FIG. 1 by means of dotted lines.
FIG. 3 shows the reflection of the light beam 140 while plasma is transferred from the first chamber 70 and into the second chamber 71. The reflected light beam 142 is, as indicated, relatively strong.
FIG. 4 shows how the intensity of the reflected light beam 142 has dropped at the appearance of red blood cells in the slit 91. The use of the described apparatus renders it possible to achieve an instantaneous stop of the movement of the piston rod 8 in such a manner that red blood cells are not transferred to the second chamber 75.
The optical blood cell detector is of a conventionally known type, and for instance a photometer may be used.
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