CA1161003A - Method and apparatus for centrifugal separation - Google Patents
Method and apparatus for centrifugal separationInfo
- Publication number
- CA1161003A CA1161003A CA000418558A CA418558A CA1161003A CA 1161003 A CA1161003 A CA 1161003A CA 000418558 A CA000418558 A CA 000418558A CA 418558 A CA418558 A CA 418558A CA 1161003 A CA1161003 A CA 1161003A
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- bag
- container
- blood
- collar
- top portion
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Abstract
Title Method and Apparatus For Centrifugal Separation Abstract of the Disclosure A blood bag is described which aids in maintaining the separation of blood components. This bag is constructed of a flexible plastic, has a conical top leading to an outlet line and internal septa to reduce swirling of the bag's contents during rotor deceleration. The bag is adapted to be placed in a split sleeve prior to placement in the swinging bucket of a centrifuge rotor. A collar is placed over the top of the bag to aid in reducing wrinkles in the bag.
Methods are described for reducing contamination of separated blood components by reducing bag wrinkles, reducing swirling of the blood fractions during rotor deceleration, and reducing mixing during expression.
Methods are described for reducing contamination of separated blood components by reducing bag wrinkles, reducing swirling of the blood fractions during rotor deceleration, and reducing mixing during expression.
Description
6 ~ 3 Title ~ethod and Apparatus For Centri~ugal Separation Background of t_e Inven ion 5This invention relates to a method and apparatus for centrifugally separating particulate material Erom a liquid phase and, more particularly, to a method and apparatus for the batch separation of blood components.
It is known to use centrifugal techniques for the separation and/or fractionation of particuIate materials suspended in a liquid according to particle density, size, shape, etc. Unfortunately, during centrifuge deceleration, and subsequent 15 removal of the separated constituents, there is a tendency for remixing of the separated components.
This is particularly true in the case o blood.
The separation of blood into cellular components and plasma, in general, and preparing 20platelet rich plasma, in particular, has 'oecome of great interest to the medical co~munity. The increased use of chemotherapy and ot'ner techniques requires platelet concentrate transfusions.
Unfortunately, present blood bags and many batch type 25blood separation techniques do not facilitate good platelet separa~ion. There is always some incipient remnants or traces of red blood cells and white blood cells. Antigens on certain these blood contaminants give rise to alloimmunization of the recipients o~
30such transfusions, thereby reducing the efficency of subsequent transfusions. It therefore becomes necessary in many cases to select and type the donors -- it being no longer possible to use random donors. This greatly increases the cost. Some oE
the problems incipiently related to alloimmunization are described in an article entitled, "Correction of 5 Poor Platelet Transfusion Responses witn Leukocyte-poor HL~A-matched Platelet Concentrates" by . H. Herzig, et al., Blood, Vol. 46, No. S (Nov.), 1975.
A frequently-used blood component separation 10 procedure involves the preparation, in two centrifugation steps from a single donor unit of whole blood, of a packed red-cell fraction which also contains most of the ~hite blood cells, a concentrate of platelets suspended in plasma, and a platelet-poor 15 plasma fraction. During the first cen~riEugation, red blood cells sediment to the bottom o~ the centrifuge bucket (i.e., 2ack at the bottom of the blood bag which is oriented horizontally during centrifugation in a swinging-bucket rotor) and a 20 platelet-rich plasma layer extending from the top of the bag to the red-cell interface region is formed.
White blood cells are concentrated in the plasma layer imrnediately above the packed red-cell mass (the so-called buffy-coat region3 as well as in the upper 25 portion of the packed red-cell region. After rotor deceleration, the platelet-rich plasma layer is expressed into a satelli~e bag leaving the packed red cells and buffy-coat layer in the original draw bag.
The platelet-rich plasma is -then centrifuged to sediment the platelets, after which most cf the platelet~poor plasrna is expressed into a second satellite bag, leaving a platelet concen~rate in the first satellite hag.
One of the factors contributing to contamination (unwanted levels of white and red blood ~`~ 1 3 6~0~3 cells in platelet~rich plasma) of t'ne platelet concentrate, giving rise to alloirnmunization, is the formation of folds in the upper part of the blood bag during centrifugation. These folds permit the red 5 and white blood cells to b~ecome entrapped in the folds hence e~pressed with the platelet containing plasma causing some of the undesired contamination noted above. This tendency to fold in the top portion of t'ne bag can be aggravated by the fact that lO satellite packs, tubing and balancing pads are usually placed within the bucket with the blood bag Further, the technician in removing the bag from the swinging bucket of the centrifuge, as well as in subsequently handling the bag, can cause some 15 disturbance and remixins of the bag's contents.
A second major ~actor contributing to unwanted contamination of the platelet concentrate is the phenomena which occurs during the final stages of deceleration of the centrifuge rotor. The 20 deceleration o~ a unit of fluid on the extreme outboard side of the swinging bucket as it reassumes a vertical orientation will be greater than ~'nat of a unit on the extreme inboard side. This results in a fluid rota~ion about the bucke~ center unlt~ The 25 rotating or swirling fluid tends to cause some remixing of the components, which were separated during centri~ugation, before they can be expressed from the bag into ~he satellite bags. Efforts in the past to reduce this swirling have been directed to 30 decreasing bucke~ diameter, using oval buckets, and the like. Long, thin buckets greatly enlarge the size of the centrifuges and hence generally are not a prac~ical solution. Further, the thin, long ~ubes increase centrifugation time. Swirling can be reduced by increa~ing centri~ugation deceleration , ~.~ 1 l fi~ 3 time, but this severely reduces throughput and hence greatly increases processing costs.
Brief Description of the Invention According to one ~ethod of this invention, 5 particulate material is separated from, and maintained separated from, a fluid phase, using a storage container having either flexible or rigid walls having top, middle and bottom portions with an outlet line at the top portion, by filling the 10 container with a mixture of the particulate material in the fluid phase, sealing the container, centrifuging the container in a swinging bucket rotor, top portion up, applying a force to a portion of the container to maintain the top portion taut and 15 relatively free of wrinkles which could ot~erwise trap the par~iculate material. The force may be applied to the container in many ways. In one instance it may be accomplished by squeezing the container by use of a liquid bladder in the swinging 20 bucket or other similar technique. Alternatively, the force can be applied by a collar, positioned over the top portion o~ the container and outlet line such that the centrifugal force on the collar forms the top portion of the container tautly about the collar 25 with reduced wrinkles. Preferably the collar is in the shape of an open annulus having a U-shaped cross section. When using a collar with an open annulus, balancing weights m~y be placed in the annulus to equilize the weights of the loaded buckets placed in 30 opposing positions in the centrifuge rotors. If satellite containers are connected to the main container, they may be stored in the annulus during centrifugation.
Tn still another alternative technique the force may be applied to the container by positioning 1 6~003 a volume-displacing article under the con~ainar in the centriEuge bucke~ during cen~rifugation such that the container hydrororms about the article and takes up any unfilled space within the container, thereby 5 causing the wall~ to become taut and relatively wrinkle free.
According to still other alternative techniques, satellite containers may be separated from con~act with the main container by placing the 10 main container in a split sleeve and the split sleeve in the bucket with the satellite containers being positioned in an envelope secured in the annular space in between the bucket and the splIt sleeve.
Various techniques may be used for reducing 15 swirling within the containers during the deceleration of the centrifuge. Among these are the positioning of septa within the container.
Alternatively, radially inward protuberances or baffles may be formed on the interior of either the 20 split sleeve, which holds the container, or the bucket in which the container is placed, such that under centrifugal force, the protuberances will, in effect, form inwardly projecting baffles within the interior of the container, thereby reducing the 25 swirling and intermixing of the separated particles.
~ y forming the ~op portion of the container into the general configuration of a cone or an approximation thereof, there is reduced turbulence during removal of the separated fractions through an 30 outlet line in the top of the container. Desirably, the cone has an included angle of anywhere from 25 ~o about 160 with an angle of about 75 being preferredO
One apparatus for effecting reduced 3 intermixing of separated components is a sealed, `- 5 .
plastic fluid storage container, generally cylindrical when filled with a fluid, the container having a longitudinal axis and a top and a bottom, and a first tubular con~uit communicating with the 5 interior of the container, characterized by an interior septum lying in a plane generally parallel to the longitudinal axis, t'nereby to reduce the movement of the ~luid in the container both during centrifugal deceleration and during handling of the 10 container. Preferably the conduit lies on the longitudinal axis and the top of the container is tapered in a generally conical configuration converging at the first conduit.
According to another aspec~ of the 15 invention, a sealed, flexible, thermoplastic fluid storage container is constructed having side wall sections with laminate edge seals and a longitudinal axis, two different portions of said edge seals being parallel to said longitudinal axis~ and a first 20 tubular conduit means, sealed between said wall sections, communicating with the interior of said container and intersecting said longitudinal axis.
This container is provided with edge seals which are tapered ~rom the said different portions to said 25 first conduit means.
Alternatively, or simultaneously, the container is provided with a septum defined by a first sheet of a flexible thermoplastic having ends joined to opposite said side wall sections along -~ 30 laminate seals which are generally parallel to said longitudinal axis. In variations of this container, the taper angle at the top of the container between the edge seals may lie between 25 and 160 ~ereby to provide a generally conical container top when fluid filled~ In other alternative variations, the , 1 3~:~0~3 taper angle may be between 70 and 80 and desirably is abou~ 75.
The fluid-storage container septum is alternatively defined by first and second sheets of a flexi~le thermoplastic eac'n having ~elected ends jo.ined to selected side wall sections and each being joined together along their mid portions, the jointures occurring along laminate seals gene.rally : paralle~ to the longitudinal axis In an alternative construction, the upper portion of the side wall sections each may be formed in a double pyramidal shape with additional edge seals such that ~he top portion of the container more closely approximates a cone when fluid filled. Any additional transfusion ports or inlet tubes s'nould be connected to the bottom of the container such that there are no crevices or recesses provided within the top portion to permit the entrapment of the contaminating red and white blood cells.
~rief Descri~ion of the Drawin~s Further advantages and fea~ures of this invention will become apparent upon consideration of the following description wherein:
FIG. 1 is an exploded view of a split sleeve, fluid ~ontainer (blood bag) and collar immediakely prior to placement within the spllt sleeve for later centrifugation;
FIG. 2 is a bottom plan view of the collar illustrated in FIG. 1, FIG. 3 is a cross-sectional view taken along :~; the section lines 3-3 of the blood bag of FIG. l;
FIG. 4 is a top plan view of the split `. sleeve depicted in FIG. l;
FIG. 5 is an elevation view of a typical unfilled, flexible blood bag constructed in accordance with a preferred embodiment of this invention;
FIG. 5 is a side elevation view partly cut away of the blood bag of this inven~ion (witho~t 5 attached satellite bags or transfusion parts and inlet lines) during the initial phases of centrifugation depicting the operation of the collar ~ at the beginning of centrifuge run;
.:: FIG, 7 is an elevation view partly cut away 10 depicting the blood bag of ~IG. 6, during centrifugation depicting the smoothing effect of the collar on the top po.rtion of the blood bag;
FIG. 8 is an illustration of the same ~ype as in ~IG. 7 but depicting the operation of a collar 15 on a partially filled blood bag;
FIG. 9 is a cross-sectional view of the blood bag during centrifugation take along:the section lines 9-9 of FIG. 8;
FIG~ lQ is a fragmèntary illustsation of a 20 pyra~idal-shaped top portion of a blood bag constructed in accordance witll an alternative embodiment of this inventioni FIG. 11 is a cross-sectional view of a blood bag taken along the section line 9-9 of FIG. 8 25 constructed in accordance with an alternative embodiment of this invention to provide a single septa;
FIG. 12 is a top-plan view of a typical split sleeve constructed to have radially inward 30 projecting fins for forming temporary septa in the bag during centrifugation; and FIG. 13 is an elevation view of a centrifuged, filled blood bag depicting the separated blood components;
.
1 ~ 6~03 Description o~ the Preferred Embodiment The method o~ this invention reduces remixing o the separated fractions of particulate ~aterial during the deceleration phase of 5 centrifugation and, following centrifugation~ during handling of the container and removal by expression of successive fluid and particle containing layers from the container. While the method is applicable, as noted, to the improved separation or any 10 particulate material, or mixture of materials, for the sake of simplicity and clarity, it will be aescribed in conjunction with its use in separation of blood fractions and, in particular, application to the preparation of platelet-rich plasma and 15 maintaining the platele~-rich plasma relatively free of unwanted contamination, i.e., necessarily high levels of, by red and white blood cells.
As is noted, the contamination of separated platelet-rich plasma occurs for several reasons.
20 Among these reasons are that the top portions of flexible containers or bags used to hold the blood during centrifugation tend to fold. This results in the entrapment of blood ceIls in the folds in the top of the bag. During handling o~ the bag and/or 25 removal of the platelet-rich plasma followirlg centrifugation, the entrapped blood cells can be released into the previously separated platelet-rich plasma. Another source of contamination of the platelet-rich plasma is the resuspension o~ the cells 30 from the buffy coat and packed red-cell region during rotor deceleration. The differential force on the blood wlthin the container due to the diferences in radial distance between the inner and outer portions of the containers cause a swirling of the bag's 35 contents and resuspension of the cells during the final stages of rotor deceleration.
.
A further cause of contamination of the - platelet-rlch plasma by red and white cells is the mi.~ing brou~ht about by the handling o~ tbe bag during its removal from the centrifuge bucket or 5 bucket adapter and its placement in a typical wedge-type expressor. Still another cause of blood contamination is cellular resuspension, which occurs during the Pxpressing of the platelet-rich plasma from the bag. This remixing results from the fact 10 that the plasma must travel radially (transverse to the vertical axis) across the bag from the outer portion of the bag toward the center location of the outlet line at a relatively great speed. ~he fast moving fluid ~ends to sweep along cells from the 15 buffy coat and packed c211 interace region.
According to the method of this invention, the purity of the separated blood fractions may be maintained by reducing folding in the top of the container during centrifugation. One of the causes
It is known to use centrifugal techniques for the separation and/or fractionation of particuIate materials suspended in a liquid according to particle density, size, shape, etc. Unfortunately, during centrifuge deceleration, and subsequent 15 removal of the separated constituents, there is a tendency for remixing of the separated components.
This is particularly true in the case o blood.
The separation of blood into cellular components and plasma, in general, and preparing 20platelet rich plasma, in particular, has 'oecome of great interest to the medical co~munity. The increased use of chemotherapy and ot'ner techniques requires platelet concentrate transfusions.
Unfortunately, present blood bags and many batch type 25blood separation techniques do not facilitate good platelet separa~ion. There is always some incipient remnants or traces of red blood cells and white blood cells. Antigens on certain these blood contaminants give rise to alloimmunization of the recipients o~
30such transfusions, thereby reducing the efficency of subsequent transfusions. It therefore becomes necessary in many cases to select and type the donors -- it being no longer possible to use random donors. This greatly increases the cost. Some oE
the problems incipiently related to alloimmunization are described in an article entitled, "Correction of 5 Poor Platelet Transfusion Responses witn Leukocyte-poor HL~A-matched Platelet Concentrates" by . H. Herzig, et al., Blood, Vol. 46, No. S (Nov.), 1975.
A frequently-used blood component separation 10 procedure involves the preparation, in two centrifugation steps from a single donor unit of whole blood, of a packed red-cell fraction which also contains most of the ~hite blood cells, a concentrate of platelets suspended in plasma, and a platelet-poor 15 plasma fraction. During the first cen~riEugation, red blood cells sediment to the bottom o~ the centrifuge bucket (i.e., 2ack at the bottom of the blood bag which is oriented horizontally during centrifugation in a swinging-bucket rotor) and a 20 platelet-rich plasma layer extending from the top of the bag to the red-cell interface region is formed.
White blood cells are concentrated in the plasma layer imrnediately above the packed red-cell mass (the so-called buffy-coat region3 as well as in the upper 25 portion of the packed red-cell region. After rotor deceleration, the platelet-rich plasma layer is expressed into a satelli~e bag leaving the packed red cells and buffy-coat layer in the original draw bag.
The platelet-rich plasma is -then centrifuged to sediment the platelets, after which most cf the platelet~poor plasrna is expressed into a second satellite bag, leaving a platelet concen~rate in the first satellite hag.
One of the factors contributing to contamination (unwanted levels of white and red blood ~`~ 1 3 6~0~3 cells in platelet~rich plasma) of t'ne platelet concentrate, giving rise to alloirnmunization, is the formation of folds in the upper part of the blood bag during centrifugation. These folds permit the red 5 and white blood cells to b~ecome entrapped in the folds hence e~pressed with the platelet containing plasma causing some of the undesired contamination noted above. This tendency to fold in the top portion of t'ne bag can be aggravated by the fact that lO satellite packs, tubing and balancing pads are usually placed within the bucket with the blood bag Further, the technician in removing the bag from the swinging bucket of the centrifuge, as well as in subsequently handling the bag, can cause some 15 disturbance and remixins of the bag's contents.
A second major ~actor contributing to unwanted contamination of the platelet concentrate is the phenomena which occurs during the final stages of deceleration of the centrifuge rotor. The 20 deceleration o~ a unit of fluid on the extreme outboard side of the swinging bucket as it reassumes a vertical orientation will be greater than ~'nat of a unit on the extreme inboard side. This results in a fluid rota~ion about the bucke~ center unlt~ The 25 rotating or swirling fluid tends to cause some remixing of the components, which were separated during centri~ugation, before they can be expressed from the bag into ~he satellite bags. Efforts in the past to reduce this swirling have been directed to 30 decreasing bucke~ diameter, using oval buckets, and the like. Long, thin buckets greatly enlarge the size of the centrifuges and hence generally are not a prac~ical solution. Further, the thin, long ~ubes increase centrifugation time. Swirling can be reduced by increa~ing centri~ugation deceleration , ~.~ 1 l fi~ 3 time, but this severely reduces throughput and hence greatly increases processing costs.
Brief Description of the Invention According to one ~ethod of this invention, 5 particulate material is separated from, and maintained separated from, a fluid phase, using a storage container having either flexible or rigid walls having top, middle and bottom portions with an outlet line at the top portion, by filling the 10 container with a mixture of the particulate material in the fluid phase, sealing the container, centrifuging the container in a swinging bucket rotor, top portion up, applying a force to a portion of the container to maintain the top portion taut and 15 relatively free of wrinkles which could ot~erwise trap the par~iculate material. The force may be applied to the container in many ways. In one instance it may be accomplished by squeezing the container by use of a liquid bladder in the swinging 20 bucket or other similar technique. Alternatively, the force can be applied by a collar, positioned over the top portion o~ the container and outlet line such that the centrifugal force on the collar forms the top portion of the container tautly about the collar 25 with reduced wrinkles. Preferably the collar is in the shape of an open annulus having a U-shaped cross section. When using a collar with an open annulus, balancing weights m~y be placed in the annulus to equilize the weights of the loaded buckets placed in 30 opposing positions in the centrifuge rotors. If satellite containers are connected to the main container, they may be stored in the annulus during centrifugation.
Tn still another alternative technique the force may be applied to the container by positioning 1 6~003 a volume-displacing article under the con~ainar in the centriEuge bucke~ during cen~rifugation such that the container hydrororms about the article and takes up any unfilled space within the container, thereby 5 causing the wall~ to become taut and relatively wrinkle free.
According to still other alternative techniques, satellite containers may be separated from con~act with the main container by placing the 10 main container in a split sleeve and the split sleeve in the bucket with the satellite containers being positioned in an envelope secured in the annular space in between the bucket and the splIt sleeve.
Various techniques may be used for reducing 15 swirling within the containers during the deceleration of the centrifuge. Among these are the positioning of septa within the container.
Alternatively, radially inward protuberances or baffles may be formed on the interior of either the 20 split sleeve, which holds the container, or the bucket in which the container is placed, such that under centrifugal force, the protuberances will, in effect, form inwardly projecting baffles within the interior of the container, thereby reducing the 25 swirling and intermixing of the separated particles.
~ y forming the ~op portion of the container into the general configuration of a cone or an approximation thereof, there is reduced turbulence during removal of the separated fractions through an 30 outlet line in the top of the container. Desirably, the cone has an included angle of anywhere from 25 ~o about 160 with an angle of about 75 being preferredO
One apparatus for effecting reduced 3 intermixing of separated components is a sealed, `- 5 .
plastic fluid storage container, generally cylindrical when filled with a fluid, the container having a longitudinal axis and a top and a bottom, and a first tubular con~uit communicating with the 5 interior of the container, characterized by an interior septum lying in a plane generally parallel to the longitudinal axis, t'nereby to reduce the movement of the ~luid in the container both during centrifugal deceleration and during handling of the 10 container. Preferably the conduit lies on the longitudinal axis and the top of the container is tapered in a generally conical configuration converging at the first conduit.
According to another aspec~ of the 15 invention, a sealed, flexible, thermoplastic fluid storage container is constructed having side wall sections with laminate edge seals and a longitudinal axis, two different portions of said edge seals being parallel to said longitudinal axis~ and a first 20 tubular conduit means, sealed between said wall sections, communicating with the interior of said container and intersecting said longitudinal axis.
This container is provided with edge seals which are tapered ~rom the said different portions to said 25 first conduit means.
Alternatively, or simultaneously, the container is provided with a septum defined by a first sheet of a flexible thermoplastic having ends joined to opposite said side wall sections along -~ 30 laminate seals which are generally parallel to said longitudinal axis. In variations of this container, the taper angle at the top of the container between the edge seals may lie between 25 and 160 ~ereby to provide a generally conical container top when fluid filled~ In other alternative variations, the , 1 3~:~0~3 taper angle may be between 70 and 80 and desirably is abou~ 75.
The fluid-storage container septum is alternatively defined by first and second sheets of a flexi~le thermoplastic eac'n having ~elected ends jo.ined to selected side wall sections and each being joined together along their mid portions, the jointures occurring along laminate seals gene.rally : paralle~ to the longitudinal axis In an alternative construction, the upper portion of the side wall sections each may be formed in a double pyramidal shape with additional edge seals such that ~he top portion of the container more closely approximates a cone when fluid filled. Any additional transfusion ports or inlet tubes s'nould be connected to the bottom of the container such that there are no crevices or recesses provided within the top portion to permit the entrapment of the contaminating red and white blood cells.
~rief Descri~ion of the Drawin~s Further advantages and fea~ures of this invention will become apparent upon consideration of the following description wherein:
FIG. 1 is an exploded view of a split sleeve, fluid ~ontainer (blood bag) and collar immediakely prior to placement within the spllt sleeve for later centrifugation;
FIG. 2 is a bottom plan view of the collar illustrated in FIG. 1, FIG. 3 is a cross-sectional view taken along :~; the section lines 3-3 of the blood bag of FIG. l;
FIG. 4 is a top plan view of the split `. sleeve depicted in FIG. l;
FIG. 5 is an elevation view of a typical unfilled, flexible blood bag constructed in accordance with a preferred embodiment of this invention;
FIG. 5 is a side elevation view partly cut away of the blood bag of this inven~ion (witho~t 5 attached satellite bags or transfusion parts and inlet lines) during the initial phases of centrifugation depicting the operation of the collar ~ at the beginning of centrifuge run;
.:: FIG, 7 is an elevation view partly cut away 10 depicting the blood bag of ~IG. 6, during centrifugation depicting the smoothing effect of the collar on the top po.rtion of the blood bag;
FIG. 8 is an illustration of the same ~ype as in ~IG. 7 but depicting the operation of a collar 15 on a partially filled blood bag;
FIG. 9 is a cross-sectional view of the blood bag during centrifugation take along:the section lines 9-9 of FIG. 8;
FIG~ lQ is a fragmèntary illustsation of a 20 pyra~idal-shaped top portion of a blood bag constructed in accordance witll an alternative embodiment of this inventioni FIG. 11 is a cross-sectional view of a blood bag taken along the section line 9-9 of FIG. 8 25 constructed in accordance with an alternative embodiment of this invention to provide a single septa;
FIG. 12 is a top-plan view of a typical split sleeve constructed to have radially inward 30 projecting fins for forming temporary septa in the bag during centrifugation; and FIG. 13 is an elevation view of a centrifuged, filled blood bag depicting the separated blood components;
.
1 ~ 6~03 Description o~ the Preferred Embodiment The method o~ this invention reduces remixing o the separated fractions of particulate ~aterial during the deceleration phase of 5 centrifugation and, following centrifugation~ during handling of the container and removal by expression of successive fluid and particle containing layers from the container. While the method is applicable, as noted, to the improved separation or any 10 particulate material, or mixture of materials, for the sake of simplicity and clarity, it will be aescribed in conjunction with its use in separation of blood fractions and, in particular, application to the preparation of platelet-rich plasma and 15 maintaining the platele~-rich plasma relatively free of unwanted contamination, i.e., necessarily high levels of, by red and white blood cells.
As is noted, the contamination of separated platelet-rich plasma occurs for several reasons.
20 Among these reasons are that the top portions of flexible containers or bags used to hold the blood during centrifugation tend to fold. This results in the entrapment of blood ceIls in the folds in the top of the bag. During handling o~ the bag and/or 25 removal of the platelet-rich plasma followirlg centrifugation, the entrapped blood cells can be released into the previously separated platelet-rich plasma. Another source of contamination of the platelet-rich plasma is the resuspension o~ the cells 30 from the buffy coat and packed red-cell region during rotor deceleration. The differential force on the blood wlthin the container due to the diferences in radial distance between the inner and outer portions of the containers cause a swirling of the bag's 35 contents and resuspension of the cells during the final stages of rotor deceleration.
.
A further cause of contamination of the - platelet-rlch plasma by red and white cells is the mi.~ing brou~ht about by the handling o~ tbe bag during its removal from the centrifuge bucket or 5 bucket adapter and its placement in a typical wedge-type expressor. Still another cause of blood contamination is cellular resuspension, which occurs during the Pxpressing of the platelet-rich plasma from the bag. This remixing results from the fact 10 that the plasma must travel radially (transverse to the vertical axis) across the bag from the outer portion of the bag toward the center location of the outlet line at a relatively great speed. ~he fast moving fluid ~ends to sweep along cells from the 15 buffy coat and packed c211 interace region.
According to the method of this invention, the purity of the separated blood fractions may be maintained by reducing folding in the top of the container during centrifugation. One of the causes
2~ f folds in the flexible blood container is that varying quantities of blood are drawn into the bags.
In fact for a typical bag, containing a fixed amount of anticoagulants, the to~al amount o~ blood drawn may vary according to normal specifications by as 25 much as 10~ from a normal drawn volume of approximately 450 ml. Accordingly, the blood containers must be designed to accommodate the larger volume; and, if a smaller volume i3 drawn, the top of the bag is not fluid supported and, under çentrifugal force, wrinkles.
This wrinkling of the top of the bag is alleviated according to this invention hy several means. These include squeezing the bag during centrifugation to maintain the top portion relatively taut. Such squeezing may be accomplished by the t ~ 6:~0a3 placement of the bag in an annular bladder containing a dense solution in order to reduce the volume of t'ne swinging bucket or adapter in w'nich t'ne bag is held.
Alterna~ive1y, and preferably, an annular collar, 5 properly slotted to accommodate the outlet line for the bag, may be placed over t'ne top oE the bag such t'nat under centrifugal force the plastic bag and its contents will hydroform about the underside of the collar and thereby maintain a relatively smoot'n 10 condition. To further reduce the areas in which the components may become entrapped, the donor tube or drawline for the bag is placed at the bottom of the bag as are the transfer, addition or transfusion ports.` Only the outlet line leading the transEer 15 packs or satellite bags is placed at the top of the bag. Additional ports and/or lines may be placed at the top of the bag i they are prevented from folding over during centriEugation.
; In still another alternative, a generally 20 round object may be placed in t'ne bottom oE the swinging bucket and the blood bag allowed to hydroform around it, thereby occupying the volume of the bag not displaced by blood and maintaining the top of the bag taut and ree of wrinkles. The volume 25 of this object placed in the bottom of the swinging bucket may be varied according to the volu~e of blood in the bag. A further method o reducing wrinkling in the top of the blood bag is to keep the satellite blood bags out of contact with or in the region of 30 the top oE the blood bag. If satellite bags are not allowed to press on the top of the bag, there will be less wrinkleing of the blood bag. Satellite bags may be maintained, for example, in the top of the collar if the collar is conformed to have a U-shaped cross 35 section or is otnerwise made to be hollow and capable ~ :~ 6~(~03 of containing the satelliLe bag. Alternatively, the satellit~ bags ma~ be placed in an envelope and positioned about the periphery of the blood bag.
Preferably the blood bag itself is placed in 5 a cylindrical, sleeve-like container or adap~er whicn fits within the swinging bucket of the centrifuge.
The satellite bags then may be placed, if desired, between the exterior of the split sleeve and the inside wall of t'ne swinging bucket. To facilitate 10 their handling, the sa~$11ite bags may be placed in a thin envelope which can be wrapped about the split sleeve. The split sleeve has a particular advantage in that it reduces handling of the blood bag during removal from the swinging buc~et as well a~s during 15 removal oE the bag from the sleeve itself. The two 'nalves of the split sleeve simply may be separated or preferably they may be hinged at the bottom, as will be described hereinaf~er, so that they may be swung open, thereby permitting the split sleeve to be 20 removed from the bag rather than the bag from the sleeve. This is less disruptive of the contents of the bag than having to pull the latter from a rigid cylindrical container.
Another method of this invention used to 25 reduce swirling of the blood during rotor deceleration is to place septa or baffles within the interior of the bag. This results in a dearease of the force vectors which cause swirling of the blood in that it reduces the differential radii between the 30 smaller compartmen~s produced within the bag by the - septa. The septa are located to encompass the region in which the interfaces between pac~ed cells, buffy coat and platelet~rich plasma are formed. Preferably the septa should occupy only the lower portion of the 35 bag and not contact the bottom of t'ne bag so that ) 3 t'ney allow the lower part of the bag to have some mixing of the pacl~ed components and yet they should extend up above where the separation line between the packed cell layer, the buffy coat region, and the 5 platelet-rich plasma so that t'ne contaminating red and white blood cells components cannot swirl and thereby cont~minate the platelet-rich plasma. At the same time the septa should not extend up so far as to interfere with the hydroforming top regions of the 10 bag. The septa further act to stabilize t'ne handling of the bag following centrifugation in that they compartmentalize the bag's contents.
During expression it is desirable that the : blood bag be placed higher up in the expressor than 15 normal so that the top portion of the plasma is not disturbed unnecessarily by the clamping or squeezing movements of the expressor. Finaliy, during expression of pla~elet-rich plasma from the bag, contamination, as noted earlier, occurs through the 20 movement of the cells ~rom the periphery of the bag to the center for removal from the bag. T'nis resuspension is reduced, according to t'ne method of this invention, by positioning the outlet or transfer line of the bag at the top middle and feeding the 25 outlet line with a funnel or approximatiorl thereof.
To this end, the top of the bag may be ~ormed in pure con.ical shape, although this is most desirable from a performance standpoint, it results in a somewhat more expensive construction in most cases. Alternatively, 30 and at a lower cost usually, the conical-shaped funnel may be approximated by forming the top portion of the bag in triangular or pyramidal-like sections whic'n are joined together typically by hea~ sealing, as will be described, to approxi~ate the ~unnel.
1 :~ B1003 A blood bag and associated equipment which is particularly adapted ~o implement the me~'nods oE
this inven-tion is now described.
Description of the Preferred Embodiment There may be -seen with particular reference to FIG. 1 an exploded view of one form of flexible container or hag 10 which, in use, is positioned in a clam-shell-like split sleeve 12. As in tne case of the method, the apparatus will be described in the 10 environment of blood separation. Hence the bag 10 will be referred to as a blood bag, the fluid phase as blood, and the particulate material as blood ce~ls.
The blood bag 10 is illustrated as a flat-~ype bag constructed in a generally conventional 15 manner. It has two side wall sections 16 and 18 ~FIG, 3) o flexible, chemically inert to blood and nonporous to fluids, thermoplastic sheet or film material. This thermoplastic material may be any of those that are suitable for the manufacture of blood 20 bags. Included among those presently known types of materials are polyvinyl chloride, polyethylene, polypropylene, polyester, and many of the - fluorocarbons. The side wall sections 16 and 18 are formea into the flat-type blood bag by edge seals 20 25 which are applied along the bottom edge 22, side edges 24, and top edges 26.
For simplicity o illustration, a single tubular conduit or line 28~ for introducing fluids into the bags or withdrawing fluids from the bag is 30 shown. This line 28 is typically sealed be~ween the edge seams at the top portion of the bag and is termed the outlet line. A fully ported bag having an inlet or draw conduit or line 47 and trans~er or other auxilliary ports 48 is depicted in FIG. 5 for 35 completeness of disclosure. This inlet line 28 is ; 14 ` ' .
11 ~ 3 normally placed along a generally horizontal or slightly curved or tapered edge.
In accordance with this invention the top edges 26 are tapered to a point at the location where 5 the tubular conduit 28 joins the bag itself. The purpose o~ this taper is to afford a generally conical funnel shape to the bag, which enhances laminar flow, and reduces transverse shear at the inter~ace of the separated blood fractions, as the 10 expressed fluid approaches the exit or por~ for the outlet line 28. ~y forming this conlcal exit, as the fluid approaches tne exit port, its transverse velosity and shear is reduced, in view o~ the gradual transition produced ~y the taper itself. Most 15 desirahly the included angle of the taper may vary between 25 and 160 (170 being the typical angle used in the bags of the prior art). The 160 maximum angle is important since in this range the transverse shear begins increasing at a relatively high 20 exponential rate. The 25 minimum angle is also importar,t since in tnis range tne tangent ~unction ` approaches high values and requires bags having an unweildly cone length. In a pre~erred embodiment of this invention the angle of the t~per will vary 25 between 70 and 80 and most desirably will approximate 75.
With the reduced shear and laminar flow, which occurs as the platelet-rich plasma/white blood cell red blood cell interface approaches the exit 30 port, there is less turbulence created and therefore fewer red and white blood cells are expressed with the platelet enriched plasma fraction through the outlet line 28.
The problem caused by the swirling of the contents of the bag 10 during deceleration of the .
6~0~3 centrifuge rotor is reduced, in accordance with t'nis invention, by placing septa or partitions 32 in the interior of the bag. Four septa 32 are illustrated in FIG. 1. The septa are formed from strips of the - ssame plasti~ used for the bag and the ends of these septa 32, in a preferred embodimen~ of the invention, are heat sealed to opposite interior walls 16 and 18 of the bag itself and joined at their mid portion along an axis of joinder which is generally parallel 10 to the longitudinal or vertical axis of the bag. In ; this manner, when the line of joinder follows an axis which is also generally paralle~ to the longitudinal bag axis, vertical compartments are found and, as described earlier, tlle swirling is reduced. The 15 vertical dimension of this septa is such th~t the septa does not extend entirely to the bottom of the bag but provides a small space in the bottom to allow mixing of any anticoagulants or additives which are typically used in blood processing. The limiting 20 location for the bottom of the septa is that the septa should extend downwardly to a point w'nere it will rest on the bottom of the adapter after the container has hydroEormed to the adapter during centrifugation.
The upward dimension o~ the septa is such that the septa will extend to a point above ~he normal interface point between the platelet enriched plasma fraction and the white cells ~buf~y coat) and underlying packed red blood cell layer which extends 30 to the bottom of the bag. Recall that the neight of the packed cell interface will vary somewhat depending on the volume of blood drawn and the red cell content (hematocrit) of the blood. Accordingly, these interfaces must vary in position to some extent 35 based on an average basis and allows some degree of 6~0~3 freedom as to the actual quantity of whole blood ~hat can be placed in the bag. In the usual case the blood placed in a bag may be 450 ~ 45 ml.
A further limi~ation on ~he upward dimension of the septa is determined by the collar 14, which will be described. The collar preferably should not interfere with the septa during centrifugation, i.e., it must not con~ac~ or deform the septa when it moves, during centrifugation, toward the bottom of the 'Dag. The leng~h lhorizontal) dimension of the septa is such as to permit the full expansion of the bag in a diametrical sense such that it may expand to the space permitted by the clam-shell like receptacle 12 (to be described). The septa 32 should be relatively taut so as to provide an effective barrier to prevent the swirling described above. The end of the septa are secured to the bag at locations determined by the lengths of the septa -- they are secured at locations preferably that will permit the bag to lie flat. This generally results in their having an X-shaped cross section when the bag is full as seen in FIG. 3, i.e., the cavities formed thereby are of approximate equal volume as seen in ~IG. 9.
In an alternative embodiment o the invention depicted in FIG. 11, a single transverse septa 34 may be employed. This is not as desirable as the embodiment depicted in FIG. 3 for the simple reason that the larger cavities or volumes permit greater swlrling, an undesirable occurrence which can increase mixing between the separated fractions.
Greater swirlîng is the result of the larger differential radii as explained earlier.
The bag thus constructed is adapted to be placed within a hollow, cylindrical receptacle or split sleeve 12 which is closed at the bottom end 38 by a "living" hinge (~he receptacle having been constructed of an appropriate rigid plastic such as nylon, polypropylene or polycarbonate)~ The receptacle 12 is constructed of two clam-shell halves S which join together at their bottom and along a diametrical axis ~o form the split sleeve.
Alternatively, t'ne sleeve could be hinged along one : side wall on a longitudinal axis and swing toge~her from the side. The advantage of the sleeve is that 10 the blood bag can be enclosed and removed from the sleeve, or more properly, the sleeve is removed from the bag simply by opening the clam-shell halves of the sleeve rather than attempting to withdraw the ~ receptacle from a cylindrical container, a procedure 15 which tends to be dlsruptive of the separated fractions within the bag. In the case illustrated, as may be seen particularly i.n FIG. 4, the two halves 40, 42 of the sleeve are joined along mating longitudinal sections by inc~ined wedges 44 engaging 20 complementary tapered wall sections 46.
To insure that the top portion of the bag 10 does not wrinkle during centrifugation, a collar 14 is employed. This collar is basically an annulus, which in cross section is generally U-shaped or at 25 least the interior wall of the annulus forms a conical section adapted generally to mate with the taper of the kop portion of the bag 10 -- actually the taper o~ the bag when fla~ should be greater than that of the collar since the conical angle decreases 30 as the bag is filled. The collar may be formed of a suitable plastic or any other suitable rigid material and is formed to have a radial slot 46 so as to permit its placement over the outlet line 28. As noted, the bottom portion of a typical bag, as seen 35 in FIG. S, is the location at which the blood draw lg line 47 and additional tubular inserts or transfer ,oorts 48 (none are shown in FIG. 1 for clarity) are formed. This permits a smooth surface at t'ne top portion of the bag, free of crevices, which could 5 otherwise cause entrapment of undesired contaminating hlood cells.
In using the blood bag, constructed in accordance with this invention, the bag is filled with whole blood through the draw line 47 (FIG. 5).
10 With reference to FI~. 6 (the lines 47 and 48 are not shown~ this blood bag 10 is placed within the split sleeve 12 such that it is generally cylindrical with the septa 32 in a taut condition (FIG. 9). The collar 14 ls placed over the outlet tubular conduit 15 28 and the split sleeve placed in the swingin~ bucket of a centrifuge. T'ne satellite bags and lines are handled as previously described so as to not cause wrinkles in the bag by placing tllem in the annulus of the collar, etc.
As is known, as the centrifuge rotor accelerates, the swinging bucket swing~ outwardly and upwardly to assume the horizontal orientation illustrated in FIG. 6, with the centrifugal force being in the sense indicated by the arrows 50. Under 25 these conditions the collar (assuming the bag is completely illed with blood) tends to mov~ ~to the left in the drawing) outwardly from a centrifugal force standpoint so as to engage a portion of the top section of the bag 10, causing the top o~ the bag to 30 assume a conical shape and drape itself over and about the U-shaped cross section of the collar 14.
In this manner, as can be seen particularly with reference to FIG. 7, the top portion of the bag is taut and generally free of wrinkles which would 35 otherwise tend to entrap cells. During deceleration, swirling is prevented by the septa described above.
o -"` 1 36~i)3 ,~.
In the event that the bag contains a lesser amount o~ blood, the collar 14/ as depicted in FIG.
8, automatically assumes a greaker radial outward displacement, draping a greater por~ion oE the top of 5 tne bag 10 over i~s U-shaped annulus, still maintaining a relatively smooth surface for ~he entire top portion of the bag such that there are f~wer places left Eor entrapment of cells in t'ne undesired folds. It will be noted in this 10 coniguration that the radial displacement of the collar is such as to be just above the topmost portion of the septa and this is, of course, the limiting factor in establis'ning the height of the septa within the bag, as noted earlier.
Following centrifugation~ the split sleeve receptacle 12 is easily removed from the swinging bucket and by virtue of the clam-shell type configuration, spread open~ permitting the bag to be removed (or more properly, the split sleeve is ; 20 removed from the bag) and placed in a typical blood expressor assembly of the type whic'n is commercially available. The plasma enriched fraction at the top portion of the bag may be expressed. This fraction is relatively free of contaminating red and white 25 blood cells due to the features described above in this invention.
In an alternative embodiment of this invention, it is noted, particularly with reference to FIG. 10, that an additional seam 24 is formed at 30 the top portion of the blood bag such that there are now four pyramidal sec~ions instead of ~wo. The Eour sections are more capable of approximating a conical funnel than two. This is a preferred configuration, although its construction with four seams at the top 35 rather than two may in some cases be slightly more ~ ~6~003 expensive than that of the double searn version depicted in FIG. 1. In this configuration the top portions 60 of tne respective side walls of the flat blood bag 10 are double triangles or pyramidal in 5 shape.
While the blood bag descrioed heretofore has been described as a flat bag formed of a thermoplastic material and joined at the side seams, it is to be understood that the bag alternatively may 10 be formed of a flexible plastic using blow moldi~g techniques such that there are no side seams.
Alternatively, the bag may be constructed to be of relatively rigid or semirigid material l~aving internal se~ta~ In this eventuality, there is less 15 p~ssibility of entrapment at the top. Hence the utilization of a collar may not be necessary although the internal septa and the funnel-shaped outlet is most certainly used. In this event, the rigid or semirigid material would form the cone shaped top, 20 and no split sleeve is needed.
In an alternative embodiment of the invention which may be a subs~itute for the utilization of internal septa, there is depicted in E'IG. 12 a split sleeve having internally dixected or 25 radially inwardly directed vertical fins. rrhese fins will cause the bag, when placed within the split sleeve to deform inwardly and form a substitute for the septa in that it would tend (not as effectively as internal septa) to reduce the deceleration effect 30 or swirling during decelera~ion. The vertical fins are depicted as having only a small radial dimension and as only four in number. The radial dimension may be increased to further reduce swirling, but the number of fins should remain small. Alternatively and preferably, fins having alternating greater and lesser radial dimensions may be used.
A further alternative embodimen~ of the invention is depicted in FIG. 13 which is an alternative s~ructure of the invention in which satellite bags sucb as those connected to the sa~ellite line of FIG. 5 may be ~laced in an envelope which is wrapped around in an annulus which may be provided for ~etween the exterior or periphery o~ the split sleeve 42 and a centrifuge bucket 70. The envelope 72 need not be used, ~ut it does greatly facilitate the placement of the satellite bags and lines in the small annulus between the split sleeve and the swinging bucket. Alternatively, the satellite bags may, i~ desired, be placed within the annular space 74 ~FIG. 1) of the collar 14. In still lS another alternative embodiment, this annular space 74 may be used for the placement of balancing weights for the swinging bucket centrifuge as previously described. In this figure the bag is partially cut away to show the platelet-rich plasma 80, the bu~fy coat 78, packed red cells 74 and the interface 76 therebetween.
There has thus been described a relatively simple method of and blood bag for centrifuging blood bags, which method and apparatus greatly facilitates the preparation of platelet concentrates relatively free of unwanted blood cell contamination. Although described in connection with blood separations, it is to be understood that the method and apparatus are equall~ useful for a wide range of particulate separations. Further, the bags or containers may be formed using any of the forming techniques known in the plastics and like industries and include injection moldings, centrifugal casting and the like.
This application is a division of copending Canadian Application Serial No. 359,581, filed September 4, 1980.
In fact for a typical bag, containing a fixed amount of anticoagulants, the to~al amount o~ blood drawn may vary according to normal specifications by as 25 much as 10~ from a normal drawn volume of approximately 450 ml. Accordingly, the blood containers must be designed to accommodate the larger volume; and, if a smaller volume i3 drawn, the top of the bag is not fluid supported and, under çentrifugal force, wrinkles.
This wrinkling of the top of the bag is alleviated according to this invention hy several means. These include squeezing the bag during centrifugation to maintain the top portion relatively taut. Such squeezing may be accomplished by the t ~ 6:~0a3 placement of the bag in an annular bladder containing a dense solution in order to reduce the volume of t'ne swinging bucket or adapter in w'nich t'ne bag is held.
Alterna~ive1y, and preferably, an annular collar, 5 properly slotted to accommodate the outlet line for the bag, may be placed over t'ne top oE the bag such t'nat under centrifugal force the plastic bag and its contents will hydroform about the underside of the collar and thereby maintain a relatively smoot'n 10 condition. To further reduce the areas in which the components may become entrapped, the donor tube or drawline for the bag is placed at the bottom of the bag as are the transfer, addition or transfusion ports.` Only the outlet line leading the transEer 15 packs or satellite bags is placed at the top of the bag. Additional ports and/or lines may be placed at the top of the bag i they are prevented from folding over during centriEugation.
; In still another alternative, a generally 20 round object may be placed in t'ne bottom oE the swinging bucket and the blood bag allowed to hydroform around it, thereby occupying the volume of the bag not displaced by blood and maintaining the top of the bag taut and ree of wrinkles. The volume 25 of this object placed in the bottom of the swinging bucket may be varied according to the volu~e of blood in the bag. A further method o reducing wrinkling in the top of the blood bag is to keep the satellite blood bags out of contact with or in the region of 30 the top oE the blood bag. If satellite bags are not allowed to press on the top of the bag, there will be less wrinkleing of the blood bag. Satellite bags may be maintained, for example, in the top of the collar if the collar is conformed to have a U-shaped cross 35 section or is otnerwise made to be hollow and capable ~ :~ 6~(~03 of containing the satelliLe bag. Alternatively, the satellit~ bags ma~ be placed in an envelope and positioned about the periphery of the blood bag.
Preferably the blood bag itself is placed in 5 a cylindrical, sleeve-like container or adap~er whicn fits within the swinging bucket of the centrifuge.
The satellite bags then may be placed, if desired, between the exterior of the split sleeve and the inside wall of t'ne swinging bucket. To facilitate 10 their handling, the sa~$11ite bags may be placed in a thin envelope which can be wrapped about the split sleeve. The split sleeve has a particular advantage in that it reduces handling of the blood bag during removal from the swinging buc~et as well a~s during 15 removal oE the bag from the sleeve itself. The two 'nalves of the split sleeve simply may be separated or preferably they may be hinged at the bottom, as will be described hereinaf~er, so that they may be swung open, thereby permitting the split sleeve to be 20 removed from the bag rather than the bag from the sleeve. This is less disruptive of the contents of the bag than having to pull the latter from a rigid cylindrical container.
Another method of this invention used to 25 reduce swirling of the blood during rotor deceleration is to place septa or baffles within the interior of the bag. This results in a dearease of the force vectors which cause swirling of the blood in that it reduces the differential radii between the 30 smaller compartmen~s produced within the bag by the - septa. The septa are located to encompass the region in which the interfaces between pac~ed cells, buffy coat and platelet~rich plasma are formed. Preferably the septa should occupy only the lower portion of the 35 bag and not contact the bottom of t'ne bag so that ) 3 t'ney allow the lower part of the bag to have some mixing of the pacl~ed components and yet they should extend up above where the separation line between the packed cell layer, the buffy coat region, and the 5 platelet-rich plasma so that t'ne contaminating red and white blood cells components cannot swirl and thereby cont~minate the platelet-rich plasma. At the same time the septa should not extend up so far as to interfere with the hydroforming top regions of the 10 bag. The septa further act to stabilize t'ne handling of the bag following centrifugation in that they compartmentalize the bag's contents.
During expression it is desirable that the : blood bag be placed higher up in the expressor than 15 normal so that the top portion of the plasma is not disturbed unnecessarily by the clamping or squeezing movements of the expressor. Finaliy, during expression of pla~elet-rich plasma from the bag, contamination, as noted earlier, occurs through the 20 movement of the cells ~rom the periphery of the bag to the center for removal from the bag. T'nis resuspension is reduced, according to t'ne method of this invention, by positioning the outlet or transfer line of the bag at the top middle and feeding the 25 outlet line with a funnel or approximatiorl thereof.
To this end, the top of the bag may be ~ormed in pure con.ical shape, although this is most desirable from a performance standpoint, it results in a somewhat more expensive construction in most cases. Alternatively, 30 and at a lower cost usually, the conical-shaped funnel may be approximated by forming the top portion of the bag in triangular or pyramidal-like sections whic'n are joined together typically by hea~ sealing, as will be described, to approxi~ate the ~unnel.
1 :~ B1003 A blood bag and associated equipment which is particularly adapted ~o implement the me~'nods oE
this inven-tion is now described.
Description of the Preferred Embodiment There may be -seen with particular reference to FIG. 1 an exploded view of one form of flexible container or hag 10 which, in use, is positioned in a clam-shell-like split sleeve 12. As in tne case of the method, the apparatus will be described in the 10 environment of blood separation. Hence the bag 10 will be referred to as a blood bag, the fluid phase as blood, and the particulate material as blood ce~ls.
The blood bag 10 is illustrated as a flat-~ype bag constructed in a generally conventional 15 manner. It has two side wall sections 16 and 18 ~FIG, 3) o flexible, chemically inert to blood and nonporous to fluids, thermoplastic sheet or film material. This thermoplastic material may be any of those that are suitable for the manufacture of blood 20 bags. Included among those presently known types of materials are polyvinyl chloride, polyethylene, polypropylene, polyester, and many of the - fluorocarbons. The side wall sections 16 and 18 are formea into the flat-type blood bag by edge seals 20 25 which are applied along the bottom edge 22, side edges 24, and top edges 26.
For simplicity o illustration, a single tubular conduit or line 28~ for introducing fluids into the bags or withdrawing fluids from the bag is 30 shown. This line 28 is typically sealed be~ween the edge seams at the top portion of the bag and is termed the outlet line. A fully ported bag having an inlet or draw conduit or line 47 and trans~er or other auxilliary ports 48 is depicted in FIG. 5 for 35 completeness of disclosure. This inlet line 28 is ; 14 ` ' .
11 ~ 3 normally placed along a generally horizontal or slightly curved or tapered edge.
In accordance with this invention the top edges 26 are tapered to a point at the location where 5 the tubular conduit 28 joins the bag itself. The purpose o~ this taper is to afford a generally conical funnel shape to the bag, which enhances laminar flow, and reduces transverse shear at the inter~ace of the separated blood fractions, as the 10 expressed fluid approaches the exit or por~ for the outlet line 28. ~y forming this conlcal exit, as the fluid approaches tne exit port, its transverse velosity and shear is reduced, in view o~ the gradual transition produced ~y the taper itself. Most 15 desirahly the included angle of the taper may vary between 25 and 160 (170 being the typical angle used in the bags of the prior art). The 160 maximum angle is important since in this range the transverse shear begins increasing at a relatively high 20 exponential rate. The 25 minimum angle is also importar,t since in tnis range tne tangent ~unction ` approaches high values and requires bags having an unweildly cone length. In a pre~erred embodiment of this invention the angle of the t~per will vary 25 between 70 and 80 and most desirably will approximate 75.
With the reduced shear and laminar flow, which occurs as the platelet-rich plasma/white blood cell red blood cell interface approaches the exit 30 port, there is less turbulence created and therefore fewer red and white blood cells are expressed with the platelet enriched plasma fraction through the outlet line 28.
The problem caused by the swirling of the contents of the bag 10 during deceleration of the .
6~0~3 centrifuge rotor is reduced, in accordance with t'nis invention, by placing septa or partitions 32 in the interior of the bag. Four septa 32 are illustrated in FIG. 1. The septa are formed from strips of the - ssame plasti~ used for the bag and the ends of these septa 32, in a preferred embodimen~ of the invention, are heat sealed to opposite interior walls 16 and 18 of the bag itself and joined at their mid portion along an axis of joinder which is generally parallel 10 to the longitudinal or vertical axis of the bag. In ; this manner, when the line of joinder follows an axis which is also generally paralle~ to the longitudinal bag axis, vertical compartments are found and, as described earlier, tlle swirling is reduced. The 15 vertical dimension of this septa is such th~t the septa does not extend entirely to the bottom of the bag but provides a small space in the bottom to allow mixing of any anticoagulants or additives which are typically used in blood processing. The limiting 20 location for the bottom of the septa is that the septa should extend downwardly to a point w'nere it will rest on the bottom of the adapter after the container has hydroEormed to the adapter during centrifugation.
The upward dimension o~ the septa is such that the septa will extend to a point above ~he normal interface point between the platelet enriched plasma fraction and the white cells ~buf~y coat) and underlying packed red blood cell layer which extends 30 to the bottom of the bag. Recall that the neight of the packed cell interface will vary somewhat depending on the volume of blood drawn and the red cell content (hematocrit) of the blood. Accordingly, these interfaces must vary in position to some extent 35 based on an average basis and allows some degree of 6~0~3 freedom as to the actual quantity of whole blood ~hat can be placed in the bag. In the usual case the blood placed in a bag may be 450 ~ 45 ml.
A further limi~ation on ~he upward dimension of the septa is determined by the collar 14, which will be described. The collar preferably should not interfere with the septa during centrifugation, i.e., it must not con~ac~ or deform the septa when it moves, during centrifugation, toward the bottom of the 'Dag. The leng~h lhorizontal) dimension of the septa is such as to permit the full expansion of the bag in a diametrical sense such that it may expand to the space permitted by the clam-shell like receptacle 12 (to be described). The septa 32 should be relatively taut so as to provide an effective barrier to prevent the swirling described above. The end of the septa are secured to the bag at locations determined by the lengths of the septa -- they are secured at locations preferably that will permit the bag to lie flat. This generally results in their having an X-shaped cross section when the bag is full as seen in FIG. 3, i.e., the cavities formed thereby are of approximate equal volume as seen in ~IG. 9.
In an alternative embodiment o the invention depicted in FIG. 11, a single transverse septa 34 may be employed. This is not as desirable as the embodiment depicted in FIG. 3 for the simple reason that the larger cavities or volumes permit greater swlrling, an undesirable occurrence which can increase mixing between the separated fractions.
Greater swirlîng is the result of the larger differential radii as explained earlier.
The bag thus constructed is adapted to be placed within a hollow, cylindrical receptacle or split sleeve 12 which is closed at the bottom end 38 by a "living" hinge (~he receptacle having been constructed of an appropriate rigid plastic such as nylon, polypropylene or polycarbonate)~ The receptacle 12 is constructed of two clam-shell halves S which join together at their bottom and along a diametrical axis ~o form the split sleeve.
Alternatively, t'ne sleeve could be hinged along one : side wall on a longitudinal axis and swing toge~her from the side. The advantage of the sleeve is that 10 the blood bag can be enclosed and removed from the sleeve, or more properly, the sleeve is removed from the bag simply by opening the clam-shell halves of the sleeve rather than attempting to withdraw the ~ receptacle from a cylindrical container, a procedure 15 which tends to be dlsruptive of the separated fractions within the bag. In the case illustrated, as may be seen particularly i.n FIG. 4, the two halves 40, 42 of the sleeve are joined along mating longitudinal sections by inc~ined wedges 44 engaging 20 complementary tapered wall sections 46.
To insure that the top portion of the bag 10 does not wrinkle during centrifugation, a collar 14 is employed. This collar is basically an annulus, which in cross section is generally U-shaped or at 25 least the interior wall of the annulus forms a conical section adapted generally to mate with the taper of the kop portion of the bag 10 -- actually the taper o~ the bag when fla~ should be greater than that of the collar since the conical angle decreases 30 as the bag is filled. The collar may be formed of a suitable plastic or any other suitable rigid material and is formed to have a radial slot 46 so as to permit its placement over the outlet line 28. As noted, the bottom portion of a typical bag, as seen 35 in FIG. S, is the location at which the blood draw lg line 47 and additional tubular inserts or transfer ,oorts 48 (none are shown in FIG. 1 for clarity) are formed. This permits a smooth surface at t'ne top portion of the bag, free of crevices, which could 5 otherwise cause entrapment of undesired contaminating hlood cells.
In using the blood bag, constructed in accordance with this invention, the bag is filled with whole blood through the draw line 47 (FIG. 5).
10 With reference to FI~. 6 (the lines 47 and 48 are not shown~ this blood bag 10 is placed within the split sleeve 12 such that it is generally cylindrical with the septa 32 in a taut condition (FIG. 9). The collar 14 ls placed over the outlet tubular conduit 15 28 and the split sleeve placed in the swingin~ bucket of a centrifuge. T'ne satellite bags and lines are handled as previously described so as to not cause wrinkles in the bag by placing tllem in the annulus of the collar, etc.
As is known, as the centrifuge rotor accelerates, the swinging bucket swing~ outwardly and upwardly to assume the horizontal orientation illustrated in FIG. 6, with the centrifugal force being in the sense indicated by the arrows 50. Under 25 these conditions the collar (assuming the bag is completely illed with blood) tends to mov~ ~to the left in the drawing) outwardly from a centrifugal force standpoint so as to engage a portion of the top section of the bag 10, causing the top o~ the bag to 30 assume a conical shape and drape itself over and about the U-shaped cross section of the collar 14.
In this manner, as can be seen particularly with reference to FIG. 7, the top portion of the bag is taut and generally free of wrinkles which would 35 otherwise tend to entrap cells. During deceleration, swirling is prevented by the septa described above.
o -"` 1 36~i)3 ,~.
In the event that the bag contains a lesser amount o~ blood, the collar 14/ as depicted in FIG.
8, automatically assumes a greaker radial outward displacement, draping a greater por~ion oE the top of 5 tne bag 10 over i~s U-shaped annulus, still maintaining a relatively smooth surface for ~he entire top portion of the bag such that there are f~wer places left Eor entrapment of cells in t'ne undesired folds. It will be noted in this 10 coniguration that the radial displacement of the collar is such as to be just above the topmost portion of the septa and this is, of course, the limiting factor in establis'ning the height of the septa within the bag, as noted earlier.
Following centrifugation~ the split sleeve receptacle 12 is easily removed from the swinging bucket and by virtue of the clam-shell type configuration, spread open~ permitting the bag to be removed (or more properly, the split sleeve is ; 20 removed from the bag) and placed in a typical blood expressor assembly of the type whic'n is commercially available. The plasma enriched fraction at the top portion of the bag may be expressed. This fraction is relatively free of contaminating red and white 25 blood cells due to the features described above in this invention.
In an alternative embodiment of this invention, it is noted, particularly with reference to FIG. 10, that an additional seam 24 is formed at 30 the top portion of the blood bag such that there are now four pyramidal sec~ions instead of ~wo. The Eour sections are more capable of approximating a conical funnel than two. This is a preferred configuration, although its construction with four seams at the top 35 rather than two may in some cases be slightly more ~ ~6~003 expensive than that of the double searn version depicted in FIG. 1. In this configuration the top portions 60 of tne respective side walls of the flat blood bag 10 are double triangles or pyramidal in 5 shape.
While the blood bag descrioed heretofore has been described as a flat bag formed of a thermoplastic material and joined at the side seams, it is to be understood that the bag alternatively may 10 be formed of a flexible plastic using blow moldi~g techniques such that there are no side seams.
Alternatively, the bag may be constructed to be of relatively rigid or semirigid material l~aving internal se~ta~ In this eventuality, there is less 15 p~ssibility of entrapment at the top. Hence the utilization of a collar may not be necessary although the internal septa and the funnel-shaped outlet is most certainly used. In this event, the rigid or semirigid material would form the cone shaped top, 20 and no split sleeve is needed.
In an alternative embodiment of the invention which may be a subs~itute for the utilization of internal septa, there is depicted in E'IG. 12 a split sleeve having internally dixected or 25 radially inwardly directed vertical fins. rrhese fins will cause the bag, when placed within the split sleeve to deform inwardly and form a substitute for the septa in that it would tend (not as effectively as internal septa) to reduce the deceleration effect 30 or swirling during decelera~ion. The vertical fins are depicted as having only a small radial dimension and as only four in number. The radial dimension may be increased to further reduce swirling, but the number of fins should remain small. Alternatively and preferably, fins having alternating greater and lesser radial dimensions may be used.
A further alternative embodimen~ of the invention is depicted in FIG. 13 which is an alternative s~ructure of the invention in which satellite bags sucb as those connected to the sa~ellite line of FIG. 5 may be ~laced in an envelope which is wrapped around in an annulus which may be provided for ~etween the exterior or periphery o~ the split sleeve 42 and a centrifuge bucket 70. The envelope 72 need not be used, ~ut it does greatly facilitate the placement of the satellite bags and lines in the small annulus between the split sleeve and the swinging bucket. Alternatively, the satellite bags may, i~ desired, be placed within the annular space 74 ~FIG. 1) of the collar 14. In still lS another alternative embodiment, this annular space 74 may be used for the placement of balancing weights for the swinging bucket centrifuge as previously described. In this figure the bag is partially cut away to show the platelet-rich plasma 80, the bu~fy coat 78, packed red cells 74 and the interface 76 therebetween.
There has thus been described a relatively simple method of and blood bag for centrifuging blood bags, which method and apparatus greatly facilitates the preparation of platelet concentrates relatively free of unwanted blood cell contamination. Although described in connection with blood separations, it is to be understood that the method and apparatus are equall~ useful for a wide range of particulate separations. Further, the bags or containers may be formed using any of the forming techniques known in the plastics and like industries and include injection moldings, centrifugal casting and the like.
This application is a division of copending Canadian Application Serial No. 359,581, filed September 4, 1980.
Claims (10)
1. A method of separating and maintaining separated particulate material from a fluid phase using a storage container having flexible walls and top, middle and bottom portions with an outlet line at the top portion, by filling said container with said fluid phase, sealing said container, centrifuging said container in the bucket of a swinging bucket centrifuge top portion up, compris-ing the steps of:
applying force to the top portion of said container by positioning a collar in the shape of an annulus having a V-shaped cross-section over said top portion and said outlet line, whereby centrifugal force on said collar causes the top portion of said container to drape tautly about said collar's V-shaped cross-section and remove wrinkles therefrom.
applying force to the top portion of said container by positioning a collar in the shape of an annulus having a V-shaped cross-section over said top portion and said outlet line, whereby centrifugal force on said collar causes the top portion of said container to drape tautly about said collar's V-shaped cross-section and remove wrinkles therefrom.
2. A method according to Claim 1 wherein said collar has an open annulus, and placing said outlet line in said collar during centrifugation.
3. A method according to Claim 1 comprising of the additional steps of:
providing radially inwardly extending baffles within said container extending between said middle and bottom portions to prevent swirling of said fluid phase during centrifuge deceleration.
providing radially inwardly extending baffles within said container extending between said middle and bottom portions to prevent swirling of said fluid phase during centrifuge deceleration.
4. A method according to Claim 2 with the additional step of providing radially inwardly extending baffles within said container extending between said middle and bottom portions up to the point of separation between said fluid phase and said particulate material to prevent swirling of said particulate material during centrifuge deceleration.
5. A method according to Claim 4 with the additional step of forming the top portion of said con-tainer to the general configuration of a cone, thereby to reduce turbulence between separated fractions during removal thereof, said cone having an included angle of 25° to about 160°.
6. A sealed, plastic blood centrifuge container, generally cylindrical when filled with blood, said container having a longitudinal axis and a top and bottom, and a first tubular conduit communicating with the interior of said container, characterized by an interior septum lying in a plane generally parallel to said longitudinal axis, thereby to reduce movement of a fluid in said container during centrifugation, said sep-tum extending along said longitudinal axis from a point just above said bottom to a point below said conical top just above the separation line that occurs when blood is separated into plasma on the one hand and packed cells and a buffy coat on the other.
7. A container according to Claim 6 wherein conduit lies on said longitudinal axis.
8. A container according to Claim 7 wherein the top of said container is tapered in a generally conical configuration converging at said first conduit, thereby to reduce fluid intermixing during expression.
9. A container according to Claim 8 wherein said top portion is curvilinear with a decreasing taper toward said first conduit.
10. A container according to Claim 8 which includes a second tubular conduit communicating with the interior of said container at the bottom thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000418558A CA1161003A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US074,098 | 1979-09-10 | ||
| US06/074,098 US4413771A (en) | 1979-09-10 | 1979-09-10 | Method and apparatus for centrifugal separation |
| CA000359581A CA1150695A (en) | 1979-09-10 | 1980-09-04 | Method and apparatus for centrifugal separation |
| CA000418558A CA1161003A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1161003A true CA1161003A (en) | 1984-01-24 |
Family
ID=27166811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000418558A Expired CA1161003A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1161003A (en) |
-
1982
- 1982-12-23 CA CA000418558A patent/CA1161003A/en not_active Expired
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