CA1161004A - Method and apparatus for centrifugal separation - Google Patents
Method and apparatus for centrifugal separationInfo
- Publication number
- CA1161004A CA1161004A CA000418559A CA418559A CA1161004A CA 1161004 A CA1161004 A CA 1161004A CA 000418559 A CA000418559 A CA 000418559A CA 418559 A CA418559 A CA 418559A CA 1161004 A CA1161004 A CA 1161004A
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- receptacle
- adapter
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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 ~
Ti tle ~ethod and Apparatus For Centrifugal Separation Background of the Invention 5This invention relates to a method and apparatus for centrifugally separating particulate material from a liquid phase and, more particularly, to a method and apparatus for the batch separation of blood components.
It is known to use centrifugal ~echniques for the separation and/or fractionation of partic~late materials suspended in a liquid according to particle density, size, shape, etc. Unfortunately, during centrifuge deceleration, and subsequent 15 removal of the separated constituen~s, there is a tendency for remixing of the separated components.
This is particularly true in the case of blood.
The separation of blood into cellular components and plasma, in general, and preparing 20 platelet rich plasma, in particular, has become oE
great interest to the medical community. The - increas2d use o~ chemotherapy and other techniques requires platelet concentrate transfusions.
Unfortunately, present blood bags and many-batch type ; ~5blood separation techni~ues do not facilitate good platelet separation. 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 of 30such transfusions, thereby reducing the efficency of subsequent transfusions. It therefore becomes necessary in many cases to select and ~ype tne : 3 5 ~J
'' .
6~00~1 donors ~~ it being no longer possible to use random donors. This greatly increases the cost. Some of the problems incipiently related to alloimmuni~ation are described in an article entitled, "Correction of Poor Platelet Transfusion Responses with Leukocyte-poor HL-A-matched Pla~elet Concentrates" by R. a. Herzig, et al.~ Blood, Vol. 46, No. 5 (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 white blood cells, a concentrate - of platelets suspended in plasma, and a platelet-poor 15 plasma fraction. During the first centrifugation, red blood cells sediment to the bottom oE the centrifuge bucket ~i.e., pack at the bottom of the blood bag which is oxiented horiæontally 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 immediately above the packed red-cell mass (the so-called buEfy-coat region) as well as in the upper 25 portion of the packed red-cell reyion. After rotor deceleration, the platelet-rich plasma layer is expressed into a satellite 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 of the platelet-poor plasma is expressed into a second satellite bag, leaving a platelet concentrate in the first satellite bag.
One of the factors contributing to contamination (unwanted levels of white and red blood ~ ;~6l~a4 cells in platelet-rich plasma) of the platelet concentrate, giving rise to alloimmunization, is the formation of fo~ds in the upper part of the blood bag during centrifugation. These folds permit the red 5 and white blood cells to become entrapped in the folds hence expressed with the platelet containing plasma causing some o the undesired contamination noted above. This tendency to fold in the top portion of t'ne bag can be aggravated by the fact that 10 satellite packs, tubing and balancing pads are usually placed within the bucket with the blood bag.
Further, the technician in remo~ing the bag from the swinging bucket of the centrifuge, as well as in subsequently handling the bag, can cause some 15 disturbance and remixing of the bag's contents.
A second major factor contributing to unwanted contamination of the platelet concentrate is tl}e phenomena which occurs during the final stages of deceleration of the centrifuge rotor. The 20 deceleration of a unit of Eluid on the extreme outboard side of the swinging bucket as it reassumes a vertical orientation will be greater than that of a - unit on the extreme inboard side. This results in a fluid rotation about the buc~et center unit. The 25 rotating or swirling fluid ~ends to cause some remixing of the components, which were separated during centrifugation, be~ore they can be expressed from the bag into the satellite bags. ~fforts in the past to reduce this swirling have been directed to 30 decreasing bucket diameter, using oval buckets, and the like~ Long, thin buckets greatly enlarge the size of the centrifuges and hence generally are not a practical solution. Further, the t'nin, long tubes increase centrifugation time. Swirling can be reduced by increasing centrifugation deceleration --~ :11&;~ 4 time, but this severely reduces throughput and hence greatly increases processing costs.
Brief Descrip~ion of the Inven~ion According to one method of this invention, 5 particulate material is se arated ~rom, and maintained separated from, a fluid p'nase, 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 lO 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 otherwise trap the particulate material. The force may be applied to the container in many ways. In one ins~ance it may be'accomplished by squeeæing the container by use o, 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 porkion of the container and~outlet line such' that the centrifugal ~orce on the collar ~orms ~he top portion of the container tautly about the collar 25 with reduced w~inkles. 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, ~alancing weights may be placed in the annulus to equiliæe the weights of the loaded buckets placed in 30 opposing positions in the centrifuge rotors. If satellite containers are connected to t'ne main container, they may be stored in -the annulus during centrifugation.
In still another alternative technique the force may be applied to the container by positioning . . .
a~
a volume-displacing article under the contain~r in the centriEuge bucket during centriEugation such that the container hydroforms about the article and ta~es up any unfilled space within the con~ainer~ thereby 5 causing the walls to become taut and relatively wrinkle free.
According to still other alternative techniques, satellite containers may be separated from contact with the main container by placing the 10 main container in a split sleeve and the split sleeve in the bucket with the satelli~e containers being positioned in an envelope secured in the annular space in between the ~ucket and the split sleeve.
Various techniques may be used for reducing 15 swirling within the containers during the deceleration of ~he centrifuge. Among thèse are the positioning of septa within the container.
Alternatively, radially inward protuberances or - ba~fles may be for~ed 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 baf1es within the interior of the container, thereby reducing the 25 swirling and intermixing of the separated particles.
By forming the top portion of the container into the general configuration of a cone or an approximation thereo~, 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 to about 160 with an angle of about 75 being preferred.
One apparatus for effecting reduced 35 intermixing of separated components is a sealed, 1 ~ B ~
plastic fluid storage container r generally cylindrical when ~illed wi-th a fluid, the ~ontainer having a longitudinal axis and a top and a Gottom, and a first tu~ular conduit communicating with the 5 interior o~ the container, characterized by an interior septum lying in a plane generally parallel to the lonyitudinal axis, thereby to reduce the movement of the fluid 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 ~o ano~her aspect oE the 15 invention, a sealed, flexibl~, thermoplastic fluid storage container is constructed having side wall sections with laminate edge seals and a longitudinal axis, two different portions of said edge seais being parallel to said longitudinal axis, and a ~irst 20 tubular conduit means, sealed between said wall sections, communicating with the interior o~ said container and intersecting said longitudinal axis.
This container is provided with edge seals which are tapered from the said different portions to said 25 first conduit means.
Alternatively, or simultaneously, the container is providecl with a septum defined by a first sheet o~ 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 sontainer between tne edge seals may lie between 25 and 160 thereby to provide a generally conicai container top when fluid filled. In other alternative variations, the 0 ~
taper angle may be between 70 and 80 and desirably is about 75.
The fluid-storage container septum is alterna-tively deLined ~y f iLSt and second s'neets of a flexible thermoplastic each having selected ends joined to selected side wall sections and each being joined together along their mid portions, the jointures occurring along laminate s~als generally parallel 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 the top portion of the container more closely approximates a cone when fluid filled. Any additional transfusion ports or inlet tubes should be connected to the bottom of tlle 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.
Brief Description of the DrawingS
Further advantages and features of this invention will become apparent upon consideration of the following description wherein:
FIG. 1 is an exploded view of a split sleeve, fluid container ~blood bag) and collar immediately prior to placement within the sp:Lit sleeve for later centrifugation;
FIG. 2 is a bottom plan view of the collar illustrated in FIG. l;
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 o~
accordance with a preferred embodiment.of this invention;
FIG. 6 is a side elevation view partly cut away of the blood bag of t'nis invention (without S attached satellite bags or transfusion parts and inlet lines) during the ini~ial p'nases of centrifuga-tion 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 FIG. 6, during centrifugation depicting the smoothing ~ffect of the collar on the top portion of the blood bag;
FIG. 8 is an illustration of the same type as in FIG. 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. lO is a fragmentary illustration of a 20 pyramidal-shaped top portion of a blood bag : constructed in accordance Witll an alternative embodiment of this invention;
FIG. 11 is a cross-sectional view of a blood - bag taken along the section line 9-9 of F~G. 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 t'ne bag during centrifugation; and FIG. 13 is an elevation view of a centrifuged, filled blood bag depicting the separated blood components;
Descri~tion of the Preferred Embodiment The method oE this invention reduces remixing of the separated ractions of particulate material during the deceleration phase of ~ 5 centrifugation and, following centrifuga~ion, during handling of the container and removal ~y expression of successive fluid and particle containing layers from the container. While the method is applicable, as noted, to the impro~ed separation of an~
10 particulate material, or mixture of materials, for the sake of simplicity and clarity, it will be described 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 ~lasma occurs Eor 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 o~ blood cells in the fold~ in the top of the bag. During handling of the bag and/or 25 removal o~ the platelet-rich plasma following centriEuga~ion, the en~rapped blood cells can be released into the previously separated platelet-rich plasma~ Another source of con~amination of the platelet-rich plasma is the resuspension of the cells 30 rom the buffy coat and packed red-cell region during rotor deceleration. The differential force on the blood within the con~ainer due to the differences 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 de~eleration.
-` 1 1$1004 A furt'ner cause of contamination of the platelet-rich plasma by red and whi-te cells is the mi~ing brought about by the handling of the bag during its removal from the centriuge 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 expressing o 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. The fast moving fluid tends to sweep along celIs from the 15 bu~fy coat and packed cell interface region.
According to the method of this invention, the purity o~ the separated blood fractions may be - maintained by reducing folding in the top of the container during centrifugation. One of the causes 20 f folds in the flexible blood container is t'nat varying quantities of blood are drawn into the bags~
In fact ~or a typical bag, containing a ixed amount of anticoagulants, the total amoun~ o blood drawn may vary according to normal specifications by as 25 much as 10% from a normal drawn volume oE
approximately 450 ml. Accordingly, the blood containers must be designed to accommodate the larger volume; and, if a smaller volume is drawn, the top of the bag is not fluid supported and, under centrifugal force, wrinkles.
This wrinkling of the top oE the bag is alleviated according to this invention by several means. These include squeezing the bag during centrifugation to maintain the top portion relatively taut. Such squeezing may be accomplished ~y the . . .
~ 1 6100~
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.
Alternatively, and preferably, an annular collar, 5 properly slotted to accommodate the outlet line Eor the bag, may be placed over the top oE the bag such - that under centrifugal force the plastic bag and its contents will hydroform about the underside of the ; collar and thereby maintain a relatively smoot'n 1~ condition. To further reduce the areas in which the components may ~ecome 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 transfer 15 packs or sateIlite bags is placed at the top oE the ba~. Additional ports and/or lines may be placed at the top of the bag if they are prevented from folding over during centrifugation.
In sti].l another alternative, a generally 20 round object may be placed in t'ne bottom of the swinging bucket and t'ne blood bag allowed to hydroform around it, thereby occupying the volume of the bag not displaced by blood and maintaining the top o~ the bag taut and ~ree of wrinkles. The ~olume 25 o this object placed in the bottom o~ the swin~ing bucket may be varied according to the volume of blood in the bag. A further method of reducing wrinkling in the top o the blood bag is to keep the satellite blood bags out of contact with or in the region of 30 the top o 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 o the collar if the collar is con~ormed to have a U-shaped cross 35 section or is ot'nerwise made to be hollow and capable 6i~4 of containing the satellite bag. Alternatively, the satellite bags may be placed in an envelope and positioned about the periphery OL the blood bag.
Preferably the hlood bag itself is placed in S a cylindrical, sleeve-like container or adap~er which fits within the swinging bucket of the centriEuge.
The satellite bags then may be placed, if deslred, between the exterior of the split sleeve and the inside wall of the swinging bucket. To facilitate 10 their handling, the satellite bags may be placed in a thin envelope which can be wrapped about the split sleeveO The split sleeve has a particular advantage in that it reduces handling of the blood bag during removal from the swinging bucket as well as during 15 removal of the bag from the sleeve itself. The two halves of the split sleeve simply may be separated or preferably they may be hinged at the bottom, as will be described he~einafter, so that they may ~e 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 oE t'ne contents of the bag than having to pull the lat~er from a rigid cylindrical container.
Another mekhod of this invention used to 25 reduce swirling o~ the blood during rotor deceleration is to place septa or baffles within the interior of the bag. This results in a decrease of the force ve~tors which cause swirling of the blood in that it reduces the differential radii between the 30 smaller compartments produced within the bag by the septa. The septa are losated to encompass t'ne region in which the interfaces between packed 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 the bag so that , -they allow the lower part o~ the bag to have some ` mixing o~ the packed components and yet they should extend up above where the separa~ion line between ~he packed cell layer, the buffy coa-t region, and the 5 platelet-rich plasma so that t'ne contaminating red and white blood cells components cannot swirl and thereby contaminate the platelet~rich plasma. At the -~ same time the septa should not extend up so far as to inter~ere with the hydro~orming top regions of the 10 bag. The septa further act to stabilize the 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. Finally, during expression of platelet rich plasma from the bagj contamination, as noted earlier, occurs through the 20 movement of the cells from the periphery of the bag to the center for removal from the bag. This resuspension is reduced, according to the method of this invention, by positioning the outlet or transfer line of the bag at the top middle and feediny the 25 outlet line wikh a funnel or approximation thereof.
To this end, the top of the bag may be Eormed in pure conical shape, although this is most desirable from a performance standpoint, it results in a ~omewhat more expensive construction in most cases. Alternatively, 30 and at a lower cost usuallyt the conical-shaped funnel may be approximated by forming the top portion of the bag in triangular or pyramidal-like sections which are joined together typically by heat sealing, as will be described, to approximate the funnel~
0~
A blood bag and associated equipment which is particularly adapted to implement the met'nods of this invention is now descri~ed.
Description of the Preferred Embodiment There may be seen with particular reference to FIG. l an exploded view of one form of Elexible container or bag lO which, in use, is positioned in a clam-shell-like split sleeve 12. As in the case of the methodl the apparatus will be described in the lO envircnment of blood separation. Hence ~he bag 10 ~- will be referred to as a blood bag, the fluid phase as blood, and the particula~e material as blood cells~
The blood bag 10 is illustrated as a flat-type 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 o blood 20 bags. Included among those presently known types of materials are polyvinyl chloride, polyethylene, polypropylene, polyester, and many o the ~luorocarbons. The side wall sections 16 and 18 are formed 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 of 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 between 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 transfer or othee auxilliary ports 48 is depicted in FIG. 5 for 35 completeness of disclosure. This inlet line 28 is .1ilB11004 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 tne tubu~ar conduit 28 joins the bag itself. Th~
purpose of t~is taper is to afford a generally conical funnel shape to the bag, which enhances laminar flow, and reduces transverse shear at the interace of the separated blood fractions, as the 10 expressed fluid approaches the exit or port for the outlet line 28. By forming tnis conical exit, as the Eluid approaches the exit port, its transverse velocity and shear is reduced, in view oE the gradual transition produced by the taper itself. Most 15 desirably the included angle oE 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 25Q minimum angle is also important since in this range t'ne tangent function approaches high values and requires bags having an unweildly cone length. In a preferred embodiment oE
this invention ~he angle of the taper will vary 25 between 70 and 80 and most desirably will approxima~e 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 Eewer 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 centrifuge rotor is reduced, in accordance with this 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 plastic used for the bag and the ends oE these septa 32, in a preferred embodiment 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 parallel to the longitudinal bag axis, vertical compartments are found and, as described earlier, the swirling is reduced. The 15 vertical dimension of this septa is such that 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 antlcoagulants or addi~ives which are typically used in blood processing. The limiting 20 location for the bottom of the septa is tllat the septa should extend downwardly to a point where it will rest on the bottom of the adapter after the container has hydroformed to the adapter during centrifugation.
The upward dimension of the septa is such that the septa will extend to a point above the normal interace point between the platelet enriched plasma fraction and the white cells (buffy coat) and underlying packed red blood cell layer which extends 30 to the bottom of the bag. Recall that the height 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 posi~ion to some extent 35 based on an average basis and allows some degree of 1~
~ ~1 16~0~ .
freedom as to the actual quantity of whole blood that can be placed in the ~ag. In the usual case the blood placed in a bag may be 450 ~ 45 ml.
A further limitation on t'ne upward dimension o~ the septa is determined by the collar 14, which will be described. The collar pre~erably should not interfere with the septa during centri~ugation, i.e., it must not contact or de~orm the septa when it moves, during centrifugation, toward the bottom of 13 the bag. The length (horizontal) 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 ull 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 of 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 or the simple reason that the larger cavities or volumes permit greater swirling, an undesirable occurrence which can increase mixing between the separated fractions.
Greater swirling is the result oE 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 botto~ end 38 ~10~
1~
by a "living" hinge (the receptacle 'naving been constructed of an appropria~e rigid plastic such as nylon, polypropylene or polycarbonate). The receptacle 12 is constructed of two clam-shell halves 5 which join together at their bottom and along a diametrical axis to form the split sleeve.
Alternatively, t'ne sleeve could be hinged along one side wall on a longitudinal axis and swing together 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 attem~ting to withdraw the receptacle from a cylindrical container, a procedure 15 which tends to be disruptive of the separated fractions within the bag. In the case illustrated, as may be seen particularly in FIG. 4, the two halves 40, 42 of the sleeve are joined along mating longitudinal sections by inclined wedges 44 engaging 20 complementary tapered wall sections 46.
To insure that the top portion of the bag lO
does not wrinkle during centrifugation, a collar 14 is employe~. This collar is basically an annulus~
which in cross section is generally U-shaped or at 25 least the interior wa~l of the annulus forms a conical sec~ion adapted generally to mate with the taper o~ the top portion of the bag 10 -- actually the taper of the bag when flat 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 Eormed 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. 5, is the location at which the blood draw ~` ?1~10~
line 47 and additional tubular inserts or transfer ports 48 (none are shown in FIG. 1 for clarity) are formed. This permits a smooth surface at the top portion of the bag, fr~e of crevices, which could 5 otherwise cause entrapment of undesired contaminating blood 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 re~erence to FI~. 6 (the lines 47 and 48 are not shown~ this b~ood bag 10 is placed within the spli~
sleeve 12 such that it is yenerally cylindrical with the septa 32 in a taut condition (FIG. 9). The collar 14 is placed over the outlet tubular conduit 15 28 and the split sleeve placed in the swinging 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 them in the annulus of the collar, etc.
As is known, as the centriEuge rotor accelerates, the swinging bucket swings outwardly and upwardly to assume the horizontal orientation illustrated in FIG. 6, with the centrifugal force being in the sense indicated by ~he arrows 50. Under 25 these conditions the collar (assuming the bag is completely filled with hlood) tends to move (to the le~t in the drawing) outwardly from a centrlfugal force standpoint so as to engage a portion of the top section of the bag 10, causing the top of 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 wlth reference to FIG. 7, t'ne to~ portion of the bag is taut and ~enerally free of wrinkles which would 35 o~herwise tend to entrap cells. During deceleration, swirling is prevented by the septa described above.
61~10~
In the event that the bag contains a lesser amount of blood, the collar 14, as depicted in F'IG.
8, automatically assumes a greater radial outward displacement, draping a greater portion of the top o~
5 tne bag 10 over.its U-shaped annulus, still maintaining a relatively smooth surface for the entire top portion of t'ne bag such tnat there are fewer places left for entrapment of cells in the undesired folds~ It will be noted in this 10 configuration that the radiaL di~placement 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 es~ablishing the heig'nt of the septa within the bag, as noted earlier.
lS 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 whicih is commercially availableO The plasma enriched fraction at the top portion o the bag may be expressed. This Eraction 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 no~ed, par~icularly with reference to FIG. lO, that an additional seam 24 is for~ed at 30 the top portion of the blood bag such that there are now four pyramidal sections instead of two. The four 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 ma~ in some cases be slightly more ~ ~6~
expensive than that of the dou~le searn ver~ion depicted in FIG. 1. In this configuration the top portions 60 of tne respective side walls o~ the flat blood bag 10 are double triangles or pyramidal in 5 shape.
While the blood bag described 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 moIding techniques such that ~here are no side seams.
Alternatively, the bag may be constructed to be of relatively rigid or semirigid material having internal septa. In this eventuality, there is les~
15 possibility of entrapment at the top. Hence the utilization o~ 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 sha~ed top, 20 and no split sleeve is needed.
In an alternative embodiment o~ the invention which may be a substitute for the utilization of internal septa, t'nere is depicted in FIG. 12 a split sleeve having internally directed or 25 radially inwardly directed vertical fins. These 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 ef~ectively as in~ernal septa) to reduce the deceleration effect 30 or swirling during deceleration. The vertical fins are depicted as having only a small radial dim nsion and as only four in number. The radial dimension may be increased to further reduce swirling, but the number of fins s'nould remain small. AltPrnatively and pre~erably, fins 'naving alternating greater and lesser radial dl~ensions may ~e used.
~g6~04 A further alternative embodiment of the invention is depicted in FI~. 13 which is an alternative structure of the invention in wnic'n satellite bags such as those connected to the satellite line of FIG. 5 may be ~laced in an envelope which is wrapped around in an annulus which may be provided for between the exterior or perip'nery of the split sleeve 42 and a centrifuge bucket 70. The envelope 72 need not be used, but 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, if desired, be placed within the annular space 74 (FIG. l) of the collar 1~. In still another al~ernative embodiment, this annular space 74 may be used for the placement of balancing weights for the swinging bucket centrifuge as previously descri~ed. In this figure the bag is partially cut away to show the platelet-rich plasma 80, the buffy coat 78, packed red cells 74 and the interface ~6 therebetween.
-There has thus been described a relatively simple method of and blood bag for centriEuging blood bags, which method and apparatus greatly facilitates - 25 the preparation of platelet concentrates re]atively free of unwanted blood cell contamination. Although described in connection with blood separations, it is to be unders~ood that the method and apparatus are equally useful for a wide ran~e 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.
Ti tle ~ethod and Apparatus For Centrifugal Separation Background of the Invention 5This invention relates to a method and apparatus for centrifugally separating particulate material from a liquid phase and, more particularly, to a method and apparatus for the batch separation of blood components.
It is known to use centrifugal ~echniques for the separation and/or fractionation of partic~late materials suspended in a liquid according to particle density, size, shape, etc. Unfortunately, during centrifuge deceleration, and subsequent 15 removal of the separated constituen~s, there is a tendency for remixing of the separated components.
This is particularly true in the case of blood.
The separation of blood into cellular components and plasma, in general, and preparing 20 platelet rich plasma, in particular, has become oE
great interest to the medical community. The - increas2d use o~ chemotherapy and other techniques requires platelet concentrate transfusions.
Unfortunately, present blood bags and many-batch type ; ~5blood separation techni~ues do not facilitate good platelet separation. 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 of 30such transfusions, thereby reducing the efficency of subsequent transfusions. It therefore becomes necessary in many cases to select and ~ype tne : 3 5 ~J
'' .
6~00~1 donors ~~ it being no longer possible to use random donors. This greatly increases the cost. Some of the problems incipiently related to alloimmuni~ation are described in an article entitled, "Correction of Poor Platelet Transfusion Responses with Leukocyte-poor HL-A-matched Pla~elet Concentrates" by R. a. Herzig, et al.~ Blood, Vol. 46, No. 5 (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 white blood cells, a concentrate - of platelets suspended in plasma, and a platelet-poor 15 plasma fraction. During the first centrifugation, red blood cells sediment to the bottom oE the centrifuge bucket ~i.e., pack at the bottom of the blood bag which is oxiented horiæontally 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 immediately above the packed red-cell mass (the so-called buEfy-coat region) as well as in the upper 25 portion of the packed red-cell reyion. After rotor deceleration, the platelet-rich plasma layer is expressed into a satellite 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 of the platelet-poor plasma is expressed into a second satellite bag, leaving a platelet concentrate in the first satellite bag.
One of the factors contributing to contamination (unwanted levels of white and red blood ~ ;~6l~a4 cells in platelet-rich plasma) of the platelet concentrate, giving rise to alloimmunization, is the formation of fo~ds in the upper part of the blood bag during centrifugation. These folds permit the red 5 and white blood cells to become entrapped in the folds hence expressed with the platelet containing plasma causing some o the undesired contamination noted above. This tendency to fold in the top portion of t'ne bag can be aggravated by the fact that 10 satellite packs, tubing and balancing pads are usually placed within the bucket with the blood bag.
Further, the technician in remo~ing the bag from the swinging bucket of the centrifuge, as well as in subsequently handling the bag, can cause some 15 disturbance and remixing of the bag's contents.
A second major factor contributing to unwanted contamination of the platelet concentrate is tl}e phenomena which occurs during the final stages of deceleration of the centrifuge rotor. The 20 deceleration of a unit of Eluid on the extreme outboard side of the swinging bucket as it reassumes a vertical orientation will be greater than that of a - unit on the extreme inboard side. This results in a fluid rotation about the buc~et center unit. The 25 rotating or swirling fluid ~ends to cause some remixing of the components, which were separated during centrifugation, be~ore they can be expressed from the bag into the satellite bags. ~fforts in the past to reduce this swirling have been directed to 30 decreasing bucket diameter, using oval buckets, and the like~ Long, thin buckets greatly enlarge the size of the centrifuges and hence generally are not a practical solution. Further, the t'nin, long tubes increase centrifugation time. Swirling can be reduced by increasing centrifugation deceleration --~ :11&;~ 4 time, but this severely reduces throughput and hence greatly increases processing costs.
Brief Descrip~ion of the Inven~ion According to one method of this invention, 5 particulate material is se arated ~rom, and maintained separated from, a fluid p'nase, 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 lO 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 otherwise trap the particulate material. The force may be applied to the container in many ways. In one ins~ance it may be'accomplished by squeeæing the container by use o, 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 porkion of the container and~outlet line such' that the centrifugal ~orce on the collar ~orms ~he top portion of the container tautly about the collar 25 with reduced w~inkles. 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, ~alancing weights may be placed in the annulus to equiliæe the weights of the loaded buckets placed in 30 opposing positions in the centrifuge rotors. If satellite containers are connected to t'ne main container, they may be stored in -the annulus during centrifugation.
In still another alternative technique the force may be applied to the container by positioning . . .
a~
a volume-displacing article under the contain~r in the centriEuge bucket during centriEugation such that the container hydroforms about the article and ta~es up any unfilled space within the con~ainer~ thereby 5 causing the walls to become taut and relatively wrinkle free.
According to still other alternative techniques, satellite containers may be separated from contact with the main container by placing the 10 main container in a split sleeve and the split sleeve in the bucket with the satelli~e containers being positioned in an envelope secured in the annular space in between the ~ucket and the split sleeve.
Various techniques may be used for reducing 15 swirling within the containers during the deceleration of ~he centrifuge. Among thèse are the positioning of septa within the container.
Alternatively, radially inward protuberances or - ba~fles may be for~ed 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 baf1es within the interior of the container, thereby reducing the 25 swirling and intermixing of the separated particles.
By forming the top portion of the container into the general configuration of a cone or an approximation thereo~, 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 to about 160 with an angle of about 75 being preferred.
One apparatus for effecting reduced 35 intermixing of separated components is a sealed, 1 ~ B ~
plastic fluid storage container r generally cylindrical when ~illed wi-th a fluid, the ~ontainer having a longitudinal axis and a top and a Gottom, and a first tu~ular conduit communicating with the 5 interior o~ the container, characterized by an interior septum lying in a plane generally parallel to the lonyitudinal axis, thereby to reduce the movement of the fluid 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 ~o ano~her aspect oE the 15 invention, a sealed, flexibl~, thermoplastic fluid storage container is constructed having side wall sections with laminate edge seals and a longitudinal axis, two different portions of said edge seais being parallel to said longitudinal axis, and a ~irst 20 tubular conduit means, sealed between said wall sections, communicating with the interior o~ said container and intersecting said longitudinal axis.
This container is provided with edge seals which are tapered from the said different portions to said 25 first conduit means.
Alternatively, or simultaneously, the container is providecl with a septum defined by a first sheet o~ 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 sontainer between tne edge seals may lie between 25 and 160 thereby to provide a generally conicai container top when fluid filled. In other alternative variations, the 0 ~
taper angle may be between 70 and 80 and desirably is about 75.
The fluid-storage container septum is alterna-tively deLined ~y f iLSt and second s'neets of a flexible thermoplastic each having selected ends joined to selected side wall sections and each being joined together along their mid portions, the jointures occurring along laminate s~als generally parallel 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 the top portion of the container more closely approximates a cone when fluid filled. Any additional transfusion ports or inlet tubes should be connected to the bottom of tlle 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.
Brief Description of the DrawingS
Further advantages and features of this invention will become apparent upon consideration of the following description wherein:
FIG. 1 is an exploded view of a split sleeve, fluid container ~blood bag) and collar immediately prior to placement within the sp:Lit sleeve for later centrifugation;
FIG. 2 is a bottom plan view of the collar illustrated in FIG. l;
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 o~
accordance with a preferred embodiment.of this invention;
FIG. 6 is a side elevation view partly cut away of the blood bag of t'nis invention (without S attached satellite bags or transfusion parts and inlet lines) during the ini~ial p'nases of centrifuga-tion 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 FIG. 6, during centrifugation depicting the smoothing ~ffect of the collar on the top portion of the blood bag;
FIG. 8 is an illustration of the same type as in FIG. 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. lO is a fragmentary illustration of a 20 pyramidal-shaped top portion of a blood bag : constructed in accordance Witll an alternative embodiment of this invention;
FIG. 11 is a cross-sectional view of a blood - bag taken along the section line 9-9 of F~G. 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 t'ne bag during centrifugation; and FIG. 13 is an elevation view of a centrifuged, filled blood bag depicting the separated blood components;
Descri~tion of the Preferred Embodiment The method oE this invention reduces remixing of the separated ractions of particulate material during the deceleration phase of ~ 5 centrifugation and, following centrifuga~ion, during handling of the container and removal ~y expression of successive fluid and particle containing layers from the container. While the method is applicable, as noted, to the impro~ed separation of an~
10 particulate material, or mixture of materials, for the sake of simplicity and clarity, it will be described 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 ~lasma occurs Eor 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 o~ blood cells in the fold~ in the top of the bag. During handling of the bag and/or 25 removal o~ the platelet-rich plasma following centriEuga~ion, the en~rapped blood cells can be released into the previously separated platelet-rich plasma~ Another source of con~amination of the platelet-rich plasma is the resuspension of the cells 30 rom the buffy coat and packed red-cell region during rotor deceleration. The differential force on the blood within the con~ainer due to the differences 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 de~eleration.
-` 1 1$1004 A furt'ner cause of contamination of the platelet-rich plasma by red and whi-te cells is the mi~ing brought about by the handling of the bag during its removal from the centriuge 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 expressing o 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. The fast moving fluid tends to sweep along celIs from the 15 bu~fy coat and packed cell interface region.
According to the method of this invention, the purity o~ the separated blood fractions may be - maintained by reducing folding in the top of the container during centrifugation. One of the causes 20 f folds in the flexible blood container is t'nat varying quantities of blood are drawn into the bags~
In fact ~or a typical bag, containing a ixed amount of anticoagulants, the total amoun~ o blood drawn may vary according to normal specifications by as 25 much as 10% from a normal drawn volume oE
approximately 450 ml. Accordingly, the blood containers must be designed to accommodate the larger volume; and, if a smaller volume is drawn, the top of the bag is not fluid supported and, under centrifugal force, wrinkles.
This wrinkling of the top oE the bag is alleviated according to this invention by several means. These include squeezing the bag during centrifugation to maintain the top portion relatively taut. Such squeezing may be accomplished ~y the . . .
~ 1 6100~
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.
Alternatively, and preferably, an annular collar, 5 properly slotted to accommodate the outlet line Eor the bag, may be placed over the top oE the bag such - that under centrifugal force the plastic bag and its contents will hydroform about the underside of the ; collar and thereby maintain a relatively smoot'n 1~ condition. To further reduce the areas in which the components may ~ecome 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 transfer 15 packs or sateIlite bags is placed at the top oE the ba~. Additional ports and/or lines may be placed at the top of the bag if they are prevented from folding over during centrifugation.
In sti].l another alternative, a generally 20 round object may be placed in t'ne bottom of the swinging bucket and t'ne blood bag allowed to hydroform around it, thereby occupying the volume of the bag not displaced by blood and maintaining the top o~ the bag taut and ~ree of wrinkles. The ~olume 25 o this object placed in the bottom o~ the swin~ing bucket may be varied according to the volume of blood in the bag. A further method of reducing wrinkling in the top o the blood bag is to keep the satellite blood bags out of contact with or in the region of 30 the top o 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 o the collar if the collar is con~ormed to have a U-shaped cross 35 section or is ot'nerwise made to be hollow and capable 6i~4 of containing the satellite bag. Alternatively, the satellite bags may be placed in an envelope and positioned about the periphery OL the blood bag.
Preferably the hlood bag itself is placed in S a cylindrical, sleeve-like container or adap~er which fits within the swinging bucket of the centriEuge.
The satellite bags then may be placed, if deslred, between the exterior of the split sleeve and the inside wall of the swinging bucket. To facilitate 10 their handling, the satellite bags may be placed in a thin envelope which can be wrapped about the split sleeveO The split sleeve has a particular advantage in that it reduces handling of the blood bag during removal from the swinging bucket as well as during 15 removal of the bag from the sleeve itself. The two halves of the split sleeve simply may be separated or preferably they may be hinged at the bottom, as will be described he~einafter, so that they may ~e 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 oE t'ne contents of the bag than having to pull the lat~er from a rigid cylindrical container.
Another mekhod of this invention used to 25 reduce swirling o~ the blood during rotor deceleration is to place septa or baffles within the interior of the bag. This results in a decrease of the force ve~tors which cause swirling of the blood in that it reduces the differential radii between the 30 smaller compartments produced within the bag by the septa. The septa are losated to encompass t'ne region in which the interfaces between packed 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 the bag so that , -they allow the lower part o~ the bag to have some ` mixing o~ the packed components and yet they should extend up above where the separa~ion line between ~he packed cell layer, the buffy coa-t region, and the 5 platelet-rich plasma so that t'ne contaminating red and white blood cells components cannot swirl and thereby contaminate the platelet~rich plasma. At the -~ same time the septa should not extend up so far as to inter~ere with the hydro~orming top regions of the 10 bag. The septa further act to stabilize the 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. Finally, during expression of platelet rich plasma from the bagj contamination, as noted earlier, occurs through the 20 movement of the cells from the periphery of the bag to the center for removal from the bag. This resuspension is reduced, according to the method of this invention, by positioning the outlet or transfer line of the bag at the top middle and feediny the 25 outlet line wikh a funnel or approximation thereof.
To this end, the top of the bag may be Eormed in pure conical shape, although this is most desirable from a performance standpoint, it results in a ~omewhat more expensive construction in most cases. Alternatively, 30 and at a lower cost usuallyt the conical-shaped funnel may be approximated by forming the top portion of the bag in triangular or pyramidal-like sections which are joined together typically by heat sealing, as will be described, to approximate the funnel~
0~
A blood bag and associated equipment which is particularly adapted to implement the met'nods of this invention is now descri~ed.
Description of the Preferred Embodiment There may be seen with particular reference to FIG. l an exploded view of one form of Elexible container or bag lO which, in use, is positioned in a clam-shell-like split sleeve 12. As in the case of the methodl the apparatus will be described in the lO envircnment of blood separation. Hence ~he bag 10 ~- will be referred to as a blood bag, the fluid phase as blood, and the particula~e material as blood cells~
The blood bag 10 is illustrated as a flat-type 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 o blood 20 bags. Included among those presently known types of materials are polyvinyl chloride, polyethylene, polypropylene, polyester, and many o the ~luorocarbons. The side wall sections 16 and 18 are formed 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 of 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 between 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 transfer or othee auxilliary ports 48 is depicted in FIG. 5 for 35 completeness of disclosure. This inlet line 28 is .1ilB11004 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 tne tubu~ar conduit 28 joins the bag itself. Th~
purpose of t~is taper is to afford a generally conical funnel shape to the bag, which enhances laminar flow, and reduces transverse shear at the interace of the separated blood fractions, as the 10 expressed fluid approaches the exit or port for the outlet line 28. By forming tnis conical exit, as the Eluid approaches the exit port, its transverse velocity and shear is reduced, in view oE the gradual transition produced by the taper itself. Most 15 desirably the included angle oE 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 25Q minimum angle is also important since in this range t'ne tangent function approaches high values and requires bags having an unweildly cone length. In a preferred embodiment oE
this invention ~he angle of the taper will vary 25 between 70 and 80 and most desirably will approxima~e 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 Eewer 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 centrifuge rotor is reduced, in accordance with this 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 plastic used for the bag and the ends oE these septa 32, in a preferred embodiment 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 parallel to the longitudinal bag axis, vertical compartments are found and, as described earlier, the swirling is reduced. The 15 vertical dimension of this septa is such that 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 antlcoagulants or addi~ives which are typically used in blood processing. The limiting 20 location for the bottom of the septa is tllat the septa should extend downwardly to a point where it will rest on the bottom of the adapter after the container has hydroformed to the adapter during centrifugation.
The upward dimension of the septa is such that the septa will extend to a point above the normal interace point between the platelet enriched plasma fraction and the white cells (buffy coat) and underlying packed red blood cell layer which extends 30 to the bottom of the bag. Recall that the height 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 posi~ion to some extent 35 based on an average basis and allows some degree of 1~
~ ~1 16~0~ .
freedom as to the actual quantity of whole blood that can be placed in the ~ag. In the usual case the blood placed in a bag may be 450 ~ 45 ml.
A further limitation on t'ne upward dimension o~ the septa is determined by the collar 14, which will be described. The collar pre~erably should not interfere with the septa during centri~ugation, i.e., it must not contact or de~orm the septa when it moves, during centrifugation, toward the bottom of 13 the bag. The length (horizontal) 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 ull 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 of 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 or the simple reason that the larger cavities or volumes permit greater swirling, an undesirable occurrence which can increase mixing between the separated fractions.
Greater swirling is the result oE 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 botto~ end 38 ~10~
1~
by a "living" hinge (the receptacle 'naving been constructed of an appropria~e rigid plastic such as nylon, polypropylene or polycarbonate). The receptacle 12 is constructed of two clam-shell halves 5 which join together at their bottom and along a diametrical axis to form the split sleeve.
Alternatively, t'ne sleeve could be hinged along one side wall on a longitudinal axis and swing together 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 attem~ting to withdraw the receptacle from a cylindrical container, a procedure 15 which tends to be disruptive of the separated fractions within the bag. In the case illustrated, as may be seen particularly in FIG. 4, the two halves 40, 42 of the sleeve are joined along mating longitudinal sections by inclined wedges 44 engaging 20 complementary tapered wall sections 46.
To insure that the top portion of the bag lO
does not wrinkle during centrifugation, a collar 14 is employe~. This collar is basically an annulus~
which in cross section is generally U-shaped or at 25 least the interior wa~l of the annulus forms a conical sec~ion adapted generally to mate with the taper o~ the top portion of the bag 10 -- actually the taper of the bag when flat 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 Eormed 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. 5, is the location at which the blood draw ~` ?1~10~
line 47 and additional tubular inserts or transfer ports 48 (none are shown in FIG. 1 for clarity) are formed. This permits a smooth surface at the top portion of the bag, fr~e of crevices, which could 5 otherwise cause entrapment of undesired contaminating blood 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 re~erence to FI~. 6 (the lines 47 and 48 are not shown~ this b~ood bag 10 is placed within the spli~
sleeve 12 such that it is yenerally cylindrical with the septa 32 in a taut condition (FIG. 9). The collar 14 is placed over the outlet tubular conduit 15 28 and the split sleeve placed in the swinging 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 them in the annulus of the collar, etc.
As is known, as the centriEuge rotor accelerates, the swinging bucket swings outwardly and upwardly to assume the horizontal orientation illustrated in FIG. 6, with the centrifugal force being in the sense indicated by ~he arrows 50. Under 25 these conditions the collar (assuming the bag is completely filled with hlood) tends to move (to the le~t in the drawing) outwardly from a centrlfugal force standpoint so as to engage a portion of the top section of the bag 10, causing the top of 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 wlth reference to FIG. 7, t'ne to~ portion of the bag is taut and ~enerally free of wrinkles which would 35 o~herwise tend to entrap cells. During deceleration, swirling is prevented by the septa described above.
61~10~
In the event that the bag contains a lesser amount of blood, the collar 14, as depicted in F'IG.
8, automatically assumes a greater radial outward displacement, draping a greater portion of the top o~
5 tne bag 10 over.its U-shaped annulus, still maintaining a relatively smooth surface for the entire top portion of t'ne bag such tnat there are fewer places left for entrapment of cells in the undesired folds~ It will be noted in this 10 configuration that the radiaL di~placement 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 es~ablishing the heig'nt of the septa within the bag, as noted earlier.
lS 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 whicih is commercially availableO The plasma enriched fraction at the top portion o the bag may be expressed. This Eraction 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 no~ed, par~icularly with reference to FIG. lO, that an additional seam 24 is for~ed at 30 the top portion of the blood bag such that there are now four pyramidal sections instead of two. The four 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 ma~ in some cases be slightly more ~ ~6~
expensive than that of the dou~le searn ver~ion depicted in FIG. 1. In this configuration the top portions 60 of tne respective side walls o~ the flat blood bag 10 are double triangles or pyramidal in 5 shape.
While the blood bag described 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 moIding techniques such that ~here are no side seams.
Alternatively, the bag may be constructed to be of relatively rigid or semirigid material having internal septa. In this eventuality, there is les~
15 possibility of entrapment at the top. Hence the utilization o~ 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 sha~ed top, 20 and no split sleeve is needed.
In an alternative embodiment o~ the invention which may be a substitute for the utilization of internal septa, t'nere is depicted in FIG. 12 a split sleeve having internally directed or 25 radially inwardly directed vertical fins. These 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 ef~ectively as in~ernal septa) to reduce the deceleration effect 30 or swirling during deceleration. The vertical fins are depicted as having only a small radial dim nsion and as only four in number. The radial dimension may be increased to further reduce swirling, but the number of fins s'nould remain small. AltPrnatively and pre~erably, fins 'naving alternating greater and lesser radial dl~ensions may ~e used.
~g6~04 A further alternative embodiment of the invention is depicted in FI~. 13 which is an alternative structure of the invention in wnic'n satellite bags such as those connected to the satellite line of FIG. 5 may be ~laced in an envelope which is wrapped around in an annulus which may be provided for between the exterior or perip'nery of the split sleeve 42 and a centrifuge bucket 70. The envelope 72 need not be used, but 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, if desired, be placed within the annular space 74 (FIG. l) of the collar 1~. In still another al~ernative embodiment, this annular space 74 may be used for the placement of balancing weights for the swinging bucket centrifuge as previously descri~ed. In this figure the bag is partially cut away to show the platelet-rich plasma 80, the buffy coat 78, packed red cells 74 and the interface ~6 therebetween.
-There has thus been described a relatively simple method of and blood bag for centriEuging blood bags, which method and apparatus greatly facilitates - 25 the preparation of platelet concentrates re]atively free of unwanted blood cell contamination. Although described in connection with blood separations, it is to be unders~ood that the method and apparatus are equally useful for a wide ran~e 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 (4)
1. Apparatus for separating particulate material from a fluid phase comprising:
a sealed, flexible plastic fluid storage container having a longitudinal axis and a first tubular conduit means sealed to said container, communicating with the interior of said container and intersecting said longitudinal axis, the portion of said container contiguous the conduit being generally conical, a hollow cylindrical centrifuging receptacle, adapted for use in a swinging bucket type centrifuge, having a longitudinal axis, being closed at one end, and adapted to receive said container, with the receptacle and container axes coincident, an adapter configured to fit over said conduit means and slide within said receptacle to engage the said container, said adapter being in the shape of an annulus having a V-shaped cross-section and an out-side diameter sufficiently less than the inside diameter of the receptacle to allow the container to drape over the V-shaped cross-section, and an inner surface which is conical in shape such that, when the adapter and receptacle are under axial centrifugal force, the adapter maintains the conical portion of said container contiguous the conduit under tension and free of wrinkles by virtue of its being draped over the V-shaped cross-section of the adapter.
a sealed, flexible plastic fluid storage container having a longitudinal axis and a first tubular conduit means sealed to said container, communicating with the interior of said container and intersecting said longitudinal axis, the portion of said container contiguous the conduit being generally conical, a hollow cylindrical centrifuging receptacle, adapted for use in a swinging bucket type centrifuge, having a longitudinal axis, being closed at one end, and adapted to receive said container, with the receptacle and container axes coincident, an adapter configured to fit over said conduit means and slide within said receptacle to engage the said container, said adapter being in the shape of an annulus having a V-shaped cross-section and an out-side diameter sufficiently less than the inside diameter of the receptacle to allow the container to drape over the V-shaped cross-section, and an inner surface which is conical in shape such that, when the adapter and receptacle are under axial centrifugal force, the adapter maintains the conical portion of said container contiguous the conduit under tension and free of wrinkles by virtue of its being draped over the V-shaped cross-section of the adapter.
2. Apparatus as set forth in Claim 1 wherein said container includes a septum defined by a first sheet of a flexible plastic positioned within the container and having ends joined to opposite interior portions of the container along seal lines which are generally parallel to the longitudinal axis, the septum extending less than the height of said container measured along Raid longitudinal axis.
3. Apparatus as set forth in Claim 1 or Claim 2 wherein the receptacle is a unitary piece defined by two hollow half cylinders each closed and hinged at one end by a living hinge.
4. Apparatus as set forth in Claim 1 or Claim 2 wherein the annulus of said adapter is hollow defining an annulus trough in which the conduit means can be deposited for centrifugation without causing wrinkles or distortions in the storage container during centrifugation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000418559A CA1161004A (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 |
| CA000418559A CA1161004A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1161004A true CA1161004A (en) | 1984-01-24 |
Family
ID=27166812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000418559A Expired CA1161004A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1161004A (en) |
-
1982
- 1982-12-23 CA CA000418559A patent/CA1161004A/en not_active Expired
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