CA1150695A - Method and apparatus for centrifugal separation - Google Patents
Method and apparatus for centrifugal separationInfo
- Publication number
- CA1150695A CA1150695A CA000359581A CA359581A CA1150695A CA 1150695 A CA1150695 A CA 1150695A CA 000359581 A CA000359581 A CA 000359581A CA 359581 A CA359581 A CA 359581A CA 1150695 A CA1150695 A CA 1150695A
- Authority
- CA
- Canada
- Prior art keywords
- bag
- container
- blood
- longitudinal axis
- wall sections
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0407—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
- B04B5/0428—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles with flexible receptacles
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
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T itle Method and Apparatus For CentriEugal separation sack~round 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 techniques for the separation and/or fractionation of particulate 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 of blood.
The separation of blood into cellular components and plasma, in general, and preparing 20platelet rich plasma, in particular, has become of great interest to the medical community. The increased use of chemotherapy and other techniques requires platelet concentrate transfusions.
Unfortunately, present blood bags and many-batch type 25blood separation techniques 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 type the donors -- it being no longer possible to use random donors~ This greatly increases the cost. Some of the problems incipiently related to alloimmunization are described in an article entitled, "Correction of 5 Poor Platelet Transfusion Responses with Leukocyte-poor HL A-matched P:Latelet Concentrates" by R. H. Herzig, et al., Blood, Vol. 46, No. 5 (Nov.), 197S.
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 of the centrifuge bucket ~i.e., pack at the bo~tom 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 immediately above the packed red-cell mass (the so-called buffy-coat region) 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 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.
On,e of the factors contributing to contamination (unwanted levels of white and red blood ~. .
' : ' . . :' .
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cells in platelet-rich plasma) of tne platelet concentrate, giving rise to alloimmunization, is the formation of folds in the upper part of the blood bag duriny 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 of the undesired contamination noted above. This tendency to fold in the top portion of the 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 remixing of the bag's contents.
A second major factor contributing to unwanted contamination of the platelet concentrate is the phenomena which occurs during the final stages of deceleration of the centrifuge rotor. The ~0 deceleration of a unit of fluid 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 bucket center unit. The 25 rotating or swirling fluid tends to cause some remixing of the components, which were separated during centrifugation, before they can be expressed from the bag into the satellite bags. Efforts 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 thin, long tubes increase centrifugation time. Swirling can be reduced by increasing centrifugation deceleration .:
-J~
time, but this severely reduces throughput and hence greatly increases processing costs.
Brief Description of the Invention According to one method 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 Up9 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 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 of 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 may 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.
In still another alternative technique the force may be applied to the container by positioning - . ~
- . . -- , -~ . .~ . . .
.. . . . ~ . - .
~: .
~ L~5~5 a volume-displacing article under the container in the centrifuge bucket during centrifugation such t'nat the container hydrororms about the article and takes up any unfilled space within the container, 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 satellite containers being positioned in an envelope secured in the annular space in between ~he bucket and the split sleeve.
~arious techniques may be used for reducing 15 swirling within the containers during the deceleration of the centrifuge. Among thes,e 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.
By forming the top 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 to about 160 with an angle of about 75 being preferred.
One apparatus for eEfecting reduced 35 intermixing of separated components is a sealed, . . . . . .
' , ' .
~ 6~ ~
plastic fluid storage container, generally cylindrical when filled with a fluid, the container having a longitudinal axis and a top and a bo-ttom, and a ~irst tubular conduit communicating with the S interior of the container, characterized by an interior septum lying in a plane generally parallel to the longitudinal axis, thereby to reduce the movement of the fluid in the container both during centrifugal deceleration and during handling o~ 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 aspect 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 from 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 1609 thereby to provide a generally conical container top when 3 fluid filled. In other alternative variations, the , . . ~ .
.
.
.
- . - .
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taper angle may be between 70 and 80 and desirably is about 75.
The fluid-storage container septum is alternatively defined by first and second sheets 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 seals 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 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.
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) ~nd collar immediately prior to placement within the split sleeve for later centrifugation;
FIG. 2 is a bottom plan view of the collar illustrated in FIG. l;
FTG. 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 .
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.
accordance with a preferred embodiment of this invention;
FIG. 6 is a side elevation view partly cut away of the blood bag of this invention (without 5 attached satellite bags or transfusion parts and inlet lines) during the initial phases of centrifugation depicting the operation of t'ne collar at the beginning of centrifuge r~n;
FIG. 7 is an elevation view partly cut away 10 depicting the blood bag of FIG. 6, during centrifugation depicting the smoothing effect 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. 10 is a ~ragmentary illustration of a 20 pyramidal-shaped top portion of a blood bag constructed in accordance with 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 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 componlents;
~:' 8 6~5 Description o~ the Pre~erred Embodiment The method of this invention reduces remixing of the separated fractions of particulate material 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 of any lO 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 t~e platelet-rich plasma relatively ~ree 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 cells in the folds in the top of the bag. During handling of the bag and/or 25 removal of the platelet-rich plasma following centrifugation, the entrapped blood cells can be released into the previously separated platelet-rich plasma. Anotber source of contamination of the platelet-rich plasma is the resuspension of the cells 30 from the buffy coat and packed red-cell region during rotor deceleration. The differential force on the blood within the container 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 ancl resuspension of the cells during the final stages of rotor deceleration.
., g 6~95i A furt'ner cause o~ contamination of the platelet-rich plasma by red and white cells is the mixing brought about by the handling of the 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 expressing 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 to~ard the center location of the outlet line at a relatively great speed. The fast moving fluid tends to sweep along cells from the 15 buffy coat: and packed cell interface region.
According to the method of this invention, the purity of the separated blood fractions may be maintained by reducing folding in the top oE the container during centrifugation. One of the causes 20 of 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 total amount of blood drawn may vary according to normal specifications by as 25 much as 10% from a no~mal drawn volume of 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 3~ force, wrinkles.
This wrinkling of the top of 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 by the ~ 10 si~5 placement of the bag in an annular bladder containing a dense solution in order to reduce the volume o~ the swinging bucket or adapter in which tne bag is held.
Alternatively, and preferably, an annular collar, 5 properly slotted to accommodate the outlet line for the bag, may be placed over the top of the bag such that under centrifugal force the plastic bag and its contents will 'nydroform about the underside o~ the collar and thereby maintain a relativ~ly smooth 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 transfer 15 packs or satellite bags is placed at the top o~ the bag. Additional ports and/or lines may be placed at the top of the bag if they are preven~ed from folding over during centrifugation.
In still another alternative, a generally 20 round object may be placed in tbe bottom of 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 free of wrinkles. The volume 25 of this object placed in the bottom of the swinging bucket may be varied according to the volume of blood in the bag. A further method of 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 of the blood bag. If satellite bags are not allowed to press on the top of the bag, there will be less wrin~leing 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 otherwise made to be hollow and capable ~, 11 :; .. , , , :
36~5 of containing the satellite bag. Alternatively, the satellite bags may 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 adapter whicn fits within the swinging bucket of the centri~uge.
The satellite bags then may be placed, i~ desired, 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 sleeve. 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 hereinafter, 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 o~ the contents of th~ bag than having to pull the latter from a rigid cylindrical conta.iner.
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 decrease of the force vectors which cause swirling of the blood in that it reduces the differential radii between the 30 smaller co~partments produced within the bag by the septa. The septa are located to encompass the 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 bott~m of the bag so that ~;, 12 , 6~
they allow the lower part of the bag to have some mixing of the packed 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 the contaminating red and white blood cells componemts 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 hydroforming top regions of the 10 bag. The septa further act to stabilize the handling o~ 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 bag, contamination, as noted earlier, occurs throu~h 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 feeding the 25 outlet line with a funnel or approximation thereof.
To this end, the top of the bag may be formed in pure conical 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-sbaped 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 clescribed, to approximate the funnel.
A blood bag and associated equipment which is particularly adapted to implement the methods of this invention is now described.
Description of the Preferred Embodiment There may be seen with partlcular re~erence to FIG. 1 an exploded view of one form of flexible container or bag 10 which, in use, is positioned in a clam-shell-like spl t sleeve 12. As in the 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 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 1~ and 18 (FI& 3) of flexible, chemically inert to blood and nonporous to fluids, thermoplastic shee~ 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 formed into the ~lat-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 other auxilliary ports 48 is depicted in FIG. 5 for 35 completeness of disclosure. This inlet line 28 is `"? 14 .
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s 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 pOillt at the location where 5 the tubular conduit 28 joins the bag itself. The purpose of this taper is to afford a generally conical funnel shape to the bag, which enhances laminar flow, and reduces transverse shear at the interface of the separated blood fractions, as the 10 expressed fluid approaches the exit or port for the outlet line 28. By forming this conical exit, as the fluid approaches the exit port, its transverse velocity and shear is reduced, in view of the gradual transition produced by the taper itself. Mo~t lS desirably 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 important since in this range t'ne tangent function approaches high values and requires bags having an unweildly cone length. In a preferred embodiment of this invention the angle of the taper will vary
T itle Method and Apparatus For CentriEugal separation sack~round 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 techniques for the separation and/or fractionation of particulate 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 of blood.
The separation of blood into cellular components and plasma, in general, and preparing 20platelet rich plasma, in particular, has become of great interest to the medical community. The increased use of chemotherapy and other techniques requires platelet concentrate transfusions.
Unfortunately, present blood bags and many-batch type 25blood separation techniques 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 type the donors -- it being no longer possible to use random donors~ This greatly increases the cost. Some of the problems incipiently related to alloimmunization are described in an article entitled, "Correction of 5 Poor Platelet Transfusion Responses with Leukocyte-poor HL A-matched P:Latelet Concentrates" by R. H. Herzig, et al., Blood, Vol. 46, No. 5 (Nov.), 197S.
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 of the centrifuge bucket ~i.e., pack at the bo~tom 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 immediately above the packed red-cell mass (the so-called buffy-coat region) 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 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.
On,e of the factors contributing to contamination (unwanted levels of white and red blood ~. .
' : ' . . :' .
.
cells in platelet-rich plasma) of tne platelet concentrate, giving rise to alloimmunization, is the formation of folds in the upper part of the blood bag duriny 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 of the undesired contamination noted above. This tendency to fold in the top portion of the 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 remixing of the bag's contents.
A second major factor contributing to unwanted contamination of the platelet concentrate is the phenomena which occurs during the final stages of deceleration of the centrifuge rotor. The ~0 deceleration of a unit of fluid 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 bucket center unit. The 25 rotating or swirling fluid tends to cause some remixing of the components, which were separated during centrifugation, before they can be expressed from the bag into the satellite bags. Efforts 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 thin, long tubes increase centrifugation time. Swirling can be reduced by increasing centrifugation deceleration .:
-J~
time, but this severely reduces throughput and hence greatly increases processing costs.
Brief Description of the Invention According to one method 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 Up9 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 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 of 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 may 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.
In still another alternative technique the force may be applied to the container by positioning - . ~
- . . -- , -~ . .~ . . .
.. . . . ~ . - .
~: .
~ L~5~5 a volume-displacing article under the container in the centrifuge bucket during centrifugation such t'nat the container hydrororms about the article and takes up any unfilled space within the container, 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 satellite containers being positioned in an envelope secured in the annular space in between ~he bucket and the split sleeve.
~arious techniques may be used for reducing 15 swirling within the containers during the deceleration of the centrifuge. Among thes,e 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.
By forming the top 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 to about 160 with an angle of about 75 being preferred.
One apparatus for eEfecting reduced 35 intermixing of separated components is a sealed, . . . . . .
' , ' .
~ 6~ ~
plastic fluid storage container, generally cylindrical when filled with a fluid, the container having a longitudinal axis and a top and a bo-ttom, and a ~irst tubular conduit communicating with the S interior of the container, characterized by an interior septum lying in a plane generally parallel to the longitudinal axis, thereby to reduce the movement of the fluid in the container both during centrifugal deceleration and during handling o~ 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 aspect 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 from 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 1609 thereby to provide a generally conical container top when 3 fluid filled. In other alternative variations, the , . . ~ .
.
.
.
- . - .
, ~ J~
taper angle may be between 70 and 80 and desirably is about 75.
The fluid-storage container septum is alternatively defined by first and second sheets 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 seals 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 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.
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) ~nd collar immediately prior to placement within the split sleeve for later centrifugation;
FIG. 2 is a bottom plan view of the collar illustrated in FIG. l;
FTG. 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 .
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.
.
accordance with a preferred embodiment of this invention;
FIG. 6 is a side elevation view partly cut away of the blood bag of this invention (without 5 attached satellite bags or transfusion parts and inlet lines) during the initial phases of centrifugation depicting the operation of t'ne collar at the beginning of centrifuge r~n;
FIG. 7 is an elevation view partly cut away 10 depicting the blood bag of FIG. 6, during centrifugation depicting the smoothing effect 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. 10 is a ~ragmentary illustration of a 20 pyramidal-shaped top portion of a blood bag constructed in accordance with 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 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 componlents;
~:' 8 6~5 Description o~ the Pre~erred Embodiment The method of this invention reduces remixing of the separated fractions of particulate material 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 of any lO 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 t~e platelet-rich plasma relatively ~ree 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 cells in the folds in the top of the bag. During handling of the bag and/or 25 removal of the platelet-rich plasma following centrifugation, the entrapped blood cells can be released into the previously separated platelet-rich plasma. Anotber source of contamination of the platelet-rich plasma is the resuspension of the cells 30 from the buffy coat and packed red-cell region during rotor deceleration. The differential force on the blood within the container 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 ancl resuspension of the cells during the final stages of rotor deceleration.
., g 6~95i A furt'ner cause o~ contamination of the platelet-rich plasma by red and white cells is the mixing brought about by the handling of the 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 expressing 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 to~ard the center location of the outlet line at a relatively great speed. The fast moving fluid tends to sweep along cells from the 15 buffy coat: and packed cell interface region.
According to the method of this invention, the purity of the separated blood fractions may be maintained by reducing folding in the top oE the container during centrifugation. One of the causes 20 of 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 total amount of blood drawn may vary according to normal specifications by as 25 much as 10% from a no~mal drawn volume of 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 3~ force, wrinkles.
This wrinkling of the top of 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 by the ~ 10 si~5 placement of the bag in an annular bladder containing a dense solution in order to reduce the volume o~ the swinging bucket or adapter in which tne bag is held.
Alternatively, and preferably, an annular collar, 5 properly slotted to accommodate the outlet line for the bag, may be placed over the top of the bag such that under centrifugal force the plastic bag and its contents will 'nydroform about the underside o~ the collar and thereby maintain a relativ~ly smooth 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 transfer 15 packs or satellite bags is placed at the top o~ the bag. Additional ports and/or lines may be placed at the top of the bag if they are preven~ed from folding over during centrifugation.
In still another alternative, a generally 20 round object may be placed in tbe bottom of 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 free of wrinkles. The volume 25 of this object placed in the bottom of the swinging bucket may be varied according to the volume of blood in the bag. A further method of 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 of the blood bag. If satellite bags are not allowed to press on the top of the bag, there will be less wrin~leing 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 otherwise made to be hollow and capable ~, 11 :; .. , , , :
36~5 of containing the satellite bag. Alternatively, the satellite bags may 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 adapter whicn fits within the swinging bucket of the centri~uge.
The satellite bags then may be placed, i~ desired, 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 sleeve. 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 hereinafter, 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 o~ the contents of th~ bag than having to pull the latter from a rigid cylindrical conta.iner.
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 decrease of the force vectors which cause swirling of the blood in that it reduces the differential radii between the 30 smaller co~partments produced within the bag by the septa. The septa are located to encompass the 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 bott~m of the bag so that ~;, 12 , 6~
they allow the lower part of the bag to have some mixing of the packed 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 the contaminating red and white blood cells componemts 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 hydroforming top regions of the 10 bag. The septa further act to stabilize the handling o~ 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 bag, contamination, as noted earlier, occurs throu~h 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 feeding the 25 outlet line with a funnel or approximation thereof.
To this end, the top of the bag may be formed in pure conical 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-sbaped 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 clescribed, to approximate the funnel.
A blood bag and associated equipment which is particularly adapted to implement the methods of this invention is now described.
Description of the Preferred Embodiment There may be seen with partlcular re~erence to FIG. 1 an exploded view of one form of flexible container or bag 10 which, in use, is positioned in a clam-shell-like spl t sleeve 12. As in the 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 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 1~ and 18 (FI& 3) of flexible, chemically inert to blood and nonporous to fluids, thermoplastic shee~ 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 formed into the ~lat-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 other auxilliary ports 48 is depicted in FIG. 5 for 35 completeness of disclosure. This inlet line 28 is `"? 14 .
.
s 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 pOillt at the location where 5 the tubular conduit 28 joins the bag itself. The purpose of this taper is to afford a generally conical funnel shape to the bag, which enhances laminar flow, and reduces transverse shear at the interface of the separated blood fractions, as the 10 expressed fluid approaches the exit or port for the outlet line 28. By forming this conical exit, as the fluid approaches the exit port, its transverse velocity and shear is reduced, in view of the gradual transition produced by the taper itself. Mo~t lS desirably 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 important since in this range t'ne tangent function approaches high values and requires bags having an unweildly cone length. In a preferred embodiment of this invention the angle of the taper will vary
2; 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
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
3 contents of the bag 10 during deceleration of the ' . " . '' ~ 3 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 fornled from strips of the ssame p]astic used for the bag and the ends of 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 bas 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 o the septa is that 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 interface point between the platelet enriched plasma fraction and the white cells (bu~fy 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 position to some extent 35 based on an average basis and allows some degree of . ~
' ' ' ~ ' ---freedom as to the actual quantity of whole blood that can be placed in the bag. In the usual case the blood placed in a bag may be 450 + 45 ml.
A further limitation on the 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 contact or deform the septa when it moves, during centrifugation, toward the bottom of 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 permit'ed 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-s~aped 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 FIG. 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 for 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 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 (the 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 5 which join together at their bottom and along a diame~rical 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 attempting 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 alo~g 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 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 top portion of the bay lO -- 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 ~illed. 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. 5, is the location at which the blood draw 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, free of crevices, which could 5 otherwise cause entrapment o 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 reference to FIG~ 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 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 centrifuge rotor accelerates, the swinging bucket swings outwardly and upwardly to assume the hori~ontal 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 filled with blood) tends to move (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 of the bas 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.
, 1 19 , ~ ,:
9~5 In the event that the bag contains a lesser amount of blood, the collar 14, as depicted in FIG.
8, automatically assumes a greater radial outward displacement, draping a greater portion of the top of 5 the bag 10 over its U-shaped annulus, still maintaining a relatively smooth surface for the entire top portion of the bag such that there are fewer places left for entrapment of cells in t~e undesired folds. It will be noted in this 10 configuration 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 establishing 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 which is commercially available. The plasma enriched fraction at the top portion of the bag may be expressed. ~his 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 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 may in some cases be slightly more .
....
expensive than that of the double seam version depicted in FIG. l~ In this configuration the top portions 60 of the respective side walls of the 1at blood bag lO are double triangles or pyramidal in 5 shape.
While the blood bag described heretofore has been described as a flat bag formed oE 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 molding techniques such that there are no side seams.
Alternatively, the bag may be constructed to be of relatively rigid or semirigid material having internal se~ta. In this eventuality, there is less 15 possibility 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 substitute for the utilization of internal septa, there 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 effectively as internal septa) to reduce the deceleration effect 3~ or swirling during deceleration. The vertical fins are depicted as having only a small radial dimension and as only four in number. The radial dimension may be increasecl 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 us2d.
. ~ . .
~ .
.. . .
.
. , .
A further alternative embodiment of the invention is depicted in FIG. 13 which is an alternative structure of the invention in which satellite bags such as those connected to the satellite line of FIG. 5 may be placed in an envelope which is wrapped around in an annulus which may be provided for between the exterior or periphery 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. 1) of the collar 14. In still another alternative embodiment, this annular space 74 may be used fox 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 buffy coat 78j 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 equally 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.
The upward dimension of the septa is such that the septa will extend to a point above the normal interface point between the platelet enriched plasma fraction and the white cells (bu~fy 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 position to some extent 35 based on an average basis and allows some degree of . ~
' ' ' ~ ' ---freedom as to the actual quantity of whole blood that can be placed in the bag. In the usual case the blood placed in a bag may be 450 + 45 ml.
A further limitation on the 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 contact or deform the septa when it moves, during centrifugation, toward the bottom of 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 permit'ed 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-s~aped 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 FIG. 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 for 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 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 (the 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 5 which join together at their bottom and along a diame~rical 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 attempting 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 alo~g 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 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 top portion of the bay lO -- 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 ~illed. 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. 5, is the location at which the blood draw 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, free of crevices, which could 5 otherwise cause entrapment o 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 reference to FIG~ 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 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 centrifuge rotor accelerates, the swinging bucket swings outwardly and upwardly to assume the hori~ontal 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 filled with blood) tends to move (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 of the bas 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.
, 1 19 , ~ ,:
9~5 In the event that the bag contains a lesser amount of blood, the collar 14, as depicted in FIG.
8, automatically assumes a greater radial outward displacement, draping a greater portion of the top of 5 the bag 10 over its U-shaped annulus, still maintaining a relatively smooth surface for the entire top portion of the bag such that there are fewer places left for entrapment of cells in t~e undesired folds. It will be noted in this 10 configuration 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 establishing 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 which is commercially available. The plasma enriched fraction at the top portion of the bag may be expressed. ~his 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 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 may in some cases be slightly more .
....
expensive than that of the double seam version depicted in FIG. l~ In this configuration the top portions 60 of the respective side walls of the 1at blood bag lO are double triangles or pyramidal in 5 shape.
While the blood bag described heretofore has been described as a flat bag formed oE 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 molding techniques such that there are no side seams.
Alternatively, the bag may be constructed to be of relatively rigid or semirigid material having internal se~ta. In this eventuality, there is less 15 possibility 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 substitute for the utilization of internal septa, there 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 effectively as internal septa) to reduce the deceleration effect 3~ or swirling during deceleration. The vertical fins are depicted as having only a small radial dimension and as only four in number. The radial dimension may be increasecl 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 us2d.
. ~ . .
~ .
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A further alternative embodiment of the invention is depicted in FIG. 13 which is an alternative structure of the invention in which satellite bags such as those connected to the satellite line of FIG. 5 may be placed in an envelope which is wrapped around in an annulus which may be provided for between the exterior or periphery 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. 1) of the collar 14. In still another alternative embodiment, this annular space 74 may be used fox 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 buffy coat 78j 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 equally 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.
Claims (7)
1. In a sealed, flexible thermoplastic blood centrifugation container having side wall sections with laminate edge seals and longitudinal axis, two different portions of said edge seals being generally parallel to said longitudinal axis, and a first tubular conduit means sealed between said wall sections, communicating with the interior of said container and intersecting said longitudinal axis, the improvement wherein:
said container includes a septum, defined by a first sheet of a flexible thermoplastic, having ends joined to opposite said side wall sections along laminate seals which are generally parallel to said longitudinal axis, said septum being positioned longitu-dinally only in the mid portion of said container in the region of said different portions with the top of said septum extending to a point 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.
said container includes a septum, defined by a first sheet of a flexible thermoplastic, having ends joined to opposite said side wall sections along laminate seals which are generally parallel to said longitudinal axis, said septum being positioned longitu-dinally only in the mid portion of said container in the region of said different portions with the top of said septum extending to a point 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.
2. A storage container according to Claim 1 wherein the edge seals are tapered from said different portions to said first conduit means.
3. A container according to Claim 2 wherein the taper angle between said edge seals lies between 25°
and 160°, thereby to provide a generally conical container top.
and 160°, thereby to provide a generally conical container top.
4. A container according to Claim 3 wherein said taper angle is about 75°.
5. A container according to any one of Claim 1, Claim 2 and Claim 4 wherein said septum is defined by first and second sheets 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 seals generally parallel to said longitudinal axis.
6. A container according to Claim 2 or Claim 4 wherein the upper portion of said side wall sections in the region of taper are double pyramidal shaped and their edges joined with an additional pair of laminate edge seals so that the taper portion of said container approximates a cone when filled.
7. 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 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 reduce swirling of said particulate material during centrifuge deceleration.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000418558A CA1161003A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
| CA000418559A CA1161004A (en) | 1979-09-10 | 1982-12-23 | Method and apparatus for centrifugal separation |
Applications Claiming Priority (2)
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1150695A true CA1150695A (en) | 1983-07-26 |
Family
ID=22117719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000359581A Expired CA1150695A (en) | 1979-09-10 | 1980-09-04 | Method and apparatus for centrifugal separation |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4413771A (en) |
| EP (1) | EP0025587A1 (en) |
| JP (1) | JPS5646464A (en) |
| CA (1) | CA1150695A (en) |
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| JPS5915951U (en) * | 1982-07-21 | 1984-01-31 | 相模ゴム工業株式会社 | urine collection bag |
| US4530691A (en) * | 1983-12-13 | 1985-07-23 | Baxter Travenol Laboratories, Inc. | Centrifuge with movable mandrel |
| EP0165254A1 (en) * | 1983-12-13 | 1985-12-27 | Baxter Travenol Laboratories, Inc. | Flexible disposable centrifuge system |
| US4969882A (en) * | 1985-02-11 | 1990-11-13 | Miles Laboratories, Inc. | Bag for separation and isolation of blood components |
| US4692136A (en) * | 1985-10-11 | 1987-09-08 | Cardiovascular Systems Inc. | Centrifuge |
| US4795419A (en) * | 1985-10-11 | 1989-01-03 | Kardiothor, Inc. | Centrifuge |
| US4718888A (en) * | 1986-03-10 | 1988-01-12 | Cardiovascular Systems, Inc. | Centrifuge bowl mount |
| US5104526A (en) * | 1987-01-30 | 1992-04-14 | Baxter International Inc. | Centrifugation system having an interface detection system |
| US4940543A (en) * | 1987-01-30 | 1990-07-10 | Baxter International Inc. | Plasma collection set |
| US5076911A (en) * | 1987-01-30 | 1991-12-31 | Baxter International Inc. | Centrifugation chamber having an interface detection surface |
| US6780333B1 (en) | 1987-01-30 | 2004-08-24 | Baxter International Inc. | Centrifugation pheresis method |
| US4806252A (en) * | 1987-01-30 | 1989-02-21 | Baxter International Inc. | Plasma collection set and method |
| US4834890A (en) * | 1987-01-30 | 1989-05-30 | Baxter International Inc. | Centrifugation pheresis system |
| US4767397A (en) * | 1987-03-09 | 1988-08-30 | Damon Corporation | Apparatus for liquid separation |
| JPH02175065A (en) * | 1988-12-27 | 1990-07-06 | Asahi Tec Corp | Tilting casting method using sand mold |
| US5102407A (en) * | 1990-03-13 | 1992-04-07 | Miles Inc. | Blood separation system |
| JP2584688B2 (en) * | 1990-08-17 | 1997-02-26 | テルモ株式会社 | Liquid separation device and compression device |
| US5154716A (en) * | 1990-11-06 | 1992-10-13 | Miles Inc. | Bottom blood bag separation system |
| US6053856A (en) * | 1995-04-18 | 2000-04-25 | Cobe Laboratories | Tubing set apparatus and method for separation of fluid components |
| US5674173A (en) * | 1995-04-18 | 1997-10-07 | Cobe Laboratories, Inc. | Apparatus for separating particles |
| US5656154A (en) * | 1995-06-07 | 1997-08-12 | Organ, Inc. | Method and apparatus for separating a fluid into components and for washing a material |
| US5736683A (en) * | 1996-03-15 | 1998-04-07 | Kliklok Corporation | Multiple hopper weighing and transfer system |
| US6334842B1 (en) | 1999-03-16 | 2002-01-01 | Gambro, Inc. | Centrifugal separation apparatus and method for separating fluid components |
| US6354986B1 (en) | 2000-02-16 | 2002-03-12 | Gambro, Inc. | Reverse-flow chamber purging during centrifugal separation |
| US6629918B2 (en) | 2001-05-21 | 2003-10-07 | Carlos G. Mesa | Centrifuge adapter |
| US8980568B2 (en) | 2001-10-11 | 2015-03-17 | Aviva Biosciences Corporation | Methods and compositions for detecting non-hematopoietic cells from a blood sample |
| US8986944B2 (en) * | 2001-10-11 | 2015-03-24 | Aviva Biosciences Corporation | Methods and compositions for separating rare cells from fluid samples |
| WO2003066457A2 (en) * | 2002-02-07 | 2003-08-14 | Scholle Corporation | An internal brace for a standup flexible container |
| DE60331794D1 (en) | 2002-04-16 | 2010-04-29 | Caridianbct Inc | Process for processing blood components |
| US7491263B2 (en) | 2004-04-05 | 2009-02-17 | Technology Innovation, Llc | Storage assembly |
| US7442178B2 (en) | 2005-03-09 | 2008-10-28 | Jacques Chammas | Automated system and method for blood components separation and processing |
| CA2657621A1 (en) | 2006-07-14 | 2008-01-17 | Aviva Biosciences Corporation | Methods and compositions for detecting rare cells from a biological sample |
| US8535591B2 (en) * | 2006-11-03 | 2013-09-17 | Green Materials, Llc | Process for preparing biodegradable articles |
| WO2010137884A2 (en) * | 2009-05-27 | 2010-12-02 | (주)차바이오메드 | Centrifugal separation method, centrifugal separation apparatus, and bag for centrifugal separation |
| EP2386283A1 (en) * | 2010-05-10 | 2011-11-16 | B. Braun Melsungen AG | Filling |
| EP2956187B1 (en) | 2013-02-18 | 2017-11-01 | Terumo BCT, Inc. | System for blood separation with a separation chamber having an internal gravity valve |
| CN111909283B (en) * | 2020-08-10 | 2022-05-13 | 新疆金正生物科技有限公司 | Desert algae polysaccharide's extraction facilities |
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| US1372893A (en) * | 1918-12-16 | 1921-03-29 | William H Miller | Hot-water bottle |
| US1725291A (en) * | 1924-01-21 | 1929-08-20 | Moore Inventions Corp | Packing for fragile articles |
| US2036987A (en) * | 1933-08-24 | 1936-04-07 | Nelson Corp | Container for heavy bulk materials |
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| US2542294A (en) * | 1947-12-02 | 1951-02-20 | Lillius E Smith | Icecap and method of making same |
| US2808200A (en) * | 1955-03-07 | 1957-10-01 | Edgar E Wishaw | Separator |
| US3074402A (en) * | 1960-01-04 | 1963-01-22 | Baxter Laboratories Inc | Blood handling equipment |
| US3288348A (en) * | 1964-03-23 | 1966-11-29 | Waldorf Paper Prod Co | Carton blank |
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| US3841838A (en) * | 1969-07-30 | 1974-10-15 | Rohe Scientific Corp | Centrifuge cups for automatic chemical analyzer |
| FR2058578A5 (en) * | 1969-09-17 | 1971-05-28 | Medicoplast Labor | |
| US3674197A (en) * | 1970-09-08 | 1972-07-04 | Sorvall Inc Ivan | Washing means for flexible bags in split enclosures |
| US3750645A (en) * | 1970-10-20 | 1973-08-07 | Becton Dickinson Co | Method of collecting blood and separating cellular components thereof |
| DE2142737C3 (en) * | 1971-08-26 | 1974-01-31 | Heraeus-Christ Gmbh, 3360 Osterode | Swivel beaker for centrifuging blood bags |
| DE2225532A1 (en) * | 1972-05-26 | 1973-12-06 | Biotest Serum Institut Gmbh | METHOD OF CENTRIFUGATING BAGS FOR BLOOD AND BLOOD DERIVATIVES AND SUPPORT BAGS FOR ITS CARRIAGE |
| US4059108A (en) * | 1974-08-15 | 1977-11-22 | Haemonetics Corporation | Process for pheresis procedure and disposable pheresis bowl therefor |
| CA1074273A (en) * | 1976-05-06 | 1980-03-25 | Sherwood Medical Industries Inc. | Phase separation device |
| US4048994A (en) * | 1976-08-24 | 1977-09-20 | Lo Liu Ying P | Self-inflating liquid container for keeping I.V. fluid or blood plasma |
| US4127155A (en) * | 1976-11-15 | 1978-11-28 | Hydorn Dennis H | Waterproof bag with waterproof divider |
| DE2701976A1 (en) * | 1977-01-19 | 1978-07-20 | Heraeus Christ Gmbh | Counter-flow type blood washing centrifuge - uses compressible receptacle of centrally and rotationally symmetrical shape |
| AT381466B (en) * | 1977-03-16 | 1986-10-27 | Ballies Uwe | SEPARATING TUBES FOR CENTRIFUGAL SEPARATION |
| US4213561A (en) * | 1978-08-25 | 1980-07-22 | Baxter Travenol Laboratories, Inc. | Flexible, collapsible container for blood and the like which is free of liquid-trapping folds |
| US4234026A (en) * | 1979-03-05 | 1980-11-18 | Baxter Travenol Laboratories, Inc. | Seal for flexible container |
-
1979
- 1979-09-10 US US06/074,098 patent/US4413771A/en not_active Expired - Lifetime
-
1980
- 1980-09-04 CA CA000359581A patent/CA1150695A/en not_active Expired
- 1980-09-10 EP EP80105410A patent/EP0025587A1/en not_active Withdrawn
- 1980-09-10 JP JP12707880A patent/JPS5646464A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5646464A (en) | 1981-04-27 |
| EP0025587A1 (en) | 1981-03-25 |
| US4413771A (en) | 1983-11-08 |
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