CA1334189C - Centrifugal fluid processing system and method - Google Patents

Centrifugal fluid processing system and method

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Publication number
CA1334189C
CA1334189C CA 613606 CA613606A CA1334189C CA 1334189 C CA1334189 C CA 1334189C CA 613606 CA613606 CA 613606 CA 613606 A CA613606 A CA 613606A CA 1334189 C CA1334189 C CA 1334189C
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Canada
Prior art keywords
fluid
chamber
area
processing
inlet
Prior art date
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Expired - Fee Related
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CA 613606
Other languages
French (fr)
Inventor
T. Michael Dennehey
Joseph C. West, Jr.
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter International Inc
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Baxter International Inc
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Filing date
Publication date
Priority to US25512788A priority Critical
Priority to US07/255,127 priority
Application filed by Baxter International Inc filed Critical Baxter International Inc
Application granted granted Critical
Publication of CA1334189C publication Critical patent/CA1334189C/en
Anticipated expiration legal-status Critical
Application status is Expired - Fee Related legal-status Critical

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B04CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04BCENTRIFUGES
    • B04B5/00Other centrifuges
    • B04B5/04Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0442Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation

Abstract

A centrifugal processing system and method introduces fluid to be processed into a centrifugation chamber, while directing the fluid away from the region of the chamber where the largest centrifugal (or "G") forces exist. The fluid is also conveyed into the force field as a generally uniform stream having reduced turbulence or being essentially free of turbulence. The system and method thereby establish, upon the entry of a high velocity fluid stream into the centrifugal field, non-turbulent and uniform flow conditions conducive to effective separation. The system and method also direct the fluid in a way the maximizes the effective surface area of the centrifugation chamber for separation. Effective separation can thereby be achieved at high inlet flow rates.

Description

13~4189 CENTRIFUGAL FLUID PROCESSING SYSTEM AND METHOD

Field ~f the Invention 5The invention generally relates to systems and methods for separating fluids by centrifugation.
More particularly, the invention relates to the cen-trifugation of large volumes of fluids at relatively high flow rates. In this respect, the invention also 10relates to systems and methods particularly well - suited for the processing of cultured cells and super-natant, such as in the fields of biotechnology and adoptive immunotherapy.
Backaround of the Invention 15Many fluid processing techniaues entail the centrifugation of large volumes of fluids. To mini-mize processing times, these techniques often require the use of relatively high flow rates. Increasingly, such techniques are being used in the medical field.
20For example, in the areas of biotechnology and adoptive immunotherapy, it is necessary to process relatively large volumes of cultured cellular products by centrifugation. Through centrifugation, cultured cells are separated from the supernatant for the pur-25pose of replacing/exchanging the culture medium; or for providing a cell-free supernatant for the subse-quent collection of antibodies or for subsequent use as an additive to culture medium; or for the collec-tion of concentrated cellular product.
In the area of adoptive immunotherapy, it has been possible to process between 10 to 50 liters of cultured LAK (Limphokine Activated Killer) cells at a rate of 175 ml/min using conventional centrifugation techniques and devices previously used in whole blood processing. However, in the processing of TIL (Tumor Infiltrating Lymphocytes), the volume of cultured cells that must be processed is increased by an order of magnitude to approximately 100 to 400 liters. Con-ventional blood processing techniques and devices can-not effectively deal with these large fluid volumes and the attendant need to increase the processing rates.
Purthermore, the necessarily high inlet flow rates can lead to confused, turbulent flow conditions within the centrifugation chamber. These flow condi-tions are not desir~able, because they can interfere with sedimentation and separation within the centrif-ugal force field. Thus, despite the high inlet flow rates, the overall effectiveness and efficiency of the process suffers.
High inlet flow rates and resulting con-fused, turbulent flow conditions can also result in a non-uniform distribution of the fluid within the cen-trifugation chamber.
Often, then, it is necessary to reduce the inlet flow rate below the desired amount in the inter-est of obtaining the flow conditions within the pro-cessing chamber conducive to optimal separation.
Summarv of the Invention The invention provides systems and methods for centrifugally processing large volumes of fluid at relatively high flow rates without sacrificing separa-tion efficiencies or damaging the end product.
In one aspect, the invention provides a cen-trifugal processing system and method in which a cen-trifugal force field is developed within a chamber.
As the fluid to be processed is introduced into the chamber, it is directed away from the region of the chamber where the largest centrifugal (or "G") forces exist. The fluid is also preferably conveyed into the force field in a generally uniform stream. As used herein, the term "generally uniform" describes a flow condition in which turbulence is reduced or eliminated to the fullest extent possible.
In accordance with this aspect of the inven-tion, the system and method establish, upon the entry of high velocity fluid into the centrifugal field, generally uniform flow conditions conducive to effec-tive separation. The system and method also direct the fluid in a way that maximizes the effective sur-- face area of the centrifugation chamber for separa-tion. Effective separation can thereby be achieved at high inlet flow rates.
Preferably, the system and method embodying the features of the invention also create within the chamber a region where the higher density materials collect, while allowing the supernatant to freely flow out of the chamber.
In another aspect of the invention, the cen-trifugation chamber takes the form of a tube or envelope. In this embodiment, a passage is formed within the tube ad~acent to its inlet end. All fluid entering the tube is directed through this passage and into the centrifugal force field. The passage creates a generally uniform stream of fluid having reduced turbulence or being essentially free of turbulence.
This stream is directed and dispensed uniformly into the region of the tube where the least centrifugal forces exist.
Various aspects of the invention are as follows:
A centrifugal chamber for positioning within a rotating field and for centrifugally processing a fluid suspension into component parts, the chamber comprising:
oppositely spaced first and second exterior walls defining a chamber having an interior processing region with an inlet, the first exterior wall, when positioned within the rotating field, being disposed closer to the rotational axis than the second exterior wall to define within the interior processing region a low-g area adjacent the first exterior wall and a high-g area adjacent the second exterior wall, inlet conduit means of a given cross sectional area for conducting the fluid suspension to be processed to the chamber, and wall means forming a fluid receiving area within the inlet of the interior processing region in communication with the inlet conduit means, the fluid receiving area including an interior wall that isolates the fluid receiving area from the interior processing region except for an exit passage that has a cross sectional are greater than the cross sectional area of the inlet conduit means and that extends transversely across the exterior wall for dispensing the fluid suspension conducted by the inlet conduit means only into the low-g area of the processing region in a generally uniform flow free or essentially free of turbulence.
A centrifugal processing system comprising a rotor rotatable about an axis, and a processing chamber carried by the rotor in an arcuate path about the rotational axis, the processing chamber having oppositely spaced first and second 4a l 3341 8~
exterior walls that enclose an interior processing region with an inlet at one arcuate location and an outlet at another accurately spaced location on the rotor, the first exterior wall, when positioned within the rotating field, being disposed closer to the rotational axis than the second exterior wall to define within the interior processing region a low-g area adjacent the first exterior wall and a high-g area adjacent the second exterior wall, inlet conduit means of a given cross sectional area for conducting the fluid suspension to be processed to the processing chamber, and wall means forming a fluid receiving area within the inlet of the processing region in communication with the inlet conduit means, the fluid receiving area including an interior wall that isolates the fluid receiving ~rea from the interior processing region except for an exit passage that has a cross sectional area greater than the cross sectional area of the inlet conduit means and that extends transversely across the first exterior wall for dispensing the fluid suspension conducted by the inlet conduit means only into the low-g area of the processing chamber in a generally uniform flow free or essentially free of turbulence.
A centrifugal processing method for separating the higher density components of a fluid from the lower density components of the fluid comprising the steps of:
providing a chamber having an interior processing region and an inlet, developing a centrifugal force field within the - interior processing region to therein create a low-g area and a high-g area, conveying the fluid to be processed through an inlet path of a given cross sectional area into a receiving area within the inlet to the processing region, the receiving area having an interior wall that isolates the interior processing region from the flow 4b 13341 8q conditions created by conveying the fluid into the receiving area, further conveying the fluid from the receiving area through an exit passage that has a cross sectional area greater than the cross sectional area of the inlet path and that dispenses the fluid in a generally uniform flow free or essentially free of turbulence only into the low-g area of the processing chamber.
Other features and advantages of the lnven-tion will become apparent upon considering the accom-panying drawings, description, and claims.
Brief DescriDtion of the Drawinas Fig. 1 is a schematic side view, fragmented and partially in section, of a centrifugal processing system embodying the features of the invention;
Fig. 2 is a top view of the centrifugal pro-cessing system taken generally along line 2-2 in Fig.
l;
Fig. 3 is an enlarged fragmented top view of the processing tube or envelope of the fluid proces-sing set associated with the system shown in Fig. l;
Fig. 4 is a side view of the processing tube or envelope taken generally along line 4-4 in Fig. 3;
Fig. 5 is an exploded perspective view of the processing tube shown in Fig. 3 showing the asso-ciated flow control means;
Fig. 6 is an enlarged schematic view, frag-mented and broken away in section, of the processing tube or envelope shown in Figs. 3 to S illustrating the flow of fluid through the tube or envelope when it - is in use in a centrlfugal fleld;
~ - Fig. 7 is a greatly enlarged schematic view, fragmented and ln section, of the collection of higher density materials in the tube or envelope shown ln Flg. 6;
Flg. 8 ls a centrifugal fluid processlng system embodylng the features of the invention and lntended to be use ln the harvestlng of cell cultures on a large volume basls; and 1 3341 8q Fig. 9 is an alternate embodiment of a cen-trifugal fluid processing system embodying the fea-tures of the invention.
Descri~tion of the Preferred Embodiments S A centrifugal fluid processing system 10 em-bodying the features of the lnvention is shown in Fig.
1. The system 10 includes a centrifuge 12 and an associated fluid processing æet 14. In the illus-trated and preferred embodiment, the set 14 is dispos-able, intended to be used once and then discarded.
The system 10 can be used to process many different types of fluid. As will become apparent, the system 10 is capable of efficiently processing large volumes of fluid at relatively high flow rates.
At the same time, the system 10 is well adapted to handle special fluids containing living cells or deli-cate organisms, such as blood or cultured cell suspen-sions, both on a clinical basis and an industrial basis. For this reason, the system 10 is particularly well suited for use in the medical field. For this reason, the system 10 will be described as being used in thls particular environment.
The centrifuge 12 can be variously con-structed. However, in the illustrated embodiment, the centrifuge 12 is shown to incorporate the principles of operation disclosed in Adams U. S. Patent No. Re 29,738.
In this arrangement (as best shown in Fig.
1), the centrifuge 12 includes a processing assembly 16 and a rotor assembly 18 each of which independently rotates about the same axis 20. The processing assem-bly 16 is connected to a first drive shaft 22. The rotor assembly 18 is connected to a second drive shaft 28. The second drive shaft is driven via a suitable pulley assembly 24 by a drive motor 26. The first 1 S34 1 8~
drive shaft 22 is driven by a suitable pulley assembly 30 associated with the second drive shaft 28.
The pulley assemblies 24 and 30 are conven-tionally arranged to cause the processing assembly 16 S to rotate in the same direction as and at twice the rotational speed of the rotor assembly 18. Examples of this type of construction are more fully disclosed in Lolachi U. S. Patent 4,113,173.
As can be best seen in Figs. 1 and 2, the processing assembly 16 includes an inner processing area 32. The processing area 32 takes the form of an arcuate slot or channel. The slot 32 can be config-ured in various ways, depending upon the intended use of the system. In the illustrated embodiment (best shown in Fig. 2), the slot 32 is generally equally radially spaced about the rotational axis 20 shared by processing assembly 16 and rotor assembly 18.
With further reference now to Figs. 3 to 5, the fluid processing set 14 includes an envelope or tube 34 defining a hollow interior chamber 36 having an inlet end 38 and an outlet end 40. The tube 34 is intended to be inserted into the processing slot 32 (see Figs. 1 and 2). As will be soon described in greater detail below, the intended centrifugal separa-tion of the processed fluid occurs within the interior chamber 36 of the tube 34 due to centrifugal forces created during rotation of the processing assembly 16.
The tube 34 is can be made from either a flexible or rigid material. When flexible, the tube 34 can be readily fitted into the slot 32 to there conform to the particular configuration of the slot 32. When rigid, the tube 34 would be preformed to match the particular configuration of the slot 32. In the illustrated embodiment, which contemplates use of the system 10 in the medical field, the tube 34 is made from a flexible medical grade plastic material, such a polyvinyl chloride.
As best shown in Fig. 1, the fluid proces-sing set 14 further includes inlet tubing 42 for con-veying fluid into the inlet end 38 of the tube chamber 36 for centrifugal separation. Likewise, the set 14 includes outlet tubing 44 for conveying fluid constit-uents from the outlet end 40 of the tube chamber 36 after processing.
In the illustrated embodiment, there are two inlet tubes 42 and three outlet tubes 44 (see Fig. 3).
Of course, the number of tubes can vary according to the intended use and function of the system 10.
In the illustrated embodiment, the inlet and outlet tubing 42 and 44 are made from flexible medical grade plastic material and are joined to form a mul-tiple lumen umbilicus 46. As best shown in Fig. 1, the umbilicus 46 is suspended from a point above and axially aligned with the rotational axis 20 of the centrifuge 12 by means of a clamp 48 attached to a support arm 50. From this point, the umbilicus 46 extends generally downwardly and radially outwardly, passing against a guide arm 52 carried by the rotor assembly 18. From there, the umbilicus 46 extends generally downwardly and radially inwardly and then upwardly through the hollow center of the drive shaft 22 into the processing assembly 16.
This looping arrangement of the umbilicus 46, coupled with the differing rotational rates of the processing assembly 16 and the rotor assembly 18 as just described, prevents the umbilicus 46 from becom-lng twisted during operation of the centrifuge 12.
The use of rotating seals between the flxed and rotat-ing parts of the system 10 is thereby avoided. How-ever, it should be appreciated that the invention is 133418q applicable for use in other types of centrifugal sys-tems, including those employing rotating seals.
Once the tube 34 is located in the proces-sing area 32 and filled with fluid, the rotation of the processing assembly 16 will create a centrifugal force field F (see Fig. 2) effecting the contents of the tube chamber 36. This force field F will create a "High G Region" 54 and a "Low G Region" 56 within the chamber 36. As shown in Fig. 2, the "High G Re-gion 54" is located adjacent to the outer wall of the chamber 36, where the force field is farthest away from the rotational axis and the contents of the cham-ber 36 are subjected to the highest rotational (or "G") forces. The "Low G Region 56" is located adja-cent to the inner wall of the chamber 36, where the force field is nearer to the rotational axis and the contents of the chamber are subjected to lesser rota-tional (or "G") forces. As best shown in Figs. 6 and 7, higher density materials present in the processed fluid (designated 101 in Figs. 6 and 7) will migrate under the influence of the force field F toward the High G Region 54, leaving the less dense materials and supernatant (designated 115 in Figs. 6 and 7) behind in the Low G Region 56.
To obtained the desired flow rate condi-tions, the fluid to be processed is introduced into the tube chamber 36 using a suitable in line pumping mechanism 58. In the illustrated embodiment (see Fig.
1), the pumping mechanism takes the form of a peris-taltic pump 58 situated upstream of the tube chamber 36.
In Fig. 8, the set 14 as just described is shown particularly configured for use to harvest TIL
cells. In this procedure, cultured TIL cell solution filling approximately 70 to 260 three liter bags 60, each filled with about 1-1/2 liters of æolution, is centrifugally processed to remove the æupernatant and obtain concentrated TIL cells (which presently con-sists of approximately 2 x lOt1 cells occupying a vol-ume which ranges between 220 to 400 ml).
In this arrangement, 5-lead and 10-lead man-ifold sets 62 are used to interconnect the many supply bags 60 to a single inlet line 64. The cultured cell fluid is then conveyed into a reservoir bag 66, using the supply pump 68, and then conducted into the tube 34, using the processing pump 58.
In this arrangement, the tube 34 is approxi-mately 32 inches long and 3 inches wide. The interior surface area of the tube 34 is approximately 200 square inches.
During centrifugation, the TIL cells are separated from the culture medium (which constitutes the supernatant). The supernatant is collected in large volume containers 72. Afterwards, the concen-trated TIL cells are transferred to a collection con-tainer 74 for administration to the patient.
In this and other applications, where rela-tively large volumes of fluid are to be processed, it is desirable to maximize the inlet flow rate of the fluid, as this will shorten the overall processing time. In the case of a TIL procedure, a nominal proc-essing rate of at least 1.5 liters per minute is attained. However, with the system 10 illustrated, it is believed that the processing rate can be increased upwards to about 4 liters per minute. This rate is significantly higher than the nominal processing rates conventionally used for blood processing (about 50 ml/min) or conventionally used for TIL cell harvesting (about 175 ml/min).
Use of these relatively high inlet flow -lo - 1 3341 89 rates can pose processing problems. In particular, such high rates can lead to confused, turbulent flow conditions within the tube chamber 36. These turbulent or otherwise confused, non-unlform flow conditions can interfere with sedimentation and separation within the centrifugal force field F, lowering the overall effec-tiveness and efficiency of the process.
High inlet flow rates and attendant con-fused, turbulent flow conditions can also result in a non-uniform distribution of the fluid within the tube chamber 36. To maximize the effective surface area along which separation occurs, the incoming fluid should preferably enter in the Low G Region 56 as soon as possible after entering the tube 34. The fluid lS components are thereby exposed to the full extent of the centrifugal force field F for the longest period of time. However, high inlet flow rates can spray or disperse the incoming fluid lndiscrlmlnately lnto both the High and Low G Regions 54 and 56 of the tube 34.
This, too, lowers the overall effectiveness and effi-ciency of the process.
To optimize the effectiveness of separa-tion at high inlet flow rates, the invention provides a fluid processing system 10 that includes means 76 located adjacent the inlet end of the tube chamber 36 for directing incoming fluid away from the High G
Region 54 and toward the Low G Region 56 of the cham-ber 36 in a generally uniform flow having reduced tur-bulence or being generally free of turbulence. Pre-ferably, the unlform flow constitutes a relatively thin stream filling the entire effective surface area of the Low G Reglon 56 adjacent to the inlet end of the chamber 36.
In accordance with the invention, the means 76 therefore establishes, upon the entry of high velo-city fluid into the centrifugal field F, the desired flow conditions for effective æeparatlon. The means 76 also directs and dispenses the fluid in a manner that maximizes the effective surface area of the tube chamber 36 for separation. Due to the invention, effective separation can be achieved, even at high in-let flow rates.
The means 76 can be variously constructed.
One embodiment is shown-in Figs. 3 to 5. In this arrangement, the means 76 is part of a port block assembly 78 situated within the inlet end 38 of the tube chamber 36. The assembly 78 lncludes top, bottom, and side walls 80; 81; and 82 defining an open interior 84. The assembly 78 also includes a first end wall 86 closing the adjacent end of the interior 84. One or more inlet ports 88 are formed on this end wall 86. The inlet tubing 42 is attached to these ports 88 to introduce fluid into the open interior 84 of the assembly 78.
In this arrangement, the means 76 comprises a partial second end wall 90 located on the end of the port block assembly 78 opposite to the end wall 86 on which the inlet ports 88 are situated. This partial end wall 90 extends from the top wall 80 toward the bottom wall 81, terminating a short distance therefrom to there define a flow passage 92 communicating with the open interior 84 of the assembly 78. As will be described in greater detail below, fluid introduced into the open interior 84 of the port block assembly 78 (via the inlet ports 88) is directed into the cen-trifugal force field through the flow passage 92.
As best shown in Fig. 4, the port block assembly 78 is situated within the inlet end of the tube chamber 36 with the flow passage 92 extending longitudinally across the entire interior surface of the tube chamber 36 which, in use, becomes the Low G
Region 56.
To assure that the interior surface of the tube 34 becomes the Low G Region 56 when situated within the processing area 32, a guide key 94 is pro-vided on the port block assembly 78 which mates with a groove 96 in the processing area 32 (see Fig 2) when the tube 34 is properly oriented.
The system lO further includes means 98 defining a region 100 for collecting high density ma-terials within the tube chamber 36. In the embodiment shown in Figs. 2 to 5, the means 98 includes a dam assembly 102 situated within the tube chamber 36 down-stream of the port block assembly 78. The dam assem-bly 102 may be variously constructed. In the illus-trated embodiment, the dam assembly 102 is part of another port block assembly as previously described.
The assembly 102 includes top and bottom walls 103/104, side walls 105, and an end wall 106.
In this arrangement, the dam assembly 102 comprises a partial end wall 108, which like the means 76 associated with the port block assembly 78, forms another flow passage 110 through which fluid must pass to exit the tube chamber 36.
The length of the end wall 108 associated with the dam assembly 102 can vary. It can be the same as or different than the end wall 90 of the port block assembly 78, depending upon the nature and type of collection area or areas sought to be established within the tube chamber 36. The sedementation of higher density materials in the region 100 is also effected by the fluid flow rate, the RPM of the cen-trifuge, and the interior thickness of the tube cham-ber 36. These variables can be adjusted to alter the collection characteristics of the tube 34.

It should also be appreciated that multiple dam assemblies of varying lengths and spacing can be used to create multiple separation and sedimentation zones within the tube chamber 36.
As shown in Figs. 6 and 7, and as will be described in greater detail below, the higher density materials (designated 101 in Figs. 6 and 7) migrating toward the High G Region 54 of the chamber 36 will collect within the area 100 bounded by the partial end wall 90 of the port block assembly 78 and the partial end wall 108 of the dam assembly 102.
In the embodiment shown in Figs. 3 to 5, the dam assembly 102 is located in the outlet end 40 of the tube chamber 36, and outlet ports 112 are accord-ingly formed on the end wall 106, as in the port block assembly 78. However, it should be appreciated that the dam assembly 102 can be located within the tube chamber 36 at a location upstream of the outlet end 40 of the chamber 36 (as shown in Fig. 6), in which case the end wall 106 would be free of ports. In this arrangement, a separate port block assembly (not - shown), without a partial end wall, would be used at the outlet end 40 of the tube chamber 36.
The port block assembly 78 and the dam assembly 102 can be made of various materials. In the illustrated embodiment, both are injection molded plastic parts that are located and sealed within the confines of the tube chamber 36 by heat sealing, sol-vent sealing, or similar techniques.
The dimensions of the flow passages 92 and 110 can vary according to the type of fluid being pro-cessed and the flow conditions desired. In the par-ticular embodiment shown in Fig. 8, the flow passages 92 and 110 are each about 3 inches wide (the same width as the associated tube) and about .025 inch in -lS~418q height. The passages 92 and 110 therefore comprises restricted flow passages.
Another embodiment of the means 76 for dir-ecting incoming fluid toward the Low G Region 56 is shown in Fig. 9. In this arrangement, the means 76 takes the form of a ridge 114 formed within the out-side (High G) side of the processing area 32 of the assembly 16. When the tube 34 is positioned within the processing area 32 (as shown in Fig. 7), the ridge 114 presses against the exterior of the outside wall of the tube 34, thereby forming a passage 92 like that formed by the partial end wall 90 of the port block assembly 78. Preferably, a recess 116 is formed in the inside (Low G) side of the processing area 32 ra-dially across from the ridge 114 to facilitate inser-tion and removal of the tube 34 and to better define the passage 92.
As also shown in Fig. 9, the means 98 for defining the collection area 100 for higher density materials can also take the form of a ridge 118 and associated recess 120 formed along the walls of the processing area 32 of the centrifuge 12.
A centrifugal processing method which embod-ies the features of the invention is shown in Figs. 6 and 7. This process will result by the operation of the above described port block assembly 78 and dam assembly 102 when the tube chamber 36 is exposed to the centrifugal field F. However, it should be appre-ciated that the process can be achieved by other means as well.
In this method, as the fluid to be processed is introduced into the centrifugal force field F, it is directed away from the region of the chamber 36 where the largest centrifugal (or "G") forces exist.
Furthermore, the fluid is directed and dispensed into 13341~
the force field as a generally uniform stream (desig-nated by arrows and number 111 in Figs 6 and 7) having reduced turbulence of being essentially free of turbu-lence.
s Referring specifically now to Figs. 6 and 7, incoming fluid entering the port block assembly 78 (via the ports 88) is immediately confined within the open interior 84. Turbulent flow conditions occasioned by the entry of fluid into the chamber 36 (indicated by swirling arrows 113 in Figs 6 and 7) are thereby effectively confined to this interior area 84 and iso-lated from the remainder of the tube chamber 36.
The fluid confined within the interior area 84 is directed by the partial end wall 90 away from the High G Region 54 and out into the tube chamber 36 via the passage 92. By virtue of the shape of the passage 92, the fluid is directed and dispensed in a generally uniform stream 111 extending across the Low G Region 56 of the tube chamber 36.
Optimal conditions for sedimentation and separation are thereby quickly established. As a result, the higher density materials 101 migrate due to the force field F toward the High G Region 54. The remaining supernatant (designated by arrows and number 115 in Figs. 6 and 7) continues to flow uniformly along the Low G Region 56 toward the outlet end 40 of the tube chamber 36.
The process also creates within the chamber 36 a region 100 where the higher density materials 101 collect, while allowing the supernatant 115 to flow freely out of the chamber 36. As can be best seen in Fig. 6, the higher density materials 101 migrating toward the High G Region 54 of the chamber 36 collect within the area 100 bounded by the partial end wall 90 of the port block assembly 78 and the partial end wall 1 334 1 8q 108 of the dam assembly 102. At the same time, the supernatant, which is free of the higher density ma-terials 101, passes through the passage 110 of the dam assembly 102 and exits the outlet end 40 of the tube chamber 36.

A tube 34 embodying the features of the in-vention was used in association with a set as gener-ally shown in Fig. 8 and an Adams-type centrifuge to harvest human red blood cells from a saline suspen-sion. Three runs were conducted.
In the first run, the suspension had an original red blood cell concentration of 1.27 x 107 per ml. This suspension was centrifugally processed through the tube at a flow rate of 1800 ml/min at 1600 RPM. During processing, concentrated red blood cells were collected at processing efficiency of 94.9%.
In the second run, the original suspension concentration was 1.43 x 107 red blood cells per ml.
During centrifugal processing at a flow rate of 1000 ml/min at 1600 RPM, concentrated red blood cells were collected at a processing efficiency of 95.7%.
In the third run, the original suspension concentration was 1.33 x 107 red blood cells per ml.
During centrifugal processing at a flow rate of 1800 ml/min at 1600 RPM, concentrated red blood cells were collected at a processing efficiency of 91.5%.

A tube 34 embodying the features of the in-vention was used in association with a set as genera-lly shown in Fig. 8 and an Adams-type centrifuge to harvest TIL cells from suspension.
During the procedure, 24,559 ml of cultured TIL cell suspension was processed through the tube a flow rates varying between 500 to 1500 ml/min at 1600 -lS3418q RPM. 445 ml of concentrated TIL cells were obtained.
Approximately 564.9 x 10~ TIL cells were contained in the suspension prior to processing. Dur-ing processing, approximately 462.8 x 10~ TIL cells were collected, for a processing efficiency of 82%.
TIL cell viability of 73% was measured prior to processing. TIL cell viability of 73% was measured after processing.
Lytic activity of the TIL cells prior to processing was 5.4%. After processing, the lytic activity was 4.3%, which does not constitute a statistically significant difference.
The foregoing examples clearly illustrate the ability of a processing system made and operated in accordance with the invention to efficiently pro-cess large volumes of cellular suspensions at rela-tively high fluid flow rates. Example 2 further dem-onstrates that processing occurs without biological damage to the cellular components.
Various features of the invention are set forth in the following claims.

Claims (5)

1. A centrifugal chamber for positioning within a rotating field and for centrifugally processing a fluid suspension into component parts, the chamber comprising:
oppositely spaced first and second exterior walls defining a chamber having an interior processing region with an inlet, the first exterior wall, when positioned within the rotating field, being disposed closer to the rotational axis than the second exterior wall to define within the interior processing region a low-g area adjacent the first exterior wall and a high-g area adjacent the second exterior wall, inlet conduit means of a given cross sectional area for conducting the fluid suspension to be processed to the chamber, and wall means forming a fluid receiving area within the inlet of the interior processing region in communication with the inlet conduit means, the fluid receiving area including an interior wall that isolates the fluid receiving area from the interior processing region except for an exit passage that has a cross sectional are greater than the cross sectional area of the inlet conduit means and that extends transversely across the exterior wall for dispensing the fluid suspension conducted by the inlet conduit means only into the low-g area of the processing region in a generally uniform flow free or essentially free of turbulence.
2. The centrifugal chamber according to Claim 1 wherein the first and second exterior walls are interconnected together to form a tubular processing chamber.
3. A centrifugal processing system comprising a rotor rotatable about an axis, and a processing chamber carried by the rotor in an arcuate path about the rotational axis, the processing chamber having oppositely spaced first and second exterior walls that enclose an interior processing region with an inlet at one arcuate location and an outlet at another accurately spaced location on the rotor, the first exterior wall, when positioned within the rotating field, being disposed closer to the rotational axis than the second exterior wall to define within the interior processing region a low-g area adjacent the first exterior wall and a high-g area adjacent the second exterior wall, inlet conduit means of a given cross sectional area for conducting the fluid suspension to be processed to the processing chamber, and wall means forming a fluid receiving area within the inlet of the processing region in communication with the inlet conduit means, the fluid receiving area including an interior wall that isolates the fluid receiving area from the interior processing region except for an exit passage that has a cross sectional area greater than the cross sectional area of the inlet conduit means and that extends transversely across the first exterior wall for dispensing the fluid suspension conducted by the inlet conduit means only into the low-g area of the processing chamber in a generally uniform flow free or essentially free of turbulence.
4. A centrifugal processing method for separating the higher density components of a fluid from the lower density components of the fluid comprising the steps of:
providing a chamber having an interior processing region and an inlet, developing a centrifugal force field within the interior processing region to therein create a low-g area and a high-g area, conveying the fluid to be processed through an inlet path of a given cross sectional area into a receiving area within the inlet to the processing region, the receiving area having an interior wall that isolates the interior processing region from the flow conditions created by conveying the fluid into the receiving area, further conveying the fluid from the receiving area through an exit passage that has a cross sectional area greater than the cross sectional area of the inlet path and that dispenses the fluid in a generally uniform flow free or essentially free of turbulence only into the low-g area of the processing chamber.
5. A centrifugal processing method according to Claim 4, and further including the step of creating within the chamber a region confining the higher density components separated within the centrifugal field while allowing the remaining components of the fluid to flow out of the chamber.
CA 613606 1988-10-07 1989-09-27 Centrifugal fluid processing system and method Expired - Fee Related CA1334189C (en)

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US5656163A (en) * 1987-01-30 1997-08-12 Baxter International Inc. Chamber for use in a rotating field to separate blood components
SE9001196L (en) * 1990-04-02 1991-10-03 Omega Teknik Hb Principle and apparatus at genomstroemningscentifug
IT1251147B (en) * 1991-08-05 1995-05-04 Ivo Panzani multilumen tube for centrifugal separator especially for blood
US6053856A (en) * 1995-04-18 2000-04-25 Cobe Laboratories Tubing set apparatus and method for separation of fluid components
US5792038A (en) * 1996-05-15 1998-08-11 Cobe Laboratories, Inc. Centrifugal separation device for providing a substantially coriolis-free pathway
DE69702979D1 (en) * 1996-05-15 2000-10-05 Gambro Inc A method and apparatus for reducing turbulence in liquid flows
US5904645A (en) * 1996-05-15 1999-05-18 Cobe Laboratories Apparatus for reducing turbulence in fluid flow
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
WO2003089027A2 (en) 2002-04-16 2003-10-30 Gambro, Inc. Blood component processing system, apparatus and method
US9248446B2 (en) 2013-02-18 2016-02-02 Terumo Bct, Inc. System for blood separation with a separation chamber having an internal gravity valve

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US2662687A (en) * 1950-04-01 1953-12-15 Laval Separator Co De Centrifugal separator for cold milk products and the like
US4091989A (en) * 1977-01-04 1978-05-30 Schlutz Charles A Continuous flow fractionation and separation device and method
DE3632500A1 (en) * 1986-09-24 1988-04-07 Fresenius Ag centrifuge arrangement

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DE363120T1 (en) 1990-09-06
DE68910928T2 (en) 1994-06-30
DE68910928D1 (en) 1994-01-05
JP2967280B2 (en) 1999-10-25
EP0363120A2 (en) 1990-04-11
JPH02172546A (en) 1990-07-04
EP0363120A3 (en) 1991-01-23
EP0363120B1 (en) 1993-11-24

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