Centrifugal separation chamber

Abstract

Disclosed is a centrifugal separation chamber (100) rotatable about an axis (AR) and having a variable volume separation space (116) therewithin and a port (102) in fluid communication with the volume for filling and emptying the volume, the chamber including a relatively rigid portion (104) proximal to the port which has walls defining a part of the volume and arranged to provide reducing dimensions of the volume toward the port, the chamber further including a flexible portion (106) distal to the port for providing said variable volume, the flexible portion including a mechanical interface (110) for transmitting movement to the flexible portion to cause said variable volume.

Claims

1. A centrifugal separation chamber rotatable about an axis (AR) and having a variable volume separation space therewithin and a port in fluid communication with the volume for filling and emptying the volume, the chamber comprising: a relatively rigid portion proximal to the port which has walls defining a part of the volume and arranged to provide reducing dimensions of the volume toward the port; and a flexible portion distal to the port for providing said variable volume, the flexible portion including a mechanical interface for transmitting movement to the flexible portion to cause said variable volume, wherein the flexible portion is configured to circumferentially bend only at a central region of the flexible portion at the mechanical interface and bend at a peripheral region immediately adjacent a circumferential edge of the flexible portion without bending between the central region and the peripheral region in response to movement of the mechanical interface.

2. The chamber as claimed in claim 1, wherein the rigid portion supports the flexible portion, the rigid portion defining a cross sectional area transverse to the axis which progressively decreases in area closer to the port.

3. The chamber as claimed in claim 1, wherein the rigid portion is shaped to taper toward the port.

4. The chamber as claimed in claim 3, wherein the flexible portion comprises a membrane a) forming a sterile barrier and/or b) operable when forced by the mechanical interface to form a shape approximating to the inner tapering shape of the relatively rigid portion, thereby to reduce the chamber volume.

5. The chamber as claimed in claim 1, wherein the chamber includes an area or areas which is/are furthest away from said axis, and that/those area(s) include a discrete conduit leading to the port or another exit of the chamber.

6. The chamber as claimed in claim 1, wherein the rigid portion includes a rotatable seal adjacent the port for allowing rotation of the chamber at the same time as a fluid tight connection to a stationary fluid conduit.

7. The chamber as claimed in claim 1, wherein the rigid portion and the flexible portion are held together in a fluid tight manner by means of a clamping ring for compressing the flexible member against the rigid portion and having complementary formations which clamp the flexible element between the clamping ring and the rigid portion in a fluid tight manner.

8. The chamber as claimed in claim 1, wherein, the flexible portion is a formed from an elastomer, selected from: Natural polyisoprene-cis-1,4-polyisoprene natural rubber (NR) and trans-1,4-polyisoprene gutta-percha; Synthetic polyisoprene (IR for isoprene rubber); Polybutadiene (BR for butadiene rubber); Chloroprene rubber (CR), polychloroprene; Butyl rubber (copolymer of isobutylene and isoprene, IIR); Halogenated butyl rubbers (chloro butyl rubber: CIIR; bromo butyl rubber: BIIR); Styrene-butadiene Rubber (copolymer of styrene and butadiene, SBR); Nitrile rubber (copolymer of butadiene and acrylonitrile, NBR); Hydrogenated Nitrile Rubbers (HNBR); EPM (ethylene propylene rubber, a copolymer of ethylene and propylene); EPDM rubber (ethylene propylene diene rubber, a terpolymer of ethylene, propylene and a diene-component); Epichlorohydrin rubber (ECO); Polyacrylic rubber (ACM, ABR); Silicone rubber (SI, Q, VMQ); Fluorosilicone Rubber (FVMQ); Fluoroelastomers (FKM, and FEPM); Perfluoroelastomers (FFKM); Polyether block amides (PEBA); Chlorosulfonated polyethylene (CSM), (Hypalon); Ethylene-vinyl acetate (EVA), and composites or combinations thereof.

9. The chamber as claimed in claim 1, wherein the rigid portion is formed from a plastics moulded material, selected from a transparent or translucent plastics.

10. A biological centrifugal separation system comprising: a separation chamber as claimed in claim 1; a chamber rotation mechanism for spinning the chamber at a sufficient rotational velocity to separate biological components held in the chamber in use; and a drive for transmitting movement having a linear component to the separation chamber via said mechanical interface to cause said varying volume.

11. The system as claimed in claim 10, wherein the drive comprises a mechanical, electrical, pneumatic or hydraulic actuator, or combinations thereof.

12. The system as claimed in claim 10, wherein the drive comprises a mechanical actuator including a rack held to said interface, the rack being in operative association with a pinion rotatable in use to move the rack and to thereby move the flexible portion to accurately change the separation volume.

13. A method for the separation of a biological fluid into its components, wherein said method comprises: a) transferring a biological fluid from a container into the separation volume of the separation chamber of the system of claim 10 by moving said flexible portion; b) operating said chamber rotation mechanism to rotate the separation chamber at a speed suitable for centrifugal separation of the biological fluid within the separation volume to obtain one or more separated components of said biological fluid; c) further transferring the or each separated component from said separation volume into one or more output containers by selective opening of one or more valves, wherein the transferring step and further transferring step are effected by changing the volume of the separating volume by moving the flexible portion of the chamber in turn by means of the mechanical interface connected to the flexible portion.

14. The method as claimed in claim 13, wherein said biological fluid is blood or a liquid cell culture.

15. The method as claimed in claim 13, wherein the one or more components include one or more of plasma, stem cells and red blood cells.

16. The chamber as claimed in claim 1, wherein the flexible portion is secured to the relatively rigid portion at the peripheral region of the flexible portion.

17. The chamber as claimed in claim 3, wherein the rigid portion has a cone shape or pyramid shape.

18. The system as claimed in claim 9, wherein the plastics moulded material comprises one or more of polyethylene terephthalate (PETE or PET), polyethylene (PE), polyvinyl Chloride (PVC), polypropylene (PP), polystyrene (PS), polylactic acid (PLA), polycarbonate (PC), acrylic (PMMA), or composites or combinations thereof.

19. The system as claimed in claim 12, wherein the pinion is driven by an electric stepper motor.

20. The chamber as claimed in claim 1, wherein the flexible portion is absent any circumferential bend between the central region and the peripheral region.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention will be further described by way of example with reference to the accompanying drawings, wherein:

(2) FIG. 1 shows a pictorial view of one embodiment of a variable volume separation system;

(3) FIGS. 2a, 2b and 2c show a schematic section through the separation chamber illustrated in FIG. 1; and

(4) FIG. 3 shows a pictorial view another embodiment of a separation chamber.

(5) Referring to FIG. 1 there is shown a separation system 10, which in practice would be used in the same manner as described in EP0912250, for example replacing the components shown in FIG. 3 of that disclosure. Thus, the system includes a fluid supply container 12 such as a blood bag, one or more fluid output containers 14, interconnecting tubing 16, a switching valve 18 and a centrifugal separating chamber 100 fluidically connected to the containers 12 or 14 selectively via the switching valve 18.

(6) That arrangement is generally known, but the construction of the separating chamber assembly 100 illustrated is novel and comprises a rigid hollow upper portion 104, having an inner area which tapers upwardly, formed in this instance, as a truncated hollow cylindrical cone and having a smooth internal transition into a port 102 at a neck portion. The neck portion includes a rotatable fluid coupling 103, for connecting to the stationary tubing 16 for said fluidic connection, and allowing the assembly 100 to rotate. A lower flexible portion 106 in this instance in the form of an elastomeric flexible membrane element is clamped to the upper portion 104 in a fluid tight manner, at a lower periphery 114 of the upper portion 104 by a clamping ring 108 which compresses a lip of the flexible membrane between the ring 108 and the lower periphery 114. The ring 108 is held to the lower periphery by means of complementary snap-fit fastenings 112.

(7) The flexible member 106 extends across the periphery 114 to close the volume formed by the upper portion 104, and includes a mechanical interface 110 which allows pushing and pulling force to be exerted on the membrane, but allowing also rotation of the chamber 100 at the same time about an axis AR. In this case the interface is a simple internal annulus. In this instance, a non-rotatable connecting rod 122 having a head which is accommodated inside the annulus is connected to a rack and pinion drive 120 for said pushing and pulling. The connecting rod and drive 120 are not part of the chamber assembly 100.

(8) FIGS. 2a, 2b and 2c show schematically, the chamber assembly in three different configurations. In FIG. 2a the membrane 106 is in a lowered condition, meaning that the volume 116 of the chamber 100 which in use is spun to separate constituents of fluids within it, is maximised. The clamping ring 108 and alternative fastening means 112 are more clearly visible in this illustration, clamping the membrane 106 in place at the periphery 114 of the rigid portion 104 of the chamber. In FIG. 2b the membrane 106 has been pushed upwardly in the direction if arrow F via the mechanical interface 110. In this condition the volume 116 of the chamber is reduced compared to that shown in FIG. 2a. In FIG. 2c, the membrane 106 has been pushed even further in the direction of arrow F to reduce further the volume 116 in the chamber 100.

(9) In use the chamber will start a process in the condition shown in FIG. 2c, and then the membrane is moved progressively to the position shown in FIG. 2b and then into the position sown in FIG. 2a, by means of an actuator acting on the mechanical interface 110 in a direction opposite to the arrow F, so that fluid is drawn into the volume 116 from the supply container 12 via the port 102. The chamber is spun, and separated constituents and then forced out of the chamber in generally distinct fractions into one or more fraction collection output containers 14 via the port 102 following a route selected via valve 18, all as a result of movement of the membrane under the influence of forces exerted by an actuator, this time, acting in the direction of arrow F. Advantageously the membrane can, if needed conform to the exact shape of an inner wall 118 (FIG. 2c) of the upper portion 104 such that virtually all the constituents can be expelled from the separation chamber 100. And further, the membrane will push against a lowermost portion of the said inner wall first meaning that a gradual, non-turbulent, and low shear complete emptying of the chamber constituents is possible.

(10) FIG. 3 shows an alternative chamber arrangement 200 with any components similar to the components of the chamber shown in FIG. 1 having the same last two reference digits, and not necessarily described again. The chamber 200 is pyramidal in shape, in this case a generally tetrahedron shape with a triangular base. However, to aid the concentration, and extraction of cells within a variable separation volume 216 the chamber faces are convex, resulting in relatively narrow and extended extremity areas 222 where the faces meet and at which cells settle and stratify during centrifugation. The extended areas 222 are internally curved to provide a smooth transition from one face of the pyramid to the other. At these areas 222, conduits 230 providing discrete fluid channels extending from those extremities 222 to a discrete exit port 203. These conduits 230 are provided to exact the heaviest constituents of the separated fluid first, for example when separating cells from a cell culture. The generally smooth internal surfaces of the chamber volume 216 together with a flexible membrane 206 operable in the same manner as described above provide for low shear, gentle manipulation of cells where after centrifugal cell separation is employed. Dead volume in the chamber is to reduced and purity and better separation of cells collected is enhanced, because the cell are concentrated in one area (222) as they are removed, sequentially, if different cell types are to be collected. It will be appreciated that the fewer or more then the three extremities 222 illustrated may be utilised, but three appears to be the most suitable number because two extremities induces vibrations in use, and more than three extremities increases dead volume.

(11) Whilst embodiments of the invention have been described above, to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods, it will be apparent that additions to, omissions from and variants of particular features of the embodiments are possible. For example, at least the upper portions 104 and 204 of the chambers 100 and 200 are intended to moulded from transparent plastics so that the separation process can be observed by eye, camera or a light sensor, e.g. a UV sensor sensing the amount of UV light passing through the chamber, or an IR sensor for temperature control. However, other manufacturing techniques could be employed, such as sheet material pressing, casting, machining or additive printing, and other materials could be employed, such as sheet metals, ceramics e.g. glass, or composite plastics. The flexible parts 106, 206 of the chambers 100, 200 are intended to be moulded from an elastomer, but could also be formed by cutting from a flexible sheet material.

(12) The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims. Where features are described collectively, those features may be claimed separately without adding to the content of the invention as claimed, and conversely, where features are described separately, their combination in the claims is not intended to add material to the content of the invention as claimed. All patents and patent applications mentioned in the text are hereby incorporated by reference in their entireties, as if they were individually incorporated.