GB2200020A

GB2200020A - Body fluid processing device

Info

Publication number: GB2200020A
Application number: GB08729300A
Authority: GB
Inventors: Andrew Gunn; Ian David Cameron
Original assignee: Individual
Current assignee: Individual
Priority date: 1986-12-17
Filing date: 1987-12-16
Publication date: 1988-07-20
Anticipated expiration: 2007-12-16
Also published as: GB8729300D0; GB2200020B; GB8630102D0

Abstract

A device 1 suitable for use in the ultra-violet irradiation of a fluid such as blood or a fraction thereof comprises a vessel 2 having an inlet 3 and an outlet 5 and a passage means 8 extending therebetween. The said passage means 8 has wall means substantially transparent to ultra-violet irradiation, and at least one irradiation zone 10 extending along and in substantially direct proximity to the wall means, and at least one mixing zone 11, formed and arranged for thoroughly mixing fluid passing therethrough so as to bring substantially the whole of it into a said irradiation zone 10 during passage between the inlet 3 and outlet 5. In use of the device 1 substantially the whole of a body of fluid passed through the vessel 2 may be exposed to a similar substantial level of u.v. irradiation. The device is used in a method of inactivation of micro-organisms and/or lymphocytes in a fluid by irradiating it with u.v. radiation. <IMAGE>

Description

BODY FLUID PROCESSING DEVICE The present invention relates to the treatment of body fluids and fractions thereof to inactivate selected components, e.g. lymphocytes and micro-organisms, including viruses and the like in human blood and in particular to a device suitable for use in such a procedure.

Conventionally inactivation of lymphocytes in human blood is generally effected by administration of immuno-suppressive drugs to the patient. This procedure involves however serious risks to the patient due to the various adverse and often severe side effects of such drugs. Whilst various procedures for extracorporeal treatment of blood have been previously proposed these do not produce complete inactivation of the lymphocyte population and/or employ apparatus which is relatively cumbersome, expensive and/or impractical to operate.

In the case of contaminating micro-organisms such as bacteria and viruses, various treatments have been proposed including for example, extended incubation at high temperatures and microwave irradiation. These are slow and/or require relatively expensive apparatus though as well as stringent safety precautions.

It is an object of the present invention to avoid or minimize one or more of the above disadvantages.

The present invention provides a device suitable for use in the ultra-violet irradiation of a body fluid or a fraction thereof containing lymphocytes and/or micro-organisms which device comprises a vessel having an inlet and an outlet and a passage means extending therebetween, said passage means having wall means substantially transparent to ultra-violet irradiation, said passage means containing at least one irradiation zone extending along and in substantially direct proximity to said wall means, and at least one mixing zone formed and arranged for thoroughly mixing a said fluid passing therethrough so as to bring substantially the whole of the fluid or fraction thereof into a said irradiation zone during passage between said inlet and said outlet, whereby in use of the device substantially the whole of a body of said fluid or fraction thereof passed through said vessel may be exposed to a similar substantial level of irradiation.

In one preferred form of the invention the vessel has between said inlet and outlet, serially and alternately arranged, a plurality of mixing chambers and irradiation zones, each said irradiation zone being constituted by a large plurality of small bore passages extending in generally side-by-side relation between adjoining mixing chambers, said small-bore passages having wall means substantially transparent to ultra-violet irradiation.

In another preferred form of the invention the vessel has, between said inlet and outlet, radially inwardly of a generally annular radially outer irradiation zone, a static flow mixing means.

Conveniently there is used a static flow mixing means in the form of an elongate screwthreaded member having alternate segments of opposite handed screwthread.

Preferably there is used a static flow mixing means of the interfacial surface generator type whereby the fluid is driven through said generator which divides the inlet fluid stream into a plurality of substreams, then reoriented and recombined the substreams into a main stream, the process being repeated until a desired degree of mixing has been achieved. An improved form of such a mixing means is described in Patent Publication No. 2018609A which document also mentions other publications relating to such mixers.

In a further aspect the present invention provides a method of inactivating lymphocytes and/or micro-organisms in a body fluid or fraction thereof comprising the steps of irradiating the fluid or fraction thereof with ultra-violet radiation whilst passing it through a device of the invention.

Thus by means of the present invention it is possible to process blood or other body fluids so as to inactivate the lymphocytes or micro-organisms contained therein in a simple and economic manner.

The abovementioned passage wall means of the device at least may be made of various u.v.-transparent materials including for example silica and other u.v.-transparent glasses such as those available under the Trade Names Spectrosil and Vitreosil; silicones; cellulose products such as Cellophane (Trade Name); and plastics materials including polyethylene, polyvinylchloride and fluorinated polyalkenes such as polytetrafluoroethylene (PTFE) and fluorinated-ethenepropene (FEP).

Further preferred features and advantages of the present invention will appear from the following detailed description given by way of example of a preferred embodiment illustrated with reference to the accompanying drawings in which: Fig. 1 is a horizontal section through a device of the invention.

Fig. 2 is a transverse vertical section through the device of Fig. 1 on an enlarged scale; Fig. 3 is a corresponding view of a modified embodiment of the same general type as that of Fig. 2; and Fig. 4 is a longitudinal section through another embodiment using a static mixer device (not sectioned).

Fig. 1 shows a device 1 of the invention comprising a vessel 2 having a first end 2a with an inlet 3 and a second end 4 with an outlet 5. As may be seen in Fig. 2 the vessel 2 has a generally flat body with first and second face walls 6, 7 between which extend, from the inlet 3 to the outlet 5, fluid passage means 8 in the form of serially alternating sets 9 of parallel small bore passages 10 and mixing chambers 11 which extend across the width of the vessel 2.

The first face. wall 6 at least is made of u.v.-transparent material selected from one of those mentioned above so that u.v. radiation from a suitable u.v. light source 12 can pass therethrough tb the interior of the small bore passages 10 thereby to irradiate the blood flow 13 passing therethrough. The small bore passages have a diameter of approximately two millimetres or less down to capillary size so as to allow a substantially. free flow of blood therethrough whilst at the same time providing for irradiation.of a substantial part of the contents thereof.

Nevertheless due to the substantially high absoprtion rate of u.v. radiation by blood cells, especially at the preferred wave length of 254nm, it is necessary to provide the mixing chambers 11 so as to perturb the axial fluid flow within the small bore passages thereby ensuring as far as possible that different parts of the fluid flow in proximity to the side walls 14 of the small bore passages 10 in the different sets of passages 9 thereby to ensure as far as possible that the whole of lymphocytes population is subjected to an inactivating dose level of u.v. radiation. Naturally if both the upper and lower face walls are of a u.v.

transmitting material then a suitable u.v. source can be provided at both sides of the vessel 2 thereby to maximize the interior volume of the small bore passages 10 receiving a high level of u.v. radiation.

The vessel may be manufactured by any suitable means. Thus for example the vessel could be manufactured from a generally flat upper sheet 15 welded 16 by suitable means (e.g. ultrasonic welding) to a lower sheet 17 on which are provided a peripheral wall 18 and a plurality of upstanding ribs 19 which define the small bore passages 10.

It will be appreciated that various modifications may be made to the above design without departing from the scope of the present invention. Thus for example, the vessel could be made in the form of an annular sheet with an axially disposed u.v. source or, as shown in Fig. 3, with generally channel-form wall means 6a allowing increased u.v.

irradiation simultaneously from two or more spaced apart u.v. lamps to allow faster treatment.

In the embodiment of Fig. 4 the device is in the form of a single tube 20 in which is mounted a static flow mixing means in the form of an elongate screwthreaded member 21 having alternate segments 22,23 of opposite-handed screwthread, displace#d rotationally from each other by 1800 so as to provide mixing zones 11 at their adjoining ends.

The screwthreaded member 21 generally has a relatively large number of such segments 22,23, e.g. 20 or more.

example 1 - Treatment of Human Blood Venous blood (250ml) is collected from a healthy young adult into a reservoir bag containing tissue culture medium, TC199 (Gibco-Blocult Ltd., Paisley, U.K.) and 2000 units of preservative-free heparin (Weddell Pharmaceuticals Ltd., London, U.K.).

Blood flow (130 ml/min) from the reservoir bag is passed through the vessel of Fig. 1 and irradiated by several UVC-emitting fluorescent tubes (TW30, Phillips Lighting, Croydon, U.K.) extending transversely each across a respective set of small bore passages at a distance of approximately 25mm therefrom. The irradiation chamber is air-cooled with a fan.

Inactivation of the lymphocytes is monitored by determining mitogen stimulated growth using a mitogen selected from PHA, Con A, and PWM and liquid scintillation, volume spectroscopy and electron microscopy as further described in A. Gunn# et al 1983 Immunology 50 477.

Example 2 Using arterio-venous shunts in sheep blood is made to flow extracorporeally through the abovedescribed device for a period up to a few (6) hours daily.

As a consequence within a few days the sheep may show substantial reductions in the peripheral blood lymophocyte count down to wimmúnosuppressivet levels.

With a treatment duration of up to 4 weeks (omitting radiation treatment on Saturdays and Sundays),a substantial reduction in lymphoid tissue at the lymph nodes, spleen, and thymus is achieved.

Claims

1. A device suitable for use in the ultra-violet irradiation of a body fluid or a fraction thereof containing lymphocytes and/or micro-organisms which device comprises a vessel having an inlet and an outlet and a passage means extending therebetween, said passage means having wall means substantially transparent to ultra-violet irradiation, said passage means containing at least one irradiation zone extending along and in substantially direct proximity to said wall means, and at least one mixing zone formed and arranged for thoroughly mixing a said fluid passing therethrough so as to bring substantially the whole of the fluid or fraction thereof into a said irradiation zone during passage between said inlet and said outlet, whereby in use of the device substantially the whole of a body of said fluid or fraction thereof passed through said vessel may be exposed to a similar substantial level of irradiation.

2. A device according to claim 1 wherein the vessel has between said inlet and outlet, serially and alternately arranged, a plurality of mixing chambers and irradiation zones, each said irradiation zone being constituted by a large plurality of small bore passages extending in generally side-by-side relation between adjoining mixing chambers, said small bore passages having wall means substantially transparent to ultra-violet irradiation.

3. A device according to claim 2 wherein said small bore passages have u.v. transparent wall means which are generally channel-form whereby to facilitate u.v.

irradiation of their interior in use of the device simultaneously from laterally spaced apart parallel disposed u.v. radiation sources.

4. A device according to claim 2 or claim 3 wherein said small bore passages have a diameter of not more than 2mm.

5. A device according to claim 4 wherein said small bore passages have diameter of from 0.2 to 1.4mm.

6. A device according to any one of claims 2 to 5 wherein said small bore passages are disposed substantially in a single plane.

7. A device according to claim 1 wherein the vessel has, between said inlet and outlet a generally annular radially outer irradiation zone, and an axially extending static flow mixing means formed and arranged so as to provide said at least one mixing zone.

8. A device according to claim 1 wherein said static flow mixing means is of the interfacial surface generator type in which the generator is formed and arranged so that when the fluid or fraction thereof is driven through the generator, in use of the device, the fluid stream is divided into a plurality of substreams, which are then reoriented and recombined into a main stream, the process being repeated several times until substantially the whole of the fluid or fraction thereof has been brought into said irradiation zone.

9. A device according to claim 8 wherein said generator comprises an elongate screwthreaded member having alternate segments of opposite-handed screwthread.

10. A device according to any one of claims 1 to 9 wherein said ultra-violet transparent wall means are of a material selected from silica, ultra-violet transparent glass, silicone, cellulose, polyethylene, polyvinylchloride and ultra-violet transparent fluorinated polyalkenes.

11. A method of inactivating lymphocytes and/or micro-organisms in a body fluid or fraction thereof which method comprises the steps of irradiating the fluid or fraction thereof with ultra-violet irradiation whilst passing it through a device according to claim 1.

12. A method according to claim 11 wherein said body fluid or fraction thereof is blood or a fraction thereof.

13. A device suitable for use in the ultraviolet irradiation of a body#fluid or a fraction thereof containing lymphocytes and/or micro-organisms which device is substantially as described hereinbefore with particular reference to Figs. 1 and 2, Fig. 3, or Fig. 4, of the accompanying drawings.

14. A method of inactivating lymphocytes and/or micro-organisms in a body fluid or fraction thereof substantially as described hereinbefore with particular reference to Figs. 1 and 2, Fig. 3 or Fig. 4, of the accompanying drawings.