WO1992020383A1

WO1992020383A1 - System for separating blood components

Info

Publication number: WO1992020383A1
Application number: PCT/GB1992/000941
Authority: WO
Inventors: Robert Gordon Hood
Original assignee: Bio-Flo Limited
Priority date: 1991-05-22
Filing date: 1992-05-22
Publication date: 1992-11-26
Also published as: GB9111028D0

Abstract

A fluid treatment system is described which is particularly suitable for treating blood or a blood derived fluid which comprises fluid delivery means (10) for delivering the fluid to membrane filtration means (16); the membrane filtration means (16) being adapted for treating the fluid to remove a filtrate stream (50) from the fluid; reservoir means (20) connected to the filtration means (16) for receiving a batch of treated fluid; treated fluid discharge means (22) connected to the reservoir means (20) for discharging treated fluid from the reservoir means (20); filtrate discharge means (18, 52) connected to the filtration means (16) for discharging filtrate therefrom; and pressure sensor means (42, 58) for sensing the trans-membrane pressure in the membrane filtration means (16) and controlling the rate of delivery of the fluid by the delivery means (10).

Description

System for separating blood components

The present invention relates to a system for treating a fluid, which is blood or blood-derived fluid in order to remove certain components from the blood; and a process for achieving this. The system is particularly applicable to the plasmapheresis of whole blood withdrawn from a donor, where a plasma stream is separated from a blood stream by means of a membrane filter.

There is a continuous need in the medical field for human blood and blood-derived products. Plasma (which is blood from which cells have been removed) is conventionally required for blood transfusions. Blood cell concentrates are used for the treatment of shock trauma, though such cell concentrates tend to have a short shelf life. Blood is also treated to remove desirable products therefrom, such as factor VIII which is a blood clotting factor used for the treatment of haemophiliacs. Conventionally, blood taken from blood donors is centrifuged in order to remove the cells and produce plasma.

European patenr application 414006 discloses an apparatus for haemapheresis wherein a membrane cross-flow filter is used to separate plasma from cellular components. The treated blood is then returned to the patient. The process disclosed requires the blood to be diluted with saline prior to passage through the cross-flow filter, in order to prevent clogging of the filter. The saline diluent is removed before the blood is recycled to the donor.

The present invention aims to provide a system and corresponding process in which plasmapheresis can be carried out without the need for a diluent in a simple integrated system.

In one aspect of the present invention there is provided a system for treating a fluid, which is blood or blood-derived fluid which comprises:

- fluid delivery means for delivering the fluid to membrane filtration means;

- the membrane filtration means being adapted for treating the fluid to remove a filtrate stream from the fluid;

- reservoir means connected to the filtration means for receiving a batch of treated fluid;

- treated fluid discharge means connected to the reservoir means for discharging treated fluid from the reservoir means;

- filtrate discharge means connected to the filtration means for discharging filtrate therefrom; and

- pressure sensor means for sensing the trans-membrane pressure in the membrane filtration means and conrroiling the rate of delivery of the fluid by the delivery means. The system is particularly intended for the plasmapheresis of blood from a donor in order to provide a plasma stream. (the filtrate) and a cell concentrate stream. The cell concentrate stream may be returned to the patient or may be stored for imminent use in the treatment of shock trauma. In a particularly preferred embodiment, blood is removed from a donor, treated and returned to the donor via a single needle inserted in the donor which is achieved by withdrawing batches of-blood from the patient, passing the blood through the membrane filtration means and storing the treated batch in the reservoir means. When the reservoir is filled to a predetermined level, withdrawal of blood from the donor is ceased and the treated blood returned to the donor through the same needle. Of course, a corresponding two needle system could be used. Usually, batches of 100 to 300ml of blood are withdrawn from the patient at a time, and in total an overall volume of 400 to 600ml of plasma is usually treated in order to minimise any effects on the donor. Thus, from 2 to 6 separate batches of blood will usually be withdrawn, treated and returned to the donor. The removal of small batches of blood in this way also minimises any adverse effects on the donor. On the other hand, the system is operated continuously to treat a certain amount of blood where there is no requirement to return the treated blood to the patient. Usually, the filtration process will be controlled such as to provide equal volumes of cell concentrate and plasma, though generally speaking separation is carried out in the ratio 2:1 to 1:2.

If required, the plasma filtrate stream (or the cell concentrate stream) is subjected to further treatment to remove desired components therefrom. In particular, plasma can be treated to remove factor VIII by further membrane filtration steps or other steps known in the art.

The fluid treatment system itself is designed to form an integrated system, which is automatically controlled and is provided as a transportable unit, for example, for donation and treatment of blood in situ for military requirements.

The fluid delivery means is a peristaltic pump, which removes blood from the patient and delivers it directly or indirectly to the membrane filter. In the case of treatment of previously withdrawn blood or blood-derived fluids, the necessary fluid delivery is achieved by means of gravity.

In one embodiment, the fluid delivery means delivers fluid to a buffer volume container equipped with sensors for controlling the rate of delivery of fluid to the filtration means. The buffer volume may be equipped with level sensor means and also pressure sensor means.

In another embodiment, the buffer volume container and associated level sensor means are emitted and an in-line fluid cushion or damper is coupled to pressure sensor means.

In a further modification of the attenative embodiment the pressure sensor and components at the • outlet of the reservoir means are omitted and the transme brane pressure sensors are located at the inlet and oulet of the filter means.

In a further embodiment the need for pre-flushing the system with saline is avoided by injecting a small volume of anti-coagulant into the line just prior to withdrawing blood. This is sufficient to ^••wet" the membrane and the need for a drainage bag and associated pumps is avoided.

In another aspect of the present invention there is provided a method of treating a fluid, which is blood or blood derived, said method comprising: delivering a volume of said fluid to a membrane filter; treating the fluid to remove a filtrate stream, storing a batch of treated fluid from said filter in a reservoir; discharging said filtrate from said reservoir, discharging said treated fluid from the reservoir, and sensing the pressure across the membrane filter and controlling the rate of delivery of the bluid by the delivery means.

Preferably the method includes collecting the filtrate in a filtrate reservoir.

Preferably the method includes pre-flushing the system with saline and collecting the saline in a separate reservoir.

Alternatively the method includes injecting a small volume of anti-coagulant into the system to wet the filter membrane prior to treating the fluid.

The various lines, volumes, reservoirs and filters are preferably formed of a transparent material which allows visual monitoring of the process; in addition to automatic control means which may be provided. These items are also preferably formed of a sterilisable material and are adapted to be discarded after use to avoid the danger of cross-infection between donors.

The membrane filtration means is usually a hollow fibre cross-flow membrane filtration system, such as that sold for use with the Bio-2000 (trademark) by Bio-Flo Limited, Glasgow, Scotland. The fibres are preferably formed of polypropylene wetted with a surfactant, such as a Pluronic, in order to make the fibres hydrophilic. However, other hydrophilic hollow fibres may also be used. The use of suitable hydrophilic hollow fibres avoids any need to dilute the blood prior to treatment. Downstream of the filter is connected a reservoir means for receiving a batch of treated fluid. This is preferably provided with control sensors, such as level sensors and pressure sensors.

Treated fluid discharge means and filtrate discharge means are provided for discharging the treated fluid and filtrate respectively. These discharge means may be in the form of pumps or may simply be lines which allow controlled discharge, either back to the donor or to suitable storage means.

The pressure sensor means sense the trans-membrane pressure in the membrane filtration system. This is preferably achieved by providing pressure sensors upstream and downstream of the membrane filter. On the assumption that the filtrate pressure is negligible, the trans-membrane pressure is generally obtained by averaging the upstream and downstream pressure elevations above atmospheric pressure. The trans-membrane pressure system operates in a manner as disclosed in applicant's co-pending published International application

The system and process of the present invention enables an integrated system to be provided which is susceptable of automatic computer control, and may treat blood in situ in an economical sterile manner in a short period of time.

The system and process described can also be adapted for use with other treatment means in place of the membrane filter. For example, the membrane filtration means might be replaced with a detoxification column (for example containing activated carbon) or an ion-exchange column for selectively removing toxins or other components from the blood prior to return to the patient. In this case, no filtrate stream is produced but otherwise the fluid is treated in an analogous manner.

An embodiment of the present invention will now be described by way of example only with reference to the accompanying drawings in which

Fig. 1 is a schematic diagram of a plasmapheresis system;

Fig. 2 is a schematic diagram of a first attenative embodiment of Fig. 1 with the first reservoir omitted;

Fig 3 is a schematic diagram of a second attenative embodiment of Fig. 2 with the first reservoir omitted and the trans-membrane pressure senors located at the filter inlet and oulet; and

Fig. 4 is a diagram similar to Fig. 3 with the pre-flushing saline drainage bag omitted.

The blood plasmapheresis system fundamentally comprises a fluid delivery pump 10 in the form of a peristaltic pump, for withdrawing blood from the arm of a donor via a single needle 12, and which delivers blood to a buffer volume 14 connected in turn to a hollow fibre membrane filter 16. The filter separates a plasma filtrate stream which goes to a plasma bag 18 and a cell concentrate stream which is collected in batches in a reservoir 20 and thence is pumped by peristaltic pump 22 back into the patient via the single needle 12.

Immediately after the blood leaves the donor it is mixed with an anti-coagulant (e.g. heparin) from an anti-coagulant bag 24 via an anti-coagulant pump 26. The amount of anti-coagulant added is such as to prevent clotting of the blood in the system, but should not be excessive. The anti-coagulant is passed through line 28 into blood line 30. The blood line 30 is also equipped with a vacuum sensor 32 which monitors any accidental reduced pressure in the line 30. Should a reduced pressure occur, for example due to a collapsed artery, tube or blockage, the system is shut down.

Line 30 passes through peristaltic pump 10 and terminates in buffer volume 14. The buffer volume is equipped with a level sensor 36 and associated level valve 38 which co-operate with the peristaltic pump 10 to maintain a fixed level of blood within the buffer volume 14. A first trans-membrane pressure sensor 42 senses the pressure in the fluid upstream of the membrane filter 16.

Blood passes from the buffer volume 14 via line 44 to the hollow fibre ultrafiltration filter 16. A drainage line controlled by a valve 46 allows for purging of the lines upstream of the filter. The filter 16 comprises a bundle of hollow polypropylene ultrafiltration fibres treated with Pluronic flake to render them hydrophilic. Within the filter, a cross-flow of blood passes through the filters from line 44 to cell concentrate line 48. A plasma filtrate which is passed through the hollow fibre membranes exits the filter through line 50. The filtrate line 50 can either be connected to a drainage bag 52 via valve 4, which is used during initial set up of the system; or via a valve 5 to plasma collection bag 18. The plasma bag is arranged on a weighing scale 54 which shuts down the system when the plasma bag is full.

The concentrated cell stream passes through line 48 to reservoir 20, and is then fed by peristaltic pump 22 through line 56 via valve 2 back to the patient through needle 12. During system set up, the concentrated cell stream may be fed through valve 3 to drainage bag 52 and can then be discarded or used soon thereafter to -treat shock trauma.

Reservoir 20 is provided with various control sensors. High (H) , low (L) and starve (S) are provided for monitoring the level of cell concentrate in the reservoir, a bubble sensor (B) is also included for monitoring the presence of any undesired bubbles in the system. When concentrate reaches the high level H, pump 22 is activated to return the treated blood to the donor. The levels H and L can be varied to vary the batch volume of blood withdrawn in accordance with each donor's physiology etc. The starve(s) level detector detects when the level is below the blood clot filter level. A second trans-membrane pressure sensor 58 senses the pressure downstream of the filter 16. A valve 60 is provided for purging the system and to provide a safety overflow relief which operates in conjunction with a fluid sensor 62.

The system is preferably mounted on an upstanding board where the blood flow can be visually observed. The line, buffer volume, filter, reservoir and other flow components are preferably formed of a transparent material. The arrangement is such that the line 30, buffer volume 14, line 44, filter 16, lines 48 and 50, reservoir 20 and line 56 are disposable after use with each donor. Items indicated by reference numeral 40 are push fit connectors which enable the disposable lines to be easily removed after use. The system is micro-processor controlled and digital indicators are provided for arterial flow rate and pressure, venous flow rate and pressure, anti-coagulant flow rate and trans-membrane pressure.

The system may be operated as follows. The needle 12 is inserted into the patient's arm and the system is primed with saline. Pump 10 is actuated to draw blood from the patient. The concentrated stream (line 48) and filtrate stream (line 50) are initially fed to (waste) drainage bag 52 via open valves 3 and 4 until the system establishes equilibrium. Then, valves 2, 3 and 4 are closed such that filtrate plasma is fed via open valve 5 to plasma bag 18 and cell concentrate is collected in reservoir 20. Operation continues until treated concentrate in reservoir 20 reaches level sensor H. The predetermined level is maintained in buffer volume 14 and the rate of delivery of blood to the filter is controlled by a micro-processor in accordance with trans-membrane pressure readings obtained from sensors 42 and 58. When reservoir 20 is filled, delivery pump 10 is switched off and valve 1 is closed. Valve 2 is opened and pump 22 is actuated to progressively return the collected concentrate from reservoir 20 back into the donor via line 56 and needle 12. When the level in reservoir 20 has fallen to a low level, the process is repeated until the required volume of plasma has collected in plasma bag 18. The contents of plasma bag 18 are monitored by the weighing scale 54.

In this way, plasma is automatically withdrawn from the donor and cell concentrate is returned to the donor thereby minimising any adverse effects on the donor. If desired, the cell concentrate can be collected for use rather than being returned to the patient.

Reference is now made to Fig. 2 of the drawings which depicts an alternative embodiment of Fig. 1 with the first reservoir 14 omitted. In this case the tubing 30 passes around delivery pump 10 and is connected to the inlet of an in-line tubing portion 70 which acts as a fluid "cushion" or damper which is coupled to the first trans-membrane pressure sensor 42 via the push foot connector 40. The outlet of the fluid damper 70 is connected to line 44 which in turn feeds into the inlet of the filter 16. The fluid damper 70 acts to mimimise pressure fluctuations and ensure that the pressures monitored by the sensor 42 are accurate. In this embodiment the level valve 38 is also not needed. The advantage of this embodiment is of course that the first reservoir is not required, thus minimising fluid circuitry. In all other respects the embodiment shown in Fig. 2 operates in the same way as that described with reference to Fig. 1.

Reference is now made to Fig. 3 of the drawings which shows a further alternative embodiment of the invention. In this embodiment like numerals refer to like parts as in the earlier embodiments. In this case the first reservoir 14 has been omitted and in this case the line 30 is connected directly to line 44. The pressure sensor 40 at the output of the second reservoir 20 and associated circuitry has been omitted as has the sensor 42 associated with the first reservoir 14. In this case the trans-membrane pressure sensors 72 and 74 are located at the inlet and outlet respectively of the filter 16. The tubing 44 which passes through sensor 72 is of increased diameter so that the sensor can detect accurately pressure fluctuations. Similarly the part of the tubing 48 which passes through sensor 74 is of increased diameter for the same reason. The sensors 72 and 74 are coupled to a micro-processor which controls the operation of the system as described above.

The advantage of this arrangement is that it further minimises the need for fluid circuitry and avoids the need for not only the first reservoir and associated components 38, 40 and 42, but also obviates the need for pressure sensor at the outlet of the second reservoir 20. In this case the sensor 72 and 74 are located next to the filter 16, further simplifying circuitry.

Reference is now made to Fig. 4 of the drawings which depicts yet a further embodiment of the present invention. In this embodiment like numerals also refer to like parts. In the arrangement shown this embodiment is most similar to that shown in Fig. 3, but additionally the drainage bag 52 and associated pumps 3 and 4 have been omitted. The reason for this is that there is now requirement in this embodiment to pre-flush the system with saline prior to drawing blood from the patient. Instead, in this embodiment, a small slug in the amount of about 1-lOml. of anti-coagulant is injected in to line 30 via reservoir 24, pump 26 on line 28. As the blood from the donor approaches junction 76 the anti-coagulant precedes the blood and passes through the circuit as shown. The anti-coagulant activates the membrane in filter 16 by "wetting" the membrane sufficiently to allow the member to function properly in the filter. It will be appreciated that some anti-coagulant will pass through the membrane to be collected in the plasma bag 18 and the remainder will be collected in the reservoir 20. However, the amount of anti-coagulant used is so small as to have a negligible adverse effect on the volume of plasma contained in the bag 18 and the cell concentrate in the - 15 - reservoir 20. It will be appreciated that the principal advantage of this arrangement is that there is no need to pre-flush the-system with saline prior to withdrawing blood from the patient, ^' thus minimising the time spent operating the system. In addition, the requirement of a drainage bag is obviated. In the embodiment shown it will be appreciated that all of the modifications which have been depicted in Fig. 3 are also included in this embodiment, but it will be understood that the systems shown in Figs. 1 and 2 could be modified in the same manner so that the drainage bag 52 and associated pumps 3 and 4 may also be omitted from these embodiments.

The system hereinbefore described with reference to the embodiments has particular application for the in situ production of blood cell concentrate and plasma as such it has significant applications for military battlefield use where blood from donor soldiers can be very quickly collected and treated for use on wounded soldiers. Moreover, the system is small and compact and can be used on ships, aircraft and in other vehicles in motion where conventional centrifuges cannot be operated since they become unstable.

Claims

CLAIMS :

1. A system-for treating a fluid, which is blood or blood-derived fluid which comprises fluid delivery means for delivering the fluid to membrane filtration means; the membrane filtration means being adapted for treating the fluid to remove a filtrate stream from the fluid; reservoir means connected to the filtration means for receiving a batch of treated fluid; treated fluid discharge means connected to the reservoir means for discharging treated fluid from the reservoir means; filtrate discharge means connected to the filtration means for discharging filtrate therefrom; and pressure sensor means for sensing the trans-membrane pressure in the membrane filtration means and controlling the rate of delivery of the fluid by the delivery means.

2. A system as claimed in claim 1 wherein the system is particularly intended for the plasmapheresis of blood from a donor in order to provide a plasma stream (the filtrate) and a cell concentrate stream.

3. A system as claimed in claim 1 or 2 wherein the cell concentrate stream may be returned to the patient or may be stored for imminent use in the treatment of shock trauma.

4. A system as claimed in claim 2 or 3 wherein blood is removed from a donor, treated and returned to the donor ia a single needle inserted in the donor which is achieved by withdrawing batches of blood from the patient, passing the blood through the membrane filtration means and storing the treated batch in the reservoir means.

5. A system as claimed in any one of claims 1 to 4 wherein batches of 100 to 300ml of blood are withdrawn from the patient at a time, and in total an overall volume of 400 to 600ml of plasma is usually treated in order to minimise any effects on the donor.

6. A system as claimed in any of claims 1 to 4 wherein the system can be operated continuously to treat a certain amount of blood where there is no requirement to return the treated blood to the patient.

7. A system as claimed in any one of claims 2 to 6 wherein the plasma filtrate stream (or the cell concentrate stream) is subjected to further treatment to remove desired components therefrom.

8. A system as claimed in any preceding claim wherein the fluid treatment system itself is designed to form an integrated system, which is automatically controlled and is provided as a transportable unit, for example, for donation and treatment of blood in situ for military requirements.

9. A system as claimed in any preceding claim wherein the fluid delivery means is a peristaltic pump, which removes blood from the patient and delivers it directly or indirectly to the membrane filter.

10. A system as claimed in any one of claims 1 to 9 wherein in the case of treatment of previously withdrawn blood or blood-derived fluids, the necessary fluid delivery is achieved by means of gravity.

11. A system as claimed in any preceding claim wherein the fluid delivery means delivers fluid to a buffer volume container equipped with sensors for controlling the rate of delivery of fluid to the filtration means.

12. A system as claimed in any one of claims 1 to 10 wherein the buffer volume container and associated level sensor means are emitted and an in-line fluid cushion or damper is coupled to pressure sensor means.

13. A system as claimed in any one of claims 1 to 10 wherein the pressure sensor and components at the outlet of the reservoir means are omitted and the transmembrane pressure sensors are located at the inlet and oulet of the filter means.

14. A system as claimed in any preceding claim wherein the need for pre-flushing the system with saline is avoided by injecting a small volume of anti-coagulant into the line just prior to withdrawing blood.

15. A method of treating a fluid, which is blood or blood derived, said method comprising: delivering a volume of said fluid to a membrane filter; treating the fluid to remove a filtrate stream, storing a batch of treated fluid from said filter in a reservoir; discharging said filtrate from said reservoir, discharging said treated fluid from the reservoir, and sensing the pressure across the membrane filter and ^* controlling the rate of delivery of the bluid by the delivery means.

16. A method as claimed in claim 15 wherein the method includes collecting the filtrate in a filtrate reservoir.

17. A method as claimed in claim 15 or 16 wherein the method includes pre-flushing the system with saline and collecting the saline in a separate reservoir.

18. A method as claimed in claim 15 or 16 wherein the method includes injecting a small volume of anti-coagulant into the system to wet the filter membrane prior to treating the fluid.