Device for Storing Blood and Method for Use Thereof

Abstract

A mass exchanger for use in storing blood or a blood product such as packed cells is described. The mass exchanger comprises an external casing, a cavity is provided within the casing having a region for storing blood and one or more channels extending within the casing for accommodating flow of a treatment fluid, the one or more channels each being at least partly bounded by a permeable membrane to allow transfer of chemical species between the channel and the cavity; wherein the casing comprises at least one flexible wall. The mass exchanger can include a region for storing blood comprising a bag. Here the bag or the casing comprise at least one flexible wall. A method of storing blood in the mass exchanger is also described.

Claims

1. A mass exchanger for use in storing blood or a blood product such as packed cells, the mass exchanger comprising an external casing, a cavity being provided within the casing having a region for storing blood and one or more channels extending within the casing for accommodating flow of a treatment fluid, the one or more channels each being at least partly bounded by a permeable membrane to allow transfer of chemical species between the channel and the cavity; wherein the casing comprises at least one flexible wall.

2. A mass exchanger according to claim 1, wherein the region for storing blood comprises a bag and wherein the bag or the casing comprise at least one flexible wall.

3. A mass exchanger according to claim 1, wherein the permeable membrane is permeable to gas but impermeable to liquids or to ionic or dissolved species.

4. A mass exchanger according to claim 1, wherein the permeable membrane is microporous.

5. A mass exchanger according to claim 1, wherein the total surface area of the permeable membranes associated with the one or more channels lies in the range 0.05 m.sup.2 to 1 m.sup.2.

6. A mass exchanger according to claim 1, wherein at least one channel has a tubular shape.

7. A mass exchanger according to claim 1, wherein the walls of the channel comprise at least one planar membrane.

8. A mass exchanger according to claim 7, wherein the planar membrane is flexible.

9. A mass exchanger according to claim 1, wherein the casing has an external layer that is impermeable to gas and an internal gas-permeable layer that is blood-compatible.

10. A mass exchanger according to claim 1, further comprising an indicator for providing information about the composition of the blood contained within the exchanger.

11. A mass exchanger according to claim 10, wherein the optical properties of the indicator vary with the composition of the blood.

12. A mass exchanger according to claim 1, further arranged to serve as a heat exchanger, wherein the treatment fluid comprises a liquid phase at a temperature, the temperature arranged so as to increase, decrease or maintain the temperature of the blood or blood product.

13. A mass exchanger according to claim 1, wherein the treatment fluid comprises a gelling agent.

14. A mass exchanger according to claim 1, wherein the treatment fluid comprising a substance arranged to reverse gelation.

15. A method of storing blood, comprising: providing a mass exchanger according to claim 1 any one of the preceding claims; introducing a blood sample into the mass exchanger; keeping the blood sample in the mass exchanger for a storage period; and introducing treatment fluid into the channel to modify the composition of the blood sample.

16. A method of storing blood, comprising the steps of: providing a mass exchanger according to claim 1; introducing a blood sample into the mass exchanger; introducing treatment fluid into the channel to modify the composition of the blood sample, and; keeping the blood sample in the mass exchanger for a storage period.

17. A method according to claim 16, wherein the blood sample is kept within the mass exchanger for a storage period of up to or around 42 days.

18. A method according to claim 16, further comprising the step of transferring the mass exchanger after the storage period to the head of a drip line and connecting it to a supply tube for transfusing the blood sample into the patient.

19. A method according to claim 16, wherein the blood sample enters and exits the mass exchanger through the same port.

20. A method according to claim 16, wherein the mass exchanger is moved at least once during the storage period, in such a way as to promote circulation of blood within the exchanger.

21. A method according to claim 16, wherein the composition of the treatment fluid is selected so as to control the concentration of oxygen and/or carbon dioxide in the blood sample.

22. A method according to claim 21, comprising reducing the concentration of oxygen and/or carbon dioxide in the blood sample, followed by the step of increasing the concentration of oxygen and/or carbon dioxide in the blood sample after a time period up to around 42 days.

23. A method according to claim 21, further comprising causing fluid to flow continuously or intermittently along the channel for up to around 42 days, the composition of the fluid being selected to control the concentration of oxygen and/or carbon dioxide in the blood sample.

24. A method according to claim 16, wherein after the storage period, treatment fluid flows along the channel, the temperature of the treatment fluid being greater than the storage temperature of the blood.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The invention will now be described by way of example with reference to the following Figures in which:

[0045] FIG. 1 shows a front view of a mass exchanger according to an embodiment of the first aspect of the invention, for use in an example of the method according to a further aspect of the invention;

[0046] FIG. 2 shows a side sectional view along a line A-A of the mass exchanger of FIG. 1 according to an embodiment of the first aspect of the invention, for use in an example of the method according to a further aspect of the invention, and

[0047] FIG. 3 shows a schematic section view of a mass exchanger according to a second embodiment of the first aspect of the invention, for use in an example of the method according to a further aspect of the invention.

DETAILED DESCRIPTION

[0048] Referring to FIG. 1 and FIG. 2, a mass exchanger 10 comprises an outer casing 11 that is relatively impervious to gases. The outer casing 11 houses the storage vessel bounded by walls 15. The walls 15 may be constructed of gas-permeable polymers, such as PVC, silicones, polymethylpentene, or polyphenylene oxide, or from microporous materials such as microporous polypropylene and may be flexible. Each of the walls 15 has an area about 0.10 m.sup.2 and the storage vessel or blood bag provides a mass transfer area of about 0.2 m.sup.2.

[0049] Upper portions 17a and lower portions 17b of the walls of the outer casing 11 can be flexible and are sloping, providing a triangular portion (in the longitudinal direction on the page in FIG. 1). The portion of the mass exchanger 10 bounded by the gas permeable walls 15 and the outer casing 11 provides fluid communication between a treatment fluid inlet 12 and a treatment fluid outlet 14. The mass exchanger 10 is further provided with an air bleed port 16 and a blood port 18. In operation blood is fed into the device through port 18, which may also provide the blood outlet when it is subsequently transfused. Alternatively, a separate outlet port (not shown) may be provided that is similar to the ports in conventional blood bags and which is then used for the subsequent transfusion. The triangular shape with sloping walls 17a, 17b facilitate charging and discharging blood without retention of bubbles and other aspects of turbulence that could occur with other shapes of entry and exit passages. When the device is full and contains no bubbles, the ports 16 and 18 are closed. The treatment fluid is fed into ports 12 in operation (which, in practice can be joined) and flows out of ports 14 (which may also be joined), The volume of the device allows storage of one unit of blood (about 450 ml).

[0050] In the illustrated embodiment the distance between walls 15 when full of blood is about 0.005 m (5 mm). There are a number of ways envisaged of maintaining or constraining the distance between the walls 15, whilst still enabling the mass exchanger apparatus to be flattened and manipulated when not in use. A long diffusion path for the blood mass transfer will significantly reduce the efficiency of the device. A distance of around 5 mm is suitable and means that at no point in the device is there any element of blood more than a few millimetres (mm) from a permeable wall. In a similar manner, the treatment fluid channel 20 between walls 11 and permeable membrane 15 should be shaped such that no element of the treatment fluid (e.g. nitrogen) is more than a few mm from the permeable membrane. The mass transfer area may be further increased by further subdividing the volume with further channels. Alternatively, further channels may be used to maintain the total mass transfer area while decreasing the area of walls 11, 15.

[0051] In certain embodiments both the outer casing 11 and the gas permeable walls 15 are flexible.

[0052] The mass transfer area may be increased by employing gas permeable tubes (hollow fibres) instead of gas permeable walls. This alternative design is discussed below with reference to FIG. 3.

[0053] Referring to FIG. 3, a mass exchanger 100 comprises a flexible casing 111 that houses a plurality of tubes. The tubes may be constructed of gas-permeable polymers, such as PVC, silicones, polymethylpentene, or polyphenylene oxide, or from microporous materials such as microporous polypropylene. Typically, the tubes provide a mass-transfer surface area of between 0.2 m.sup.2 and 1 m.sup.2.

[0054] The tubes provide fluid communication between a treatment fluid inlet 112 and a treatment fluid outlet 114. The mass exchanger is further provided with an air bleed port 116 and a blood port 118.

[0055] In some embodiments, a gas-permeable casing (as in FIG. 1) may be combined with gas-permeable membranes within the casing.

[0056] In certain embodiments, the flexible casing may comprise two layers: an external layer that is impermeable to gas diffusion and an internal layer that has good blood-compatibility, such as plasticised PVC or optionally, for reasons described in the summary of the invention, one of the other membrane examples provided earlier.

[0057] The casing is provided with an indicator 22 (shown in FIG. 1 as 22, not shown in FIG. 2, shown in FIG. 3 as 120) that assists in determining the composition of the blood held within the mass exchanger. The indicator 22, 120 may comprise e.g. a coloured surface for comparison with the colour of the blood within the exchanger, As an alternative, a dye layer may be incorporated into the mass exchanger, for example provided on the outer surface of a gas permeable membrane, and interrogated by suitable optical means to provide e.g. the oxygen and/or carbon dioxide partial pressures in the blood, as described in GB2470757.

[0058] In use, the mass exchanger is preferably oriented vertically with the blood port 18, 118 at the lowest point. The donated blood or blood product is fed into the vessel through connector 18, 118 and any gas in the vessel is released through vent 16, 116. When the vessel is full, or a complete unit of blood has been introduced, port 18, 118 is closed and the bag is squeezed to exhaust any remaining gas in the bag before vent 16, 116 is closed. Soon after transfer of the blood into the casing, a treatment fluid is caused to flow along the channels 20 or tubes to modify the composition of the blood so that it is better adapted for storage. The treatment fluid may comprise liquid and/or gaseous phases. For example, the treatment fluid may comprise an inert gas (for example, nitrogen), so as to reduce the concentration of oxygen and/or carbon dioxide in the blood. Alternatively, the treatment fluid may consist of a gas/liquid mixture (as described in co pending patent application PCT/GB2016/050098) which in operation can add or remove components that can diffuse through a microporous membrane. For example, it can add components to the blood that become depleted during storage or components that improve the long term storage of the blood. It can remove harmful components that accumulate during storage or as a consequence of damage caused by irradiation, and also components that may have been added to improve long-term storage.

[0059] In an alternative arrangement, the treatment fluid may be a liquid that dissolves oxygen and/or carbon dioxide either to transfer oxygen and/or carbon dioxide from the blood or to transfer oxygen and/or carbon dioxide to the blood. Examples of such liquids include solutions of porphyrins for oxygen transfer, alkaline solutions for absorption of carbon dioxide, suspensions of bound porphyrins which may be suspended in aqueous solutions that either absorb or deliver carbon dioxide, or liquids such as perfluorocarbons that dissolve both oxygen and carbon dioxide and may either deliver or absorb the gases depending on the concentration dissolved. The mass exchanger including a flexible casing which, when in combination with a liquid treatment fluid, is compatible with a centrifuge step and can provide an improvement over a flexible casing mass exchanger with a gaseous treatment fluid. The liquid treatment fluid cannot be compressed so occupies and maintains the flexible casing structure. This is particularly useful when a centrifuge step is used to separate blood components, the casing can distort when the treatment fluid is a gas and a centrifuge step is used.

[0060] An additional step may be included for assisting in achieving very low blood oxygen concentrations when blood is filling the mass exchanger storage portion. The first step involves the exchange with carbon dioxide (or a fluid with a high carbon dioxide concentration) to drive out the majority of the oxygen held in the blood product. The second step is then to effectively drive the carbon dioxide out of the blood, together with some residual oxygen, by exchange with nitrogen or another treatment fluid with a low, or zero, oxygen and carbon dioxide concentration, or with an affinity for carbon dioxide and oxygen.

[0061] The desired blood gas concentrations can be maintained by flows of gases, liquids or gas/liquid mixtures. Where a treatment fluid has sufficient affinity for oxygen and/or carbon dioxide, no flow may be needed once the desired low concentrations of the gases has been achieved. Thus, the blood bag may remain unconnected to a treatment fluid supply until it is required to restore oxygen concentration prior to transfusion.

[0062] In the same way as the use of treatment liquid in particular can have further advantages in maintaining the structural integrity of the mass exchanger then the low blood oxygen concentration step could be achieved with a flow of successive fluids between the cavities with flexible membranes. The flow cycle of treatment liquid could be, for example carbon dioxide then nitrogen to achieve low blood gas concentrations, then followed by a treatment liquid to maintain the low concentrations.

[0063] During this treatment period, the mass exchanger may be moved occasionally or regularly, for example, by changing its orientation, to help to prevent the formation of pockets of untreated blood.

[0064] During or immediately after this initial treatment period, the blood is refrigerated to an appropriate temperature for storage.

[0065] This treatment (that is, the flow of treatment fluid through the tubes and/or the movement of the mass exchanger) may be prolonged continuously or intermittently for the whole of the period during which the blood is stored, so as to maintain the composition of the blood in its treated condition. However, in certain cases (for example, when the treatment fluid is a liquid or gel with a strong affinity for oxygen) the flow of treatment fluid may cease during the storage period.

[0066] At the end of the storage period, the blood may be treated once more, to bring its composition and/or temperature closer to those required for transfusion of the blood to a recipient. For example, treatment fluid may be caused to flow along the channel or channels 20 or tubes, the properties of the treatment fluid being selected so as to achieve one or more of the following: [0067] replenishment of oxygen (preferably until the blood is oxygenated at least to arterial conditions), carbon dioxide, and/or nitric oxide; [0068] removal of preservative and/or removal of harmful species that may accumulate during storage such as potassium ions; [0069] an increase in blood temperature, to bring it closer to body temperature.

[0070] Verification that the blood is ready for transfusion may be achieved by visual inspection of its colour or by means of the indicator 22,

[0071] The mass exchanger is then typically transferred to the head of a drip line for transfusion to the recipient.