BLOOD SEPARATION SYSTEM AND BLOOD PRODUCTS

Abstract

A blood filtering apparatus for recovering blood components from blood comprises an inlet for the blood; a cell filter configured for filtering a portion of the blood and retaining as a retentate a fraction of the blood containing red blood cells and platelets and passing as a filtrate a fraction of the blood, in particular mainly as plasma, containing platelets and being depleted of red blood cells. The cell filter has a pore size in a range of 2,0-3.0 micron. Further, a method and a blood product are provided.

Claims

1. A blood filtering apparatus for recovering blood components from blood, the apparatus comprising an inlet for the blood; and a cell filter configured for filtering a portion of the blood and retaining as a retentate a fraction of the blood containing red blood cells and platelets and passing as a filtrate a fraction of the blood containing platelets and being depleted of red blood cells; wherein the cell filter has a pore size in a range of 2.2-2.7 microns.

2. The blood filtering apparatus according to claim 1, wherein the pore size is in a range of 2.2-2.5 microns, .

3. The blood filtering apparatus according to claim 1, wherein the apparatus comprises a platelet filter for filtering a portion of the filtrate of the cell filter into a platelet rich fraction and a platelet depleted fraction, and/or wherein the apparatus comprises a second filter for filtering a portion of the filtrate of the cell filter wherein the second filter has a pore size in a range of 0.2-0.6 microns.

4. The blood filtering apparatus according to claim 1, wherein the filter material of the cell filter comprises a polymer layer.

5. The blood filtering apparatus according to claim 1, wherein the filter material of the cell filter is a track-etched membrane.

6. The blood filtering apparatus according to claim 1, wherein the cell filter comprises plural filter portions arranged opposite each other defining a first flow path for unfiltered blood and retentate located between the opposite filter portions, and defining a second flow path comprising plural second flow path portions extending through different ones of the filter portions, for collecting filtrate downstream of the filter portions, wherein the plural second flow path portions are in fluid communication with each other at least downstream of the cell filter.

7. The blood filtering apparatus according to claim 6, wherein at least some of the opposite filter portions are spaced by a retentate spacer layer allowing flow of blood and retentate through the respective spacer layer and/or at least some of the opposite filter portions are spaced by a filtrate spacer layer allowing flow of filtrate through the respective spacer layer.

8. The blood filtering apparatus according to claim 7, wherein the spacer comprises or is at least one of a fibrous material, a mesh material, and a woven or knit cloth,.

9. The blood filtering apparatus according to , wherein the cell filter, the platelet filter and/or the second filter comprises a plurality of filter portions stacked together in a stacking direction and being configured for, seen in the stacking direction, providing alternating first flow paths for retentate of the filter and second flow paths for filtrate of the filter.

10. The blood The blood filtering apparatus according to claim 1, comprising an inlet for the blood to be filtered, connected to plural filter layers and/or comprising a first outlet for retentate of the cell filter optionally connected to plural filter layers and a second outlet for filtrate of the cell filter possibly optionally plural filter layers.

11. A method, of recovering blood components from blood, comprising separating an amount of blood comprising red blood cells and platelets into a red blood cell rich fraction and a red blood cell poor fraction, wherein the red blood cell rich fraction has a haematocrit of at least 30%; and/or the red blood cell rich fraction comprises at least 60% of the red blood cells of the ; amount of blood and wherein the red blood cell rich fraction comprises about 40-450 thousand platelets per microliter and/or the red blood cell rich fraction comprises at least 25% of the platelets of the amount of blood.

12. The of recovering blood components from blood.sub.; according to claim 11, further comprising filtering a portion of the blood using a blood filtering apparatus according to claim 1 and collecting at least one of the retentate and the filtrate, wherein the retentate is a red blood cell rich fraction and the filtrate is a red blood cell poor fraction.

13. The method according to claim 12, further comprising filtering a portion of the filtrate of the cell filter and providing a platelet rich fraction.

14. The method according claim 11, further comprising obtaining blood from a donor that is recovering or has recovered from an affliction for obtaining in the filtrate high levels of antibodies.

15. A blood product for transfusion into a human recipient, wherein the blood product has a haematocrit of at least 30% and comprises about 40-300 thousand platelets per microliter; and wherein the blood product consists essentially of blood components of a single donor individual.

16. The apparatus of claim 1, wherein the pore size is in a range of 2.3-2.4 microns.

17. The apparatus of claim 3, wherein the second filter has a pore size in a range of about 0.3-0.4 microns.

18. The apparatus of claim 4, wherein the polymer layer is a particular a polymer surface layer that is a polymer membrane comprising a polymer material selected from the group consisting of polyester polyurethane, polyethylene terephthalate, polyethylene furanoate, poly(propylene furan-2,5-dicarboxylate).

19. The method of claim 11, wherein the haematocrit is in a range of 30%-60%; the red blood cell rich fraction comprises at least 75% of the red blood cells of the amount of blood; the red blood cell rich fraction comprises about 70-400 thousand of the platelets per microliter; and the red blood cell rich fraction comprises at least 50% of the platelets of the amount of blood.

20. The blood product of claim 15, where the haematocrit is in a range of 30-60% and the blood product contains about 70-150 thousand of the platelets per microliter.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0077] The above-described aspects will hereafter be more explained with further details and benefits with reference to the drawings showing a number of embodiments by way of example.

[0078] FIG. 1 indicates a top view of a blood filtering apparatus;

[0079] FIG. 2 indicates a cross section view of the blood filtering apparatus of FIG. 1 along section II-II;

[0080] FIGS. 3 and 4 are electron microscopy photographs of filter materials;

[0081] FIGS. 5 and 6 are (electron) microscopy photographs of spacer material;

[0082] FIG. 7 shows is an exemplary embodiment;

[0083] FIG. 8 is a schematic representation of methods of filtering blood.

DETAILED DESCRIPTION OF EMBODIMENTS

[0084] It is noted that the drawings are schematic, not necessarily to scale and that details that are not required for understanding the present invention may have been omitted. The terms “upward”, “downward”, “below”, “above”, and the like relate to the embodiments as oriented in the drawings, unless otherwise specified. Further, elements that are at least substantially identical or that perform an at least substantially identical function are denoted by the same numeral, where helpful individualised with alphabetic suffixes.

[0085] Further, unless otherwise specified, terms like “detachable” and “removably connected” are intended to mean that respective parts may be disconnected essentially without damage or destruction of either part, e.g. excluding structures in which the parts are integral (e.g. welded or moulded as one piece), but including structures in which parts are attached by or as mated connectors, fasteners, releasable self-fastening features, etc. The verb “to facilitate” is intended to mean “to make easier and/or less complicated”, rather than “to enable”.

[0086] FIGS. 1 and 2 show a blood filtering apparatus comprising a filter 3 in turn comprising a plurality of filter portions 5 separated by a first set of spacer layers 7 and by a second set of spacer layers 9 stacked onto each other. The combination provides plural first filter layers F1 and second filter layers F2. The different spacer layers 7 and 9 are indicated in FIG. 2 with different hatching for clarity but their construction in the filter may be substantially identical (see below). The filter 1 may comprise more, less and/or differently sized and/or shaped filter portions. The number and/or positions of inlet(s) and/or outlets may also be chosen other than shown.

[0087] The apparatus comprises a liquid tight housing 11 around the filter 3 through which extend an inlet 13 for the blood to be filtered, an outlet 15 for retentate and an outlet 17 for filtrate. As may be seen from FIG. 1B, the inlet 13 and retentate outlet 15 are in fluid communication with the first filter layers F1 and the filtrate outlet 15 is in fluid communication with the filter layers F2.

[0088] The inlet 13 and the filter portions 5 arranged opposite each other and being separated by the first set of spacer layers 7 define a first flow path P1 for unfiltered blood and retentate between the opposite filter portions from the inlet 13 to the retentate outlet 15 through the filter layers F1. The first flow path P1 extends around the filtrate outlet 17 as may be understood from FIG. 1A.

[0089] The filter portions 5 arranged opposite each other also define a second flow path P2 comprising plural second flow path portions P2 extending through different ones of the filter portions 5, for collecting filtrate downstream of the filter portions, here at the filtrate outlet 17. The second flow path P2 extends through from the inlet 13 to the filtrate outlet 17 through both a filter layer F1 and a filter layer F2.

[0090] The inlets and/or outlets are connected to the filter portions leak tight, e.g. by welding, gluing or clamping, so that fluid communication between the filter layers F1 and F2 exists only through the pores of the filter portions so as to prevent filter bypassing of blood components from the incident side / retentate side to the filtrate side.

[0091] FIGS. 3 and 4 are electron microscopy photographs of track etched mylar membranes showing track etched membranes with pores of different sizes: 2.3 micron (FIG. 3) and 0.4 micron (FIG. 4) respectively. From these images, it may be seen that the pore sizes vary only to within a few percent, that the arrangement of pores is somewhat erratic and that the surface porosity (fraction open area of total surface area) may be on the order of 10-20%, preferably it is on the order of about 10-30% this may retain strength of the membrane, provide relatively smooth surface for relatively unobstructed flow of the blood cells over the surface, and still provide a relatively large open area and low flow resistance across the filter membrane.

[0092] Suitable filter membrane thickness may be in a range of 10-50 micron, preferably in a range 10-30 micron, more preferably in a range of 10-15 micron, e.g. about 12-13 micron, 15-20 micron e.g. about 17-18 micron, or 20-25 micron, e.g. about 23-24 micron. Such ranges are commercially readily available in smooth surface finish and high quality (no holes etc.). Note that the thicker the membrane is, the more robust it becomes and the better workable for manufacturing the filter, but also the higher the flow resistance across the filter membrane becomes. Different numbers of stacking, different amounts of blood to be filtered and/or different pressure differences across the filter membrane(s) in combination with filter size may determine an optimum selection.

[0093] FIGS. 5 and 6 show suitable spacer material. The shown material is a polyamide monofilament mesh sloth. The used wire is a round non-flattened smooth monofilament thread of diameter ca. 50 micron. The fabric is warped singular double-manifold loin-weaved. FIG. 5 shows that the cloth has a very open and substantially hexagonal structure. FIG. 6 shows that wire portions are repeatedly wound around each other and/or crossing each other, also forming loops. Thus, when arranged between filter membranes and compressed the spacer material will provide significant open structure so that red blood cells of average size 5 micron and/or clumps of RBCs of about 10 micron may readily pass the spacer material and the spacer material will provide, even then, little flow obstruction for the blood/retentate and even less for the filtrate as that contains smaller objects.

[0094] FIG. 7 shows an exemplary apparatus and a manner of operation of the apparatus. The filter 10 comprising filter 1 described hereinbefore mounted in an optional outer housing for security, is attached to a standard IV-pole 20 or another support. A blood bag 22 or other supply of blood to be filtered is attached to the IV-pole 20, above the filter 10, e.g. between about 75-150 cm above the filter 10. A retentate RBC bag 24 or other retentate container is attached to the IV-pole 20, below the filter 10, e.g. about 75-150 cm below the filter 10. A filtrate bag 26 or other filtrate container is also attached to the IV-pole 20, below the filter 10, e.g. about 75-150 cm below the filter 10. Note that instead of a common support several supports like IV-poles etc. may be used.

[0095] Referring also to FIGS. 1-2, The blood bag 22, retentate bag 24 and filtrate bag 26 (or rather: the respective containers) are connected to the inlet 13, retentate outlet 15 and filtrate outlet 17, respectively of the filter 1 with tubes 22A, 24A, 26A, respectively, or other conduits. The thus-formed assembly provides a substantially liquid tight and preferably also gas tight apparatus, preferably being sterile.

[0096] In use, the vertical arrangement of the apparatus and gravity cause blood to be filtered to flow from the blood supply 22 into the filter 1. There, the blood is flown from the inlet 13 over the filter portions 5 into and through first filter layers F1. From there, a portion of the plasma and a fraction of the platelets of the blood pass through (the pores in) the filter portions 5 into the second filter layers F2 and from there via the filtrate outlet 17 and the tubes 26A into the filtrate bag 26. Portions of the blood that have not passed a filter portion 5 form retentate are flow from the filter 1 via the retentate outlet 15 and the tubes 24A into the retentate bag 24 forming an amount of platelet rich packed cells.

[0097] Note that filtering speed and/or efficiency may be controlled by adjusting height differences between the parts 10, 22, 24, 26 in the arrangement. Also or alternatively, external pressure or suction may be applied to one or more of the bags 22, 24, 26.

[0098] After the filtering, the collected filtrate may be further filtered and/or concentrated to produce platelet rich plasma, platelet poor plasma and/or any other plasma product.

[0099] A schematic of a method is shown in FIG. 8. Blood to from which one or more blood components are to be recovered is introduced into the method at “IN”. In the filter (e.g. filter 3 in FIGS. 1-2), the blood is separated into retentate and filtrate by the cell filter. The retentate may comprise essentially all RBCs of the blood introduced into the filter. If so desired, the filter may be rinsed using a suitable fluid. A portion of the filtrate may be considered and possibly used as a platelet enriched plasma (“PEP”). Such substance is considered not achievable by other means, at least not without undue effort and costs for separating blood fractions and recombining at least part of the previously separated fractions.

[0100] The platelet enriched plasma PEP may be further processed by haemoconcentration (“HC”) into platelet rich plasma (“PRP”) (and a waste fraction being predominantly water).

[0101] Also or alternatively, a portion of the filtrate may be filtered using a second filter of about 0.4 micron to provide a fresh plasma product and particulate retentate mainly comprising platelets and cell fragments considered waste.

[0102] Uses and benefits of the various products have been explained before.

[0103] As examples, several blood filtering apparatus were provided each comprising a cell filter of the construction of FIG. 1 containing 34 membrane layers providing filter portions 5. Each membrane layer was made of 23 mm thick track etched Hostaphan PET film. The pore size of the membranes was in a range 2.2-2.6 micron, as determined by bubble-point method based on p.sub.max = (4 y cosθ) / d, p.sub.max being gas pressure at the bubble point, y surface energy of the measuring liquid, θ the wetting angle of the measurement liquid with the substrate and d the pore diameter, using nitrogen gas and as measurement liquid 30 wt% ultrapure water and 70 wt% isopropanol IPA yielding K.sub.theory = 4 γ cosθ = 0.065 N/m at room temperature.

[0104] Using apparatus with a pore size determined as 2.2-2.4 micron arranged as in FIG. 7, three 500 ml units of donated whole blood were filtered and separated, by gravity-driven filtration, into a retentate rich in RBCs and platelets (“cellular component”) and a filtrate (“plasma component”). Prior to the filtering, as an option the apparatus was primed with isotonic saline. The retentate contained all of the red blood cells (“RBCs”) and white blood cells (“WBCs”) and most of the platelets. Measurement results were: retention of 100 ± 1.63% of the RBCs, 99 ± 4.5% of the WBCs and 83 ± 3.0% of the platelets of the initial whole blood; the filtrate contained no RBCs or WBCs and 12 ± 1.9% of the initial platelets. In the measurements, no significant difference was found between haemolysis prior to (0.00 ± 0.01%), and after separation (0.04 ± 0.02%, p 0.057) and platelet functionality, morphology and activation were found comparable before and after separation. Thus, the separation appeared to have little to no adverse effects on the cellular components.

[0105] Similarly, using apparatus with a determined pore size 2.2-2.4 micron arranged as in FIG. 7, six 250 ml units of donated whole blood were diluted with 0.9 % NaCl saline to 600 ml at a haematocrit of 0.20 ± 0.01% each, which diluted blood mixtures were filtered and separated, by gravity-driven filtration, into a retentate rich in RBCs and platelets (“cellular component”) and a filtrate (“plasma component”). The thus-obtained retentate was further diluted with 300 ml 0.9 % NaCl saline and the mixture was again filtered providing a second retentate and second filtrate. The second retentate was again filtered, without further liquid addition, to concentrate the second retentate into a concentrated final retentate; the filtrate of each filtering round can be collected separately or combined with filtrate of another filtering round. Thus, the initial whole blood was washed, comparable to washing of shed blood. This washing procedure yielded recovery of RBCs of at least 87 ± 6%, of WBCs of at least 93 ± 7% and of platelet of at least 68 ± 10% of the initial whole blood into the final concentrated retentate.

[0106] In each case at least part of the retentate could be returned to the donor, transfused to a receptor and/or stored, after optional addition of SAGM or another supplement and/or agent, as usual for donated blood. The white blood cells (“WBCs”) could be removed from the platelet-rich and RBC-rich cellular component using a commercial leucocyte filter before or after storage of the retentate and before transfusion of the WBC-depleted RBC-rich and platelet-rich component to a receptor. The filtrate(s) could be stored and/or transfused as well, either unprocessed, concentrated or processed otherwise. The filtrate(s) could be subject to cooling to and storage at a temperature below -10℃, preferably below -18℃ e.g. at about -25° C. for one or more days and reheated to a suitable temperature for (re-)infusion into a receptor. This may destroy and/or incapacitate most if not all remaining RBCs and/or platelets that entered into the filtrate, thus reducing possible adverse effects of the donation, even if the donor and receptor are matched for ABO- and/or Rhesus-blood type.

[0107] Similarly these apparatus were used for filtration of whole blood from a donor convalescing from a disease resulting in antigens and/or antibodies in the donor’s blood stream. As an example, whole blood from several recovering COVID-19 patients was obtained and separated as described herein (see preceding description of the whole blood separation) in a clinical setting. In each case, the retentate / cellular fraction was returned to the donor and the filtrate / plasma fraction was transfused to another patient suffering from the same disease. As a result of the filtration, the plasma fraction was substantially depleted from RBCs and had at most a small fraction of platelets, while containing most if not all of the antibodies of interest from the initial blood. It was found that the thus-obtained plasma functioned as an effective treatment, or at least treatment assistant, against the disease in diseased receptors, e.g. resulting in one or more of reduced hospitalisation duration, reduced intensive care-treatment duration and/or significantly higher probability of survival than a control group. The filtrate is also considered an effective vaccine against the disease in healthy receptors, e.g. resulting in lower hospitalisation rates.

[0108] The disclosure is not restricted to the above described embodiments which can be varied in a number of ways within the scope of the claims.

[0109] Elements and aspects discussed for or in relation with a particular embodiment may be suitably combined with elements and aspects of other embodiments, unless explicitly stated otherwise.