Patent Application
20130292320
The present invention relates to a filtration unit intended to allow the removal of leukocytes from a fluid, and a bag-based system comprising such a filtration unit.
It applies typically to the filtration of blood or a blood component and to the separation and collection of different constituents of the blood in the bag-based system, in particular in closed circuit.
Filtration units are already known which comprise an outer casing provided with at least one input aperture and at least one output aperture between which the fluid to be filtered flows in one direction, the casing containing a porous element comprising a medium for the removal of leukocytes by adsorption and filtration of the leukocytes.
In such units, illustrated for example by the document EP-A-0 526 678, it is conventional to use, as the leukocyte-removal medium, a stack of filtering layers formed from a porous non-woven material.
This is because, in this type of filtration—referred to as depth filtration—the capacity of the filter medium to retain the leukocytes is a function in particular of the amount of material through which the fluid passes, and therefore of the thickness of the filter medium. In addition, the disposition of a plurality of fine layers makes it possible to improve the leukocyte-removal efficiency compared with a filter medium of the same total thickness formed from a single layer.
In order to improve the effectiveness of this type of filtration, that is to say increase the quantity of leukocytes retained by the leukocyte-removal medium, consideration has therefore been given to increasing the number of stacked layers.
This solution has a number of drawbacks, however.
First, it implies an increase in the overall size of the filter which, generally speaking, is not desirable. In addition, it leads to an increase in the dead volume of the filtration unit, that is to say the amount of fluid remaining in the filtration unit after filtration, this fluid consequently being either lost or difficult to recover. In particular, in filtration units intended to filter a small amount of fluid, this constraint quickly becomes prohibitive.
Next, the increase in the number of layers causes an appreciable decrease in the flow rate of the fluid passing through the leukocyte-removal medium by gravity, and therefore increases the filtration time accordingly.
Furthermore, the applicant discovered that, from a certain value, this increase no longer had a notable positive effect on the quantity of leukocytes retained by the leukocyte-removal medium.
In addition, certain characteristics of the filter may cause injury to erythrocytes and lead to hemolysis, particularly when the fiber diameter of the fibers that comprise the filter are so low that the decreased mechanical strength of the fibers causes them to be destroyed during the filtration process. The remnants of the destroyed fibers may result in finer fibers that may injure erythrocytes during filtration and cause hemolysis.
The invention therefore aims to remedy these drawbacks by proposing in particular a unit having an improved and adaptable filtration capacity, without adversely affecting the filtration flow rate, the size of the filtration unit, or and its dead volume, and without causing or contributing to hemolysis. In addition, the filtration unit can be integrated into a bag-based system, in particular in closed circuit, in order to allow, in a simple manner, the separation and collection of different constituents of the blood.
To that end, and according to a first aspect, the invention proposes a filtration unit intended to allow the removal of leukocytes from a fluid such as blood or a blood component, of the type comprising an outer casing provided with at least one input aperture and at least one output aperture between which the fluid to be filtered flows in one direction, the casing containing a porous element comprising a medium for the removal of leukocytes by adsorption and filtration of the leukocytes, said medium comprising a number of layers of one and the same type which are formed from at least one porous non-woven material, in which at least one layer has been pressed by calendering prior to the stacking thereof, said at least one calendered layer being disposed on the downstream side of the stack, while the medium comprises at least one non-calendered layer.
According to a second aspect, the invention proposes a bag-based system for the removal of leukocytes from a fluid such as blood or a blood component, which comprises a bag for collecting the filtrate, said bag being connected, by means of a tube and at an input aperture, to an output aperture of a filtration unit as described above.
The present disclosure also aims to remedy the problems described above and enhance leukocyte depletion by providing layers of decreasing average pore size of the porous non-woven material while at the same time, having layers of the same average fiber diameter such that the mechanical strength of the fibers is not compromised and does not lead to injury to erythrocytes and hemolysis. Thus, according to a third aspect, the present disclosure provides a filtration unit for removal of leukocytes from a fluid, the filtration unit comprising an outer casing comprising: at least one inlet aperture and at least one outlet aperture between which a fluid to be filtered flows in one direction from upstream near the inlet aperture to downstream near the outlet aperture; and a porous element comprising a medium which, when the fluid flows through it, removes leukocytes by adsorption and filtration, the medium comprising: a plurality of stacked layers of a porous non-woven material with substantially the same composition, having an upstream side and a downstream side, wherein the plurality of stacked layers comprises at least one first layer and at least one second layer, wherein the at least one second layer is disposed downstream of the at least one first layer, wherein the at least one first layer has an average pore size in the range of about 5 μm to about 15 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm, wherein the at least one second layer has an average pore size in the range of from about 2 μm to about 10 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm, and further wherein the average pore size of the at least one second layer is smaller than the average pore size of the at least one first layer and the average fiber diameter of the at least one first layer and the at least one second layer are the same.
In a fourth aspect, the present disclosure also provides a bag-based system for the removal of leukocytes from a fluid comprising: a filtration unit comprising an outer casing comprising, at least one inlet aperture and at least one outlet aperture between which a fluid to be filtered flows in one direction from upstream near the inlet aperture to downstream near the outlet aperture; and a porous element comprising a medium which, when the fluid flows through it, removes leukocytes by adsorption and filtration, the medium comprising, a plurality of stacked layers of a porous non-woven material with substantially the same composition, having an upstream side and a downstream side, wherein the plurality of stacked layers comprises at least one first layer and at least one second layer, wherein the at least one second layer is disposed downstream of the at least one first layer, wherein the at least one first layer has an average pore size in the range of about 5 μm to about 15 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm, wherein the at least one second layer has an average pore size in the range of from about 2 μm to about 10 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm, and further wherein the average pore size of the at least one second layer is smaller than the average pore size of the at least one first layer and the average fiber diameter of the at least one first layer and the at least one second layer are the same.
According to a fifth aspect, the present disclosure provides an apparatus for removing leukocytes from blood or a blood component, the apparatus comprising a medium having a plurality of stacked layers of a porous non-woven material with substantially the same composition, having an upstream side and a downstream side, wherein the plurality of stacked layers comprises at least one first layer and at least one second layer, wherein the at least one second layer is disposed downstream of the at least one first layer, wherein the at least one first layer has an average pore size in the range of about 5 μm to about 15 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm, wherein the at least one second layer has an average pore size in the range of from about 2 μm to about 10 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm, and further wherein the average pore size of the at least one second layer is smaller than the average pore size of the at least one first layer and the average fiber diameter of the at least one first layer and the at least one second layer are the same.
Other objects and advantages of the invention will emerge during the following description given with reference to the accompanying drawings.
The blood or a blood component, after its collection and its separation in the case of a component, is in particular intended to be transfused into a patient requiring it.
During this transfusion, it is well known that the leukocytes are undesirable in that they are liable to cause in the patient adverse and/or potentially dangerous reactions.
This is why it is recommended, indeed required in certain countries, that the leukocytes be removed from the blood or blood component prior to the transfusion thereof, at a given efficiency. To date, the optimum solution for eliminating the leukocytes is to filter the blood or blood component through a filtration unit provided with a leukocyte-removal medium.
In the embodiment depicted in
The unit 1 also comprises a porous element 5 which is disposed in the outer casing 2 so as to form an input compartment 6 in communication with the input aperture 3 and an output compartment 7 in communication with the output aperture 4.
In the description, the terms “input”, “output”, “upstream” and “downstream” are defined with respect to the direction of movement of the fluid in the filtration unit 1 (see the arrows D shown in
When the filtration unit 1 is supplied with fluid by means of the input aperture 3, said fluid fills the input compartment 6 and then passes through the porous element 5 in order to be collected in the output compartment 7. Next, the filtrate can be collected by means of the output aperture 4.
The porous element 5 comprises a medium 8 for the removal of leukocytes by adsorption and filtration of the leukocytes. The leukocyte-removal medium 8 comprises a number of layers 9 of a first type which are formed from at least one porous non-woven material. “Type” of layers means layers of material having substantially the same composition, porosity and physico-chemical properties, that is to say substantially the same leukocyte-retention capacity, prior to calendaring.
According to one embodiment, the layers 9 can be stacked on the downstream side of the leukocyte-removal medium 8 in the direction of flow D of the fluid.
In certain embodiments, at least one and not all of these layers 9 has been pressed by calendering, in particular cold calendering, prior to the stacking thereof, the calendered layer or layers 9a being disposed on the downstream side of the stack. The stack therefore comprises, from upstream to downstream, at least one non-calendered layer 9b and at least one calendered layer 9a, said layers 9a, 9b all being of the same type.
This particular embodiment makes it possible to obtain a leukocyte-removal medium 8 of which the capacity for adsorption and filtration of the leukocytes is improved compared with a stack of non-calendered layers. This is because the calendering makes it possible in particular to reduce the mean porosity and air permeability of the layer, which increases its leukocyte-retention capacity. The applicant also discovered that, by using a leukocyte-removal medium 8 according to the invention, the time between the fluid being taken and the filtration thereof could be increased without substantially reducing the leukocyte-removal level, for example when this time is 18 hours a satisfactory leukocyte-removal level is still obtained.
Moreover, compared with a stack of layers which have all been calendered, the invention makes it possible to limit the risks of clogging of the leukocyte-removal medium 8 and to maintain a flow rate and therefore an optimal filtration time.
Calendared layers have a reduced pore size or porosity, reduced thickness and reduced permeability to air as compared to the same type of non-calendared layer. This results in increased leukocyte retention capacity. In specific embodiments, non-calendared layers have an average pore size of between 5 and 15 μm. Calendared layers made of the same type of material have an average pore size of between 2 and 10 μm. In addition, the layers generally are comprised of fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm. The fibers should have an average fiber diameter to provide for sufficient mechanical strength so as to prevent fiber destruction and injury to erythrocytes during filtration that may lead to hemolysis. In certain embodiments, the layers are comprised of fibers having the same average fiber diameter, but the layers are of different average pore sizes. In certain embodiments, the first layer may have an average pore size in the range of from about 8 μm to about 10.5 μm. In certain embodiments, the average pore size of the first layer may be about 9 μm. In certain embodiments, the second layer may have an average pore size in the range of from about 6.5 μm to about 8.5 μm. In certain embodiments, the average pore size of the second layer may be about 7 μm. In certain embodiments, the fibers of both the first and second layers may have an average fiber diameter in the range of from about 0.5 μm to about 1.5 μm. In certain embodiments, the average fiber diameters of the first and second layers may be about 1 μm. In certain embodiments, for example, the first layer may have an average pore size of about 9 μm, the second layer may have an average pore size of about 7 μm, while the average fiber diameter of the first and second layers may be about 1 μm.
In certain embodiments, the porous element comprises medium which, comprises a plurality of stacked layers of a porous non-woven material with substantially the same composition and made from the same material. The plurality of stacked layers comprises at least one first layer and at least one second layer, wherein the second layer is disposed downstream of the first layer. The first layer generally has an average pore size in the range of about 5 μm to about 15 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm. The second layer generally has an average pore size in the range of from about 2 μm to about 10 μm and comprises fibers having an average fiber diameter in the range of from about 1 μm to about 3 μm. The average pore size of the second layer is generally smaller than the average pore size of the first layer, while the average fiber diameter of the first and second layers are the same. In certain embodiments, the thickness of the first layer is in the range of from about 280 μm to about 400 μm. In certain embodiments, the thickness of the second layer is in the range of from about 130 μm to 250 μm. In certain embodiments, the first layer has an air permeability in the range of from about 250 l/m2/s to about 400 l/m2/s. In certain embodiments, the second layer has an air permeability in the range of from about 130 l/m2/s to about 200 l/m2/s.
In addition, according to the invention, the number of calendered layers 9a can be adjusted according to the leukocyte-removal efficiency desired or mandated by the different national legislations.
Finally, the solution proposed by the invention makes it possible to combine the advantages mentioned above with very simple production of the stack since the calendered layers 9a or non-calendered layers 9b are of the same type, e.g. they are made of the same type of material and had the same properties before calendaring, but the calendared layer exhibits reduced pore size, thickness and permeability to air and other structural features as described herein. In one embodiment, both calendared layers 9a and non-calendared layers 9b may be made of polypropylene. Calendared layers 9a exhibit reduced pore size, thickness and permeability to air as compared to non-calendared layers 9b. Calendared layers 9a also exhibit increased leukocyte-retention capacity as compared to non-calendared layers 9b.
In a variant of the embodiment depicted in
In particular, the layer types can be different by the nature of the material forming them and/or by their physicochemical properties.
According to one embodiment, the mean porosity of the stacked layers decreases continuously or discretely in the direction of flow. Thus, it is possible to optimize the leukocyte-removal efficiency while reducing the risks of clogging of the leukocyte-removal medium 8.
The porous element 5 can also comprise a pre-filter 10 and or a post-filter 11, disposed respectively on the upstream side and the downstream side of the leukocyte-removal medium 8. The pre-filter 10 and/or the post-filter 11 can be formed from at least one layer of a non-woven material. The pre-filter 10 and/or post-filter 11 may pore sizes between 20 μm and 60 μm.
According to a first embodiment, the material or materials forming the layers 9 is/are hydrophilic, in particular made of cellulose or its derivatives, for example cellulose acetate.
According to a second embodiment, the material or materials forming the layers 9 is/are chosen from the group comprising polymers or copolymers based on polypropylene, polyester, polyamide, high or low density polyethylene, polyurethane, polyvinylidene fluoride, polyvinylpyrrolidone and their derivatives.
These polymeric products are not generally naturally hydrophilic and must be treated by physical and/or chemical methods, in order to give them said hydrophilic properties.
These treatments consist for example of grafting hydrophilic substituents, for example hydroxyl or carboxylic type groups, onto the polymer, according to known methods.
Such polymers made hydrophilic by physical and/or chemical treatment are available on the market.
A description is given below, in connection with
In the embodiment depicted, the outer casing 2 is flexible and formed by the assembly of two sheets 12, 13 of flexible plastic material assembled with one another, for example by welding, on their periphery.
The porous element 5 is held in the outer casing 2 by deformable impervious association means which are formed from a flexible frame 14.
The flexible frame 14 is formed by an assembly of two sheets 14a, 14b, for example plasticised sheets, between which the porous element 5 is placed.
These two sheets 14a, 14b are perforated in their central part and each have at least one opening 15 allowing passage of the fluid to be filtered.
The two sheets 14a, 14b are fixed to one another preferably in the region of the periphery of the porous element 5, for example by a weld seam 16, made through the porous element 5, providing both fixing of the porous element 5 and also sealing.
The welding of the sheets 14a, 14b through the porous element 5 causes a compression, forming an impervious seam around the porous element 5.
The flexible frame 14 is welded on its periphery with the outer sheets 12, 13 forming the outer casing 2, these being welded to one another over their entire circumference and in the region of their periphery, thus providing sealing.
When this welding is performed, the input aperture 3, formed from a portion of tube, is disposed on one side of the flexible frame 14 and the output aperture 4, formed from another portion of tube, is disposed on the other side of the flexible frame 14.
Thus, the input compartment 6 formed between one sheet 12 and the porous element 5 is in communication with the input aperture 3, and the output compartment 7 formed between the other sheet 13 and the porous element 5 is in communication with the output aperture 4.
In order to avoid the porous element 5 sticking against the outer casing 2, and thus interfering with the flow of the fluid, two spacing rods 17, 18 are placed inside the output compartment 7, between the porous element 5 and the outer casing 2.
These two rods 17, 18 keep the output compartment 7 clear of the porous element 5 and thus avoid the porous element 5 being flattened against the inner wall of the outer sheet 13.
The rods 17, 18 can be produced from flexible tubes welded for example at the inner wall of the sheet of the outer casing 2, for example in the region of the peripheral weld.
It is self-evident that the number of spacing rods 17, 18 can vary, depending for example on the dimensions of the filtration unit 1.
For example, provision of a single spacing rod folded so as to form a loop inside the output compartment 7 can be envisaged.
Preferably, flexible rods 17, 18 are used, in order not to interfere with the possibilities of folding the filtration unit 1.
In another embodiment (not depicted), the outer casing 2 is rigid, for example made of a rigid plastic material such as polycarbonate.
Two example embodiments of a porous element 5 for a filtration unit 1 according to the invention are given below.
The porous element 5 comprises from upstream to downstream and stacked one upon another:
In one particular example, this porous element 5 has a filtration surface between 50 and 58 cm2, for example equal to 55 cm2, so as to allow the filtration of 450 ml of fluid with a retention level of 4.8 log (that is to say that the quantity of leukocytes is divided by 104.8 in passing through the porous element 5) compared with 4.3 with a similar porous element in which the two layers 9a have not been calendered, with similar dead volume and filtration time.
Of course, depending on the leukocyte-removal objectives to be achieved, a different number of layers 9 can be calendered.
The porous element 5 comprises from upstream to downstream and stacked one upon another:
In one particular example, this porous element 5 has a filtration surface between 15 and 35 cm2, for example equal to 20 cm2, so as to allow the filtration of 200 ml of fluid.
A description will now be given, in connection with
The system also comprises means 22 of connection with a bag containing the fluid to be filtered which are connected, by means of a tube 23, to an input aperture 3 of the filtration unit 1.
Thus the fluid, once gathered, can be introduced into the bag-based system in order to be filtered by means of the filtration unit 1, the filtrate then being collected in the bag 19.
In the variant depicted in
A description is given below, in connection with
To that end, the bag-based systems comprise a gathering bag 25 intended to contain the fluid to be filtered which has previously been filled with a preservation solution for example of CPD type, said bag 25 being connected by means of a tube 26 and at one of its output apertures 27 to the input aperture 3 of the filtration unit 1 and a collecting bag 19 intended to receive the filtrate, said bag 19 being connected by means of a tube 20 and at one of its input apertures 21 to the output aperture 4 of said filtration unit 1.
The bag-based systems in addition comprise means 28 of taking whole blood connected to an input aperture 29 of the bag 25 by means of a tube 30 provided with a device 31 for collecting a sample of blood which has been taken.
The bag-based systems also comprise a set of satellite bags 32-34 connected to an output aperture 35 of the bag 19 by means of a tube 36.
The system according to the first embodiment (
The system according to the second embodiment (
In a variant, the tubes are flexible, and can be cut and welded in order to make it possible, after the filtration and before the centrifuging, to separate the filtration unit 1 from the bag-based system.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
| Number | Date | Country | Kind |
|---|---|---|---|
| FR 02/01776 | Feb 2002 | FR | national |
This application is a continuation-in-part of U.S. patent application Ser. No. 11/567,528, filed Dec. 6, 2006, which is a continuation-in-part under 35 U.S.C. §120 of U.S. patent application Ser. No. 10/364,540, filed Feb. 11, 2003, which claims priority under 35 U.S.C. §119(d) to French Patent Application Ser. No. FR02/01776, filed Feb. 13, 2002, the entire disclosures of which are hereby incorporated by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11567528 | Dec 2006 | US |
| Child | 13932857 | US | |
| Parent | 10364540 | Feb 2003 | US |
| Child | 11567528 | US |
