Film-based blood filter element

Abstract

In a first aspect, the invention relates to a filter element, preferably a blood filter element, comprising (A) a porous film, wherein the porous film comprises at least one film forming polymer and at least one film opener and is free of reactive agents; and (B) a porous support. A second aspect of the invention is directed to a process for preparing a filter element according to the first aspect. In a third aspect, the invention relates to a filter assembly, comprising (I) the filter element of the first aspect; and (II) a spreading member (C). A fourth aspect of the invention is directed to the filter element of the first aspect or the filter assembly of the third aspect, being prepared in the form of a sheet or stripe, preferably cuttable and / or punchable sheet or stripe, from which the filter element or the filter assembly is cut and / or punched in required dimensions, wherein the sheet or stripe has larger dimensions regarding length and width than the filter element or the filter assembly, allowing to cut and / or punch out at least one filter element or filter assembly, wherein in case of a filter assembly, the remaining part of spreading member (C) is optionally removed after cutting and / or punching. A fifth aspect of the invention is related to a method for preparing a filter element of the first aspect or the filter assembly of the third aspect. A sixth aspect of the invention relates to a test carrier system comprising the filter element of the first aspect, and a seventh aspect of the invention is related to a plasma separation and metering unit comprising the filter element of the first aspect. An eight aspect of the invention is directed to the use of the filter element of the first aspect or the plasma separation and metering unit of the seventh aspect for separation of blood plasma from whole blood.

Description

[0001] Film-based Blood Filter Element

[0002] Technical Field

[0003] In a first aspect, the invention relates to a filter element, preferably a blood filter element, comprising (A) a porous film, wherein the porous film comprises at least one film forming polymer and at least one film opener and is free of reactive agents; and (B) a porous support. A second aspect of the invention is directed to a process for preparing a filter element according to the first aspect. In a third aspect, the invention relates to a filter assembly, comprising (I) the filter element of the first aspect; and (II) a spreading member (C). A fourth aspect of the invention is directed to the filter element of the first aspect or the filter assembly of the third aspect, being prepared in the form of a sheet or stripe, preferably cutable and / or punchable sheet or stripe, from which the filter element or the filter assembly is cut and / or punched in required dimensions, wherein the sheet or stripe has larger dimensions regarding length and width than the filter element or the filter assembly, allowing to cut and / or punch out at least one filter element or filter assembly, wherein in case of a filter assembly, the remaining part of spreading member (C) is optionally removed after cutting and / or punching. A fifth aspect of the invention is related to a method for preparing a filter element of the first aspect or the filter assembly of the third aspect. A sixth aspect of the invention relates to a test carrier system comprising the filter element of the first aspect, and a seventh aspect of the invention is related to a plasma separation and metering unit comprising the filter element of the first aspect. An eight aspect of the invention is directed to the use of the filter element of the first aspect or the plasma separation and metering unit of the seventh aspect for separation of blood plasma from whole blood.

[0004] Background art

[0005] Blood plasma or serum are the standard sample types used in clinical laboratory analysis. Plasma is typically obtained from venous anticoagulated whole blood samples through centrifugation followed by separation from the cell pellet. Serum is the liquid fraction of whole blood that is collected after the blood is allowed to clot.

[0006] In contrast to the lab methods, point-of-care (POC) tests usually work with whole blood samples directly. The individual performing the test, the patient or a health care professional, has only to apply the whole blood sample onto the POC test carrier (test strip or test cartridge) without the need for the test user to generate plasma or serum before the testing. However, the cellular components of whole blood, and specially the red blood cells (erythrocytes), are the primary interfering substances in the assays. Many diagnostic tests are chromogenic, wherein the analyte of interest in the sample interacts with the assay reagents and form a colored mixture or a mixture with a color change. The color intensity correlates with the amount of the analyte present in the sample. The color of the whole blood sample substantially interferes with these chromogenic tests, and therefore, the highly colored red blood cells usually are separated from the plasma or serum before the sample is assayed. The presence of blood cells also can interfere with diagnostic assay in general, leading to inconsistent or inaccurate results. Examples are the hematocrit interference or interferences caused by hemolysis of the red blood cells during the assay, induced either by mechanical or chemical damage of red blood cells during the test procedure.

[0007] Therefore, most of the POC test carriers usually contain means for separating the blood cells from the whole blood sample. These means are integrated in the test carrier and the user of the test has no additional handling steps during the testing. There are a few exceptional POC tests where whole blood samples are directly assayed without any blood cell separation; here, the hematocrit value is typically determined during the test procedure and then its sample volume is automatically corrected by the POC instrument through subtraction of the cell volume.

[0008] The separation of plasma or serum from the cellular material of whole blood is typically performed by centrifugation or clotting. The cellular material collects at the bottom of the centrifuge or the sample tube and the supernatant plasma or serum is decanted. Accordingly, the interfering cellular components of whole blood are removed such that a substantial interference is avoided. However, the centrifuge method requires a long centrifuge time and appropriate expensive equipment. POC tests with centrifugal separation use cartridges with additional microfluidic structures for collecting and assaying the generated plasma after the centrifugation step leading to more expensive and complex systems with large instruments. The clotting method for obtaining serum requires a long time (30-60 minutes) for the clotting to occur and centrifugation may be required after the clotting occurs. Therefore, serum is less optimal sample matrix for POC tests.

[0009] Most of the contemporary POC test carriers usually apply blood separation materials from state-of-the-art are membranes (asymmetrical membranes) and filters (glass fiber fleeces), which perform a physical capture / filtering of the blood cells by the geometry of their pores and holding back bigger particles. Blood separation materials based on glass fiber fleece have the disadvantage that a comparatively large probe volume is required and in the comparative slowness of the system.

[0010] Some POC test strips use chemical films, which are coated in a reel-to-reel process together with the reagent films. This film method however does not allow the use of the blood separation film in pick-and-place processes since they have no mechanical stability and in addition, they always contain also specific assay reagents. For example, EP 1 824 586 Bl discloses a system wherein a membrane is coated with a reactive film, which comprises reactive agents for detection, such as enzymes, co-enzymes, mediators, indicators or indicator systems. US 8,202,490 B2 describes a reactive film coated on a membrane, wherein the reactive film comprises reactive agents for analyte detection. EP 0 575 364 Bl relates to a test carrier comprising a reactive film, which comprises a pigment, a color formation reagent and a swelling agent.

[0011] Drawbacks of known blood separation materials used are thus that their chemical properties may hold the analyte by for example hydrophobic or polar interactions, thus reducing the analyte amount for the assay and the sensitivity. Furthermore, they also consume the sample volume due to their wicking or swelling properties, thus reducing the plasma yield and thus requiring higher whole blood sample volumes, and they require a considerable period of time to perform the blood separation. Further drawbacks are that the known blood separation materials may cause hemolysis of the whole blood samples during the separation process due to shear forces, they may lead to partial blood cell leakage, for example, caused by non- uniform pore sizes and they may show clogging and thus lead to a failed separation process.

[0012] Problem to be solved

[0013] The technical problem underlying the present invention was thus the provision of a filter element, which at least partially addresses the above-mentioned technical challenges.

[0014] The invention thus relates in a first aspect to a filter element, preferably a blood filter element, comprising (A) a porous film, wherein the porous film comprises at least one film forming polymer and at least one film opener and is free of reactive agents; and

[0015] (B) a porous support.

[0016] It was found that when contacted with whole blood, the filter element allows only the blood plasma to pass, whereas the erythrocytes were kept on the porous film and could not pass through the filter element, especially not through the polymer containing film thereof The filter element, preferably the blood filter element, is preferably inert, thus avoiding nonspecific binding of the analytes, and just holding the blood cells, especially the erythrocytes, back. Furthermore, it has a minimal wi eking / swelling for allowing a plasma generation with high yield and allows a fast blood cell separation, as well as a hemolysis-free separation, by avoiding materials with sharp-edged components or fibers. It also allows for production of materials with uniform pore size, reproducible and at low-costs. The filter element can be cut to the needed dimensions / size and can be placed by pick-and-place in a POC cartridge for allowing the separation of the cellular components of the whole blood sample and the subsequent measurement of the generated plasma in a biochemical assay within the cartridge. The size of the filter element which is integrated in the POC cartridge can be chosen on the volume of whole blood that is to be separated.

[0017] As used herein, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.

[0018] Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically will be used only once when introducing the respective feature or element. Herein, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, non-withstanding the fact that the respective feature or element may be present once or more than once. Moreover, if not otherwise indicated, the term "about" relates to the indicated value with the commonly accepted technical precision in the relevant field, preferably relates to the indicated value ± 20%, more preferably ± 10%, most preferably ± 5%.

[0019] Further, as used herein, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such a way with other optional or non-optional features of the invention.

[0020] The term “sample” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary material or combination of materials taken for an analysis, testing or investigation. The sample may be a limited quantity of something which is intended to be similar to and represent a larger amount. However, the sample may also comprise a full specimen. The sample may specifically be a fluid sample, i.e. a sample which fully or partially is in a liquid state. A quantity of the sample may be describable in terms of its volume, mass or size. However, other dimensions are feasible. Specifically, the sample may comprise several materials or compounds. The sample may specifically be a biological sample. The term “biological sample” may refer to a clinical specimen, e.g. materials taken from humans or animals. The biological sample may specifically be selected from the group consisting of: blood, specifically venous blood, specifically capillary blood.

[0021] The term “whole blood” refers to body fluid in humans or animals that delivers necessary substances such as nutrients and oxygen to cells and transports metabolic waste products away from the cells. Herein, the term “whole blood” is also abbreviated as “blood”, wherein “whole blood” and “blood” are used synonymously. The whole blood comprises blood cells and plasma, also referred to as blood plasma. The blood cells may be suspended in the blood plasma. The term “blood plasma” refers to a component of blood, which is freed from blood cells. The blood plasma may comprise water and compounds such as proteins, glucose, clotting factors, electrolytes, hormones, carbon dioxide and oxygen. Examples for proteins may be serum albumin, globulin and fibrinogen. Herein, the term “blood plasma” is also abbreviated as “plasma”, wherein “blood plasma” and “plasma” are used synonymously.

[0022] With respect to any embodiment of the filter element disclosed herein, the terms “porous support” and “porous substrate” are used interchangeably.

[0023] The blood plasma may comprise at least one analyte of interest. The term “analyte” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary element, component or compound which may be present in the sample and the presence and / or the concentration of which may be of interest. Specifically, the at least one analyte may be one constituent of the plasma such as a protein, glucose, a clotting factor, an electrolyte, an hormone, carbon dioxide or oxygen. Additionally or alternatively, however, other types of analytes may be used and / or any combination of the analytes may be determined.

[0024] “Porous” regarding the porous film of (A) means that pores are formed allowing a passage through the polymer film by the film opener.

[0025] In some preferred embodiments of the filter element, less than 1 weight-% of the porous film of (A) are reactive agent based on the total weight of the film being 100 weight-%.

[0026] In some preferred embodiments of the filter element, a reactive agent is a reagent for determining a diagnostic parameter, preferably an assay reagent. Preferably, the assay reagent is an assay reagent for an immunochemistry assay or clinical chemistry assay. Preferably a diagnostic parameter in the field of cardiac disease, sepsis, or traumatic brain injury is to be determined. Biomarkers to be determined in an immunochemistry assay are, for example, troponin-T, NT-proBNP and D-Dimer. Biomarkers to be determined in a clinical chemistry assay are, for example, potassium and creatine.

[0027] In some preferred embodiments of the filter element, the porous film of (A) comprises at least one film forming polymer, at least one film opener and at least one pigment. Film opener and pigment, if present, are uniformly distributed in the film forming polymer.

[0028] In some preferred embodiments of the filter element, at least 90 weight-%, more preferably at least 92 weight-%, of the porous film of (A) consists of at least one film forming polymer, at least one film opener and at least one pigment, based on the total weight of all solids of the porous film being 100 weight-%.

[0029] In some preferred embodiments of the filter element, in the range of from 40 to 80 weight- % of the porous film of (A) consists of the at least one pigment and of at least one film forming polymer, based on the total weight of all solids of the porous film being 100 weight- %. In some preferred embodiments of the filter element, in the range of from 0.1 to 10 weight-% of the porous film of (A) consists of the at least one film opener, based on the total weight of all solids of the porous film being 100 weight-%. In some preferred embodiments of the filter element, the porous film of (A) comprises less than 1 weight-% of water, based on the total weight of the porous film being 100 weight-%.

[0030] In some preferred embodiments of the filter element, less than 10 weight-%, preferably less than 8 weight-%, of the porous film of (A) consists of one or more component s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent, based on the total weight of the porous film being 100 weight-% wherein, if agglutination agent is present, less than 5 weight-%, of the porous film of (A) consists of agglutination agent, based on the total weight of the porous film being 100 weight-%.

[0031] In some preferred embodiments of the filter element, the sum of film forming polymer, at least one film opener, at least one pigment, water and one or more component(s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent amounts to 100 weight-%, based on the total weight of the porous film being 100 weight-%.

[0032] In some preferred embodiments of the filter element, the porous film of (A) comprises, more preferably consists to at least 99 weigh-% of, at least one film forming polymer, at least one film opener, at least one pigment, water and one or more component(s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent based on the based on the total weight of the porous film being 100 weight-%.

[0033] In some preferred embodiments of the filter element, the at least one film forming polymer is selected from the group of polyvinyl ester, preferably polyvinylacetate and / or polyvinyl propionate; polyacrylic ester; poly(methylacrylic acid); polyvinylamide; polyamide; polystyrene; copolymer of butadiene, styrene and / or maleic acid alkyl ester; polyvinylpyrrolidone; and mixtures of two or more of these polymers. In some preferred embodiments of the filter element, the at least one film forming polymer comprises at least polyvinyl propionate and / or polyvinylpyrrolidone. In some preferred embodiments of the filter element, the at least one film opener is selected from the group consisting of silicone dioxide, silicate, aluminum silicate and mixtures of two or three of these components. In some preferred embodiments of the filter element, the at least one pigment is a white pigment, preferably titanium dioxide (TiCh), zirconium dioxide (ZrCh) or a mixture of TiCh and ZrCh, more preferably TiCh. In some preferred embodiments of the filter element, the dispersant is selected from the group consisting of phosphate, citric acid, sodium salt of poly acrylic acid, alkylolammonium salt of a copolymer with acidic groups (BYK 180) and mixtures of two or more thereof. In some preferred embodiments of the filter element, the thickener is selected from the group consisting of alginate, copolymers of methacrylic acid and methyl methacrylate (Eudragit), copolymers of monoalkyl esters of poly (methyl vinyl ether / maleic acid) (Gantrez), xanthan gum (Keltrol), poly (vinylalkohol) (Mowiol), hydroxyethyl cellulose (Natrosol), and mixtures of two or more thereof. In some preferred embodiments of the filter element, the wetting agent is selected from the group consisting of sulfosuccinate (Geropon T77) N-octanoyl-N-methyl glucamide (Mega-8) and mixtures thereof. In some preferred embodiments of the filter element, the adhesive is selected from the group consisting of acrylate styrene copolymer (Alberdingk AS6002, Alberdingk SC4400, Alberdingk AS6800, Alberdingk H595), acrylic-urethane hybrid polymer (Hybridur 875 polymer dispersion), polyurethane (Baycusan C1000), urethane modified acrylic copolymer (Additol VXL 6212 N)vinyl propionate (Propiofan) and mixtures of two or more thereof. In some preferred embodiments of the filter element, the defoamer is tertamyl alcohol. In some preferred embodiments of the filter element, the agglutination agent is an agent that reacts with blood cells and thereby improves filtering capacity of the filter element, preferably a lectin (which causes agglutination via hemagglutination).

[0034] In some preferred embodiments of the filter element, film forming polymer and film opener are present in the porous film in a weight-based ratio film forming polymer : film opener in the range of from 1 : 10 to 10: 1.

[0035] In some preferred embodiments of the filter element, film forming polymer and pigment are present in the porous film in a weight-based ratio film forming polymer : pigment in the range of from 1 :5 to 1 :20, preferably in the range of from 2: 1 to 1 : 10, more preferably in the range of from 1 : 1 to 1 :2. In some preferred embodiments of the filter element, the porous film (A) has a thickness of less thanl mm.

[0036] In any of the aspects or embodiments of the filter element disclosed herein, including any methods of manufacture or use of such filter element, the porous support (substrate) (B) may, in the absence of the porous film, have a pore size insufficiently small to substantially retain one or more of platelets, erythrocytes, and leukocytes present in whole blood applied to the porous support. For example, in some embodiments, the porous support has an average pore size that permits the passage of at least some, e.g., at least about 25% or about 40%, or substantially all, e.g., at least about 50.1%, at least about 65%, or at least about 80% of platelets by number (count) in a whole blood sample applied to the porous support in the absence of the porous film. In some embodiments, the porous support has an average pore size that permits the passage of at least some, e.g., at least about 25% or about 40%, or substantially all, e.g., at least about 50.1%, at least about 65%, or at least about 80% of erythrocytes by number (count) in a whole blood sample applied to the porous support in the absence of the porous film. Such retention may be determined at standard temperature of 20 °C, without applying pressure to the applied whole blood, e.g., with the applied whole blood and porous support at a pressure of 100 kPa, and without subjecting the whole blood and porous support to artificial acceleration forces, e.g., centrifugation. In any of the embodiments, the porous support may, in the absence of the porous film, have an average pore size of at least about 1 pm, at least about 2 pm, at least about 3 pm, at least about 5 pm, at least about 15 pm, at least about 25 pm, or at least about 50 pm. Such porous support may have an average pore size of about 300 pm or less, about 200 pm or less, about 150 pm or less, or about 100 pm or less. For example, such porous support may have an average pore size of about 5 pm. In any such embodiments, the porous support may have, e.g., a thickness in the range of from 0.02 to 1 mm, e.g., in the range of from 0.03 to 0.1 mm.

[0037] In some embodiments, a filter element includes a porous film, wherein the porous film comprises at least one film forming polymer and at least one film opener and is free of reactive agents; and a porous support.

[0038] In some preferred embodiments of the filter element, the porous support of (B) is a porous membrane, preferably a microporous membrane, having an average pore size of less than 1 pm, preferably in the range of from 0.1 to 0.9 pm. In some preferred embodiments of the filter element, the porous membrane comprises a polymer selected from the group consisting of polyethylene terephthalate (PET), polycarbonate (PC), poly ethersulfone and mixtures of two or more of these polymers. In some preferred embodiments of the filter element, the porous support of (B) has a thickness in the range of from 0.02 to 1 mm, preferably in the range of from 0.03 to 0.1 mm.

[0039] In some preferred embodiments of the filter element, the porous support (B) is free of reactive agents. Preferably, less than 1 weight-% of the porous support (B) are reactive agent based on the total weight of the porous support being 100 weight-%. “Reactive agents” are as defined herein above with respect to porous film (A).

[0040] In some preferred embodiments the filter element comprises a first porous film (Al) and a second porous film (A2), wherein the porous support (B) is positioned between (Al) and (A2). Preferably, porous film (A) and porous support (B) are in direct contact with each other in that a first surface of porous film (A) is in direct contact with a first surface of porous support (B). In case of (Al), (A2), the same applies in general, i.e. a first surface of (Al) is in direct contact with a first surface of (B) and a first surface of (A2) is in direct contact with a second surface of (B).

[0041] 2ndaspect - Process for preparing filter element

[0042] A second aspect of the invention relates to a process for preparing a filter element according to the first aspect comprising

[0043] (i) providing a porous substrate (B), preferably in dry state, more preferably saturated with water;

[0044] (ii) coating an aqueous mixture comprising at least a film forming polymer and at least one film opener onto the porous substrate (B), thereby obtaining the filter element in wet form;

[0045] (iii) drying filter element in wet form of (ii), thereby obtaining the filter element preferably having a water content of less than 1 weight-% based on the total weigh of the filter element being 100 weight-%.

[0046] All details, embodiments and preferred embodiments disclosed above in the section related to the first aspect of the invention, i.e. the filter element, apply also for the second aspect of the invention.

[0047] 3rdaspect - Filter assembly with spreading member

[0048] In a third aspect, the invention relates to a filter assembly, comprising (I) the filter element of the first aspect of the invention;

[0049] (II) a spreading member (C).

[0050] All details, embodiments and preferred embodiments disclosed above in the section related to the first aspect of the invention, i.e. the filter element, apply also for the second aspect of the invention. Also, the filter element of the filter assembly is prepared or preparable by a process of the second aspect of the invention.

[0051] In some preferred embodiments of the filter assembly, porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are arranged so that the porous substrate (B) is positioned between porous film (A) or one of (Al), (A2) and spreading member (C).

[0052] In some preferred embodiments of the filter assembly, porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are directly connected to each other in that a surface of the porous film (A) or a surface of one of (Al), (A2) is in direct contact with a first surface of the porous substrate (B) and a second surface of the porous substrate (B), which is opposite to the first surface of the porous substrate (B), is in direct contact with a surface of the spreading member (C).

[0053] In some preferred embodiments of the filter assembly, porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are arranged so that porous film (A) or one of (Al), (A2) is positioned between porous substrate (B) and spreading member (C).

[0054] In some preferred embodiments of the filter assembly, porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are directly connected to each other in that a surface of the porous substrate (B) is in direct contact with a first surface of the porous film (A) or a first surface of one of (Al), (A2) and a second surface of the porous film (A), which is opposite to the first surface of the porous film (A), or a second surface of one of (Al), (A2), which is opposite to the first surface of the porous film (Al), (A2), is in direct contact with a surface of the spreading member (C).

[0055] In some preferred embodiments of the filter assembly, the spreading member (C) has a length which is larger than the extension of (A) or (Al), (A2) and / or the extension of (B) in the direction parallel to the length of (C).

[0056] The spreading member (C) enables a homogeneous liquid distribution and / or liquid transport of the plasma (in this case of the plasma). In some preferred embodiments of the filter assembly, the spreading member (C) comprises, preferably consists of, a track etched polymeric membrane (made from e.g. polyethylenterephthalat (PET), polycarbonate (PC), or a symmetric or asymmetric polyethersulfone (PES).In some preferred embodiments of the filter assembly, the spreading member (C) has a thickness in the range of from 5 to 50 pm, preferably in the range of from 8 to 36 pm. In some embodiments, the spreading member (C) is coated with one or more surfactant(s) for reduction of surface tension. Spreading members are also named, for example, spreading nets and are known to the skilled person and are disclosed, for example, in EP 2 223 746 Al.

[0057] 4thaspect - Product based on stripe, sheet

[0058] A fourth aspect of the invention relates to the filter element of the first aspect or the filter assembly of the third aspect, being prepared in the form of a sheet or stripe, preferably cutable and / or punchable sheet or stripe, from which the filter element or the filter assembly is cut and / or punched in required dimensions, wherein the sheet or stripe has larger dimensions regarding length and width than the filter element or the filter assembly, allowing to cut and / or punch out at least one filter element or filter assembly, wherein in case of a filter assembly, the remaining part of spreading member (C) is optionally removed after cutting and / or punching.

[0059] As indicated above, the filter element can be cut to the needed dimensions / size and can be placed by pick-and-place in a POC cartridge for allowing the separation of the cellular components of the whole blood sample and the subsequent measurement of the generated plasma in a biochemical assay within the cartridge. The size of the filter element which is integrated in the POC cartridge can be chosen on the volume of whole blood that is to be separated.

[0060] All details, embodiments and preferred embodiments disclosed above in the section related to the first aspect of the invention or the third aspect of the invention, i.e. the filter element and / or the filter assembly, apply also for the fourth aspect of the invention. Also, the filter element of the filter assembly is prepared or preparable by a process of the second aspect of the invention.

[0061] “Cutable” means that the filter element or filter assembly can be obtained from the sheet or stripe by conventional cutting means such as cutting it out with suitable cutting devices such as scissors. “Punchable” also means that the filter element or filter assembly can be obtained from the sheet or stripe by conventional punching means. 5thaspect - Method based on stripe, sheet

[0062] A fifth aspect of the invention is related to a method for preparing a filter element of the first aspect or a filter assembly of the third aspect comprising

[0063] (a) preparing a filter element of the first aspect or a filter assembly of the third aspect in the form of a sheet or a stripe (yard ware);

[0064] (b) cutting out and / or punching out from the sheet or stripe prepared in a) the filter element or the filter assembly;

[0065] (c) optionally removing a remaining part of spreading member (C) after cutting and / or punching from a filter assembly.

[0066] All details, embodiments and preferred embodiments disclosed above in the section related to the first aspect of the invention or the third aspect of the invention, i.e. the filter element and / or the filter assembly, apply also for the fifth aspect of the invention. Also, the filter element of the filter assembly is prepared or preparable by a process of the second aspect of the invention.

[0067] 6thaspect - Test carrier system

[0068] A sixth aspect of the invention relates to a test carrier system comprising the filter element of the first aspect.

[0069] In some preferred embodiments, the test carrier system comprises

[0070] • at least one reaction and measurement cup, wherein the reaction and measurement cup is configured for receiving at least one buffer solution, wherein the reaction and measurement cup comprises at least one optical window which is received in at least one wall of the reaction and measurement cup, the optical window enabling optical analysis of the buffer solution; and

[0071] • at least one sample processing unit, wherein the sample processing unit is attachable to the reaction and measurement cup, wherein the sample processing unit comprises: at least one sample application area, wherein the sample application area is configured for receiving at least one sample, wherein the sample application area comprises at least one hollow element which opens into an interior space of the sample processing unit; and at least one chemical reagent, wherein the chemical reagent is received within the interior space of the sample processing unit or within the reaction and measurement cup; wherein the sample application area comprises at least one receptacle forming at least one sample port, wherein the filter element of the first aspect is received or receivable in the receptacle.

[0072] The test carrier system may have any suitable shape. In some embodiments, the test carrier system has a rectangular shape. In some alternative embodiments, the test carrier system is configured to be rotatable around a rotation axis of the test carrier system whereby the buffer solution is alternatively transportable to the sample application area or to the chemical reagent depending on at least one of a direction of rotation and a degree of rotation of the test carrier system around the rotation axis of the test carrier system,

[0073] All details, embodiments and preferred embodiments disclosed above in the sections related to the first aspect or the sections related to the fourth to fifth of the invention apply also for the sixth aspect of the invention. Also, the filter element of the filter assembly is prepared or preparable by a process of the second aspect of the invention.

[0074] The term “system” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a group of at least two elements which may interact with each other in order to fulfill at least one common function. The at least two components may be handled independently or may be coupled, connectable or integratable in order to form a common component. The term “test carrier system” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to o a group of at least two elements or components which for preparing at least one sample for a purpose of conducting at least one analytical measurement. Specifically, the test carrier system may be configured for receiving the sample. Further, specifically, the test carrier system may be configured for providing a metered volume of the sample. Further, specifically, the test carrier system may be configured for one or more chemicals, specifically reagent chemicals, for further preparing the sample for conducting the at least one analytical measurement.

[0075] As outlined above, the test carrier system comprises the at least one reaction and measurement cup. The term “cup” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary element creating a partially enclosed space that may be usable to contain, store and / or to transport objects or materials. The enclosed space may also be referred to as interior space. Thus, the cup may particularly be made of a durable and / or of an at least partly rigid material such as thermoformed plastic. Specifically, the cup may be manufactured by injection molding. Specifically, the cup may be made of at least one material selected from the group consisting of polycarbonate (PC), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC / COP). However, also other materials may be possible. However, other embodiments are feasible. The cup may also be referred to as container or vessel.

[0076] The term “reaction and measurement cup” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary cup being configured for conducting at least one measurement, specifically at least one analytical measurement, specifically at least one optical measurement of one or more analytes of interest. Thereby, the one or more analytes of interest may be received in the reaction and measurement cup. Specifically, the one or more analytes of interest may be dissolved or may be dissolvable in at least one fluid medium which is received in the reaction and measurement cup. Further, the term “reaction and measurement cup” may refer to an arbitrary cup which is configured for receiving and holding at least one substance, specifically at least one liquid substance, and for enabling a reaction within the cup, such as within at least one interior space of the cup. The at least one substance, specifically the at least one liquid substance, may be configured for undergoing a chemical reaction with at least one further substance. Specifically, the reaction and measurement cup may be configured for receiving the sample or at least one constituent of the sample as will further be described below in more detail. Further, specifically, the reaction and measurement cup may be configured for receiving one or more chemical reagents which may undergo a chemical reaction with the sample or with the at least one constituent of the sample within the interior space of the reaction and measurement cup as will further be described below in more detail.

[0077] As outlined above, the reaction and measurement cup comprises the at least one wall. The term “wall” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary structure, specifically a structural material, which is configured to at least partially surround an object thereby defining physical limits of the object. Further, the wall may be configured to protect a volume at least partially enclosed by the wall.

[0078] As outlined above, the at least one optical window is received in the wall of the reaction and measurement cup. The term “optical window” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a section within a wall of an arbitrary cup or container being made of at least one optically transparent material such as of at least one optically transparent plastic material or of at least one optically transparent glass. The term “being received” may generally refer to a condition of an object of being located or inserted into a receptacle or into an opening of another element. Thus, the optical window may be inserted into a receptacle or a groove within the wall of the reaction and measurement cup. Specifically, the reaction and measurement cup may be configured for performance of an optical analysis in transmission. Thus, specifically, the reaction and measurement cup may comprise at least two optical windows, specifically two optical windows. Specifically, the reaction and measurement cup may comprise at least one first optical window and at least one second optical window. The first optical window and the second optical window respectively may be received in opposing side walls of the reaction and measurement cup, specifically such that an optical analysis in transmission of an analyte received in the buffer solution is feasible.

[0079] As outlined above, the optical window enables an optical analysis of the buffer solution, specifically of at least one analyte being dissolved in the buffer solution. The term “optical analysis” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary analytical examination including a process of determining a presence and / or a quantity and / or a concentration of at least one analyte or to a process of determining a parameter of the at least one analyte which is characteristic of the properties of the analyte based on an optical detection principle. Specifically, the optical analysis may be performed via at least one measurement device. As further used herein, the term “measurement device” may refer to an arbitrary device, preferably an electronic device, which is configured to detect at least one signal. The signal may be an optical signal. The measurement device may further comprise at least one evaluation device for evaluating at least one measurement performed with the measurement device, specifically at least one processor. The measurement device may specifically comprise at least one detector, specifically at least one optical detector. As further used herein, the term “detector” may refer to an arbitrary device which is configured to detect events or changes in its environment and to provide a corresponding output. The term “optical detector” may generally refer to an arbitrary optical instrument configured for receiving electromagnetic radiation, preferably light in the infrared and / or visible and / or ultraviolet spectral range. Thus, the optical detector may be configured for recording images, which may be stored locally, transmitted to another location or both. Further, the measurement device may comprise at least one light source.

[0080] As outlined above, the reaction and measurement cup is configured for receiving the at least one buffer solution. Thus, the reaction and measurement cup may be provided as being filled with the at least one buffer solution. Specifically, the reaction and measurement cup may be filled with the buffer solution and the reaction and measurement cup may be sealed with at least one sealing foil. Specifically, at least one opening of the reaction and measurement cup may be sealing with the at least one sealing foil. The sealing foil may be removed from the reaction and measurement cup before the sample processing unit is attached to the reaction and measurement cup. Alternatively, the sealing foil may be opened during attachment of the sample processing unit to the reaction and measurement cup. Exemplarily, the sealing foil may be pierced during attachment of the sample processing unit to the reaction and measurement cup. Thus, the sample processing unit and the reaction and measurement cup may be fluidically connected. Alternatively, the reaction and measurement cup may be provided empty and the reaction and measurement cup may be filled with the buffer solution in a separate step. The reaction and measurement cup may specifically be filled with the buffer solution such that the at least one optical window is completely covered with the buffer solution.

[0081] The term ’’buffer solution” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary solution which is an acid or a base aqueous solution comprising a mixture of a weak acid and its conjugate base, or vice versa. Its pH value may change little when a small amount of strong acid or base is added to it. The buffer solution may be configured for being used as means of keeping the pH value at a nearly constant value in a wide variety of chemical applications. The buffer solution may also be referred to as a pH buffer solution. The buffer solution may specifically be a washing buffer solution. The washing buffer solution may be configured for washing or eluting the sample or compounds of the sample from the capillary of the sample application area. The term “sample processing unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary unit which is configured for receiving at least one sample and for transferring the sample from one component of the sample processing unit to another component of the sample processing unit. Specifically, the sample processing unit may be configured for performing at least one sample preparation procedure. During the sample preparation procedure, the sample may be prepared for performing an analyte measurement as will further be described below in more detail. Specifically, the sample preparation procedure may include separating compounds of the sample from other compounds of the sample as will further be described below in more detail. Further, the sample processing unit may be configured for providing a metered volume of the sample, specifically of one or more compounds of the sample as will further be described below in more detail.

[0082] The sample processing unit may specifically comprise at least one sample processing unit housing having at least one sample processing unit opening. The term “sample processing unit housing” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an element or component of the sample processing unit having at least one interior space and at least one wall partially surrounding the at least one interior space and providing protection to the interior space, such as one or more of a mechanical protection or a protection against environmental influences such as one or more of moisture, oxygen or microbial contaminations. The sample processing unit housing may also provide a basis for attachment and / or holding the chemical reagents as will further be described below in more detail. Thus, the term “interior space” may refer to a space which is partially enclosed by the walls of the sample processing unit housing. The interior space of the sample processing unit, specifically of the sample processing unit housing, may be accessible via the sample processing unit opening. In an assembled state of the test carrier system, the interior space of the sample processing unit may face the reaction and measurement cup which is configured for receiving the at least one buffer solution of the sample processing unit to the reaction and measurement cup may specifically be a reversible attachment. However, an irreversible attachment may also be feasible. The sample processing unit may specifically be attachable to the reaction and measurement cup such that a leakage of fluids such as the buffer solution and / or the chemical reagent and / or the sample is prevented. The sample processing unit is attachable to the reaction and measurement cup via at least one mechanism selected from the group consisting of a turning mechanism, a rotation mechanism, a gasket or tight fit between the respective surfaces of the sample processing unit and the reaction and measurement cup. In an embodiment, the turning mechanism or rotation is driven by an electrical motor. In a further embodiment, said electrical motor is a stepper motor. The stepper motor may also be referred to as step motor or stepping motor. The stepper motor may be an electrical motor that rotates in a series of small angular steps. Stepper motors may be digital controlled electromagnetic actuators. The stepper motor may be a brushless DC electric motor that divides a full rotation into a number of equal steps. A motor's position can be commanded to move and hold at one of these steps without any position sensor for feedback. An electronic may control the direction and angel of rotation. In a further embodiment, said electrical motor is an electrical motor in combination with a photoelectric sensor for rotation detection, e.g. a full-circle optical rotary sensor, and an electronics controlling the direction and angle of rotation. The person skilled in the art is aware of selecting the correct motor to the application in respect to torque and speed.

[0083] The sample processing unit may specifically be attachable to the reaction and measurement cup such that the sample processing unit opening faces a reaction and measurement cup opening of the reaction and measurement cup. Thus, after attachment of the sample processing unit to the reaction and measurement cup, the reaction and measurement cup may be flui dically connected to the sample processing unit via the sample processing unit opening and the reaction and measurement cup opening.

[0084] As outlined above, the sample processing unit comprises the sample application area. The term “sample application area” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an area or section of the sample processing unit configured for receiving, accepting or making contact to the sample. As outlined above, the sample application area is configured for receiving at least one sample. Specifically, the sample application area may comprise at least one receptacle forming at least one sample port. The receptacle may specifically be an open receptacle having at least one opening. The sample may be applied via the opening of the receptacle. The receptacle may specifically be a cavity within the sample processing unit housing.

[0085] The sample processing unit, specifically the sample application area, may comprise at least one filter element. The at least one filter element may be received in the receptacle. The term “filter element” as used herein is the filter element described above in the section related to the first aspect of the invention.

[0086] The filter element may specifically have a sample application side facing the sample application area and a plasma side opposing the sample application side. The terms “sample application side” and “plasma side” as used herein are broad terms and are to be given its ordinary and customary meaning to a person of ordinary skill in the art and are not to be limited to a special or customized meaning. The terms specifically may refer, without limitation, to opposing sides of the filter element, specifically to two opposing longitudinal sides of the filter element. The sample application side may face an outer environment of the sample processing unit. When the sample is applied to the sample processing unit, the sample may get into contact with the sample application side of the filter element. Thus, the sample may cover a surface of the sample application side of the filter element at least partially. The plasma may be transferred from the sample application side to the opposing plasma side. Underneath the plasma side, the plasma may be collected.

[0087] The filter element may be received in the receptacle of the housing. Specifically, the filter element may be attached to at least one surface of the receptacle by at least one adhesive, specifically by at least one double-sided adhesive. Specifically, the adhesive may be a circumferential adhesive element. The circumferential adhesive element may be configured for adhering an outer rim of the filter element to the surface of the receptacle. Further, the filter element may be irreversibly attached to the at least one surface of the receptacle by at least one method selected from the group consisting of thermobonding; ultrasonic welder; laser welding; adhesive bonding. Also other embodiments for attaching the filter element to the surface of the receptacle may be feasible.

[0088] As outlined above, the sample application area further comprises the at least one hollow element. The term “hollow element” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary small, elongate void volume such as a small channel or tube. Generally, the hollow element may comprise dimensions in the millimeter or sub-millimeter range. In some embodiments, a fluidic medium may migrate through the hollow element by capillary action wherein the fluidic medium may flow in narrow spaces of the hollow element without an assistance of external forces like gravity due to intermolecular forces between the fluidic medium and a surface of the hollow element facing the fluidic medium. In some embodiments, movement of the fluidic medium may be caused or at least assisted by pressure (differences) or external forces such as rotation.

[0089] The “hollow element” may be a channel or a capillary. A “channel” is an element enclosed by a wall only in the directions facing away from the filter element, i.e. a channel is wallless in the direction facing towards the filter element. As further used herein, the term “wall” may generally refer to an arbitrary structure, specifically a structural material, which is configured to at least partially surround the channel. Channels or channel structures are known to the skilled person and are described, for example, in EP 1 522 343 Al. A “capillary” may specifically be a plasma metering capillary. The term “plasma metering capillary” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a capillary which is configured for providing a metered amount of plasma. Thus, the plasma metering capillary may be configured for metering the amount of plasma to an exact volume. The void volume may specifically have a precise geometry of a known volume. The plasma metering capillary may be configured for being filled accurately and repeatably with the known volume leading to the plasma being metered to the known volume prior to eluting the plasma from the plasma metering capillary.

[0090] The capillary may specifically have at least one channel. The void volume as described above may be formed by the channel. The term “channel” may generally refer to an arbitrary element which may have an elongate shape and which may provide a free volume or lumen and which enables a flow of a fluid medium there through. Consequently, the channel may be configured to receive a fluid medium and / or to provide a transfer of the fluid medium from one end of the channel to the other end of the channel. The term “lumen” generally refers to an interior volume of an arbitrary element. The interior volume may specifically be an open interior volume. Thus, the interior volume may not be fully enclosed or surrounded by a wall of the element. Instead, a flow of a fluid medium or an insertion of another object from one end of the element to a further end through the lumen may be feasible.

[0091] The channel may specifically be a straight channel. As further used herein, the term “straight” may refer to a continuous extension of the channel in one direction without a bend, angle or curve. Consequently, the channel may essentially extend in one dimension. However, small aberrations of the channel from the extension in one dimension may be existent specifically due to slight inaccuracies during manufacturing of the capillary. The capillary may specifically be a micro capillary. As further used herein, the term “micro capillary” may refer to a capillary having a channel with dimensions at a small, typically sub-millimeter scale. Specifically, the capillary may have an inner diameter in the range of 0.1 mm to 3 mm, preferably of 0.25 mm to 2 mm, most preferably of 0.5 mm to 1.3 mm. The inner diameter of the capillary may refer to a diameter of the channel. The channel may specifically at least partially have a round cross-section. Still, other shapes are also possible. Further, the capillary may have an outer diameter in the range of 0.5 mm to 5 mm, preferably of 0.75 mm to 4 mm, most preferably of 1 mm to 3 mm. Further, the capillary may have a length in the range of 0.5 mm to 20 mm, preferably of 0.75 mm to 15 mm, most preferably of 1 mm to 10 mm. Also other dimensions may be feasible.

[0092] The channel of the capillary may be at least partially enclosed by a capillary wall of the capillary. As further used herein, the term “capillary wall” may generally refer to an arbitrary structure, specifically a structural material, which is configured to at least partially surround a channel of a capillary thereby defining physical limits of the channel. The capillary wall may circumferentially enclose the channel of the capillary. The term “circumferentially enclosing” may generally refer to a property of an arbitrary object or volume of being folly enclosed by another object in at least two dimensions. Specifically, the channel of capillary may be at least partially enclosed by the capillary wall in directions perpendicular to a longitudinal axis of the capillary.

[0093] As outlined above, the capillary opens into the interior space of the sample processing unit. Specifically, the capillary may extend from the sample processing unit housing, specifically from a wall of the sample processing unit housing. Specifically, the capillary may be arranged such that the longitudinal axis of the capillary is oriented transverse, specifically perpendicular, to a longitudinal axis of the filter element.

[0094] The capillary may comprise an application end and an opposing outlet end. The terms “application end” and “outlet end” as used herein are broad terms and are to be given its ordinary and customary meaning to a person of ordinary skill in the art and are not to be limited to a special or customized meaning. The terms specifically may refer, without limitation, to opposing ends of the capillary. The application end may be fluidically connected to the receptacle. Specifically, the application end may face the filter element, specifically the plasma side of the filter element. The application end of the capillary may be at least partially received within the sample processing unit housing. The outlet end may open into the interior space of the sample processing unit. The sample, specifically compounds of the sample, specifically the plasma, may migrate through the channel of the capillary from the application end to the outlet end by capillary action. The outlet end may be configured for eluting the sample, specifically the compounds of the sample, specifically the plasma, from the capillary, specifically from the channel of the capillary.

[0095] The term “fluidically” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to property of two or more elements, wherein the two or more elements are connected such that a transfer of an arbitrary fluid medium from one of the two elements to the other one of the two elements or vice versa is provided.

[0096] The capillary may be arranged directly underneath the filter element. The filter element and the capillary may be spaced apart from each other, e.g. in a distance to each other. Thus, at least one void volume may be formed between the filter element and the capillary. Specifically, the receptacle may comprise at least one funnel compartment arranged adjacent to the application end of the capillary, specifically above the application end of the capillary. The funnel compartment may specifically refer to a conically tapered compartment. A diameter of the funnel compartment may gradually decrease, specifically along a direction perpendicular to a direction of extension of the filter element. The filter element may be received in the receptacle of the sample processing unit housing such that the funnel compartment is covered at least partially, preferably fully, by the filter element. The funnel compartment may be configured for collecting the sample, specifically the compounds of the sample, specifically the plasma, specifically after the sample, specifically the compounds of the sample, specifically the plasma, has passed through the filter element. The funnel compartment may open into the capillary, specifically into the application end of the capillary. The funnel compartment may be configured for guiding the sample, specifically the compounds of the sample, specifically the plasma, into the application end of the capillary.

[0097] At least one surface of the sample processing unit housing, specifically at least one surface of the receptacle may comprise at least one surface profiling. Specifically, the surface may be a surface of the funnel compartment. The surface profiling may comprise a plurality of microstructures. Thus, the surface profiling may be a micro-profiling. The term “microprofiling” may generally refer to an arbitrary surface profiling in which elevations and / or depressions of the surface have dimensions in the range of 1 or more micrometers, i.e. of 1 pm to 1000 pm, preferably of 10 pm to 500 pm. The dimensions may specifically refer to a height, a width and / or a depth of the elevations or the depressions. Specifically, the surface profiling may comprise an at least partially periodically arrangement of at least one element selected from the group consisting of a rectangle, a square, a pillar. Exemplarily, the surface profiling may comprise a plurality of pillars having a diameter of 10 pm to 500 pm, a height of 10 pm to 500 pm and a distance between individual pillars (edge-to-edge) of 10 pm to 1000 pm. However, also other types of elements may be feasible.

[0098] The surface profiling may specifically have a large number of the elements. The elements may be designed as an elevation on the surface. Specifically, the elements may be isolated elements which are arranged at a distance from adjacent elements. The elements may be designed to be free of contact with one another. Alternatively, the elements may at least partially touch each other. The elements may extend from the surface of the housing, in particular the elements may extend transversely, preferably perpendicularly, to the surface of the housing.

[0099] Thus, the surface profiling may be a periodic surface profiling. The term "periodic surface profiling" may generally refer to a profiling of any free surface, which occurs repetitively in a recurring sequence. In particular, as already stated above, the surface profiling may comprise the arrangement of elevations and depressions which occur repeatedly in a recurring sequence on the free surface. The arrangement of elevations and depressions may form a unit and several of the units may be arranged on the free surface.

[0100] Further, additionally or alternatively, the sample processing unit may further comprise at least one further filter element arranged between the filter element and the capillary. At least one surface of the further filter element may comprise at least one surface profiling. With regard to further details concerning the design of the surface profiling, reference may be made to the description of the surface profiling of the at least one surface of the receptacle of the housing above.

[0101] The capillary may comprise an outlet opening. The term “outlet opening” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an opening located at the outlet end of the capillary. Specifically, the outlet opening may be located at a front side of the capillary. The channel may open into the outlet opening. Further, the capillary may comprise at least one lateral opening in the capillary wall. The term “lateral opening” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an opening located at the outlet end of the capillary. Specifically, the lateral opening may be located at a longitudinal side of the capillary. Specifically, the lateral opening may be an opening within the capillary wall. The lateral opening may be located on a shell surface of the capillary wall. Thus, the lateral opening may refer to an opening which is different from the outlet opening. The lateral opening and the outlet opening may refer to two different openings of the capillary. Exemplarily, the lateral opening may be a through hole within the capillary wall. However, preferably, the lateral opening may comprise at least one slot extending along a longitudinal axis of the capillary. The term “slot” may generally refer to an opening, specifically a passage opening, a slit or to a notch in the capillary wall of the capillary. Specifically, the slot may extend from the outlet end of the capillary.

[0102] The lateral opening may be located adjacent to the outlet opening. Specifically, as outlined above, the outlet opening may be located at the front side of the capillary and the lateral opening may be located on the longitudinal side of the capillary. Thereby, the outlet opening and the lateral opening may be arranged in a distance to each other. Thus, the lateral opening may be a through hole within the capillary wall and the outlet opening and the lateral opening may be separated from each other by at least one section of the capillary wall. Further, alternatively, the outlet opening may be located at the front side of the capillary and the lateral opening may be located on the longitudinal side of the capillary and, thereby, the outlet opening and the lateral opening may be in direct contact with each other. Thus, the lateral opening may extend from the outlet end of the capillary. The lateral opening may be a slot extending from the outlet end and may form a recess within the outlet opening. The lateral opening may have a length of 0.5 mm to 20 mm, preferably of 0.75 mm to 15 mm, most preferably of 1 mm to 10 mm. However, also other lengths may be feasible. The term “length” as further used herein may be viewed in a direction along the longitudinal axis of capillary.

[0103] The lateral opening may specifically be the slot and the slot may comprise longitudinal side walls being formed in the capillary wall. The longitudinal side walls may extend along the longitudinal axis of the capillary. In a top view of the outlet end of the capillary, the side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle of 5° to 90°, preferably of 10° to 80°, most preferably of 15° to 65°. The top view of the outlet end of the capillary may correspond to a view on the front side of the capillary. Further, alternatively, in the top view of the outlet end of the capillary the longitudinal side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle of essentially 180°. In this context, the term “essentially” is to be understood as meaning that deviations from the angle of 180° may be present. For example, in the top view of the outlet end of the capillary the longitudinal side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle which is 0.01% to 0.5% larger or smaller than the angle of 180°. Specifically, the capillary may comprise one single slot wherein in the top view of the outlet end of the capillary the longitudinal side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle of essentially 180°.

[0104] Further, specifically, capillary may comprise at least two of the lateral openings, specifically of the slots. Specifically, the capillary may comprise two of the lateral openings, specifically of the slots. The longitudinal side walls of at least two of the lateral openings may, in the top view of the outlet end of the capillary, with respect to the longitudinal axis as vertex, be arranged at an angle of 15° to 45°. Specifically, the angle of the at least two lateral openings may be identical. The lateral openings may be, in the top view of the outlet end of the capillary, arranged opposite to each other.

[0105] Specifically, the capillary and the sample processing unit housing may form an integral unit. Thus, the capillary and the sample processing unit housing may be designed integrally. The term “integrally” may refer to a state wherein two or more components permanently built into at least another one of the two or more components. Exemplarily, the capillary may be fixedly attached to the sample processing unit housing. Further, exemplarily, the capillary and the sample processing unit housing may form a single piece.

[0106] The sample application area comprising the receptacle, the capillary and the filter element may specifically form a plasma separation and metering unit. The term “plasma separation and metering unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary unit which is configured for separating plasma from the biological sample which may specifically be blood. Further, the term may refer to an arbitrary unit which is configured for providing a metered volume of plasma.

[0107] As outlined above, the sample processing unit further comprises the at least one chemical reagent. The term “chemical reagent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary substance which may be configured for undergoing a chemical reaction with at least one further substance.

[0108] The chemical reagent may specifically be configured for changing at least one detectable property in the presence of the analyte. Specifically, this property may be an optically detectable property, such as a color change and / or a change in remissive properties. Specifically, the chemical reagent may be a highly selective chemical reagent, which only changes the property if the analyte is present in the sample, whereas no change occurs if the analyte is not present. More preferably, the degree or change of the property may be dependent on the concentration of the analyte, in order to allow for a quantitative detection of the analyte.

[0109] The chemical reagent may specifically be configured for performing at least one optically detectable detection reaction. As used herein, the term “optically detectable detection reaction” refers to a detection of an optically detectable property of the analyte itself or an auxiliary compound which is produced or converted with a detection reaction depending on the presence and / or concentration of the analyte in the sample, such as a color change and / or a change in remissive properties. The optically detectable detection reaction may be analyte specific. Further, the optically detectable detection reaction may be a qualitative and / or a quantitative detection.

[0110] Specifically, the chemical reagent may be a dry chemical reagent. As further used herein, the term “dry” may refer to a property of an arbitrary chemical of being at least to a large extend free from moisture. Specifically, the dry chemical reagent may be in the solid aggregate state. Molecules in a solid aggregate state may be closely packed together and may comprise a least amount of kinetic energy. A solid may be characterized by a structural rigidity and a resistance to a force applied to a surface of the solid. The dry chemical reagent may specifically be provided as a pellet. The dry chemical reagent, specifically the pellet, may be attached to a wall of the sample processing unit facing the interior space of the sample processing unit. Specifically, the dry chemical reagent may be attached to the wall of the sample processing unit by at least one adhesive material. The dry chemical reagent may be dissolvable or soluble in the buffer solution. Thus, when the dry chemical reagent may get in direct contact with the buffer solution the dry chemical reagent may be dissolved. Specifically, the sample processing unit may comprise at least two of the dry chemical reagents.

[0111] The at least two dry chemical reagents may be arranged adjacent to each other. The term “adjacent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a property of an arbitrary element of being in proximity of another element. The term “adjacent” may also be referred to as “contiguous”, “adjoint”, “besides” or further related terms. Consequently, the element and the other element may be arranged in a neighboring fashion with respect to each other. Specifically, the term “adjacent” may refer to an arrangement of the at least two of the dry chemical reagents in different angular orientations or angular positions with respect to the rotation axis, specifically such that the at least two dry chemical reagents may be triggered subsequently, specifically depending on an angle of rotation.

[0112] The sample processing unit may, as outlined above, comprise the sample processing unit housing having the at least one sample processing unit opening. The sample processing unit housing may specifically be formed by a top part and one or more side walls. The top part may extend in a horizontal plane and the side walls may extend transverse, specifically perpendicular, to the top part. The interior space may be enclosed by the top part and the side walls. The sample processing unit and the chemical reagent, specifically the at least two dry chemical reagents, may be arranged on the top part of the sample processing unit. Further, specifically, the sample application area and the chemical reagent, specifically the dry chemical reagent, may be arranged adjacent to each other, specifically on the top part of the sample processing unit. Specifically, the sample application area and the at least two chemical reagents, specifically the at least two dry chemical reagents, may be arranged adjacent to each other, specifically on the top part of the sample processing unit. Further, specifically, the at least two dry chemical reagents may be separated from each other by at least one separation wall. The separation wall may be located in the interior space of the sample processing unit. The separation wall may be oriented transverse, specifically perpendicular, to the top part of the sample processing unit. The separation wall may extend from the at least one wall of the sample processing unit, specifically from at least one all of the top part of the sample processing unit into the interior space of the sample processing unit.

[0113] Further, specifically, the chemical reagent may be a liquid chemical reagent. As used herein, the term “liquid” may refer to a property of a material of being a nearly incompressible fluid which may specifically be conform to a shape of a container where the material is received. Further, the term may refer to a property of a material of retaining an essentially constant volume independent of pressure. Specifically, the liquid chemical reagent may be located or arranged on the top part of the sample processing unit. Further, specifically, the liquid chemical reagent may be received in the interior space of the sample processing unit. Specifically, the sample processing unit may comprise at least one chamber and the liquid chemical reagent may be received in the chamber. The chamber may be arranged at the wall of the sample processing unit. Specifically, the chamber may be formed by a section of the wall of the sample processing unit, specifically by a section of a wall of the top part of the sample processing unit, and by at least one side wall extending from the wall of the sample processing unit. The chamber may be arranged adjacent to the sample application area. The chamber may be sealed with at least one chamber sealing foil. Specifically, at least one chamber opening of the chamber may be sealing with the chamber sealing foil. The chamber opening may be formed by the one side wall extending from the wall of the sample processing unit. The chamber sealing foil may specifically extend in a horizontal plane. The chamber sealing foil may face the opening of the reaction and measurement cup.

[0114] Specifically, the reaction and measurement cup may comprise at least one opening mechanism which is configured for opening the chamber sealing foil, specifically during movement of the sample processing unit to the reaction and measurement cup. The opening mechanism may specifically comprise at least one sharp-shaped element which is configured for piercing the chamber sealing foil. The sharp-shaped element may specifically be located in the interior space of the reaction and measurement cup. Specifically, the sharp-shaped element may extend from a wall, specifically from an interior wall of the reaction and measurement cup. The sharp-shaped element may extend parallel to a longitudinal axis of the reaction and measurement cup. In an assembled state of the reaction and measurement cup and the sample processing unit, the sharp-shaped element may be placed underneath the chamber, specifically underneath the chamber sealing foil. Specifically, in the assembled state of the reaction and measurement cup and the sample processing unit, the chamber sealing foil may be arranged transverse, specifically perpendicular, to the sharp-shaped element.

[0115] The chemical reagent may exemplarily be selected from an ALT / GPT (Alanine Aminotransferase acc. to IFCC without pyridoxal phosphate activation) assay, e.g. Material- Nos.: 05850797188, 05850797190, 05850797214, or from an CREP2 (Creatinine plus ver.2) assay, e.g. Material-Nos.: 05168589214, 05401470190, 08057524190. The materials are available from Roche Diagnostics GmbH. However, also other materials may be applied. The sample processing unit may be moveable with respect to the reaction and measurement cup. Thus, the reaction and measurement cup may be receivable at least partially into the interior space of the sample processing unit. The at least one side wall of the sample processing unit may enclose the at least one side wall of the reaction and measurement cup at least partially. The reaction and measurement cup may be configured for sliding into the sample processing unit, specifically, into the interior space of the sample processing unit. The sliding movement may be performed by pressing the sample processing unit towards the reaction and measurement cup, specifically manually such as by a user or a patient. Optionally, the side wall of the sample processing unit, specifically an inner surface of the side wall of the sample processing unit may comprise at least one sliding guide rail and the side wall of the reaction and measurement cup, specifically an outer surface of the reaction and measurement cup, may comprise at least one sliding receptacle, or vice versa. The sliding guide rail may be receivable in the sliding receptacle and may be configured for moving within the sliding receptacle.

[0116] As outlined above, the sample processing unit may comprise two of the chemical reagents. One of the chemical reagents may be dissolved within the buffer solution. Specifically, the sample processing unit may comprise two of the chemical reagents. The two chemical reagents may respectively be liquid chemical reagents. One of the two chemical reagents may be received in the chamber and the other one of the two chemical reagents may be dissolved within the buffer solution.

[0117] The test carrier system is configured to be rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to the sample application area and to the chemical reagent, specifically subsequently. The term “rotation axis” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a straight line that describes a rotation of an arbitrary object. As outlined above, by rotating the test carrier system around the rotation axis the buffer solution may be transported to the sample application area and to the chemical reagent, specifically subsequently. The term “transporting” may generally refer to an active transfer of an arbitrary material from one location to another location. By rotating the test carrier system around the rotation axis, the reaction and measurement cup may be tilted such that the buffer solution may leave the reaction and measurement cup and may be transferred into the interior space of the sample processing unit. The rotation of the test carrier system may specifically refer to a two-dimensional rotation. The test carrier system may be configured to be rotatable around the rotation axis in at least two possible directions. One of the two directions may refer to a clockwise motion. The clockwise motion may correspond to a direction of hands of an arbitrary clock, specifically from the top to the right, then down and then to the left, and back up to the top. Further, another one of the two directions may refer to a counterclockwise or anticlockwise motion. The anticlockwise motion may correspond to an opposite sense of rotation.

[0118] Specifically, the test carrier system may be configured to be rotatable around the rotation axis of the test carrier system whereby the washing is transported subsequently to the sample application area and to the chemical reagent. Thus, the test carrier system may configured to be firstly rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to the sample application area by a clockwise motion of the test carrier system and to be secondly rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to the chemical reagent by a counterclockwise motion of the test carrier system, or vice versa. Thus, the test carrier system may be configured to be firstly rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to the sample application area by a counterclockwise motion of the test carrier system and to be secondly rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to the chemical reagent by a clockwise motion of the test carrier system. A degree of rotation may be chosen such that, during rotation of the test carrier system around the rotation axis whereby the buffer solution is transported to the sample application area, the sample processing unit, specifically the capillary of the sample processing unit, is flooded with the buffer solution and the chemical reagent is not flooded with the buffer solution. Further, the degree of rotation may be chosen such that, during rotation of the test carrier system around the rotation axis whereby the buffer solution is transported to the chemical reagent, the chemical reagent, is flooded with the buffer solution and the sample processing unit, specifically the capillary of the sample processing unit, is not flooded with the buffer solution.

[0119] Optionally, as outlined above, the sample processing unit may comprise two of the chemical reagents. Thereby, the test carrier system may be configured to be firstly rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to the sample application area and to a first one of the two chemical reagents such as by a counterclockwise motion of the test carrier system and to be secondly rotatable around the rotation axis of the test carrier system whereby the buffer solution is transported to a second one of the chemical reagents such as by a clockwise motion of the test carrier system. A degree of rotation may be chosen such that, during rotation of the test carrier system around the rotation axis whereby the buffer solution is transported to the sample application area and to the first one of the two chemical reagents, the sample processing unit, specifically the capillary of the sample processing unit, and the first one of the two chemical reagents are flooded with the buffer solution and the second one of the chemical reagents is not flooded with the buffer solution. Further, the degree of rotation may be chosen such that, during rotation of the test carrier system around the rotation axis whereby the buffer solution is transported to the second one of the chemical reagent, the second one of the chemical reagent, is flooded with the buffer solution and the sample processing unit, specifically the capillary of the sample processing unit, and the first one of the two chemical reagents are not flooded with the buffer solution.

[0120] 7thaspect - Plasma separation and metering unit

[0121] A seventh aspect of the invention relates to a plasma separation and metering unit comprising the filter element of the first aspect.

[0122] All details, embodiments and preferred embodiments disclosed above in the sections related to the first aspect or the sections related to the fourth to sixth of the invention apply also for the seventh aspect of the invention. Also, the filter element of the filter assembly is prepared or preparable by a process of the second aspect of the invention.

[0123] In some preferred embodiments, the plasma separation and metering unit comprises:

[0124] • at least one housing, wherein the housing comprises at least one receptacle forming at least one sample port for receiving at least one biological sample comprising plasma, specifically a blood sample;

[0125] • at least one filter element of the first aspect, wherein the filter element is received in the receptacle of the housing, wherein the filter element comprises a sample application side facing the sample port and a plasma side opposing the sample application side;

[0126] • at least one plasma metering capillary extending from the housing, wherein an application end of the plasma metering capillary is fluidically connected to the plasma side of the filter element and is configured for receiving the plasma separated from the biological sample by the filter element, wherein an outlet end opposing the application end of the plasma metering capillary comprises an outlet opening, and wherein the plasma metering capillary further comprises a lateral opening in a capillary wall, the lateral opening being located adjacent to the outlet end; wherein the sample application side of the filter element is preferably on a porous film (A) or at least one of first porous film (Al), second porous film (A2) of the filter element and the plasma side of the filter element is preferably on the porous support (B) of the filter element.

[0127] As indicated above, the plasma separation and metering unit comprises at least one housing. The housing comprises at least one receptacle forming at least one sample port for receiving at least one biological sample comprising plasma, specifically at least one blood sample. Further, the plasma separation and metering unit comprises at least one filter element. The filter element is fluidically connected to the receptacle of the housing. Specifically, the filter element may be received in the receptacle of the housing. Further, there may be intermediate structure between the filter element and the receptacle of the housing such as a transport channel. The filter element comprises a sample application side facing the sample port and a plasma side opposing the sample application side. Further, the plasma separation and metering unit comprises at least one plasma metering capillary extending from the housing. An application end of the plasma metering capillary is fluidically connected to the plasma side of the filter element and is configured for receiving the plasma separated from the biological sample by the filter element. An outlet end opposing the application end of the plasma metering capillary comprises an outlet opening. The plasma metering capillary further comprises a lateral opening in a capillary wall, the lateral opening being located adjacent to the outlet end.

[0128] The term “plasma separation and metering unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary unit which is configured for separating a component of the biological sample from other components of the biological sample. Specifically, the plasma separation and metering unit may be configured for separating plasma from the biological sample which may specifically be blood. For this purpose, the plasma separation and metering unit comprises the filter element which is further described herein in the section related to the first aspect of the invention in more detail. Further, the term “plasma separation and metering unit” may refer to an arbitrary unit which is configured for providing a metered volume of the biological sample, specifically of a component of the biological sample, specifically of plasma. For this purpose, the plasma separation and metering unit comprises the plasma metering capillary which will further be described below in more detail. The plasma separation and metering unit may comprise the filter element and the plasma metering capillary and these may interact with each other in order to fulfill at least one common function as will further be described below in more detail. As outlined above, the housing comprises the at least one receptacle. The receptacle may specifically be an open receptacle having at least one opening. The biological sample may be applied via the opening of the receptacle. The receptacle may have an arbitrary shape. Specifically, the receptacle may have a cross-section having a shape which corresponds to a shape of the filter element. As outlined above, the receptacle forms the sample port for receiving the biological sample. The term “sample port” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary unit or subunit of the plasma separation and metering unit configured for receiving, accepting or making contact to the biological sample to be separated into different components by the filter element. The sample port may specifically be a cavity within the housing of the plasma separation and metering unit.

[0129] Specifically, the housing may be manufactured by injection molding. Specifically, the housing may be made of at least one material selected from the group consisting of polycarbonate (PC), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC / COP). However, also other materials may be possible.

[0130] As indicated already above, the “filter element” is the filter element described above in the section related to the first aspect.

[0131] The terms “sample application side” and “plasma side” as used herein are broad terms and are to be given its ordinary and customary meaning to a person of ordinary skill in the art and are not to be limited to a special or customized meaning. The terms specifically may refer, without limitation, to opposing sides of the filter element, specifically to two opposing longitudinal sides of the filter element. The sample application side may face an outer environment of the plasma separation and metering unit. When the biological sample is applied to the plasma separation and metering unit, the biological sample may get into contact with the sample application side of the filter element. Thus, the biological sample may cover a surface of the sample application side of the filter element at least partially. As described above, the filter element is permeable for plasma. Thus, the plasma may be transferred from the sample application side to the opposing plasma side. Underneath the plasma side, the plasma may be collected.

[0132] As outlined above, the filter element is fluidically connected to the receptacle of the housing. Specifically, the filter element may be attached to at least one surface of the receptacle by at least one adhesive, specifically by at least one double-sided adhesive. Specifically, the adhesive may be a circumferential adhesive element. The circumferential adhesive element may be configured for adhering an outer rim of the filter element to the surface of the receptacle. Further, the filter element may be irreversibly attached to the at least one surface of the receptacle by at least one method selected from the group consisting of thermobonding; ultrasonic welder; laser welding; adhesive bonding. Also other embodiments for attaching the plasma separation membrance to the surface of the receptacle may be feasible.

[0133] As outlined above, the plasma separation and metering unit comprises the plasma metering capillary. The term “capillary” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary small, elongate void volume such as a small tube. Generally, the capillary may comprise dimensions in the millimeter or sub-millimeter range. Commonly, a fluidic medium may migrate through the capillary by capillary action wherein the fluidic medium may flow in narrow spaces of the capillary without an assistance of external forces like gravity due to intermol ecul ar forces between the fluidic medium and a surface of the capillary facing the fluidic medium. The term “plasma metering capillary” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a capillary which is configured for providing a metered amount of plasma. Thus, the plasma metering capillary may be configured for metering the amount of plasma to an exact volume. The void volume may specifically have a precise geometry of a known volume. The plasma metering capillary may be configured for being filled accurately and repeatably with the known volume leading to the plasma being metered to the known volume prior to eluting the plasma from the plasma metering capillary.

[0134] The capillary may specifically have at least one channel. The void volume as described above may be formed by the channel. The term “channel” may generally refer to an arbitrary element which may have an elongated shape and which may provide a free volume or lumen and which enables a flow of a fluid medium there through. Consequently, the channel may be configured to receive a fluid medium and / or to provide a transfer of the fluid medium from one end of the channel to the other end of the channel. The term “lumen” generally refers to an interior volume of an arbitrary element. The interior volume may specifically be an open interior volume. Thus, the interior volume may not be fully enclosed or surrounded by a wall of the element. Instead, a flow of a fluid medium or an insertion of another object from one end of the element to a further end through the lumen may be feasible. The channel may specifically be a straight channel. As further used herein, the term “straight” may refer to a continuous extension of the channel in one direction without a bend, angle or curve. Consequently, the channel may essentially extend in one dimension. However, small aberrations of the channel from the extension in one dimension may be existent specifically due to slight inaccuracies during manufacturing of the plasma metering capillary.

[0135] The plasma metering capillary may specifically be a micro capillary. As further used herein, the term “micro capillary” may refer to a capillary having a channel with dimensions at a small, typically sub-millimeter scale. Specifically, the plasma metering capillary may have an inner diameter of 0.1 mm to 3 mm, preferably of 0.25 mm to 2 mm, most preferably of 0.5 mm to 1.3 mm. The inner diameter of the plasma metering capillary may refer to a diameter of the channel. The channel may specifically at least partially have a round crosssection. Still, other shapes are also possible. Further, the plasma metering capillary may have an outer diameter of 0.5 mm to 5 mm, preferably of 0.75 mm to 4 mm, most preferably of 1 mm to 3 mm. Further, the plasma metering capillary may have a of 0.5 mm to 20 mm, preferably of 0.75 mm to 15 mm, most preferably of 1 mm to 10 mm. Also other dimensions may be feasible.

[0136] The channel of the plasma metering capillary may be at least partially enclosed by a capillary wall of the plasma metering capillary. As further used herein, the term “wall” may generally refer to an arbitrary structure, specifically a structural material, which is configured to at least partially surround another object or volume thereby defining physical limits of an object. Further, the wall may be configured to protect the volume or the other object at least partially enclosed by the wall. The capillary wall may circumferentially enclose the channel of the plasma metering capillary. The term “circumferentially enclosing” may generally refer to a property of an arbitrary object or volume of being fully enclosed by another object in at least two dimensions. Specifically, the channel of the plasma metering capillary may be at least partially enclosed by the capillary wall in directions perpendicular to a longitudinal axis of the plasma metering capillary.

[0137] As outlined above, the plasma metering capillary extends from the housing. Specifically, the plasma metering capillary may be arranged such that the longitudinal axis of the plasma metering capillary is oriented transverse, specifically perpendicular, to a longitudinal axis of the filter element. The terms “application end” and “outlet end” as used herein are broad terms and are to be given its ordinary and customary meaning to a person of ordinary skill in the art and are not to be limited to a special or customized meaning. The terms specifically may refer, without limitation, to opposing ends of the plasma metering capillary. The application end may face the filter element, specifically the plasma side of the filter element. The application end of the plasma metering capillary may be at least partially received within the housing of the plasma separation and metering unit. The plasma may migrate through the channel from the application end to the outlet end by capillary action. The outlet end may be configured for eluting the plasma from the plasma metering capillary, specifically from the channel of the plasma metering capillary as will further be described below in more detail.

[0138] As outlined above, the application end is fluidically connected to the plasma side of the filter element. The term “fluidically” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to property of two or more elements, wherein the two or more elements are connected such that a transfer of an arbitrary fluid medium from one of the two elements to the other one of the two elements or vice versa is provided.

[0139] The plasma metering capillary may be arranged directly underneath the filter element. The filter element and the plasma metering capillary may be spaced apart from each other, e.g. in a distance to each other. Thus, at least one void volume may be formed between the filter element and the plasma metering capillary. Specifically, the receptacle may comprise at least one funnel compartment arranged adjacent to the application end of the plasma metering capillary, specifically above the application end of the plasma metering capillary. The funnel compartment may specifically refer to a conically tapered compartment. A diameter of the funnel compartment may gradually decrease, specifically along a direction perpendicular to a direction of extension of the filter element. The filter element may be fluidically connected to the receptacle of the housing such that the funnel compartment is covered at least partially, preferably fully, by the filter element. The funnel compartment may be configured for collecting the plasma, specifically after the plasma has passed through the filter element. The funnel compartment may open into the plasma metering capillary, specifically into the application end of the plasma metering capillary. The funnel compartment may be configured for guiding the plasma into the application end.

[0140] At least one surface of the housing, specifically at least one surface of the receptacle of the housing may comprise at least one surface profiling. Specifically, the surface may be a surface of the funnel compartment. The surface profiling may comprise a plurality of microstructures. Thus, the surface profiling may be a micro-profiling. The term “microprofiling” may generally refer to an arbitrary surface profiling in which elevations and / or depressions of the surface have dimensions in the range of 1 or more micrometers, i.e. of 1 pm to 1000 pm, preferably of 10 pm to 500 pm. The dimensions may specifically refer to a height, a width and / or a depth of the elevations or the depressions.

[0141] Specifically, the surface profiling may comprise an at least partially periodical arrangement of at least one element selected from the group consisting of: a rectangle, a square, a pillar. Exemplarily, the surface profiling may comprise a plurality of pillars having a diameter of 10 pm to 500 pm, a height of 10 pm to 500 pm and a distance between individual pillars (edge-to-edge) of 10 pm to 1000 pm. However, also other types of elements may be feasible.

[0142] The surface profiling may specifically have a large number of the elements. The elements may be designed as an elevation on the surface. Specifically, the elements may be isolated elements which are arranged at a distance from adjacent elements. The elements may be designed to be free of contact with one another. Alternatively, the elements may at least partially touch each other. The elements may extend from the surface of the housing, in particular the elements may extend transversely, preferably perpendicularly, to the surface of the housing.

[0143] Thus, the surface profiling may be a periodic surface profiling. The term "periodic surface profiling" may generally refer to a profiling of any surface, which occurs repetitively in a recurring sequence. In particular, as already stated above, the surface profiling may comprise the arrangement of elevations and depressions which occur repeatedly in a recurring sequence on the surface. The arrangement of elevations and depressions may form a unit and several of the units may be arranged on the surface.

[0144] Further, additionally or alternatively, the plasma separation and metering unit may further comprise at least one further membrane arranged between the filter element and the plasma metering capillary. At least one surface of the further membrane may comprise at least one surface profiling. With regard to further details concerning the design of the surface profiling, reference may be made to the description of the surface profiling of the at least one surface of the receptacle of the housing above.

[0145] As outlined above, the plasma metering capillary comprises the outlet opening. The term “outlet opening” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an opening located at the outlet end of the plasma metering capillary. Specifically, the outlet opening may be located at a front side of the plasma metering capillary. The channel may open into the outlet opening.

[0146] Further, as outlined above, the plasma metering capillary comprises the lateral opening in the capillary wall. The term “lateral opening” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an opening located at the outlet end of the plasma metering capillary. Specifically, the lateral opening may be located at a longitudinal side of the plasma metering capillary. Specifically, the lateral opening may be an opening within the capillary wall. The lateral opening may be located on a shell surface of the capillary wall.

[0147] Thus, the lateral opening may refer to an opening which is different from the outlet opening. The lateral opening and the outlet opening may refer to two different openings of the plasma metering capillary. Exemplarily, the lateral opening may be a through hole within the capillary wall. However, preferably, the lateral opening may comprise at least one slot extending along a longitudinal axis of the plasma metering capillary. The term “slot” may generally refer to an opening, specifically a passage opening, a slit or to a notch in the capillary wall of the plasma metering capillary. Specifically, the slot may extend from the outlet end of the plasma metering capillary.

[0148] As outlined above, the lateral opening is located adjacent to the outlet opening. The term “adjacent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a property of an arbitrary element of being in proximity of another element. The term “adjacent” may also be referred to as “contiguous”, “adjoint”, “besides” or further related terms. Consequently, the element and the other element may be arranged in a neighboring fashion with respect to each other. Specifically, as outlined above, the outlet opening may be located at the front side of the plasma metering capillary and the lateral opening may be located on the longitudinal side of the plasma metering capillary. Thereby, the outlet opening and the lateral opening may be arranged in a distance to each other. Thus, the lateral opening may be a through hole within the capillary wall and the outlet opening and the lateral opening may be separated from each other by at least one section of the capillary wall. Further, alternatively, the outlet opening may be located at the front side of the plasma metering capillary and the lateral opening may be located on the longitudinal side of the plasma metering capillary and, thereby, the outlet opening and the lateral opening may be in direct contact with each other. Thus, the lateral opening may extend from the outlet end of the plasma metering capillary. The lateral opening may be a slot extending from the outlet end and may form a recess within the outlet opening.

[0149] The lateral opening may have a length of 0.5 mm to 20 mm, preferably of 0.75 mm to 15 mm, most preferably of 1 mm to 10 mm. However, also other lengths may be feasible. The term “length” as further used herein may be viewed in a direction along the longitudinal axis of the plasma metering capillary.

[0150] The lateral opening may specifically be the slot and the slot may comprise longitudinal side walls being formed in the capillary wall. The longitudinal side walls may extend along the longitudinal axis of the plasma metering capillary. In a top view of the outlet end of the plasma metering capillary, the side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle of 5° to 90°, preferably of 10° to 80°, most preferably of 15° to 65°. The top view of the outlet end of the plasma metering capillary may correspond to a view on the front side of the plasma metering capillary.

[0151] Further, alternatively, in the top view of the outlet end of the plasma metering capillary the longitudinal side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle of essentially 180°. In this context, the term “essentially” is to be understood as meaning that deviations from the angle of 180° may be present. For example, in the top view of the outlet end of the plasma metering capillary the longitudinal side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle which is 0.01% to 0.5% larger or smaller than the angle of 180°. Specifically, the plasma metering capillary may comprise one single slot wherein the in the top view of the outlet end of the plasma metering capillary the longitudinal side walls, with respect to the longitudinal axis as vertex, may be arranged at an angle of essentially 180°.

[0152] Further, specifically, the plasma metering capillary may comprise at least two of the lateral openings, specifically of the slots. The longitudinal side walls of at least two of the lateral openings may, in the top view of the outlet end of the plasma metering capillary, with respect to the longitudinal axis as vertex, be arranged at an angle of 15° to 45°. Specifically, the angle of the at least two lateral openings may be identical. The lateral openings may be, in the top view of the outlet end of the plasma metering capillary, arranged opposite to each other.

[0153] Specifically, the plasma metering capillary and the housing may form an integral unit. Thus, the plasma metering capillary and the housing may be designed integrally. The term “integrally” may refer to a state wherein two or more components may be permanently built into at least another one of the two or more components. Exemplarily, the plasma metering capillary may be fixedly attached to the housing. Further, exemplarily, the plasma metering capillary and the housing may form a single piece.

[0154] 8thaspect - Use

[0155] An eight aspect of the invention is related to the use of the filter element of the first aspect or the plasma separation and metering unit of the seventh aspect for separation of blood plasma from whole blood.

[0156] All details, embodiments and preferred embodiments described in the sections related to the first to the seventh aspect apply also for the eight aspect of the invention.

[0157] The eight aspect of the invention also comprises a method for or separating blood plasma from whole blood.

[0158] The method for separating blood plasma from whole blood, preferably comprises

[0159] (i) providing a filter element of the first aspect of the invention;

[0160] (ii) applying a sample of whole blood onto an outer surface of the filter element, preferably onto a surface of the porous film (A) or one of (Al), (A2);

[0161] (iii) optionally applying pressure to the surface onto which the sample of whole blood has been applied in (ii);

[0162] (iv) allowing the plasma part of the whole blood sample to pass through the porous film (A) or (Al, (A2) and through the porous support (B).

[0163] Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:

[0164] Embodiment 1: A filter element, preferably a blood filter element, comprising

[0165] (A) a porous film, wherein the porous film comprises at least one film forming polymer and at least one film opener and is free of reactive agents (B) a porous support.

[0166] Embodiment 2: The filter element of embodiment 1, wherein the porous support has, in the absence of the porous film, a pore size insufficiently small to substantially retain one or more of platelets, erythrocytes, and leukocytes present in whole blood applied to the porous support.

[0167] Embodiment 3: The filter element of embodiment 2, wherein .the porous support has an average pore size that permits the passage of at least some, e.g., at least about 25% or about 40%, or substantially all, e.g., at least about 50.1%, at least about 65%, or at least about 80% of platelets by number (count) in a whole blood sample applied to the porous support in the absence of the porous film.

[0168] Embodiment 4: The filter element of any embodiment 2 or 3, wherein .the porous support has an average pore size that permits the passage of at least some, e.g., at least about 25% or about 40%, or substantially all, e.g., at least about 50.1%, at least about 65%, or at least about 80% of erythrocytes by number (count) in a whole blood sample applied to the porous support in the absence of the porous film.

[0169] Embodiment 5: The filter element of any of embodiments 1 to 4, wherein the porous support has, in the absence of the porous film, an average pore size of at least about 1 pm, at least about 2 pm, at least about 3 pm, at least about 5 pm, at least about 15 pm, at least about 25 pm, or at least about 50 pm.

[0170] Embodiment 6: The filter element of any of embodiments 1 to 5, wherein the porous support has, in the absence of the porous film, an average pore size of about 300 pm or less, about 200 pm or less, about 150 pm or less, or about 100 pm or less.

[0171] Embodiment 7: The filter element of any of embodiments 1 to 6, wherein the porous support has, in the absence of the porous film, an average pore size of at least about 5 pm, e.g., an average pore size of about 5 pm.

[0172] Embodiment 8: The filter element of any of embodiments 1 to 7, wherein less than 1 weight- % of the porous film of (A) are reactive agent based on the total weight of the film being 100 weight-%. Embodiment 9: The filter element of embodiment 1 to 8, wherein a reactive agent is a reagent for determining a diagnostic parameter, preferably an assay reagent.

[0173] Embodiment 10: The filter element of any one of embodiments 1 to 9, wherein the porous film of (A) comprises at least one film forming polymer, at least one film opener and at least one pigment.

[0174] Embodiment 11 : The filter element of embodiment 10, wherein at least 90 weight-%, preferably at least 92 weight-%, of the porous film of (A) consists of at least one film forming polymer, at least one film opener and at least one pigment, based on the total weight of all solids of the porous film being 100 weight-%.

[0175] Embodiment 12: The filter element of embodiment 10 or 11, wherein in the range of from 40 to 80 weight-% of the porous film of (A) consists of the at least one pigment and of at least one film forming polymer, based on the total weight of all solids of the porous film being 100 weight-%.

[0176] Embodiment 13: The filter element of any one of embodiments 1 to 12, wherein in the range of from 0.1 to 10 weight-% of the porous film of (A) consists of the at least one film opener, based on the total weight of all solids of the porous film being 100 weight-%.

[0177] Embodiment 14: The filter element of any one of embodiments 1 to 13, wherein the porous film of (A) comprises less than 1 weight-% of water, based on the total weight of the porous film being 100 weight-%.

[0178] Embodiment 15: The filter element of any one of embodiments 10 to 14, wherein less than 10 weight-%, preferably less than 8 weight-%, of the porous film of (A) consists of one or more component s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent, based on the total weight of the porous film being 100 weight-% wherein, if agglutination agent is present, less than 5 weight-%, of the porous film of (A) consists of agglutination agent, based on the total weight of the porous film being 100 weight-%.

[0179] Embodiment 16: The filter element of any one of embodiments 10 to 15, wherein the sum of film forming polymer, at least one film opener, at least one pigment, water and one or more component(s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent amounts to 100 weight-%, based on the total weight of the porous film being 100 weight-%.

[0180] Embodiment 17: The filter element of any one of embodiments 1 to 16, wherein the porous film of (A) comprises, preferably consists to at least 99 weigh-% of, at least one film forming polymer, at least one film opener, at least one pigment, water and one or more component(s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent based on the based on the total weight of the porous film being 100 weight-%.

[0181] Embodiment 18: The filter element of any one of embodiments 1 to 17, wherein the at least one film forming polymer is selected from the group of polyvinyl ester, preferably polyvinylacetate and / or polyvinyl propionate; polyacrylic ester; poly(methylacrylic acid); polyvinylamide; polyamide; polystyrene; copolymer of butadiene, styrene and / or maleic acid alkyl ester; polyvinylpyrrolidone; and mixtures of two or more of these polymers.

[0182] Embodiment 19: The filter element of any one of embodiments 1 to 18, wherein the at least one film forming polymer comprises at least polyvinyl propionate and / or polyvinylpyrrolidone.

[0183] Embodiment 20: The filter element of any one of embodiments 1 to 19, wherein the at least one film opener is selected from the group consisting of silicone dioxide, silicate, aluminum silicate and mixtures of two or three of these components.

[0184] Embodiment 21 : The filter element of any one of embodiments 10 to 20, wherein the at least one pigment is a white pigment, preferably titanium dioxide (TiCh), zirconium dioxide (ZrCh) or a mixture of TiCh and ZrCh, more preferably TiCh.

[0185] Embodiment 22: The filter element of any one of embodiments 15 to 21, wherein the dispersant is selected from the group consisting of phosphate, citric acid, sodium salt of poly acrylic acid, alkylolammonium salt of a copolymer with acidic groups (BYK 180) and mixtures of two or more thereof.

[0186] Embodiment 23: The filter element of any one of embodiments 15 to 22, wherein the thickener is selected from the group consisting of alginate, copolymers of methacrylic acid and methyl methacrylate (Eudragit), copolymers of monoalkyl esters of poly (methyl vinyl ether / maleic acid) (Gantrez), xanthan gum (Keltrol), poly (vinylalkohol) (Mowiol), hydroxy ethyl cellulose (Natrosol), and mixtures of two or more thereof.

[0187] Embodiment 24: The filter element of any one of embodiments 15 to 23, wherein the wetting agent is selected from the group consisting of sulfosuccinate (Geropon T77) N-octanoyl-N- methyl glucamide (Mega-8) and mixtures thereof

[0188] Embodiment 25: The filter element of any one of embodiments 15 to 24, wherein the adhesive is selected from the group consisting of acrylate styrene copolymer (Alberdingk AS6002, Alberdingk SC4400, Alberdingk AS6800, Alberdingk EI595), aery lic-ur ethane hybrid polymer (Elybridur 875 polymer dispersion), polyurethane (Baycusan Cl 000), urethane modified acrylic copolymer (Additol VXL 6212 N)vinyl propionate (Propiofan) and mixtures of two or more thereof

[0189] Embodiment 26: The filter element of any one of embodiments 15 to 25, wherein the defoamer is tert-amyl alcohol.

[0190] Embodiment 27: The filter element of any one of embodiments 15 to 26, wherein the agglutination agent is an agent that reacts with blood cells and thereby improves filtering capacity of the filter element, preferably a lectin (which causes agglutination via hemagglutination).

[0191] Embodiment 28: The filter element of any one of embodiments 1 to 27, wherein film forming polymer and film opener are present in the porous film in a weight-based ratio film forming polymer : film opener in the range of from 1 : 10 to 10: 1

[0192] Embodiment 29: The filter element of any one of embodiments 10 to 28, wherein film forming polymer and pigment are present in the porous film in a weight-based ratio film forming polymer : pigment in the range of from 1 :5 to 1 :20, preferably in the range of from2: 1 to 1 :10, more preferably in the range of from 1 : 1 to 1 :2.

[0193] Embodiment 30: The filter element of any one of embodiments 1 to 29, wherein the porous film (A) has a thickness of less thanl mm.

[0194] Embodiment 31 : The filter element of any one of embodiments 7 to 30, wherein the porous support of (B) is a porous membrane, preferably a microporous membrane, having an average pore size of less than 1 pm, preferably in the range of from 0.1 to 0.9 pm. Embodiment 32: The filter element of embodiment 31, wherein the porous membrane comprises a polymer selected from the group consisting of polyethylene terephthalate (PET), polycarbonate (PC), polyethersulfone and mixtures of two or more of these polymers.

[0195] Embodiment 33: The filter element of any one of embodiments 1 to 32, wherein the porous support of (B) has a thickness in the range of from 0.02 to 1 mm, preferably in the range of from 0.03 to 0.1 mm.

[0196] Embodiment 34: The filter element of any one of embodiments 1 to 30, wherein the porous support of (B) is a porous membrane, preferably a microporous membrane, having an average pore size of at least about 1 pm, at least about 2 pm, at least about 3 pm, at least about 5 pm, at least about 15 pm, at least about 25 pm, or at least about 50 pm and / or an average pore size of about 300 pm or less, about 200 pm or less, about 150 pm or less, or about 100 pm or less.

[0197] Embodiment 35: The filter element of embodiment 34, wherein the porous membrane comprises a polymer selected from the group consisting of polyethylene terephthalate (PET), polycarbonate (PC), polyethersulfone and mixtures of two or more of these polymers.

[0198] Embodiment 36: The filter element of embodiment 35, wherein the porous support of (B) has a thickness in the range of from 0.02 to 1 mm, preferably in the range of from 0.03 to 0.25 mm, e.g., in the range of from about 0.03 to about 1 mm.

[0199] Embodiment 37: The filter element of any one of embodiments 1 to 36, comprising a first porous film (Al) and a second porous film (A2), wherein the porous support (B) is positioned between (Al) and (A2).

[0200] Embodiment 38: A process for preparing a filter element according to any one of embodiments 1 to 38, comprising:

[0201] (i) providing a porous substrate (B), preferably in dry state, more preferably saturated with water;

[0202] (ii) coating an aqueous mixture comprising at least a film forming polymer and at least one film opener onto the porous substrate (B), thereby obtaining the filter element in wet form; (iii) drying filter element in wet form of (ii), thereby obtaining the filter element preferably having a water content of less than 1 weight-% based on the total weigh of the filter element being 100 weight-%.

[0203] Embodiment 40: A filter assembly, comprising

[0204] (I) the filter element of any one of embodiments 1 to 38;

[0205] (II) a spreading member (C).

[0206] Embodiment 41: The filter assembly of embodiment 40, wherein porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are arranged so that the porous substrate (B) is positioned between porous film (A) or one of (Al), (A2) and spreading member (C).

[0207] Embodiment 42: The filter assembly of embodiment 41, wherein porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are directly connected to each other in that a surface of the porous film (A) or a surface of one of (Al), (A2) is in direct contact with a first surface of the porous substrate (B) and a second surface of the porous substrate (B), which is opposite to the first surface of the porous substrate (B), is in direct contact with a surface of the spreading member (C).

[0208] Embodiment 44: The filter assembly of embodiment 40, wherein porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are arranged so that porous film (A) or one of (Al), (A2) is positioned between porous substrate (B) and spreading member (C).

[0209] Embodiment 44: The filter assembly of embodiment 43, wherein porous film of (A) or (Al), (A2), porous substrate (B) and spreading member (C) are directly connected to each other in that a surface of the porous substrate (B) is in direct contact with a first surface of the porous film (A) or a first surface of one of (Al), (A2) and a second surface of the porous film (A), which is opposite to the first surface of the porous film (A), or a second surface of one of (Al), (A2), which is opposite to the first surface of the porous film (Al), (A2), is in direct contact with a surface of the spreading member (C).

[0210] Embodiment 45: The filter assembly of any one of embodiments 40 to 44, wherein the spreading member (C) has a length which is larger than the extension of (A) or (Al), (A2) and / or the extension of (B) in the direction parallel to the length of (C). Embodiment 46: The filter assembly of any one of embodiments 40 to 45, wherein the spreading member (C) comprises, preferably consists of, a track etched polymeric membrane (made from e.g. polyethylenterephthalat (PET), polycarbonate (PC), or a symmetric or asymmetric polyethersulfone (PES).

[0211] Embodiment 47: The filter assembly of any one of embodiments 40 to 46, wherein the spreading member (C) has a thickness in the range of from 5 to 50 pm, preferably in the range of from 8 to 36 pm.

[0212] Embodiment 48: The filter element of any one of embodiments 1 to 37 or the filter assembly of any one of embodiments 40 to 47, being prepared in the form of a sheet or stripe, preferably cutable and / or punchable sheet or stripe, from which the filter element or the filter assembly is cut and / or punched in required dimensions, wherein the sheet or stripe has larger dimensions regarding length and width than the filter element or the filter assembly, allowing to cut and / or punch out at least one filter element or filter assembly, wherein in case of a filter assembly, the remaining part of spreading member (C) is optionally removed after cutting and / or punching.

[0213] Embodiment 49: A method for preparing a filter element of any one of embodiments 1 to 39 or a filter assembly of any one of embodiments 40 to 47 comprising

[0214] (a) preparing a filter element of any one of embodiments 1 to 39 or a filter assembly of any one of embodiments 40 to 47 in the form of a sheet or a stripe (yard ware);

[0215] (b) cutting out and / or punching out from the sheet or stripe prepared in a) the filter element or the filter assembly;

[0216] (c) optionally removing a remaining part of spreading member (C) after cutting and / or punching from a filter assembly.

[0217] Embodiment 50: A test carrier system comprising the filter element of any one of embodiments 1 to 39.

[0218] Embodiment 51 : The test carrier system of embodiment 50 comprising

[0219] • at least one reaction and measurement cup, wherein the reaction and measurement cup is configured for receiving at least one buffer solution, wherein the reaction and measurement cup comprises at least one optical window which is received in at least one wall of the reaction and measurement cup, the optical window enabling optical analysis of the buffer solution; and • at least one sample processing unit, wherein the sample processing unit is attachable to the reaction and measurement cup, wherein the sample processing unit comprises: at least one sample application area, wherein the sample application area is configured for receiving at least one sample, wherein the sample application area comprises at least one hollow element which opens into an interior space of the sample processing unit; and at least one chemical reagent, wherein the chemical reagent is received within the interior space of the sample processing unit or within the reaction and measurement cup; wherein the sample application area comprises at least one receptacle forming at least one sample port, wherein the filter element of any one of embodiments 1 to 28 is received or receivable in the receptacle.

[0220] Embodiment 52: A plasma separation and metering unit comprising the filter element of any one of embodiments 1 to 39.

[0221] Embodiment 53: The plasma separation and metering unit of embodiment 52 comprising:

[0222] • at least one housing, wherein the housing comprises at least one receptacle forming at least one sample port for receiving at least one biological sample comprising plasma, specifically a blood sample;

[0223] • at least one filter element of any one of embodiments 1 to 39, wherein the filter element is received in the receptacle of the housing, wherein the filter element comprises a sample application side facing the sample port and a plasma side opposing the sample application side;

[0224] • at least one plasma metering capillary extending from the housing, wherein an application end of the plasma metering capillary is fluidically connected to the plasma side of the filter element and is configured for receiving the plasma separated from the biological sample by the filter element, wherein an outlet end opposing the application end of the plasma metering capillary comprises an outlet opening, and wherein the plasma metering capillary further comprises a lateral opening in a capillary wall, the lateral opening being located adjacent to the outlet end; wherein the sample application side of the filter element is preferably on a porous film (A) or at least one of first porous film (Al), second porous film (A2) of the filter element and the plasma side of the filter element is preferably on the porous support (B) of the filter element. Embodiment 54: Use of the filter element of any one of embodiments 1 to 39 or the plasma separation and metering unit of embodiment 52 or 53 for separation of blood plasma from whole blood.

[0225] Embodiment 55: A method for separating blood plasma from whole blood, comprising

[0226] (i) providing a filter element of any one of embodiments 1 to 39;

[0227] (ii) applying a sample of whole blood onto an outer surface of the filter element, preferably onto a surface of the porous film (A) or one of (Al), (A2);

[0228] (iii) optionally applying pressure to the surface onto which the sample of whole blood has been applied in (ii);

[0229] (iv) allowing the plasma part of the whole blood sample to pass through the porous film (A) or (Al), (A2) and through the porous support (B).

[0230] Examples

[0231] The present invention is further illustrated by the following reference examples, comparative examples, and examples.

[0232] Chemicals Example 1: Preparation of blood filter element

[0233] An aqueous mixture according to Table 1 was prepared, wherein the components were mixed according to the step sequence indicated in Table 1.

[0234] Table 1

[0235] The resulting aqueous mixture having a weight of 250 g was applied onto a given porous support material made of polyethersulfone (Supor 5000) having about the dimensions of a DIN A4 paper sheet, which was preferably saturated with water, wherein the application was done by knife coating / table coating / slot die coating at room temperature (in the range of from 20 to 25 °C). Afterwards, the resulting polymer containing film was dried at a temperature range from 80 - 120 °C - the composition of the resulting dry film is indicated in Table 1. Dried polymer containing film and porous support material together were considered as blood filter element.

[0236] Example 2: Separation of whole blood sample

[0237] A whole blood sample, to which a blue colorant such as prussian blue had been added, was applied onto the blood filter element of Example 1, wherein the sample was applied onto the dried polymer containing film. After a period of time of at least 2 minutes, the surface of the carrier substrate facing away from the dried polymer containing film showed a colored area, which was blue only. Both sides of the blood filter element are shown in Fig. 1, wherein Fig. 1A shows the side of the blood filter element with view onto the polymer containing film and Fig. IB shows the opposite side of the filter element, i.e. the surface of the carrier substrate facing away from the polymer containing film.

[0238] It was apparent that only the blood plasma with blue colorant could pass through the filter element (see blue spot, shown in light grey in Fig. IB), whereas the erythrocytes were kept on the polymer containing film and could not pass through the filter element, especially not through the polymer containing film thereof (see dark red spot, shown in black in Fig. 1 A).

[0239] Short description of the Figures

[0240] Fig. 1 shows the filter element of Example 2, wherein Fig. 1 A shows the remaining dark red (here black) spot after application of a whole blood sample (supplemented with colorant), indicating that the erythrocytes were retained on the application side, while Fig. IB shows a blue (here in grey) spot indicating that the plasma had passed through the filter element.

[0241] Fig. 2A shows a filter element (100) with a porous film (101) and a porous support (102).

[0242] Fig. 2B shows a filter element (200) with a first porous film (201), a second porous film (201) and a porous support (202) between first and second porous film.

[0243] Fig. 3A shows a filter element (100) comprising a porous film (101) arranged on top of a porous substrate (102), which in turn is arranged on top of a spreading member (300), together with a schematic drop of whole blood (400). Fig. 3B shows a filter element (100) comprising a porous substrate (102) arranged on top of a porous film (101), which in turn is arranged on top of a spreading member (300), together with a schematic drop of whole blood (400).

[0244] Fig. 3C shows a filter element (200) with a first porous film (201), a second porous film (201) and a porous support (202) between first and second porous film, the filter element (200) being arranged on top of a spreading member (300), together with a schematic drop of whole blood (400).

[0245] Reference Numbers

[0246] 100 Filter element

[0247] 101 Porous film (A)

[0248] 102 Porous substrate (B)

[0249] 200 Filter element

[0250] 201 First porous film (Al)

[0251] 202 Porous substrate (B)

[0252] 203 Second porous film (A2)

[0253] 300 spreading member (C)

[0254] 400 drop of whole blood

[0255] Cited Literature

[0256] EP 1 824 586 Bl

[0257] US 8,202,490 B2

[0258] EP 0 575 364 Bl

[0259] EP 2 223 746 Al

[0260] EP 1 522 343 Al

[0261] European patent application no. EP24158143.8, “Film-Based Blood Filter Element” is incorporated herein by reference in its entirety.

Claims

Claims1. A filter element, preferably a blood filter element, comprising(A) a porous film, wherein the porous film comprises at least one film forming polymer and at least one film opener and is free of reactive agents;(B) a porous support; wherein the porous film of (A) consists to at least 99 weight-% of at least one film forming polymer, at least one film opener, at least one pigment, water and one or more component(s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent, based on the based on the total weight of the porous film being 100 weight-%.

2. The filter element of claim 1, wherein a reactive agent is a reagent for determining a diagnostic parameter, preferably an assay reagent, more preferably an assay reagent.

3. The filter element of claim 1 or 2, wherein the porous film of (A) comprises at least one film forming polymer, at least one film opener and at least one pigment wherein preferably at least 90 weight-%, more preferably at least 92 weight-%, of the porous film of (A) consists of at least one film forming polymer, at least one film opener and at least one pigment, based on the total weight of all solids of the porous film being 100 weight-%.

4. The filter element of claim 3, wherein less than 10 weight-%, preferably less than 8 weight-%, of the porous film of (A) consists of one or more component(s) selected from the group consisting of dispersant, thickener, wetting agent, adhesive, precipitant, defoamer, and agglutination agent, based on the total weight of the porous film being 100 weight-% wherein, if agglutination agent is present, less than 5 weight-%, of the porous film of (A) consists of agglutination agent, based on the total weight of the porous film being 100 weight-%.

5. The filter element of any one of claims 1 to 4, wherein film forming polymer and film opener are present in the porous film in a weight-based ratio film forming polymer : film opener in the range of from 1 : 10 to 10: 1.

6. The filter element of any one of claims 1 to 5, comprising a first porous film (Al) and a second porous film (A2), wherein the porous support (B) is positioned between (Al) and (A2).

7. The filter element of any one of claims 1 to 6, wherein the porous support of (B) is a porous membrane, preferably a microporous membrane, having an average pore size of less than 1 pm, preferably in the range of from 0.1 to 0.9 pm.

8. The filter element of claim 7, wherein the porous membrane comprises a polymer selected from the group consisting of polyethylene terephthalate (PET), polycarbonate (PC), polyethersulfone and mixtures of two or more of these polymers.

9. A process for preparing a filter element according to any one of claims 1 to 8 comprising(i) providing a porous substrate (B), preferably in dry state, more preferably saturated with water;(ii) coating an aqueous mixture comprising at least a film forming polymer and at least one film opener onto the porous substrate (B), thereby obtaining the filter element in wet form;(iii) drying filter element in wet form of (ii), thereby obtaining the filter element preferably having a water content of less than 1 weight-% based on the total weigh of the filter element being 100 weight-%.

10. A filter assembly, comprising(I) the filter element of any one of claims 1 to 8;(II) a spreading member (C).

11. The filter element of any one of claims 1 to 8 or the filter assembly of claim 10, being prepared in the form of a sheet or stripe, preferably cuttable and / or punchable sheet or stripe, from which the filter element or the filter assembly is cut and / or punched in required dimensions, wherein the sheet or stripe has larger dimensions regarding length and width than the filter element or the filter assembly, allowing to cut and / or punch out at least one filter element or filter assembly,wherein in case of a filter assembly, the remaining part of spreading member (C) is optionally removed after cutting and / or punching.

12. A method for preparing a filter element of any one of claims 1 to 8 or a filter assembly of claim 10 comprising(a) preparing a filter element of any one of claims 1 to 8 or a filter assembly of claim 10 in the form of a sheet or a stripe (yard ware);(b) cutting out and / or punching out from the sheet or stripe prepared in a) the filter element or the filter assembly;(c) optionally removing a remaining part of spreading member (C) after cutting and / or punching from a filter assembly.

13. A test carrier system comprising the filter element of any one of claims 1 to 8, wherein the test carrier system preferably comprises:• at least one reaction and measurement cup, wherein the reaction and measurement cup is configured for receiving at least one buffer solution, wherein the reaction and measurement cup comprises at least one optical window which is received in at least one wall of the reaction and measurement cup, the optical window enabling optical analysis of the buffer solution; and• at least one sample processing unit, wherein the sample processing unit is attachable to the reaction and measurement cup, wherein the sample processing unit comprises: at least one sample application area, wherein the sample application area is configured for receiving at least one sample, wherein the sample application area comprises at least one hollow element which opens into an interior space of the sample processing unit; and at least one chemical reagent, wherein the chemical reagent is received within the interior space of the sample processing unit or within the reaction and measurement cup; wherein the sample application area comprises at least one receptacle forming at least one sample port, wherein the filter element of any one of claims 1 to 8 is received or receivable in the receptacle.

14. A plasma separation and metering unit comprising the filter element of any one of claims 1 to 8, wherein the plasma separation and metering unit of preferably comprises:at least one housing, wherein the housing comprises at least one receptacle forming at least one sample port for receiving at least one biological sample comprising plasma, specifically a blood sample;• at least one filter element of any one of claims 1 to 8, wherein the filter element is received in the receptacle of the housing, wherein the filter element comprises a sample application side facing the sample port and a plasma side opposing the sample application side;• at least one plasma metering capillary extending from the housing, wherein an application end of the plasma metering capillary is fluidically connected to the plasma side of the filter element and is configured for receiving the plasma separated from the biological sample by the filter element, wherein an outlet end opposing the application end of the plasma metering capillary comprises an outlet opening, and wherein the plasma metering capillary further comprises a lateral opening in a capillary wall, the lateral opening being located adjacent to the outlet end; wherein the sample application side of the filter element is preferably on a porous film(A) or at least one of first porous film (Al), second porous film (A2) of the filter element and the plasma side of the filter element is preferably on the porous support(B) of the filter element.

15. Use of the filter element of any one of claims 1 to 8 or the plasma separation and metering unit of claim 14 for separation of blood plasma from whole blood.

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