Microfluidic device for plasma production

Abstract

The invention relates to a microfluidic device (100) for obtaining blood plasma, comprising a blood collection module (110) (101) having a first membrane (111A) designed to separate the plasma and a specific surface (112) arranged downstream of said first membrane (111A) for extracting the plasma. Said device (100) further comprises a capillary channel (120) in fluidic connection with said specific surface (112), arranged to circulate said plasma in said channel (120), and with a flow outlet (130). The capacity of the collection module (110) is greater than the capacity of the capillary channel (120), and said capillary channel (120) is arranged such that the combined effect of capillarity and gravity is greater than the surface tension of the plasma as it flows through said capillary channel (120). Figure to be published with the abbreviation: Fig 1

Description

Title of the invention: Microfluidic device for obtaining plasma. Technical field

[0001] The present invention relates generally to the field of blood testing devices. It relates in particular to a microfluidic device for obtaining blood plasma. Previous technique

[0002] In 2019, according to the World Health Organization, seven of the ten leading causes of death worldwide were chronic diseases, and the percentage of deaths related to such diseases is constantly increasing. Chronic diseases are defined as progressive diseases with a duration of several months. Numerous studies have shown that early detection of such diseases increases a patient's chances of survival. For example, in the case of several types of cancer, survival can be more than three times higher when the cancer is diagnosed early (stage one or two).Similarly, early detection of markers linked to acute diseases or symptoms, as well as pathogens such as, for example, the Covid-19 virus, the pathogen associated with Lyme disease or that linked to septicemia, or the Human Immunodeficiency Virus (known by the acronym HIV), makes it possible to assess the risk of severe pathological form and to quickly guide management, which may need to be immediate and vital in some cases, in order to promote recovery.

[0003] For this reason, blood biomarkers, which are biological characteristics, are attracting increasing interest as indicators of normal or pathological biological processes. Each biomarker has its own specific characteristics that allow it to provide information related to an underlying pathophysiological process and / or data on disease progression. By analogy, biomarkers are to doctors what fingerprints are to police officers: veritable signatures that allow the identification not of an individual, but of a disease. Biomarkers consist of molecules (proteins, hormones, etc.) and cells whose presence or abnormal concentration in the blood, particularly in blood plasma, confirms the existence of a pathology.Blood plasma is the liquid component of blood devoid of red blood cells, white blood cells, platelets and other contaminants, constituting approximately fifty-five percent of the total blood volume and containing at least three hundred proteins.

[0004] A biomarker may be present in patients with a specific disease and absent in healthy individuals or those affected by other diseases. However, precise quantification of a biomarker allows it to reflect the progression of a pathology. For example, the quantity of a biomarker may increase or decrease depending on whether the disease worsens or improves, and vice versa. Thus, such quantitative indicators allow; - to refine a prognosis by delivering complete information to characterize a disease (or the presence of a pathogen) in an individual and optimize their management; - to adapt the treatment best suited to each patient. In this respect, depending on their metabolism, some people assimilate a medication particularly quickly. In this case, the medication can pass more rapidly into the blood, its effects are increased, and it is therefore necessary to reduce the doses usually prescribed; - to monitor the effects of a therapy. For example, in the case of cancer, cancer cells release various molecules into the bloodstream. If their concentration increases over time, this may indicate that the cancer is recurring. Quantifying blood biomarkers therefore appears to be an essential tool for personalized medicine.

[0005] Traditionally, such quantification is possible using the conventional and proven process of blood collection. However, this process requires a large quantity of blood, the intervention of qualified personnel, and the use of specialized equipment. In this case, blood plasma is currently separated from the other blood components by centrifugation: this involves placing the blood collected during the blood draw in a centrifuge, which spins and separates the blood cells from the liquid. Besides the fact that such a centrifugation step is not within the reach of every user, particularly in terms of available resources, this step also requires qualified personnel because improper handling after collection and / or excessive centrifugation can lead to a known phenomenon of hemolysis, whereby red blood cells can break and alter the obtained blood plasma.Indeed, the cellular components released (e.g., potassium, magnesium, iron, lactate dehydrogenase, hemoglobin, phosphate) during such destruction of red blood cells can alter the relevance and accuracy of subsequent protein quantification from the hemolyzed plasma, thus leading to falsified final results. Therefore, such a process proves costly, time-consuming, and unsuitable for most users.

[0006] It is known that devices for obtaining blood plasma do not use such a centrifugation step, such as, for example, the device disclosed in the US document 2012 / 0275955A1. However, such a device requires a negative pressure chamber to create a flow and forcibly separate blood plasma from a blood sample through a membrane. This forced filtration can deform the membrane and may even cause hemolysis, thus altering the resulting blood plasma. Description of the invention

[0007] The present invention therefore aims to improve upon this observation. To this end, it proposes a simplified microfluidic device that can be implemented by any user in order to ultimately obtain a quantity of plasma in a rapid and reliable manner, allowing for subsequent quantification of a blood biomarker.

[0008] To this end, a first object of the invention relates to a microfluidic device for obtaining a quantity of plasma comprising: - a blood collection module comprising: • a first microporous membrane arranged to receive a quantity of blood and designed to separate, by gravity and by capillarity, when said first membrane is substantially horizontal, the constituents of the blood according to their sizes and thus trap said constituents other than blood plasma; • a specific surface exhibiting hydrophobic, hydrophilic and surface tension properties and arranged downstream of said first membrane in order to extract, by capillarity, the blood plasma from said first membrane; - a capillary channel having a first end with said specific surface, the latter being arranged to circulate said blood plasma by capillary action within said capillary channel, and a second end in fluidic connection with a flow outlet. Furthermore, the capacity of the collection module is greater than the capacity of the capillary channel, and the latter is arranged such that the combined effect of capillarity and gravity is greater than the surface tension of the blood plasma when said blood plasma flows through said capillary channel.

[0009] In a preferred embodiment, to enhance filtration, the collection module may further comprise a second microporous membrane. The first and second microporous membranes are then arranged so that the first membrane is positioned horizontally on the second membrane; that each of the first and second membranes has an upstream surface and a downstream surface, and that the upstream surface of said second membrane fully supports the downstream surface of said first membrane. Furthermore, said surface specific is then arranged downstream of said first and second membranes and upstream of the first end of the capillary channel in order to extract, by capillary action, the blood plasma filtered by the first and second membranes and to circulate it in said capillary channel.

[0010] For such a preferred embodiment, the first microporous membrane can be an asymmetric membrane and the second microporous membrane can be an isometric membrane.

[0011] In order to reduce surface tension due to the walls of the blood capillary, the second end of the capillary channel can be in the form of a bevel.

[0012] A second object of the invention consists of a method for implementing such a microfluidic device for obtaining blood plasma according to the invention. Such a method includes a step of depositing a minimal quantity of blood into said collection module to allow the flow of blood plasma from the collection module to the capillary channel and through the flow outlet. Brief description of the drawings

[0013] The invention will be better understood and other features and advantages thereof will become apparent from the following description of particular embodiments of the invention, given by way of illustrative and non-limiting examples, and with reference to the accompanying drawings, among which: - [Fig. 1] shows a preferred example of the implementation of a device microfluidics for obtaining a quantity of plasma according to the invention; - [Fig.2] is an illustrative schematic view of the collection module according to the invention; - [Fig.3] is a schematic view of the device according to the invention illustrating the implementation of said device according to the invention; - [Fig.4] is an illustrative schematic view of the collection module according to a variant of the invention; - [Fig.5] is a schematic view of a variant of the device according to the invention; - [Fig. 6] is a schematic view of the device according to the invention illustrating the implementation of said device according to the invention. Description of the implementation methods

[0014] To simplify the description, the same reference numeral is used in different figures to designate the same object or element. Thus, when the description cites a referenced object or element, that object or element can be identified in several figures. Furthermore, the figures and the description are given as non-limiting examples of embodiments.

[0015] A preferred example of a microfluidic device 100 for obtaining blood plasma, according to the invention, is shown in [Fig. 1]. Said device 100 comprises at least one blood plasma collection module 110 102 in fluidic connection with a first end 120a of a capillary channel 120, itself in fluidic connection with a flow outlet 130 at a second end 120b of the capillary channel 120.

[0016] The blood plasma collection module 110 is arranged to receive a quantity of blood 101, or any blood fluid (e.g., previously treated blood), taken directly from a person, for example, from their finger. Such a collection module 110 comprises: - a first microporous membrane 11 IA through which the collected blood 101 can flow; - and a specific surface 112 having hydrophobic, hydrophilic and surface tension properties for extracting blood plasma 102 from said first microporous membrane 111A and circulating said blood plasma 102 into said capillary channel 120.

[0017] This first 11 IA membrane uses the principle of membrane filtration, thus acting as a physical barrier with a calibrated porosity ensuring selective permeability of certain blood constituents below a given size. As illustrated in [Fig.2], said first microporous membrane 11 IA is arranged to receive a quantity of blood 101 and to separate, by gravity when said first microporous membrane 111A is substantially horizontal, the constituents of the blood according to their sizes so that white blood cells WBC having a diameter substantially between twelve and eighteen micrometers, red blood cells RBC having a diameter substantially between six and eight micrometers, platelets PL having a diameter substantially equal to two micrometers and the other constituents of large diameter can be substantially trapped in said first membrane 11 IA in contrast to the blood plasma 102 being able to flow through said first membrane 111 A. .

[0018] Such a first membrane 11 IA preferably consists of an asymmetric membrane, in this case a membrane having a pore structure, for example an average pore size, which varies throughout the membrane. As such, said first membrane 111A has an upstream surface 111 As and a downstream surface 111 Ai with pores of larger cross-sectional dimensions at the upstream surface 11 As than at the downstream surface 11 Ai. More broadly, for the purposes of the invention, the "upstream surface" of a microporous membrane means the upper surface of said membrane, the surface being the highest when the microporous membrane is positioned horizontally, and the "downstream surface" of a microporous membrane, the lower surface of said membrane, the surface being the lowest when the microporous membrane is positioned horizontally. By way of illustration but not limitation, such a membrane 111A may be characterized by a thickness of three hundred to three hundred and fifty micrometers with an average pore size on the upstream surface 111As of approximately one hundred micrometers and of 1.8 to 2 micrometers on the downstream surface 111Ai. As an example, membranes of the Pall Vivid® brand are known and available on the market.

[0019] As illustrated in Figures 1 and 2, the last essential component of the collection module 110, in this case said specific surface 112, is positioned downstream of the downstream surface 111 Ai of the first membrane 111A and upstream of the first end 120a of the capillary channel 120. Such a specific surface 112 has hydrophobic, hydrophilic and surface tension properties to extract by gravity the blood plasma 102 from the first membrane 111A and to circulate and advance said blood plasma 102 in said capillary channel 120 by capillarity, thus allowing the continuity of said plasma 102 in said device 100, and not just its retention, as illustrated in [Fig.3].In other words, in order to absorb blood plasma 102 from said first membrane 111A and passively set it in motion within the capillary channel 120, such a specific surface 112 must exhibit an optimized balance between hydrophobic and hydrophilic properties. Indeed, since blood plasma 102 is primarily hydrophilic (composed of approximately ninety percent water) but also contains hydrophobic material, said specific surface 112 must have a suitable surface tension and be made of a hydrophilic material without being soluble in water.In this respect, the specific surface 112 may preferably be made of polymethyl methacrylate, a thermoplastic polymer known by the acronym PMMA, which is predominantly hydrophilic (the contact angle with water is approximately sixty-eight degrees) and has a good balance between hydrophobic (methylene) and hydrophilic (carbonyl) groups. However, those skilled in the art should not limit themselves to such a material and may consider any other type of material that provides similar properties or equivalent ones, such as, for example, derivatives of polyacrylamide, polyurethane, poly(hydroxyethyl methacrylamide), or poly(ethylene glycol).As an alternative or complement, it is possible to optimize or even improve the hydrophilic characteristics of the chosen material(s) by using treatments that functionalize the surfaces of said materials, in particular by modifying their surface tension, such as, for example, plasma gas treatments (argon, oxygen, ...), Corona treatments or even chemical treatments (with sodium hydroxide, polyvinyl alcohol, or hydroxypropylmethylcellulose, ...).

[0020] It should be noted that said first membrane 111A may also have one or more surface treatments designed to improve certain of its surface characteristics. Such surface treatments may have defects that may allow certain blood constituents 101 to pass through, which are to be filtered by said first membrane 111A, such as, for example, red blood cells (RBCs) and / or platelets (PLs). Thus, in addition, in such a case where the first membrane 11IA may prove inadequate in terms of filtration, the collection module 110 may advantageously include a second microporous membrane 11IB positioned horizontally, like the first membrane 11IA, and so as to support the entirety of the latter, as illustrated in [Fig. 4]. Such a second membrane 11IB has an upstream surface 11IBs and a downstream surface 11IBi.Thus, such a second membrane 11 IB is arranged to receive the residual blood plasma 102, still potentially "contaminated" by other blood components 101, from said first membrane 111A by capillary action in order to complete the filtration. To this end, said second microporous membrane 11 IB preferentially exhibits hydrophilic characteristics in order to draw blood plasma 102 from the first membrane 111A and it allows the separation, by gravity and capillary action, of the remaining blood components other than blood plasma 102 (example: red blood cells RBCs, platelets PLs), which remain trapped in said second membrane 11 IB, from the blood plasma 102, which can then flow through said second membrane 11 IB. As such, the "contaminated" blood plasma 102 from the downstream surface 111 Ai of said first membrane 111A passes by capillarity to the upstream surface 11 IBs of said second membrane 11 IB.Advantageously, the upstream surface 11 IBs of said second membrane 11 IB has dimensions, in the longitudinal direction when positioned horizontally, substantially equal to or even greater than the downstream surface 111 Ai of said first membrane 111A so that the latter is fully supported by said second membrane 11 IB and thus guarantee continuous surface contact between the two membranes 111A and 11 IB. Said upstream surface 11 IBs of the second membrane 11 IB could, however, be slightly smaller to avoid the risk of allowing some constituents to pass through. Furthermore, in order to facilitate the passage of the "contaminated" blood plasma 102 from one 11 IA to the other 11 IB, direct contact is preferred; in this case, the space between the two membranes 11 IA and 11 IB must be sufficiently small. We therefore seek to minimize the difference between the downstream surface 111 Ai of the first membrane 111A and the upstream surface 11 IBs of the second membrane 11 IB.It should be noted that [Fig.4] is only a schematic view to illustrate the membrane filtration phenomenon observed with the use of the two membranes 11 IA and 11 IB. As such, on such a [Fig.4], the difference between the two. membranes 11 IA and 11 IB has been intentionally maximized and is not representative of reality.

[0021] Furthermore, for such an embodiment of said device 100 employing a second microporous membrane 11 IB, said specific surface 112 is then positioned downstream of the downstream surface 11 IBi of the second membrane 11 IB and upstream of the first end 120a of the capillary channel 120. Such a specific surface 112 has hydrophobic, hydrophilic and surface tension properties to extract by gravity the blood plasma 102 from the second membrane 11 IB and to circulate and advance said blood plasma 102 in said capillary channel 120 by capillarity.

[0022] Such a second membrane 11 IB preferably consists of an isometric membrane, in this case a membrane having a pore structure, for example an average pore size, which is substantially the same throughout the membrane. As such, said second membrane 11 IB has pores of the same size at the upstream surface 11 IBs as at the downstream surface 11 IBi. By way of illustration but not limitation, such a membrane 11 IB may be characterized by a thickness of twenty to twenty-five micrometers, in this case a factor substantially equal to ten compared to the first membrane 111 A, with an average pore size of less than two micrometers throughout said second membrane 11 IB.For example, it is possible to use polycarbonate membranes treated with polyvinylpyrrolidone (also known as PVP), a hydrophilic polymer that makes the surface of said membrane hydrophilic. However, those skilled in the art should not limit themselves to such materials and may consider any other type of material capable of fulfilling this function. Furthermore, such a second membrane 11 IB may advantageously possess properties that limit non-specific interactions of proteins and / or other analytes contained in blood plasma 102.

[0023] In addition, as illustrated in [Fig.5], in order to concentrate the blood 101 on said membranes 11 IA and 11 IB and to prevent the blood 101 from spreading outside the separation / filtration surface, delimited by the edges of said membranes 111A and 111B, the collection module 110 may further include a membrane holder 113 positioned so as to press and hold the edges of said membranes 111A and 11 IB. Such a membrane carrier 113 is dimensioned to allow a (mechanical) clearance to permit movement, translation, and / or relative expansion between the two membranes 11A and 11B in both horizontal and vertical directions, while ensuring continuous horizontal surface contact between the downstream surface 11A of the first membrane 11IA and the upstream surface 11IBs of the second membrane 11IB. This relative clearance prevents, under pressure With the membrane holder 113, membranes 11IA and 11IB bulge or even swell, but this also allows for the evacuation or expulsion of any air that may be present between the first membrane 11IA and the second membrane 11IB. This air could create bubbles and prevent cohesion between the water molecules in the plasma. As an illustrative example, for membranes 11IA and 11IB and a circular membrane holder 113, the diameter of the membrane holder 113 will be slightly larger than the diameter of membranes 11IA and 11IB. However, those skilled in the art should not limit themselves to such a membrane holder 113 and may consider any other type of device capable of fulfilling these functions. It should be noted that such a membrane carrier 113 could only be applied to the first microporous membrane 11 IA in the case where the collection module 110 only includes a first microporous membrane 11 IA.Thus, such a membrane carrier 113 would be positioned so as to press and hold the edges of the first membrane 111A in order to concentrate the blood 101 on said first membrane 11 IA and to prevent the blood 101 from spreading outside the separation / filtration surface, delimited by the edges of said first membrane 111 A. .

[0024] As illustrated in [Fig. 6], the capillary channel 120, at its first end 120a, is in fluidic connection with the collection module 110 at the specific surface 112 so that the blood plasma 102 can move automatically from the specific surface 112 to the capillary channel 120 by capillarity, and thus flow vertically (from top to bottom according to [Fig. 6]) along said channel 120 from the first end 120a to the second end 120b of said capillary channel 120. The first 120a and second 120b ends of the capillary channel 120 are respectively considered to be the upper and lower parts of said capillary channel 120 when said capillary channel 120 is oriented in space as shown in [Fig. 6].

[0025] Such a capillary channel 120 is arranged so that the capacity of said capillary channel 120 is strictly less than the capacity of the collection module 110. In other words, the volume of blood plasma 102 at the specific surface 112, and therefore by extension the volume of blood 101 collected in the collection module 110, must be significantly greater than the volume of blood plasma 102 contained in said capillary channel 120 in order to allow the flow of said plasma 102 out of said capillary channel 120, through said flow outlet 130. The volume of plasma 102 at the inlet, in this case that at the specific surface 112 in the collection module 110, thus exceeds the volumetric capacity of said capillary channel 120, which creates a surplus of blood plasma 102. This surplus promotes a natural flow of blood plasma 102 at the outlet. the species at the level of said flow outlet 130.

[0026] By way of illustrative but not limiting example, for an inlet volume of blood 101 of approximately one millilitre and one or more membranes 111 A, 11 IB having a surface area of ​​sixteen square centimetres, a capillary channel 120 having a length between two and six centimetres, corresponding to the distance defined between the first end 120a and the second end 120b of said capillary channel 120, allows, by gravity and by capillarity, the aspiration of the filtered blood plasma 102 from the specific membrane 112 towards the capillary channel 120 as well as its flow and its extraction at the outlet at the level of the flow outlet 130.

[0027] The capillary channel 120 is further arranged so that the combined effect of capillarity and gravity necessary for the circulation of the blood plasma 102 from the collection module 110 to the capillary channel 120 is greater than the surface tension of the blood plasma 102 when the blood plasma 102 flows into the capillary channel 120. As such, capillary action can only occur when the adhesion forces (of the surface of the capillary channel 120) are stronger than the cohesive forces between the water molecules of the blood plasma 102 (the attraction that the water molecules have to each other), which induce a surface tension of the blood plasma 102. Such a surface tension will be a function of the viscosity of the blood plasma 102. The standard viscosity values ​​of human blood plasma are between 1.4 and 1.8 centipoise at thirty-seven degrees.However, inflammation and / or tissue damage leading to changes in plasma proteins and an increased presence of proteins in the blood plasma can alter such values.

[0028] Such a capillary channel 120 can be made of glass, plastic, or any other material with suitable characteristics (hydrophilic properties, capillary-enhancing properties, electrostatic properties, and even mechanical properties such as elasticity). However, plastics are preferentially chosen because functionalizing their surface (making it possible, in particular, to increase hydrophilic properties and / or improve capillarity) is easier than with other materials. Furthermore, such a capillary channel 120 can be integrated into said device 100 as a separate component.However, alternatively, in the case where the device 100 comprises a flexible or rigid body, not shown in the figures for simplification purposes, housing the components of said device 100, such as the collection module 110, the capillary channel 120, and the flow outlet 130, such components could be created directly by molding or additive manufacturing of said body or by removing material from the latter using laser technology or machining.

[0029] In addition, to reduce the adhesion forces of the walls of the blood capillary 120 relative to the cohesive forces of the water molecules and therefore to the tension of blood plasma surface 102, the capillary channel 120 may have a particular arrangement, such as for example having its second end 120b in the form of a bevel, a smaller volume of blood 101 will thus be required at the entrance of the device 100, allowing a flow of blood plasma 102 out of the capillary channel 120 more freely / easily.

[0030] The implementation of such a microfluidic device 100 for obtaining blood plasma is carried out by a process, not shown for the sake of simplification, comprising a step of depositing a minimum quantity of blood 101 in said collection module 110 to allow the flow of blood plasma 102 from the collection module 110 towards the capillary channel 120 and finally through the flow outlet 130. Capillary forces (capillarity) will extract the blood plasma 102, contained in the collection module 110, and carry it into the capillary channel 120. The weight of the blood 101, being in volume significantly greater than the volumetric capacity (capacity) of the capillary channel 120, will push the blood plasma 102 into the capillary 120 by gravity, in the form of a drip.

[0031] In a preferred embodiment of the invention, as shown in [Fig. 6], it may be possible to collect the blood plasma 102 obtained in a collector 140 positioned downstream of the flow outlet 130, such as, for example, an Eppendorf-type tube of various sizes, from 0.2 to 2 milliliters; a Greiner tube, for example, of the Vacuette type; or a Becton Dickinson tube, for example, of the Vacutainer type. Such a collector 140 can then be used directly by a laboratory to obtain a quantification of the blood biomarker of interest and be integrated manually or automatically into the measurement circuit of said laboratory.

[0032] It will be appreciated by those skilled in the art that this disclosure is not limited to what is particularly shown and described above. Other modifications may be envisaged without departing from the scope of the present invention as defined by the attached claims.

Claims

Demands

1. Microfluidic device (100) for obtaining blood plasma (102) comprising: - a blood (101) collection module (110) comprising: i. a first microporous membrane (11 IA) arranged to receive a quantity of blood (101) and designed to separate, by gravity and capillarity, when said first membrane (11 IA) is substantially horizontal, the constituents of the blood according to their sizes and thus trap said constituents other than the blood plasma (102); ii. a specific surface (112) arranged downstream of said first membrane (11 IA) and having hydrophobic, hydrophilic and surface tension properties determined to cause an extraction, by gravity and capillarity, of said blood plasma (102) from said first membrane (11 IA);- a capillary channel (120) having a first end (120a) in fluidic connection with said specific surface (112), said specific surface (112) and said capillary channel (120) being mutually arranged to cause the circulation, by capillarity, of said blood plasma (102) in said capillary channel (120), and a second end (120b) in fluidic connection with a flow outlet (130); characterized in that the capacity of the collection module (110) is greater than the capacity of the capillary channel (120) and that said capillary channel (120) is arranged so that the combined effect of capillarity and gravity is greater than the surface tension of the blood plasma (102) when the latter flows in said capillary channel (120).

2. A microfluidic device (100) for obtaining blood plasma (102) according to the preceding claim, wherein the collection module (110) comprises a second microporous membrane (11 IB), the first and second microporous membranes (111 A, 11 IB) being mutually arranged such that the first membrane (11 IA) is positioned horizontally on the second membrane (11 IB); wherein each of the first and second membranes (11 IA, 11 IB) comprises an upstream surface (11 IAs, 11 IBs) and a downstream surface (11 IAi, 11 IBi), and that the surface upstream (11 IBs) of said second membrane (11 IB) fully supports the downstream surface (11 lAi) of said first membrane (11 IA); and that said specific surface (112) is arranged downstream of said first and second membranes (111 A, lllB) and upstream of the first end (120a) of the capillary channel (120) in order to extract, by capillarity, the blood plasma (102) filtered by the first and second membranes (11 IA, 11 IB) and to circulate it in said capillary channel (120).

3. Microfluidic device (100) for obtaining blood plasma (102) according to the preceding claim, wherein the first microporous membrane (111 A) is an asymmetric membrane and the second microporous membrane (11 IB) is an isometric membrane.

4. Microfluidic device (100) for obtaining blood plasma (102) according to any one of the preceding claims, wherein the second end (120b) of the capillary channel (120) is in the form of a bevel.

5. Method of implementing a microfluidic device (100) for obtaining blood plasma (102) arranged according to any one of the preceding claims, said method comprising a step of depositing a minimum quantity of blood (101) into said collection module (110) to allow the flow of blood plasma (102) from the collection module (110) to the capillary channel (120) and through the flow outlet (130).

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