FR3161749A1 - Microfluidic device for plasma production - Google Patents

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. The 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

Microfluidic device for plasma production

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

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 illnesses lasting 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.

For this reason, blood biomarkers, or 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; it constitutes approximately fifty-five percent of the total blood volume and contains at least three hundred proteins.

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 disease. 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 us to:
- 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.

Traditionally, such quantification is possible using the conventional and proven process of blood collection. However, this process requires a significant quantity of blood, the intervention of qualified personnel, and the use of specialized equipment. In this case, blood plasma is currently separated from 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 accessible to all users, 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 called hemolysis, in which 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 impair the relevance and accuracy of subsequent protein quantification from the hemolyzed plasma, thus leading to falsified final results. Therefore, such a process is costly, time-consuming, and unsuitable for most users.

Devices for obtaining blood plasma that do not use a centrifugation step are known, such as the device disclosed in 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 obtained blood plasma.

The present invention therefore aims to improve this situation. 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.

• un module de collecte de sang comportant :
  • une première membrane microporeuse agencée pour recevoir une quantité de sang et conçue pour séparer, par gravité et par capillarité, lorsque ladite première membrane est sensiblement horizontale, les constituants du sang selon leurs tailles et ainsi piéger lesdits constituants autres que le plasma sanguin ;
  • une surface spécifique présentant des propriétés hydrophobes, hydrophiles et de tension de surface et agencée en aval de ladite première membrane afin d’extraire, par capillarité, le plasma sanguin de ladite première membrane ;
• un canal capillaire présentant une première extrémité avec ladite surface spécifique, cette dernière étant agencée pour faire circuler par capillarité ledit plasma sanguin dans ledit canal capillaire, et une deuxième extrémité en connexion fluidique avec une sortie d’écoulement. En outre, la contenance du module de collecte est supérieure à la contenance du canal capillaire et ce dernier est agencé de sorte que l’effet conjugué de capillarité et de gravité soit supérieur à la tension de surface du plasma sanguin lorsque ledit plasma sanguin s’écoule dans ledit canal capillaire.

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 as said blood plasma flows through said capillary channel.

In a preferred embodiment, to enhance filtration, the collection module may further include a second microporous membrane. The first and second microporous membranes are arranged such that the first membrane is positioned horizontally on the second membrane; each of the first and second membranes has an upstream and a downstream surface, and the upstream surface of the second membrane fully supports the downstream surface of the first membrane. Furthermore, this specific surface is arranged downstream of the first and second membranes and upstream of the first end of the capillary channel to extract, by capillary action, the blood plasma filtered by the first and second membranes and to circulate it through the capillary channel.

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

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.

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.

• FIG. 1montre un exemple préféré de mise en œuvre d'un dispositif microfluidique d'obtention d’une quantité de plasma selon l'invention ;
• FIG. 2est une vue schématique illustrative du module de collecte selon l’invention ;
• FIG. 3est une vue schématique du dispositif selon l'invention illustrant la mise en œuvre dudit dispositif selon l'invention ;
• FIG. 4est une vue schématique illustrative du module de collecte selon une variante de l’invention ;
• FIG. 5est une vue schématique d’une variante du dispositif selon l'invention ;
• FIG. 6est une vue schématique du dispositif selon l'invention illustrant la mise en œuvre dudit dispositif selon l'invention.

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 microfluidic device 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.

To simplify the description, the same reference is used in different figures to designate the same object or element. Therefore, 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 provided as non-limiting examples of implementation.

A preferred example of a microfluidic device 100 for obtaining blood plasma, according to the invention, is shown in the FIG. 1 . Said device 100 is composed of 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 the level of a second end 120b of the capillary channel 120.

The blood plasma collection module 110 is designed to receive a quantity of blood 101, or any blood fluid (e.g., pre-treated blood), taken directly from a person, for example, from their fingertip. Such a collection module 110 comprises:
- a first microporous membrane 111A 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.

This first 111A membrane uses the principle of membrane filtration, acting as a physical barrier with a calibrated porosity that ensures selective permeability of certain blood components below a given size. As illustrated in FIG. 2 , said first microporous membrane 111A 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 GB having a diameter substantially between twelve and eighteen micrometers, red blood cells GR 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 111A in contrast to the blood plasma 102 being able to flow through said first membrane 111A.

Such a first membrane 111A 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 111As and a downstream surface 111Ai with pores of larger cross-sectional dimensions at the upstream surface 111As than at the downstream surface 111Ai. 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 means 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 can 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 1.8 to 2 micrometers on the downstream surface 111Ai. As an example, membranes from the Pall Vivid® brand are known and available on the market.

As illustrated in Figures 1 and 2, the last essential component of the collection module 110, namely the specific surface 112, is positioned downstream of the downstream surface 111Ai of the first membrane 111A and upstream of the first end 120a of the capillary channel 120. This specific surface 112 has hydrophobic, hydrophilic, and surface tension properties to extract blood plasma 102 from the first membrane 111A by gravity and to circulate and advance said blood plasma 102 into said capillary channel 120 by capillarity, thus enabling the continuity of said plasma 102 within said device 100, and not merely 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. Accordingly, 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 in addition, it is possible to optimize or even improve the hydrophilic characteristics of the chosen material(s) by using treatments to functionalize the surfaces of said materials, in particular to modify their surface tension, such as, for example, plasma gas treatments (argon, oxygen, etc.), Corona treatments or even chemical treatments (with sodium hydroxide, poly-vinyl alcohol, or hydroxypropylmethylcellulose, etc.).

It should be noted that the 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 could allow certain blood components 101 to pass through, components that are to be filtered by the 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 111A may prove inadequate in terms of filtration, the collection module 110 may advantageously include a second microporous membrane 111B positioned horizontally, like the first membrane 111A, and so as to support its entirety, as illustrated in FIG. 4 Such a second membrane 111B has an upstream surface 111Bs and a downstream surface 111Bi. Thus, such a second membrane 111B 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 111B 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 (e.g., red blood cells, platelets), which remain trapped in said second membrane 111B, from the blood plasma 102, which can then flow through said second membrane 111B. Accordingly, the "contaminated" blood plasma 102 from the downstream surface 111Ai of said first membrane 111A passes by capillary action to the upstream surface 111Bs of said second membrane 111B. Advantageously, the upstream surface 111Bs of said second membrane 111B has dimensions, in the longitudinal direction when positioned horizontally, substantially equal to or even greater than the downstream surface 111Ai of said first membrane 111A so that the latter is fully supported by said second membrane 111B and thus ensure continuous surface contact between the two membranes 111A and 111B. Said upstream surface 111Bs of the second membrane 111B 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 111A to the other 111B, direct contact is preferred; in this case, the space between the two membranes 111A and 111B must be sufficiently small. Therefore, the aim is to minimize the gap between the downstream surface 111Ai of the first membrane 111A and the upstream surface 111Bs of the second membrane 111B. It should be noted that the FIG. 4 is only a schematic view to illustrate the membrane filtration phenomenon observed with the use of the two membranes 111A and 111B. As such, on such a FIG. 4 The gap between the two membranes 111A and 111B has been deliberately maximized and is not representative of reality.

Furthermore, for such an embodiment of said device 100 employing a second microporous membrane 111B, said specific surface 112 is then positioned downstream of the downstream surface 111Bi of the second membrane 111B 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 111B and to circulate and advance said blood plasma 102 in said capillary channel 120 by capillarity.

Such a second membrane 111B 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 111B has pores of the same size at the upstream surface 111Bs as at the downstream surface 111Bi. By way of illustration, but not limitation, such a membrane 111B may be characterized by a thickness of twenty to twenty-five micrometers, in this case a factor of approximately ten compared to the first membrane 111A, with an average pore size of less than two micrometers throughout said second membrane 111B. By way of example, it is possible to use polycarbonate membranes treated with polyvinylpyrrolidone (also known by the acronym PVP), in this case a hydrophilic polymer that makes the surface of said membrane hydrophilic. However, a person 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 111B may advantageously possess properties that limit non-specific interactions of proteins and/or other analytes contained in blood plasma 102.

In addition, as illustrated on the FIG. 5 In order to concentrate the blood 101 on said membranes 111A and 111B 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 111B. Such a membrane holder 113 is dimensioned so as to leave a (mechanical) clearance to allow movement, translation and/or relative expansion, between the two membranes 111A and 111B in a horizontal and a vertical direction while ensuring continuous horizontal surface contact between the downstream surface 111Ai of the first membrane 111A and the upstream surface 111Bs of the second membrane 111B. This relative clearance prevents membranes 111A and 111B from buckling or even swelling under the pressure of the membrane holder 113. It also allows for the evacuation or expulsion of any air that might be present between the first membrane 111A and the second membrane 111B. This air could create bubbles and prevent cohesion between the water molecules in the plasma. For example, with membranes 111A and 111B and a circular membrane holder 113, the diameter of the membrane holder 113 will be slightly larger than the diameter of membranes 111A and 111B. 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 holder 113 could only be applied to the first microporous membrane 111A in the case where the collection module 110 only had a first microporous membrane 111A. Thus, such a membrane holder 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 111A and to prevent the blood 101 from spreading outside the separation/filtration surface, delimited by the edges of said first membrane 111A.

As illustrated on the 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 automatically move from the specific surface 112 to the capillary channel 120 by capillarity, and thus flow vertically (from top to bottom according to the 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 indicated by the FIG. 6 .

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 of 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, in this case at said flow outlet 130.

As an illustrative but not limiting example, for an inlet blood volume 101 of approximately one millilitre and one or more membranes 111A, 111B 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.

The capillary channel 120 is further arranged so that the combined effect of capillarity and gravity necessary for the circulation of 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 the increased presence of proteins in blood plasma can alter such values.

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 preferred because their surface can be functionalized (particularly to increase hydrophilic properties and/or improve capillary action) more easily than other materials. Furthermore, such a capillary channel 120 can be integrated into the 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.

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 surface tension of the blood plasma 102, the capillary channel 120 may have a particular arrangement, such as presenting 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 the blood plasma 102 out of the capillary channel 120 more freely/easily.

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.

In a preferred mode of the invention, as shown in the 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 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 for manual or automatic integration into the laboratory's measurement circuit.

It will be appreciated by those skilled in the art that this disclosure is not limited to what is specifically 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 (5)

Microfluidic device (100) for obtaining blood plasma (102) comprising:
- a blood collection module (110) (101) comprising:
i. a first microporous membrane (111A) arranged to receive a quantity of blood (101) and designed to separate, by gravity and by capillarity, when said first membrane (111A) is substantially horizontal, the constituents of the blood according to their sizes and thus trap said constituents other than blood plasma (102);
ii. a specific surface (112) arranged downstream of said first membrane (111A) and having hydrophobic, hydrophilic and surface tension properties determined to cause extraction, by gravity and by capillarity, of said blood plasma (102) from said first membrane (111A);
- 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 into said capillary channel (120). Microfluidic device (100) for obtaining blood plasma (102) according to the preceding claim, wherein the collection module (110) comprises a second microporous membrane (111B), the first and second microporous membranes (111A, 111B) being mutually arranged such that the first membrane (111A) is positioned horizontally on the second membrane (111B); that each of the first and second membranes (111A, 111B) comprises an upstream surface (111As, 111Bs) and a downstream surface (111Ai, 111Bi) and that the upstream surface (111Bs) of said second membrane (111B) fully supports the downstream surface (111Ai) of said first membrane (111A); and that said specific surface (112) is arranged downstream of said first and second membranes (111A, 111B) 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 (111A, 111B) and to circulate it in said capillary channel (120). Microfluidic device (100) for obtaining blood plasma (102) according to the preceding claim, wherein the first microporous membrane (111A) is an asymmetric membrane and the second microporous membrane (111B) is an isometric membrane. 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. 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) in 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).