Microfluidic device for obtaining optimized plasma promoting homogenization of blood

Abstract

The invention relates to a microfluidic plasma device (100) comprising: - a blood collection module (110) having: i. a microporous membrane (111A); ii. a specific surface (112); - a capillary channel (120) having a first end (120a), in fluidic connection with the specific surface, a second end (120b), in fluidic connection with an outlet (130); the capacity of the module being greater than that of the channel, and the channel being arranged such that the combined effect of capillarity and gravity is greater than the surface tension of the plasma when it flows. The module comprises a plate (113) positioned upstream of the membrane and having a through-hole and a downstream surface bearing peripherally on the membrane, allowing blood to flow along the downstream surface into the membrane.

Description

[0001] Optimized microfluidic plasma production device promoting blood homogenization

[0002] The present invention relates generally to the field of blood testing devices. It specifically concerns a microfluidic device for obtaining an optimized quantity of plasma to promote good homogenization of the collected blood.

[0003] 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.

[0004] 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, constituting about fifty-five percent of the total blood volume and is thought to contain at least three hundred proteins.

[0005] 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:

[0006] - 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;

[0007] - 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;

[0008] - 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.

[0009] Traditionally, such quantification is possible using the conventional and proven process of blood collection. However, this process requires a significant amount of blood, the intervention of qualified personnel, and the use of specialized equipment, resulting in a costly and time-consuming technique. Indeed, it requires a doctor's prescription for a blood test, scheduling an appointment with a nurse or laboratory (assuming the availability of both healthcare professionals and the patient), waiting for the blood tests to be performed in the laboratory, and the transmission of the results to the doctor, followed by their interpretation.

[0010] To overcome these aforementioned drawbacks, patent application WO 2023 / 179927A1 proposes a microfluidic device for obtaining a quantity of plasma in order to ultimately provide a direct and rapid quantification of a blood biomarker, usable from a drop of blood and which can be implemented by any user, at home, without third-party equipment (centrifuge or other), while ensuring reliability and reproducibility of the results.

[0011] To achieve this, such a device includes, in particular, a collection module and a capillary channel. The collection module has a microporous membrane designed to receive a quantity of blood and to separate, by gravity when the microporous membrane is substantially horizontal, the blood components according to their size, thus trapping components other than blood plasma. It also has a specific surface area designed to circulate the resulting blood plasma by capillary action through a capillary channel. However, during the filtration of larger blood components by the microporous membrane, when these components are retained at the pores of the membrane, the pores can become clogged and prevent the filtration process from continuing.It is therefore important to maintain constant ratios between the incoming blood volume and the filtration surface area, and consequently, it is necessary to ensure that a constant volume of blood is deposited on the surface. Furthermore, in such a device, the collected blood will not necessarily distribute itself uniformly and homogeneously across the microporous membrane, potentially slowing down the circulation of the resulting blood plasma to the capillary channel. The collected blood may concentrate in only a specific area of ​​the microporous membrane, causing a "boiling" effect. This requires a longer time to clear the excess blood from that area and, consequently, to fully circulate the blood throughout the device.

[0012] The present invention therefore aims to improve upon this observation. To this end, it proposes a microfluidic device for obtaining a quantity of plasma as described above, the collection module of which further comprises a plate positioned upstream of the microporous membrane in order to promote the deposition of a constant volume of blood and a uniform, continuous and homogeneous distribution of the blood on the microporous membrane, allowing efficient filtration of the blood so as to elute a greater volume of plasma and thus promote capillarity and the initiation of said plasma, capillarity being able to begin in a few seconds instead of a few minutes currently.

[0013] To this end, the invention relates to a microfluidic device for obtaining a quantity of plasma comprising:

[0014] - a blood collection module comprising: i. 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; ii. a specific surface exhibiting hydrophobic, hydrophilic and surface tension properties;

[0015] - a capillary channel having a first end in fluidic connection 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; the capacity of the collection module being greater than the capacity of the capillary channel and determined such that when said collection module is filled with blood, the specific surface has an excess of blood plasma promoting a natural flow of blood plasma into said capillary channel, the latter being arranged such that the combined effect of capillarity and gravity is greater than the surface tension of the blood plasma as it flows into said capillary channel. Said collection module further comprises a plate positioned upstream of the first microporous membrane and parallel to the surface of said membrane.The said plate has a substantially flat upstream surface, a through hole having a cross-section whose area is drastically small compared to the area of ​​the said upstream surface of the said plate, the said hole being arranged to allow blood to flow out and a downstream surface bearing peripherally on the said first microporous membrane so as to circulate blood along the said downstream surface into the said first microporous membrane.

[0016] In a preferred embodiment, said downstream surface is substantially conical in shape.

[0017] Preferably, said hole is positioned substantially in the center of said plate.

[0018] The said plate can be glued to the microporous membrane at the peripheral support with double-sided hydrophilic adhesive tape.

[0019] In a preferred embodiment, the downstream surface of said plate may include at least one groove opening into said hole.

[0020] According to the previously mentioned method, the downstream surface of said plate may have a plurality of radial grooves.

[0021] In addition, the microfluidic device for obtaining a quantity of plasma may further comprise a second microporous membrane, the first and second microporous membranes are mutually arranged such 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, and that said specific surface is arranged downstream of said first and second membranes and upstream of the first end of the capillary channel in order to extract the blood plasma filtered by said first and second membranes and to circulate it in said capillary channel.

[0022] 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:

[0023] - Figure 1 shows a preferred example of a microfluidic device for obtaining a quantity of plasma according to the invention;

[0024] - Figure 2 is a schematic view of the device according to the invention illustrating the implementation of said device according to the invention;

[0025] - Figure 3 is a schematic view of the collection module according to the invention;

[0026] - Figure 4A is a schematic view of the underside of the plate according to a preferred mode of the invention;

[0027] - Figure 4B is a schematic top view of the plate according to one embodiment of the invention;

[0028] - Figure 5 is a schematic view of the device according to the invention illustrating the implementation of said device according to the invention;

[0029] - Figure 6 is a schematic view of a variant of the collection module according to the invention;

[0030] - Figures 7 and 8 are schematic views of the device according to the invention illustrating the implementation of said device according to the invention.

[0031] To simplify the description, the same reference numeral is used in different figures to designate the same object or element. Thus, when the description refers to a referenced object or element, that object or element may be identified in several figures. Furthermore, the figures and the description are given as non-limiting examples of embodiments. More broadly, for the purposes of the invention, the "upstream surface" of an element of said device 100 means the upper surface, the surface being the highest when said element is positioned horizontally, and the "downstream surface" means the lower surface, the surface being the lowest when said element is positioned horizontally.

[0032] A preferred example of a microfluidic device 100 for obtaining blood plasma, according to the invention, is shown in Figure 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.

[0033] As illustrated in Figures 2 and 3, the blood plasma collection module 110 102 is designed to receive a quantity of blood 101 (from a few microliters to a few milliliters), or any blood fluid (e.g., pre-treated blood), taken directly from a person, or from any other device dedicated to the collection of a quantity of blood, for example, a pipette. Such a collection module 110 comprises:

[0034] - a first microporous membrane 1 1 1 A through which the collected blood 101 can flow;

[0035] - a plate 113 positioned upstream of the first microporous membrane 1 1 1 A and parallel to the surface of said membrane 1 11 A;

[0036] - and a specific surface 1 12 having hydrophobic, hydrophilic and surface tension properties for extracting blood plasma 102 from said first microporous membrane 1 11 A and circulating said blood plasma 102 into said capillary channel 120.

[0037] As illustrated in Figures 1 to 3, said plate 113, positioned upstream of the first microporous membrane 111A, has a substantially flat upstream surface 113s, a through hole 113T arranged to allow the flow of blood 101, and a downstream surface 113i bearing peripherally 113AP (circled in dashes in Figures 1 and 2), in this case at its ends, on said first microporous membrane 111A, allowing the blood 101 to be guided from hole 113T towards said first membrane 111A. Accordingly, as illustrated in Figures 4A and 4B, said hole 113T has a cross-section whose area is significantly smaller than the area of ​​said upstream surface 113s of said plate 113, advantageously between one and twenty-five percentages of the area of ​​said upstream surface 113s, preferably three percent.Thus, the blood 101 is circulated from the hole 113T to the peripheries to homogeneously saturate said first microporous membrane 111A. In other words, the blood 101 spreads continuously and homogeneously along the downstream surface 113i of said plate 113 to the first microporous membrane 111A. Preferably, in an optimized manner, said downstream surface 113i may have a substantially conical or more broadly concave shape, thus giving said plate 113 the shape of an inverted funnel.

[0038] As mentioned above, plate 113 is affixed to the first microporous membrane 111A at the level of the peripheral support 113AP. To this end, in a preferred embodiment, plate 113 is adhered to the first membrane 111A at the level of the peripheral support 113AP with double-sided hydrophilic adhesive tape. Such an attachment system contains the blood 101 and prevents it from overflowing to the sides, specifically the peripheral areas, particularly if the device 100 were to be overturned; such adhesive tape would act as a seal. Ideally, such adhesive tape should be sufficiently thin, like a "spacer," in this case a micro-thickness, promoting a fixed gap and maximum contact between plate 113 and the first microporous membrane 111A.By way of illustration, but not limitation, such an adhesive tape could be an acrylic adhesive tape with a thickness between forty and one hundred and sixty micrometers. However, a person skilled in the art should not limit themselves to such a fastening system and may consider any other type of fastening system between the plate 113 and the first microporous membrane 111A meeting the aforementioned specifications, such as a gasket made of an inert material.

[0039] To promote uniform dispersion of the blood 101, the downstream surface 113i may include a groove 113R opening into the hole 113T. Such a groove 113R is thus engraved on the downstream surface 113i to form, for example, a conduit through which the blood 101 flows and progresses by capillary action and gravity to the first microporous membrane 111A. Alternatively, as illustrated in Figure 4A, the downstream surface 113i may include a plurality of grooves 113R, preferably radial, opening, in this case, into the hole 113T, thereby optimizing the distribution of the collected blood 101. The grooves 113R may, for example, be in the form of a cross or a star.Furthermore, advantageously, each groove 1 13R may have a vent at its so-called "lower" end, in this case the end closest to the microporous membrane 11 1 A, in other words, the end located at the peripheral support 1 13AP. For this purpose, such a vent allows the air displaced by the incoming blood to escape so that the blood can continue its free flow in each of said grooves 1 13R. Preferably, such a vent may have a diameter of one to two millimeters. It is possible to optimize the number of grooves 1 13R in relation to the volume of blood 101 collected: ideally, but not exclusively, the total volume of the grooves 1 13R is substantially equivalent to the volume of blood 101 collected by said device 100.

[0040] Furthermore, such a plate 113 may preferably be made of polymethyl methacrylate, a thermoplastic polymer known by the acronym PMMA, in order to limit non-specific interactions of proteins and / or other analytes contained in blood plasma 102, since this type of material is relatively inert and has a density that is approximately average for a plastic, which is advantageous in this application because a plate 113 that is too heavy would be detrimental to its use in the invention, particularly with the risk of clogging pores and / or restricting air exchange. However, those skilled in the art should not limit themselves to such a material and may consider any other type of material that provides such properties, such as, for example, polypropylene, polycarbonate, or polyethylene.

[0041] The hole 113T through the plate 113 can have a cross-section of various shapes, such as a circle, square, spiral, or any other customized shape. Advantageously, as illustrated in Figure 4B, the hole 113T is substantially positioned in the center of the plate 113 to allow the blood 101 to spread from the center to the periphery, promoting the homogeneous circulation of the blood 101 into the first microporous membrane 111A. However, the invention is not limited to this configuration, and it is entirely possible to have a hole 113T outside of a central region.

[0042] The said first microporous membrane 11 1 A, for its part, uses the principle of membrane filtration, it thus acts as a physical barrier with a calibrated porosity ensuring selective permeability of certain blood constituents below a given size.As illustrated in Figure 3, 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 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 111A in contrast to the blood plasma 102 being able to flow through said first membrane 111A.

[0043] 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. By way of illustration, but not limitation, such a membrane 111A may be characterized by a thickness of three hundred to four hundred 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.

[0044] As illustrated in Figures 3 and 5, the last essential component of the collection module 110, in this case said 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. Such a specific surface 112 has hydrophobic, hydrophilic and surface tension properties to extract by gravity and capillarity 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 Figure 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 matter, said specific surface 112 must have a suitable surface tension and be made of a hydrophilic material without being soluble in water.As such, the specific surface area 112 can 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, ...), Corona treatments or even chemical treatments (with sodium hydroxide, poly-vinyl alcohol, or hydroxypropylmethylcellulose, ...).

[0045] 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, as illustrated in Figure 6, 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. 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 constituents 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 the blood plasma 102 from the first membrane 111A and it allows the separation, by gravity and capillary action, of the last blood constituents other than blood plasma 102 (example: red blood cells RBCs, platelets PLs), which remain trapped in said second membrane 111B, from the blood plasma 102, which can flow through said second membrane 111B.As such, the "contaminated" blood plasma 102 from the downstream surface 1 11 Ai of said first membrane 11 1 A passes by capillary action to the upstream surface 1 1 1 Bs of said second membrane 1 1 1 B. Advantageously, the upstream surface 1 1 1 Bs of said second membrane 1 1 1 B has dimensions, in the longitudinal direction when positioned horizontally, substantially equal to or even greater than the downstream surface 1 1 1 Ai of said first membrane 1 1 1 A so that the latter is totally supported by said second membrane 1 1 1 B and thus guarantee continuous surface contact between the two membranes 1 1 1 A and 1 1 1 B. Said upstream surface 1 1 1 Bs of the second membrane 1 1 1 B could however be slightly smaller to avoid the risk of allowing some constituents to pass through.Furthermore, to facilitate the passage of the "contaminated" blood plasma 102 from one membrane 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 Figure 6 is only a schematic view to illustrate the membrane filtration phenomenon observed with the use of the two membranes 111A and 111B. As such, in Figure 6, the gap between the two membranes 111A and 111B has been intentionally maximized and is not representative of reality.

[0046] 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.

[0047] 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 over the entire length of said second membrane 111B.For example, polycarbonate membranes treated with polyvinylpyrrolidone (also known as PVP), a hydrophilic polymer that makes the membrane surface hydrophilic, can be used. 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 111B may advantageously possess properties that limit non-specific interactions of proteins and / or other analytes contained in blood plasma 102.

[0048] As illustrated in Figure 7, 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 Figure 7) 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 Figure 7.

[0049] 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 entering, in this case that found in the collection module 110 at the specific surface 112, 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 out, in this case to level of said flow outlet 130.

[0050] As an illustrative but not limiting example, for an inlet blood volume 101 of approximately five hundred microlitres to 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.

[0051] The capillary channel 120 is further arranged so that the combined effect of capillarity and gravity necessary for circulating the blood plasma 102 from the collection module 110 towards 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. Standard viscosity values ​​for 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.

[0052] 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 capillarity) 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.

[0053] 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.

[0054] In a preferred embodiment of the invention, as shown in Figure 8, 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 and be integrated manually or automatically into the measurement circuit of said laboratory.

[0055] 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 annexed claims. For example, the microfluidic device for obtaining plasma 100 has been described herein with a plate 113 having a single through hole 113T; however, it could be envisaged to have several holes 113T having cross-sections of the same or different shapes and giving rise, where applicable, to one or more grooves 113R.

Claims

DEMANDS 1. Microfluidic device (100) for obtaining a quantity of 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) having hydrophobic, hydrophilic and surface tension properties; - a capillary channel (120) having a first end (120a) in fluidic connection with said specific surface (112), the latter being arranged to circulate, by capillarity, said blood plasma (102) in said capillary channel (120), and a second end (120b) in fluidic connection with a flow outlet (130); the capacity of the collection module (110) being greater than the capacity of the capillary channel (120) and determined so that when said collection module (110) is filled with blood (101), the specific surface (112) has an excess of blood plasma (102) promoting a natural flow of blood plasma (102) into said capillary channel (120), the latter being 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);characterized in that the collection module (1 10) further comprises a plate (1 13) positioned upstream of the first membrane; microporous (11 1 A) and parallel to the surface of said membrane (1 1 1 A), said plate (1 13) having an upstream surface (1 13s) substantially flat, a hole (1 13T) through which has a cross-section whose area is drastically small in relation to the area of ​​said upstream surface (1 13s) of said plate (1 13), said hole being arranged to allow blood (101) to flow out and a downstream surface (1 13i) taking peripheral support on said first microporous membrane (1 1 1 A) so as to put blood (101) into circulation along said downstream surface (1 13i) into said first microporous membrane (1 1 1 A).

2. Microfluidic device (100) for obtaining a quantity of plasma (102) according to the preceding claim, wherein said downstream surface (1 13i) is substantially conical in shape.

3. Microfluidic device (100) for obtaining a quantity of plasma (102) according to any one of the preceding claims wherein said hole (1 13T) is substantially positioned at the center of said plate (1 13).

4. Microfluidic device (100) for obtaining a quantity of plasma (102) according to any one of the preceding claims wherein said plate (113) is glued to the first microporous membrane (111A) at the level of the peripheral support with double-sided hydrophilic adhesive tape.

5. Microfluidic device (100) for obtaining a quantity of plasma (102) according to any one of the preceding claims wherein the downstream surface (1 13i) of said plate (1 13) has at least one groove (1 13R) opening into said hole (1 13T).

6. Microfluidic device (100) for obtaining a quantity of plasma (102) according to the preceding claim, wherein the downstream surface (1 13i) of said plate (1 13) has a plurality of radial grooves.

7. Microfluidic device (100) for obtaining a quantity of plasma (102) according to any one of the preceding claims, wherein the collection module (110) comprises a second microporous membrane (111B), the first and second microporous membranes (111A, 111B) are 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 the blood plasma (102) filtered by said first and second membranes (111A, 111B) and to circulate it in said capillary channel (120).

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