Optimized microfluidic plasma production device promoting blood homogenization

Abstract

The invention relates to a microfluidic plasma device (100) comprising: - a blood collection module (110) including: i. a microporous membrane (111A); ii. a specific surface (112); - a capillary channel (120) having a first end (120a) in fluidic connection with said specific surface, a second end (120b) in fluidic connection with an outlet (130); the capacity of said module being greater than that of said channel and said channel being arranged so that the combined effect of capillarity and gravity is greater than the surface tension of the plasma as it flows. Said module includes a plate (113) positioned upstream of the membrane and having a through hole and a downstream surface bearing peripherally on said membrane allowing the blood to circulate along said downstream surface into said membrane. Figure to be published with the abbreviation: Fig. 1

Description

Title of the invention: Optimized microfluidic device for obtaining plasma promoting blood homogenization. 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 an optimized quantity of plasma in order to promote good homogenization of the collected blood. 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, biological characteristics, are attracting increasing interest as indicators of normal or pathological biological processes. As such, each biomarker has its own 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, more specifically in blood plasma, attests to the existence of a pathology. Blood plasma is the liquid component of blood devoid of red blood cells, white blood cells, and other blood cells. platelets and other contaminants, constituting about fifty-five percent of the total blood volume and would contain 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, 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 (presupposing the availability of both healthcare personnel 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.

[0006] To overcome these aforementioned drawbacks, patent application WO 2023 / 179927Al proposes a microfluidic device for obtaining a quantity of plasma in order to ultimately have 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.

[0007] To this end, such a device includes, in particular, a collection module and a capillary channel. Said collection module has a microporous membrane The system is designed to receive a quantity of blood and, when the microporous membrane is substantially horizontal, to separate the blood components by gravity according to their size, thus trapping components other than blood plasma. A specific surface area is 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 membrane's pores, the pores can become clogged, preventing continuous filtration. Therefore, it is important to maintain constant ratios between the incoming blood volume and the filtration surface area, and consequently, a constant volume of blood must be deposited on the surface.Furthermore, for such a device, the collected blood will not necessarily be distributed uniformly and homogeneously on the microporous membrane, which can lead to a slowdown in the process of circulating the resulting blood plasma to the capillary channel: the collected blood may concentrate only on a specific area of ​​the microporous membrane, causing a "clogging" effect, thus requiring a longer time to clear the excess blood present in said area and consequently for its complete circulation throughout the device. Description of the invention

[0008] 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 larger 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.

[0009] To this end, the invention relates to a microfluidic device for obtaining a quantity of plasma comprising: - 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; - a capillary channel having a first end in fluidic connection with said specific surface, the latter being arranged to circulate, by capillarity, said blood plasma in said capillary channel, and a second end in fluidic connection with a flow outlet; The collection module has a capacity greater than that of the capillary channel, and the capillary channel is arranged so that the combined effect of capillarity and gravity exceeds the surface tension of the blood plasma as it flows through the capillary channel. The collection module further comprises a plate positioned upstream of the first microporous membrane. This plate has an upstream surface, a through hole arranged to allow blood to flow through, and a downstream surface bearing peripherally on the first microporous membrane, thus circulating blood along the downstream surface into the first microporous membrane.

[0010] In a preferred embodiment, said downstream surface is substantially conical in shape.

[0011] Preferably, said hole is substantially positioned in the center of said plate.

[0012] Said plate can be glued to the microporous membrane at the level of the peripheral support with hydrophilic double-sided adhesive tape.

[0013] In a preferred embodiment, the downstream surface of said plate may include at least one groove opening into said hole.

[0014] According to the previously mentioned mode, the downstream surface of said plate may include a plurality of radial grooves.

[0015] 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. Brief description of the drawings

[0016] 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 attached drawings, among which: - [Fig.1] shows a preferred example of a microfluidic device for obtaining a quantity of plasma according to the invention; - [Fig.2] is a schematic view of the device according to the invention illustrating the implementation of said device according to the invention; - [Fig.3] is a schematic view of the collection module according to the invention; - [Fig.4A] is a schematic view of the underside of the plate according to a preferred mode of the invention; - [Fig.4B] is a schematic top view of the plate according to one embodiment of the invention; - [Fig.5] is a schematic view of the device according to the invention illustrating the implementation of said device according to the invention; - [Fig.6] is a schematic view of a variant of the collection module according to the invention; - [Fig.7] and [Fig.8] are schematic views of the device according to the invention illustrating the implementation of said device according to the invention. Description of the implementation methods

[0017] 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.

[0018] More broadly in the sense 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.

[0019] 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.

[0020] As illustrated in Figures 2 and 3, the blood plasma collection module 110 102 is arranged to receive a quantity of blood 101 (from a few microliters to a few milliliters), or of any blood fluid (e.g., previously treated blood), taken directly from a person, or from any other device dedicated to collection of a quantity of blood, for example a pipette. Such a collection module 110 includes: - a first microporous membrane 11 IA through which the collected blood 101 can flow; - a plate 113 positioned upstream of the first microporous membrane 11 IA; - and a specific surface 112 having hydrophobic, hydrophilic and surface tension properties to extract the blood plasma 102 from said first microporous membrane 111A and circulate said blood plasma 102 in said capillary channel 120.

[0021] As illustrated in Figures 1 to 3, said plate 113, positioned upstream of the first microporous membrane 111A, has an upstream surface 113s, a through hole 113T arranged to allow the blood 101 to flow, and a downstream surface 113i bearing peripheral support 113AP (circled in dashes in Figures 1 and 2), in this case at its ends, on said first microporous membrane 11 IA, allowing the blood 101 to be guided from the hole 113T towards said first membrane 11 IA. As such, 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 shape, thus giving said plate 113 the shape of an inverted funnel.

[0022] As mentioned above, said plate 113 is affixed to said first microporous membrane 11 IA at the level of the peripheral support 113AP. To this end, in a preferred embodiment, said plate 113 is bonded to said first membrane 11 IA at said peripheral support 113AP with double-sided hydrophilic adhesive tape. Such an attachment system makes it possible to contain the blood 101 and prevent it from overflowing to the sides, in this case 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 the plate 113 and the first microporous membrane 111 A.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 an attachment system and may consider any other type of attachment system between the plate 113 and the first microporous membrane 11 IA meeting the aforementioned specifications, such as a gasket made of an inert material.

[0023] In order to promote uniform dispersion of the blood 101, said downstream surface 113i may include a groove 113R opening into said hole 113T. A Such a groove 113R is thus engraved on the downstream surface 113i to form, for example, a conduit in which the blood 101 circulates and progresses by capillary action and gravity to the first microporous membrane 11 IA. Alternatively, as illustrated in [Fig. 4A], the downstream surface 113i may have a plurality of grooves 113R, preferably radial and opening, originating in the hole 113T, which optimizes 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 113R may have a vent at its so-called "lower" end, in this case the end closest to the microporous membrane 111 A, in other words, the end located at the peripheral support 113AP.For this purpose, such a vent allows the air displaced by the incoming blood to escape, so that the blood can continue to flow freely in each of the grooves 113R. Preferably, such a vent may have a diameter of one to two millimeters. It is possible to optimize the number of grooves 113R in relation to the volume of blood 101 collected: ideally, but not exclusively, the total volume of the grooves 113R is substantially equivalent to the volume of blood 101 collected by said device 100.

[0024] 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 because it 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 the pores and / or limiting 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.

[0025] Said through hole 113T in the plate 113 may have a cross-section of various shapes, such as a circle, square, spiral, or any other customized shape. Advantageously, as illustrated in [Fig. 4B], said hole 113T is substantially positioned in the center of said plate 113 to allow the blood 101 to spread from the center to the periphery, promoting the homogeneous circulation of the blood 101 into said first microporous membrane 111A. However, the invention is not limited to this configuration, and it is entirely conceivable to have a hole 113T outside of a central region.

[0026] Said first microporous membrane 111 A, for its part, uses the principle of membrane filtration, thus acting as a physical barrier with a porosity calibrated ensuring selective permeability of certain blood constituents below a given size. As illustrated in [Fig.3], said first microporous membrane 11 IA is arranged to receive a quantity of blood 101 and separate, by gravity when said first microporous membrane 111A is substantially horizontal, the blood constituents according to their sizes so that white blood cells (WBCs) having a diameter substantially between twelve and eighteen micrometers, red blood cells (RBCs) having a diameter substantially between six and eight micrometers, platelets (PLs) having a diameter substantially equal to two micrometers and the other large-diameter constituents can be substantially trapped in said first membrane 11 IA, unlike blood plasma 102 which can flow through said first membrane 111A.

[0027] 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. By way of example, membranes of the Pall Vivid brand are known and available on the market.

[0028] 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 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 and by 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 [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 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, said... 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 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, ...).

[0029] 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, as illustrated in [Fig. 6], 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. 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. The second membrane 11 IB has dimensions, in the longitudinal direction when positioned horizontally, that are substantially equal to or even greater than the downstream surface 111 Ai of the first membrane 111A, so that the latter is fully supported by the second membrane 11 IB and thus ensure continuous surface contact between the two membranes 111A and 11 IB. The 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, 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. Therefore, the aim is 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 the [Fig.Figure 6 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, in such a [Fig. 6], the gap between the two membranes 11 IA and 11 IB has been deliberately maximized and is not representative of reality.

[0030] 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.

[0031] 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 the membrane hydrophilic. However, those skilled in the art should not limit themselves to such materials and may consider any other type of material that can fulfill this function. In addition, such a second membrane 11 IB may advantageously exhibit properties enabling the limitation of non-specific interactions of proteins and / or other analytes contained in the blood plasma 102.

[0032] As illustrated in [Fig.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 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.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 [Fig.7].

[0033] 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.

[0034] By way of illustrative but not limiting example, for an inlet volume of blood 101 of approximately five hundred microlitres to 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.

[0035] Said capillary channel 120 is further arranged so that the combined effect of capillarity and gravity necessary for the circulation of blood plasma 102 from said collection module 110 to said capillary channel 120 is greater than the surface tension of blood plasma 102 when said blood plasma 102 flows into the capillary channel 120. As such, the capillary action can only occur when The adhesion forces (of the capillary canal surface 120) are stronger than the cohesive forces between the water molecules of the blood plasma 102 (the attraction that water molecules have with each other), which induce a surface tension of the blood plasma 102. This 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 these values.

[0036] 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.

[0037] 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, for example, 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.

[0038] In a preferred embodiment of the invention, as shown in [Fig. 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-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.

[0039] 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 plasma-generating device 100 has been described herein with a plate 113 having a single hole through 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 (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 by 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) 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 said capillary channel (120) 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 (110) further comprises a plate (113) positioned upstream of the first microporous membrane (11 IA), said plate (113) having an upstream surface (113s), a through hole (113T) arranged to allow the blood (101) to flow through and a downstream surface (113i) bearing peripherally on said first microporous membrane (111 A) so as to circulate blood (101) along said downstream surface (113i) into said first microporous membrane (111 A).;

2. Microfluidic device (100) for obtaining a quantity of plasma (102) according to the preceding claim, wherein said downstream surface (113i) 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 (113T) is substantially positioned in the center of said plate (113).

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 (11 IA) 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 (113i) of said plate (113) has at least one groove (113R) opening into said hole (113T).

6. Microfluidic device (100) for obtaining a quantity of plasma (102) according to the preceding claim, wherein the downstream surface (113i) of said plate (113) 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 (11 IB), the first and second microporous membranes (111 A, 11 IB) are mutually arranged such that the first membrane (11 IA) is positioned horizontally on the second membrane (11 IB); that 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 upstream surface (11 IBs) of said second membrane (11 IB) fully supports the downstream surface (11 IAi) of said first membrane (11 IA);and that said specific surface (112) is arranged downstream of said first and second membranes (11 IA, 11 IB) 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 (11 IA, 11 IB) and to circulate it in said capillary channel (120).

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