BE1029228B1 - Microfluidic device - Google Patents

Abstract

The present invention relates to a microfluidic device (100) comprising a permeable element (200) located in a sensing chamber (150) and attached to the top (20) of the microfluidic device so as to be readable through said top ( 20) and without there being any space between the porous support (210) and said upper part (20) which would be likely to accommodate condensation.

Description

Microfluidic device Technical field

The present invention relates in particular to a microfluidic device for detecting the presence of an analyte in a liquid. Prior art

[0002] || is known from the prior art, for example from WO2019/068806, to detect an analyte in a liquid using a permeable element. Such a permeable element generally comprises a porous support, for example a membrane. Summary of the invention

[0003] The invention proposes a microfluidic device comprising: e a permeable element comprising a porous support, the porous support comprising a reading zone, e an upper part fixed to the permeable element and transparent at least above the reading zone, and e a lower part arranged to form, with the upper part, a detection chamber in which the permeable element is located; the porous support being, at least above the reading zone, joined to the upper part by a transparent junction and such that there is no free space between the reading zone and the upper part.

[0004] When the inventors placed a permeable element in a microfluidic device comprising a transparent upper part, they observed that the detection through the upper part was of poor quality, and understood that this poor quality of detection was due to the appearance of condensation on the underside of the transparent upper part. The solution proposed by the present invention is to join the porous support and the upper part by a junction, direct or indirect,

transparent and without free space. Thus, there is no gap between the reading zone of the porous medium and the upper part in which condensation could form, and a detector can pick up electromagnetic radiation coming from the reading zone of the porous medium and having passed through the junction and the upper part.

[0005] The chamber makes it possible to prevent the measurement carried out on the liquid from being influenced by the atmospheric conditions, for example by the level of humidity outside the microfluidic device. In one embodiment, the lower part and the upper part form a support for the microfluidic device.

[0006] The junction is located at least between the reading zone and a transparent part of the upper part. It may for example comprise a transparent adhesive.

[0007] The porous support has a first face and a second face separated by a thickness.

[0008] The upper part is preferably totally transparent. Preferably, it is more laterally extended than the permeable element.

According to one embodiment, the junction between the porous support and the upper part comprises a structural support for the permeable element. The structural support is part of the permeable element and extends over the entire first face of the permeable element. It is preferably, at least above the reading zone, in direct contact with the upper part and with the porous support. The structural support is transparent at least above the reading area. It is preferentially transparent everywhere.

According to one embodiment, there is at least one free space between the lower part and the permeable element.

[0011] According to one embodiment, the lower part has a higher absorbance than that of the upper part at a wavelength between 700 nm and 100 μm. In other words, the lower part absorbs more radiation in that wavelength interval than the upper part. This improves radiant heating.

[0012] According to one embodiment, the microfluidic device comprises, between the lower part and the porous support, at least below the reading zone, a contrast-enhancing element having a reflectance of at least 20% at a wavelength between 350 and 750 nm. This improves the reading of the permeable element, especially if the lower part is dark.

According to one embodiment, the detection chamber comprises, in length and successively, a first part, a second part and a third part, the second part being wider than the first part and than the third part, the second part housing the reading area. This widening makes it possible to avoid the edge effects linked to capillarity in the permeable element. Its width also allows the algorithm performing the reading of the permeable element to easily locate the reading zone. The width preferably extends as a circumferential direction if the microfluidic device is circular.

[0014] According to one embodiment, the microfluidic device is arranged to rotate around an axis, and in which the permeable element is of elongated shape and is arranged radially. The radial arrangement makes it easy to place a plurality of microfluidic tracks on the microfluidic device. The rotation makes it possible to control, at least partially, the displacement of the liquid in the tracks.

[0015] The invention further proposes a detection system comprising a microfluidic device according to the invention, and a piloting device comprising: e a device location provided for placing the microfluidic device and comprising a detection zone, e a detector arranged to sensing electromagnetic radiation from the read zone when the microfluidic device is located at the device location such that the read zone is within the detection zone.

[0016] The detection zone is a volume, preferably fixed with respect to the detector, and in which the detector can carry out detection.

[0017] According to one embodiment, the device slot comprises a heating zone encompassing at least part of the microfluidic device when the microfluidic device is located at the device slot; and the control device comprises a heating module arranged to heat the heating zone. The heating zone is a volume, preferably fixed with respect to the heating module, and in which the heating module can heat.

According to one embodiment, the heating module allows heating by electromagnetic waves, preferably by radiation or induction.

According to one embodiment, the detection system is provided for rotating the microfluidic device around an axis, the heating module comprising a plurality of heating elements located at different radial distances from the axis and/or offset circumferentially. This makes it possible to heat different parts of the microfluidic device, for example different chambers located at different radial distances and/or circumferentially offset.

According to one embodiment, the control device is configured to control the heating elements in groups and/or independently of each other. This makes it possible to choose which parts of the microfluidic device, for example which chambers, are heated.

[0021] The invention further proposes a method of using a microfluidic device, in which: e a liquid comprising reagents progresses in the porous support and enters the reading zone where it produces a modification of the reading ; and said modification of the read zone is detected via electromagnetic radiation having passed through the junction and the upper part above the read zone.

[0022] The method preferably comprises heating the reading zone. It can be carried out with a microfluidic device having characteristics originating from any embodiment of the invention.

According to one embodiment, the reading zone comprises a measurement reagent, and the modification of the reading zone is produced by a reaction of at least one of the reagents of the liquid with the measurement reagent.

[0024] The invention further proposes a method of manufacturing a microfluidic device, in which: e a permeable element is provided comprising a porous support having a reading zone; e a lower part of the microfluidic device is provided; e an upper part of the microfluidic device, transparent at least in places, is provided; and e the lower part, the upper part, and the permeable element are assembled, so that the lower part and the upper part form a detection chamber housing the permeable element, so that at least above of the reading zone, the permeable element and the upper part are joined: - by a transparent junction and such that there is no free space between the reading zone and the upper part, and - so that the upper part is transparent at least above the reading area.

[0025] For example, the permeable element is placed on the lower part of the microfluidic device and the upper part is laminated above.

This document describes three aspects of an invention. A first aspect relates to a microfluidic device comprising a permeable element and an upper part. A second aspect relates to a control device designed to receive a microfluidic device and comprising several modules having different functions. A third aspect relates to a microfluidic device comprising, along a fluid path, an upstream valve, an intermediate location, and a downstream valve. The characteristics of the different aspects can be combined with each other. The preferred embodiment of the invention combines features of all three aspects. Brief description of figures

[0027] Other characteristics and advantages of the invention will appear on reading the detailed description which follows for the understanding of which reference will be made to the appended figures, among which: - Figure 1a is a top view of a device microfluidics according to one embodiment of the invention, illustrating in particular microfluidic tracks, - figure 1b is a view in vertical section along line Ib of figure 1a, - figure 2 is a view from above of any of the tracks of a microfluidic device according to one embodiment of the invention, - Figure 3 is a vertical sectional view illustrating in particular a detection chamber according to one embodiment of the invention, it makes it possible to illustrate in particular the first aspect of the invention, - figure 4 makes it possible to illustrate, very schematically and according to a horizontal view, elements of a piloting device according to an embodiment of the invention, it makes it possible to illustrate nota mment the second aspect of the invention, - Figure 5 illustrates, very schematically and in a vertical view, elements of a control device and a microfluidic device according to one embodiment of the invention,

- Figure 6 illustrates, very schematically and in a horizontal view, modules of a control device according to one embodiment of the invention, - Figures 7a, 7b, 7c illustrate, very schematically and according to a horizontal view, orientations of a microfluidic device according to one embodiment of the invention with respect to the modules represented in FIG. 6, - FIGS. 8a and 8b make it possible to illustrate, very schematically and according to a horizontal view , elements of a microfluidic device according to an embodiment of the third aspect of the invention, FIGS. 9a and 9b make it possible to illustrate, very schematically and according to a vertical section, elements of a microfluidic device according to one mode embodiment of the third aspect of the invention, - Figure 10 is a flowchart of a method according to the third aspect of the invention, - Figure 11 illustrates, very schematically and in a horizontal view the, elements of a microfluidic device according to an embodiment of the third aspect of the invention, - figure 12 makes it possible to illustrate, very schematically and according to a horizontal view, elements of a microfluidic device according to a mode of embodiment of the third aspect of the invention, and - Figure 13 is a flowchart of a method comprising characteristics from the three aspects of the invention described below. Embodiments of the Invention

The present invention is described with specific embodiments and references to figures, but the invention is not limited thereto. The drawings or figures described are only schematic and are not limiting. Furthermore, the functions described can be performed by other structures than those described in this document.

[0029] In the context of this document, the terms “first” and “second” only serve to differentiate the various elements and do not imply an order between these elements.

In the figures, identical or similar elements may bear the same references.

In the context of this document, an “analyte” is a substance or a chemical product, for example a biological molecule. It may include at least one of the following elements: one or more functional groups (antigens in particular), molecules, particles, macromolecules, DNA, RNA, antibiotics, hormones, toxins, molecules endogenous or exogenous to the matrix tested, cells , bacteria, viruses, mycotoxins, veterinary and/or human drugs, pesticides, hormones, antibodies…

[0032] In the context of this document, a “liquid” is preferably an aqueous liquid or an aqueous liquid preparation, for example blood, milk, urine, saliva, tears, any other physiological liquid, rain, swimming pool, surface, river or drainage water. The liquid may be edible and/or intended for use in the food industry. It may comprise a food matrix. Its composition may vary as it progresses through the microfluidic device.

The invention can be used in particular in the context of a measurement for detecting the presence, and possibly of the quantity, of an analyte in a liquid, and/or in the context of measuring physical parameters and/or of a liquid, for example its viscosity.

In the context of this document, the adjective "transparent" means allowing light to pass at least in the interval 350 to 750 nm.

Figure 1a is a top view of a microfluidic device 100 according to one possible embodiment of the invention. The microfluidic device 100 comprises a support 105, preferably of circular shape, and arranged to rotate around an axis 101, and a permeable element 200 (visible in FIG. 2 in particular). The permeable element 200 is configured so that a liquid can move through it by capillarity. It is preferably formed of a strip, for example the strip described in WO2019/068806.

The microfluidic device 100 preferably comprises a plurality of microfluidic tracks 102a to 102f distributed circumferentially, and which will be generally designated by the reference

102. The tracks 102 are preferably identical, but could be different while remaining within the scope of the invention. FIG. 1a also illustrates a radial direction 103, and a circumferential direction 104, perpendicular to the radial direction 103. The height 106 (visible in FIG. 3) is the direction of the axis 101. The thickness of the constituents of the permeable element 200, in particular of the porous support 210, is measured parallel to the height 106.

Figure 1b is a sectional view of the support 105, at line Ib of Figure 1a. The support 105 preferably comprises a lower part 10 and an upper part 20. The lower part 10 comprises recesses 11 which form the tracks 102, the recesses being separated by projections 12. The upper part 20 is preferably flat. The upper part 20 forms a cover over at least part of the recesses 11 and is glued on the projections 12. The upper part 20 is transparent at least in places, preferably everywhere. The upper part 20 may include an adhesive on its lower surface, allowing it to adhere to the lower part 10. The lower part 10 and the upper part 20 are preferably different parts fixed together. They can be in different materials. The lower part 10 is designed to absorb more electromagnetic radiation in the interval between 700 nm and 100 μm than the upper part 20. It preferably has a reflectance of less than 10% between 700 nm and 100 μm. The upper part 20 is preferably located above the lower part 10.

Figure 2 is an enlargement of one of the tracks 102. Each track 102 includes a plurality of chambers and passages so as to form an upstream-downstream fluid path. In one embodiment of the invention, each track 102 comprises, from upstream to downstream: an inlet chamber 110, a first passage 111, a volume fixing chamber 120, a second passage 121, a chamber reagent 130, third passage 131, transfer chamber 140, and detection chamber 150. Each of the inlet 110, volume uptake 120, first reagent 130, and transfer preparation ". Further, each track 102 includes a collection chamber 160 communicating with the first passage 111 through a collection passage 161. Each track 102 also includes a plurality of vents 170.

The first passage 111 comprises a first valve 112 preferably having an opening condition which causes it to open from an angular velocity V112. The second passage 121 comprises a second valve 122 preferably having an opening condition which causes it to open from an angular velocity V122. The third passage 131 comprises a third valve 132 preferably having an opening condition which causes it to open from an angular velocity V132. The microfluidic device 100 is preferably provided so that V132 > V122 2 V112. This makes it possible to control the time that the liquid spends in the inlet chamber 110, in the volume fixation chamber 120, and in the first reagent chamber 130, by controlling the angular velocity of the microfluidic device 100.

The part of the tracks 102 making it possible to prepare the liquid before it enters the permeable element 200 can be called the preparation part

180. Each track 102 includes a build portion 180 and a sensing chamber 150. The build portion 180 advances liquid radially outward. The speed of the progression is controlled there by a first type of fluidic displacement, that is to say by the speed of rotation of the microfluidic device 100. The detection chamber 150 causes the liquid to progress radially inwards. The speed of progression is in particular controlled there by a second type of fluidic displacement, that is to say by the capillarity of the permeable element.

200. The microfluidic device 100 is preferentially stopped during the migration of the liquid in the permeable element 200. However, it is possible, while remaining within the scope of the invention, that the rotation of the disc be used during the displacement of the liquid in the permeable element 200, for example in order to slow down this displacement.

The inlet chamber 110 makes it possible to introduce a liquid potentially comprising an analyte. The volume fixing chamber 120 makes it possible to fix the volume of liquid which will leave towards the first reagent chamber 130, the excess volume going towards the collection chamber 160. The first reagent chamber 130 comprises a first reagent. The transfer chamber 140 is used to bring the liquid to the end of the detection chamber 150 where it is absorbed, at least partially by the permeable element 200 which preferably comprises a measurement reagent.

The first reagent can comprise one or more chemical and/or biochemical compounds. The first reagent can be present in a buffer 800, and/or dried on a container and/or on a porous filter, and/or placed on the bottom of the cavity 330 in the liquid or solid state. The first reagent is potentially labeled so as to be optically detectable. For example, it can be detectable by fluorescence and/or comprise nanoparticles of metal (gold, silver, etc.), polymer (latex, cellulose), and/or magnetic nanoparticles.

The measurement reagent is provided to react with the first reagent. In a first type of immunological test, the measurement reagent is provided to enter into competition with the analyte and with the first reagent by direct competition of the measurement reagent with the analyte and the first reagent, so as to carry out an immunological test by competition directly between the analyte and the first reactant. For example, the analyte, if present in the liquid, comprises a first antigen, the first reagent comprises a labeled second antigen, and the measuring reagent comprises an antibody capable of binding the first and the second antigens. In a second type of immunological test, the first reagent is provided to react with the analyte and with the measuring reagent so as to carry out an immunological test by indirect competition between the analyte and the measuring reagent. For example, the analyte, if present in the liquid, includes a first antigen, the measuring reagent includes a second antigen, and the first reagent includes a labeled antibody capable of binding the first and second antigens. In a third type of immunoassay, the measurement reagent and the first reagent are designed to react with the analyte so as to produce a sandwich immunoassay in which the analyte is bound by the measurement reagent and is labeled by the first reactant.

The detection chamber 150 is elongated radially, so that the permeable element 200 is arranged radially. The detection chamber 150 preferably comprises, successively, a first part 151, a second part 152 and a third part 153. The second part 152 is wider, circumferentially, than the first part 151 and than the third part 153. A zone 213 , 214 for reading the porous support 210 of the permeable element 200, as described in the context of this document, is preferably located in the second part 152.

Figure 3 is a sectional view of the possible arrangement of the permeable element 200 in the detection chamber 150. Figure 3 illustrates in particular certain characteristics of the first aspect of the invention. The fluidic inlet of the permeable element 200 is at its radially outer end. The permeable element 200 comprises a porous support

210, preferably nitrocellulose, including the measuring reagent. The porous support 210 has a first face 211 and a second face 212 separated by a thickness. || is preferably a membrane. The first face 211 is preferably fixed, for example glued, to a structural support 220, which is transparent at least in places and preferably everywhere. In a non-illustrated embodiment of the first aspect of the invention, the first face 211 is directly joined to the upper part 20. There is preferably at least one free space between the lower part 10 and the permeable element 200.

The porous support 210 is preferably made of nitrocellulose. It has a thickness between 100 um and 300 um. It is preferably glued to the structural support 220 over its entire length and its entire width.

The porous support 210 comprises at least one reading area 213,

214. In the context of this document, a reading zone 213, 214 is a part of the porous support 210 configured to be able to measure a parameter there. For example, it may include the measuring reagent. The upper part 20 is transparent at least above the reading area 213, 214.

The porous support 210 can comprise for example a first reading zone 213 to react with a measurement reagent, and a second reading zone 214, preferably separated from the first 213, to react with another measuring reagent. It can comprise more than two reading zones, for example three or four. In the context of this document, a “reading zone” is a zone of the permeable element 200 intended to be read, preferably optically. It can be for example the first, the second or all of the read zone(s).

The structural support 220, which is optional, is preferably waterproof. It is preferably made of polymer material. It has for example a thickness between 100 μm and 800 μm.

If the structural support 220 is present, it is secured on the one hand to the upper part 20 and on the other hand to the porous support 210, above the reading zone 213, 214, and the structural support 220 and the upper part 20 are transparent above the reading area 213, 214.

The porous support 210 has two opposite ends. The first end 210a is radially external. It is closer to the transfer chamber 140 than the second end 210. The second end 210b is radially internal.

The permeable element 200 preferably comprises a first porous element 230 and fixed to the structural support 220. The first element 230 is in contact with a first end 210a of the porous support 210. It projects beyond the first end 210a radially outwards. , and down. The first element 230 serves as a reservoir making it possible to supply the permeable element 200 progressively, according to its absorption by capillarity. It may have a filtration function. It can comprise several parts, for example one of its parts could comprise a conjugate reagent.

The permeable element 200 preferably comprises a second porous element 240 fixed to the structural support 220. The second porous element 240 makes it possible to absorb the liquid at the end of the permeable element 200. It makes it possible to maintain the flow of liquid on the porous support 210 once it has been completely soaked.

The microfluidic device 100 preferably comprises a contrast enhancement element 159 located, in the detection chamber 150 and, at least below the reading zone 213, 214, between the lower part 10 and the porous support. 20. The contrast enhancement element 159 is arranged to create contrast between the reading area 213, 214 and the image background when taking an image of the reading area 213, 214. reading through structural support 220 and top

20. It preferably has a reflectance of at least 20% at a wavelength between 450 and 600 nm. || is preferably fixed to the permeable element 200 via the first element 230 and second element 240. It can be a sheet.

Figure 4 is a very schematic view of a control device 500 according to one embodiment of the invention. It makes it possible to visualize the circumferential and radial positions of certain elements of the piloting device 500. FIGS. 4 to 7 make it possible to illustrate in particular certain characteristics of the first and of the second aspects of the invention.

The piloting device 500 comprises a device slot 510 provided for placing the microfluidic device 100. The microfluidic device 100 is preferably placed at the device slot 510 with the upper part 20 above the lower part 10. The device slot 510 is arranged so as to rotate the microfluidic device 100 around an axis 501 of the steering device 500, which coincides with the axis 101 of the microfluidic device 100. The device slot 510 comprises a detection zone 511 and a heating zone 512 offset circumferentially from each other. Thus, at least part of the microfluidic device 100, for example the detection chamber 150, is movable between the detection zone 511 and the heating zone 512 by rotation around the axis 501.

The control device 500 comprises a detection module 520 comprising a detector 521 designed to pick up electromagnetic radiation coming from the detection zone 511, and in particular from the reading zone 213, 214 when it is in the zone of detection 511. Detector 521 preferably comprises a camera and/or a photographic sensor. The sensing module 520 provides sensing information, which may include images and/or liquid position information.

The control device 500 is preferably configured so that the detector 521 is able to check at least one of the following points: e whether the liquid is actually present in each of the tracks 102, e the position of the liquid in the track 102, e the position of the permeable element 200 in the detection chamber 150, e the progression of the liquid in the permeable element 200, e the modification of the reading zone 213, 214 of the permeable element 200 due to the absence or the presence of the analyte in the liquid introduced into the track 102.

The detection module 520 can also comprise an illumination element 522, for example a lamp, provided to illuminate the detection zone 511 in a wavelength interval perceptible by the detector 521 and suitable for observing, by The detector 521 changes in the permeable element 200, for example related to detection of the analyte. The illumination wavelength range can be for example between 350 and 750 nm. It is possible that the wavelength interval emitted by the illumination element 522 is identical to that perceived by the detector 521, or is different from that perceived by the detector 521 (in fluorescence for example).

The control device 500 comprises a heating module 530 arranged to heat the heating zone 512. The heating module 530 is preferably offset circumferentially from the detection module

520. The heating module 530 preferentially allows electromagnetic heating, preferably by radiation or induction. Heating by infrared radiation, for example at a wavelength between 700 nm and 100 μm, can for example be employed. It is also possible to use electromagnetic induction heating, for example by incorporating metal balls in the plate 515 (visible in Figure 5) or in the lower part 10.

The heating module 530 preferably comprises a plurality of heating elements 531 located at different radial distances from the axis 501 and/or offset circumferentially. They can be arranged in a T as illustrated in FIG. 4, but could be arranged in rectangles, crosses or in any other way while remaining within the scope of the present invention. An arrangement of the heating elements 531 where they are more numerous above the inlet chamber 110 is preferred because the liquid, potentially cold when it is introduced (in particular if it is milk), is brought to a reference temperature in the inlet chamber 110, which requires high heating power. Then, during the steps in the other chambers 120, 130, 140, 150, 160, the temperature can be modified or maintained, but the temperature increase is less than in the entrance chamber 110.

The heating elements 531 can be controlled independently and/or in groups. Each radial line (or each circumferential line) of heating elements 531 can form a group. The division of the 531 heating elements into groups can also be controlled via the control unit

590. Each of the chambers 110, 120, 130, 140, 150, 160 can correspond to a group of heating elements 531. A heating element 531 can be in several groups. For example, it is possible for a heating element 531 to be in a first group which corresponds to the first reagent chamber 130 and to a second group which corresponds to the detection chamber 150. The heating elements 531 can for example be diodes infrared.

The control device 500 is preferably provided so that different areas of the microfluidic device 100 can be heated to different temperatures. For example, first reagent chamber 130 may be heated to a first temperature and detection chamber 150 may be heated to a second temperature different from the first temperature.

The control device 500 preferably comprises a measurement module 540 arranged to measure a parameter, preferably a temperature, of the microfluidic device. The device location 510 comprises for example a measurement zone 513 circumterentially offset from the detection zone 511 and from the heating zone 512, and the measurement module 540 being arranged to measure the parameter on the measurement zone 513. The measurement module 540 is preferentially offset circumferentially from the detection module 520 and from the heating module 530. The temperature measurement is preferentially carried out by measuring the infrared emission, for example between 700 nm and 100 μm of wavelength . The measurement module 540 provides temperature information, which can include a temperature as a function of a position in the measurement zone 513. The pilot device 500, preferably the control unit 590, can then decide to heat more a position, via the heating module 530, if the temperature measured there is lower than a reference temperature. Similarly, if too low a temperature is measured on a track 102, the control device 500 can decide to bring this track 102 into the heating zone 512 to be heated there.

The measurement module 540 preferably comprises a plurality of measurement elements 541 located at different radial distances from the axis 501 and/or offset circumferentially. They can be arranged in a line as illustrated in FIG. 4, but could be arranged in a T, rectangle, cross or in any other way while remaining within the scope of the present invention. They can be controlled independently and/or in groups. Each radial line (or each circumferential line) of measuring element 541 can form a group. The division of the measuring elements 541 into groups can also be controlled via the control unit 590.

Each of the chambers 110, 120, 130, 140, 150, 160 can correspond to a measuring element group 541. A measuring element 541 can be in several groups. For example, it is possible for a measuring element 541 to be in a first group which corresponds to the first reagent chamber 130 and, potentially after rotation, to a second group which corresponds to the detection chamber 150. The measuring elements 541 are for example infrared detectors.

Although the microfluidic device 100 is rotating so that some of its elements pass from one zone to another, the microfluidic device 100 is preferably stopped during detection (preferably optical) by the module detection 520, heating by the heating module 530 and measurement (preferably of temperature) by the measurement module 540.

The control device 500 preferably comprises a control unit 590 configured for at least one of the following operations: e receiving, and preferably analyzing, detection information, for example images, coming from the detector 521, e generating a message error (intended for example to be displayed on a screen of the control device 500) if the detection information does not correspond to an expected reference situation (for example, if the liquid is supposed to be in one of the chambers 110, 120 , 130, 140, 150, 160 but it is not there on the images), e controlling the illumination element 522, e receiving, and preferably analyzing, temperature information coming from the measurement module 540, e control the heating module 530, preferably according to the temperature measured by the measurement module 540 and/or the position of the liquid detected via the detector 521, e control the heating elements 531 in groups and/or independently of each other,

e controlling the measuring elements 541 in groups and/or independently of each other, e controlling the orientation of the microfluidic device 100 (in particular passing the microfluidic tracks 102a-102f between the detection zone 511, the heating zone 512, and preferably the measurement zone 513), potentially depending on the temperature measured by the measurement module 540 and/or the position of the liquid detected via the detector 521, e control the speed of rotation of the microfluidic device 100, which can make it possible to successively open the first valve 112, then the second valve 122, then the third valve 132, potentially depending on the temperature measured by the measurement module 540 and/or the position of the liquid detected via the detector 521.

The 590 control unit is able to sequence all operations in a harmonious manner.

The control unit 590 may include a processor, a central processing unit (CPU), a digital signal processor (DSP), an application specific integrated circuit (ASIC), an array of programmable gates per field (FPGA), or the like, or any combination thereof, and may include discrete digital or analog circuit elements or electronic components, or combinations thereof. It is preferably configured to run one or more computer program(s) making it possible to implement any method of using the various aspects of the present invention.

The piloting device 500 can comprise a liquid introduction module 550, or filling module, comprising at least one opening 551 through which liquid can be introduced into the inlet chamber 110. It is also possible that the liquid is introduced into the inlet chamber 110 before being placed in the device location 510.

[0070] Figure 5 is a very schematic vertical view of a detection system 1 according to one embodiment of the invention. The detection system 1 comprises the microfluidic device 100 and the steering device 500. The microfluidic device 100 is intended to be used only once and then to be discarded, and the steering device 500 is intended to be reused. The control device 500 comprises for example a hub 515 located in a drawer so as to be able to mechanically couple the microfluidic device 100 to the hub 515 when the drawer is open. When the drawer is closed, the hub 515 assumes a position such that the microfluidic device 100 is at the device location 510. The hub 515 can be significantly less wide than illustrated in FIG. elements of the control device 500, the device location 510 is preferably a space located lower than the modules 520, 530, 540, 550, as shown in Figure 5.

[0071] Figure 6 is a top view to illustrate a possible arrangement of the modules 520, 530, 540 of the control device 500, different from the arrangement of Figure 4. Any other arrangement of the modules is possible, and a or several modules could be present several times while remaining within the scope of the present invention. Figures 7a, 7b, 7c make it possible to illustrate different possible orientations of the microfluidic device 100, and in particular of its first 102a, second 102b and third 102c microfluidic tracks, with respect to the positions of the modules 520, 530, 540 illustrated in FIG. 6. The microfluidic device 100 passes from one orientation to the other by a rotation controlled by control unit 590, preferably by rotation of the hub 515.

FIG. 7a illustrates a first orientation 591 of the microfluidic device 100, in which at least the reading zone 213, 214 of the permeable element 200 of the detection chamber 150a of the first track 102a is in the detection zone 511 and is detectable by the detection module 520. Preferably, the preparation part 180a of the first track 102a is also, at least partly, in the detection zone

511.

FIG. 7b illustrates a second orientation 592 of the microfluidic device 100 obtained by rotation with respect to FIG. 7a. In the second orientation 592, at least the reading zone 213, 214 of the permeable element 200 of the detection chamber 150a of the first track 102a is in the heating zone 512 and can be heated by the heating module

530. Preferably, the preparation part 180a of the first track 102a is also, at least partly, in the heating zone 512. In particular, at least one of the following parts can be in the heating zone 512: the chamber of inlet 110, and the first reagent chamber 130. Heating the liquid in the inlet chamber 110 makes it possible to standardize the temperature of the samples of liquid introduced. Heating the liquid in the first reagent chamber 130 facilitates incubation of the analyte with the first reagent 130.

In the second orientation 592, at least the reading zone 213, 214 of the permeable element 200 of the detection chamber 150b of the second track 102b is in the detection zone 511 and is detectable by the detection module 520. Preferably, the preparation part 180b of the second track 102b is also, at least partly, in the detection zone 511.

FIG. 7c illustrates a third orientation 593 of the microfluidic device 100 obtained by rotation with respect to FIG. 7b. In the third orientation 593, at least the reading zone 213, 214 of the permeable element 200 of the detection chamber 150a of the first track 102a is in the measurement zone 513 and its temperature can be measured by the measurement module 540. Preferably, the preparation part 180a of the first track 102a is also, at least partly, in the measurement zone

513. In particular, at least one of the following parts can be in the measurement zone 513: the inlet chamber 110, the volume fixation chamber 120, and the first reagent chamber 130. Measuring the temperature makes it possible to adapt the heating carried out by the heating module in order to obtain a determined temperature in one of the chambers 110, 120, 130, 140,

150.

Preferably, in the third orientation 593, at least the reading zone 213, 214 of the permeable element 200 of the detection chamber 150b of the second track 102b is in the heating zone 512 and can be heated by the heating module 530. Preferably, the preparation part 180b of the second track 102b is also, at least partly, in the heating zone 512. .

Preferably, in the third orientation 593, at least the reading zone 213, 214 of the permeable element 200 of the detection chamber 150c of the third track 102c is in the detection zone 51 1 and is detectable by the detection module 520. Preferably, the preparation part 180c of the third track 102c is also, at least partly, in the detection zone 511.

Although Figures 7a, 7b, 7c show only three orientations, it is possible that there are more within the scope of the present invention. Furthermore, any intermediate orientation between the three illustrated orientations is possible within the scope of the present invention, for example to target one of the chambers.

Figures 8 to 12 illustrate in particular certain characteristics of the third aspect of the invention. A microfluidic device 100 for manipulating a volume of liquid 2 according to the third aspect of the invention can have any of the characteristic(s) described in this document. An assembly according to the third aspect of the invention comprises, in addition to the microfluidic device 100, a volume of liquid. The liquid volume potentially includes an analyte.

Figures 8a and 8b illustrate a possible arrangement of part of a microfluidic device according to the third aspect of the invention. The microfluidic device preferably comprises, from upstream to downstream, a first upstream location 310, an upstream passage 311 which ends in an upstream valve 312, a first intermediate location 320 comprising a first function zone 350, a downstream passage 321 which ends in a downstream valve 322, and a downstream location 340. The downstream valve 322 is preferably farther from the axis 101 than the upstream valve 312.

The upstream valve 312 has an opening condition (called first opening condition) which is satisfied when a pressure obtained by centrifugal force exerted by the liquid on the upstream valve 312 is greater than a capillary pressure exerted by the upstream valve 312 on the liquid. This occurs from a first angular speed V1 because the pressure obtained by centrifugal force increases with the angular speed. The downstream valve 322 has an opening condition (called the second opening condition) which is satisfied when a pressure obtained by centrifugal force exerted by the liquid on the downstream valve 322 is greater than a capillary pressure exerted by the downstream valve 322 on the liquid, which occurs from a second angular velocity V2. The microfluidic device is such that V2 is greater than or equal to V1 in order to be able to retain the volume of liquid, at least in part, in the intermediate location 320 for a first duration. This allows a first function, intended to be performed in the first intermediate location 320, to be implemented on the liquid during the first duration. The first function can also be called first step, or intermediate step.

The first upstream location 310 can be configured for a second function which requires keeping the liquid there for a second period. The second function can also be called second stage, or upstream stage. The second function is therefore carried out before the first function on an upstream-downstream path. The first and the second function are preferably different. They can be, for example: detection, fixing of the volume of liquid, heat treatment, chemical treatment, for example incubation with a reagent. In one embodiment, the microfluidic device comprises a permeable element 200 immobilizing a measurement reagent (for example a permeable element as described in relation to the first and/or second aspect(s) of the invention), and the first function is an incubation with a first reagent present in the first intermediate location

320. Heating may also be involved in the first and/or the second function, for example as described in relation to the second aspect of the present invention.

The locations are preferably located in chambers of a microfluidic device 100. The third aspect of the invention can be implemented in several ways on a track 102 as described in particular in relation to FIG. 2. In a first implementation of the third aspect of the invention, the first upstream location 310 is in the inlet chamber 110, the first intermediate location 320 is in the volume attachment chamber 120, the downstream location 340 is in the first reagent chamber 130, the upstream valve 312 is the first valve 112, and the downstream valve 322 is the second valve 122. In a second implementation of the third aspect of the invention (illustrated partially in FIG. 11), the first upstream location 310 is in the chamber volume fixing 120, the first intermediate location 320 is in the first reagent chamber 130, the downstream location 340 is in the transfer chamber 140, the v Upstream cell 312 is the second valve 122, and the downstream valve 322 is the third valve 132. The volume of liquid 2 is preferably that kept by the volume fixing chamber 120.

[0084] In Figure 8a, the volume of liquid 2 is blocked by the upstream valve

312. In FIG. 8b, it is blocked by the downstream valve 322. FIG. 9a is a sectional view at the level of the upstream passage 311, and FIG. 9b is a sectional view at the level of the downstream passage 321. FIGS. , 8b, 9a, 9b make it possible to illustrate parameters which are listed in the table below, with a preferred value interval.

Param Description Values Units: R, Radial distance between axis 101 and a [10-150] mm:: radially internal wall 315 of:: volume of liquid 2 blocked by valve 9: R, Radial distance between axis 101 and the [ 10-150] mm A...: 8} Angle of contact between the liquid and the [0-180]: Deg 9 upper part 20 of the device: | : microfluidic at the location of the : 6} Contact angle between the liquid and the [0-180] : Deg 9 : lower part 10 of the device 9 { : microfluidic at the location of the : : H, _ Height of the upstream valve 312: [100-1000] μm | M Width of the upstream valve 312 [100-1000] μm: Rp Radial distance between the axis 101 and a [10-150] mm:: radially internal wall 315 of::: volume of liquid 2 blocked by the valve 9: R, Radial distance between the axis 101 and the [10-150] mm Vele aval322 ee: 62 Angle of contact between the liquid and the [0-180]: Deg 9 upper part 20 of the device:; : microfluidic at the location of the 9 ‚ 62 Contact angle between the liquid and the [0-180]: Deg 9: lower part 10 of the device 9: microfluidic at the location of the: Hz Height of the downstream valve322 [100 -1000] um: W, _ Downstream valve width 322 [100-1000]: um

6;,2 is the contact angle with the bottom wall and the sides, which are formed from the bottom part 10. 64, + 6.4, > 90° and 052 + 6; > 90° . In one embodiment of the invention, the liquid is milk, the lower part

10 is made of PMMA and the upper part 20 is an adhesive film based on acrylate. In this case, 0.1 = 0.1 = 65° and 0.5 = 0.52 = 115°.

In one embodiment, the first open condition is 177; ( cos (0, + 5) + cos(85- ) 2 cos (87: + 2 7 PV1 (Re, Rh) >0 e= T Cow and the second opening condition is 1 2702; ( cos (9, 2 + 5) +cos(85,) 2cos (9,2 + 2 „PVi (Ré Rp) > 0 TUE p is the density of the liquid and 0 is the surface tension of the liquid.

Figure 10 shows different steps of a method according to the third aspect of the invention. The method includes the following steps. It is preferred that one step be completed before the next begins. The volume of liquid 2 is positioned 410 upstream of the upstream valve 312 so as to be blocked by the upstream valve 312. The microfluidic device is then accelerated 420 so that its angular velocity exceeds V1, and the volume of liquid 2 crosses the upstream valve 312. It arrives in the intermediate location 320 in which it is kept 430 during the first duration. The first duration is preferably less than the lapse of time separating 420 and 440. It is blocked there by the downstream valve 322. The microfluidic device is then accelerated 440 so that its angular velocity exceeds V2, and the volume of liquid 2 crosses the downstream valve 322. The rotation of the microfluidic device is preferably controlled by a computer program running on the control unit 590.

Figure 11 is a top view of a valve 322 in one embodiment of the invention. This embodiment is particularly suitable for the downstream valve 322, but could also be used for the upstream valve 312. The channel 321 has an inlet 321a which opens into the first intermediate location 320 and outlet 321b which forms the downstream valve 322 and opens in the downstream location 340. Preferably, the outlet 321b is radially more internal than the inlet 321a.

Figure 12 is a top view of part of a microfluidic device according to one embodiment of the third aspect of the invention. It illustrates an embodiment of the third aspect of the invention with a second intermediate location 330, and an additional valve 332. The second intermediate location 330 is configured for a third function which requires maintaining the liquid there for a third term. The third function can also be called third stage, or downstream stage. The additional valve 332 has a third opening condition which is satisfied when a pressure obtained by centrifugal force exerted by the liquid on the additional valve 332 is greater than a capillary pressure exerted by the additional valve 332 on the liquid, which produced from a third angular velocity V3, the third angular velocity V3 being greater than or equal to the second angular velocity V2.

[0089] Figure 12 also illustrates another implementation of the third aspect of the invention with respect to the microfluidic track 112. It illustrates a possible arrangement of the locations 310, 320, 330, 340 with respect to the chambers 110, 120 , 130, 140 of the microfluidic track 102: the first upstream location 310 is in the inlet chamber 110, the first intermediate location 320 is in the volume fixing chamber 120, second intermediate location 330 is in the first reagent chamber 130, the downstream location 340 is in the transfer chamber 140, the upstream valve 312 is the first valve 112, the downstream valve 322 is the second valve 122, and the additional valve 332 is the third valve 132. The first function comprises a fixing of the volume of the liquid, the second function comprises an introduction of liquid, the third function comprises an incubation with the first reagent.

Figure 13 illustrates a method 600 combining the three aspects of the invention. Those skilled in the art will understand that the steps, although described as successive, can take place partly in parallel. At step 610, the microfluidic device 100 is fabricated. Each lane 102 includes a permeable element 200 and a first reagent. The permeable elements 200 can be identical or different. The first reagent of each lane 102 corresponds to the measurement reagent of the permeable element 200 of this lane 102.

At step 620, liquid comprising an analyte is introduced into the inlet chambers 110 of the various tracks 102 of the microfluidic device.

100. It can be one liquid for all lanes or different liquids. For example, if milk is being tested, different analytes from the same milk can be tested in parallel using different first reagents and permeable elements 200 and/or multiple milks can be tested against the same analyte. When introduced, the liquid may be at a low temperature, for example if it has been refrigerated. The inlet chamber 110 of each track 102 then passes from the heating zone 512 to the measurement zone 513 until the temperature of the liquid there reaches a first threshold. In addition, the entry chamber 110 of each track 102 passes into the detection zone 511 to verify the actual presence of a liquid. If no liquid is present, the 590 control unit can send an alert.

When the temperature of the liquid has reached the first threshold, the microfluidic device 100 is accelerated beyond the speed V112 in order to open the first valve 112 and the liquid passes 630 into the volume fixing chamber 120. A volume of liquid is kept in the volume fixing chamber 120 and the surplus passes into the collection chamber 160. The volume fixing chamber 120 of each track 102 passes into the detection zone 511 to verify the effective presence of a liquid. If no liquid is present, the 590 control unit can send an alert.

When the liquid has been detected in each of the volume fixing chambers 120, the microfluidic device 100 is accelerated beyond the speed V122 in order to open the second valve 122 and the liquid passes 640 into the first chamber. reagent 130. The first reagent chamber 130 of each track 102 then passes from the heating zone 512 to the measurement zone 513 until the temperature of the liquid there reaches a second threshold. Furthermore, the first reagent chamber 130 of each track 102 passes through the detection zone 511 to verify the actual presence of a liquid. If no liquid is present, the 590 control unit can send an alert. When the temperature of the liquid has reached the second threshold, the liquid is left in the first reagent chamber 130 for a time sufficient for incubation of the analyte with the first reagent. This duration is an example of the second duration, or third duration, mentioned in the description of the third aspect of the invention.

The microfluidic device 100 is then accelerated beyond the speed V132 in order to open the third valve 132 and the liquid passes 650 into the transfer chamber 140. Its temperature there is controlled by passages in the measurement zone. 513 and possibly increased by passages in the heating zone 512.

The liquid then arrives 660 in the detection chamber 150, at the radially outer end of the permeable element 200. The detection chamber 150 of each track 102 then passes from the heating zone 512 to the measurement zone 513 until the temperature of the liquid and/or of the permeable element 200 reaches a third threshold there. In addition, the detection chamber 150 of each track 102 passes through the detection zone 51 1 to verify the actual presence of a liquid and its progress in the permeable element 200.

A part of the liquid is preferentially absorbed by the first element 230 and progresses in the porous support 210 radially inwards. When the liquid arrives in the first reading zone 213, it can react with the first measurement reagent, and when it arrives in the second reading zone 214, it can react with the second measurement reagent. These reactions cause a modification in the reading zones 213, 214 which is detectable by the detector 521 when the reading zones 213, 214 pass through the detection zone 511. This detection is particularly effective when the permeable element 200 is attached, without free space, at the upper part 20 of the microfluidic device 100.

At any time, the control unit can send an alert if an unexpected event occurs, for example if one of the temperature thresholds cannot be reached on one of the tracks.

In other words, according to a first aspect, the invention relates to a microfluidic device 100 comprising a permeable element 200 fixed to the upper part 20 of the microfluidic device so as to be able to be read through said upper part 20 and without that there is no space between the porous support 210 and said upper part 20 which would be likely to accommodate condensation.

The present invention has been described in relation to specific embodiments, which are purely illustrative and should not be construed as limiting. In general, the present invention is not limited to the examples illustrated and/or described above. The use of the verbs "understand", "include", "compose", or any other variant, as well as their conjugations, can in no way exclude the presence of elements other than those mentioned. The use of the indefinite article "un", "une", or of the definite article "le", "la" or "['", to introduce an element does not exclude the presence of a plurality of these elements. The reference numbers in the claims do not limit their scope.

Claims (14)

Claims 1. Microfluidic device (100) comprising: e a permeable element (200) comprising a porous support (210), the porous support (210) comprising a reading zone (213, 214), e an upper part (20) fixed to the permeable element (200) and, transparent at least above the reading zone (213, 214), and e a lower part (10) arranged to form, with the upper part (20), a detection chamber (150) in which the permeable element (200) is located; the porous support (210) being, at least above the reading zone (213, 214), joined to the upper part (20) by a transparent junction and such that there is no free space between the reading zone (213, 214) and the upper part (20). 2. Microfluidic device (100) according to the preceding claim, in which the junction between the porous support (210) and the upper part (20) comprises a structural support (220) of the permeable element (200). 3. Microfluidic device (100) according to any one of the preceding claims, in which there is at least one free space between the lower part (10) and the permeable element (200). 4. Microfluidic device (100) according to the preceding claim, in which the lower part (10) has a higher absorbance than that of the upper part (20) at a wavelength between 700 nm and 100 μm. 5. Microfluidic device (100) according to any one of the preceding claims, comprising, between the lower part (10) and the porous support (210), at least below the reading zone (213, 214), a contrast enhancement element (159) having a reflectance of at least 20% at a wavelength between 350 and 750 nm. 6. Microfluidic device (100) according to any one of the preceding claims, in which the detection chamber (150) comprises, in length and successively, a first part (151), a second part (152) and a third part ( 153), the second part (152) being wider than the first part (151) and than the third part (153), the second part (152) housing the zone (213, 214) for reading. 7. Microfluidic device (100) according to any one of the preceding claims, arranged to rotate around an axis (101), and in which the permeable element (200) is of elongated shape and is arranged radially. 8. Detection system (1) comprising a microfluidic device (100) according to any one of the preceding claims, and a piloting device (500) comprising: e a device slot (510) provided for placing the microfluidic device (100 ) and comprising a detection zone (511), and a detector (521) arranged to pick up electromagnetic radiation coming from the reading zone (213, 214) when the microfluidic device (100) is located at the device location ( 510) so that the read zone (213, 214) is in the detection zone (511). 9. Detection system (1) according to the preceding claim, in which the device location (510) comprises a heating zone (512) encompassing at least a part of the microfluidic device (100) when the microfluidic device (100) is located at the device location (510); and the control device (500) comprises a heating module (530) arranged to heat the heating zone (512). 10. Detection system (1) according to the preceding claim, wherein the heating module (530) allows heating by electromagnetic waves, preferably by radiation or induction. 11. Detection system (1) according to claim 9 or 10, provided for rotating the microfluidic device (100) around an axis (501), and in which the heating module (530) comprises a plurality of elements heater (531) located at different radial distances from the axis (501) and/or offset circumterentially. 12. Detection system (1) according to the preceding claim, in which the control device (500) is configured to control the heating elements (531) in groups and/or independently of each other. 13. Method of using a microfluidic device (100) according to any one of claims 1 to 7, in which: e a liquid comprising reagents progresses in the porous support (210) and enters the zone (213, 214) of reading where it produces a modification of the zone (213, 214) of reading; and said modification of the read area (213, 214) is detected via electromagnetic radiation having passed through the junction and the upper part (20) above the read area (213, 214). 14. Method of use according to the preceding claim, in which the zone (213, 214) for reading comprises a measuring reagent, and in which the modification of the zone (213, 214) for reading is produced by a reaction of at least one of the reagents of the liquid with the measurement reagent. 15, A method of making a microfluidic device (100), wherein: e Oonprovides a permeable element (200) comprising a porous support (210) having a read zone (213, 214); e a lower part (10) of the microfluidic device (100) is provided; e an upper part (20) of the microfluidic device (100), transparent at least in places, is provided; and e assembling the lower part (10), the upper part (20), and the permeable element (200), so that the lower part (10) and the upper part (20) form a detection chamber (150) housing the permeable element (200), that at least above the reading zone (213, 214), the permeable element (200) and the upper part (20) are joined: - by a transparent junction such that there is no free space between the reading zone (213, 214) and the upper part (20), and - so that the upper part (20) is transparent at least above the reading area (213, 214).