Microfluidic platform and associated setup for monitoring the ageing and / or degradation of a material of interest in a simulated medium

Abstract

The invention relates to a microfluidic platform (2) for monitoring the ageing of a material of interest in a simulated environment, the platform comprising: - a microfluidic chip (9) delimited by two plates stacked one on top of the other to form a fluid circuit (10) comprising an inlet microfluidic channel (10a), a microfluidic chamber (10b) downstream of the inlet microfluidic channel and an outlet microfluidic channel (10c) downstream of the microfluidic chamber; - a housing (11) comprising two blocks (11a, 11b) that are joined together for accommodating the microfluidic chip, a fluid inlet (12) upstream of the inlet microfluidic channel through which a fluid is intended to be injected when the microfluidic chip is accommodated in the housing and a fluid outlet (13) downstream of the outlet microfluidic channel through which the fluid is intended to be discharged when the microfluidic chip is accommodated in the housing.

Description

[0001] Description

[0002] Title: Microfluidic platform and associated installation for monitoring the aging and / or degradation of a material of interest in a simulated environment.

[0003] Technical field

[0004] The present invention relates to the field of monitoring the aging or degradation of a material of interest in a simulated environment.

[0005] Prior art

[0006] When designing or choosing to use a material, it is important to be able to study its aging and / or degradation in the environment in which it is intended to be present.

[0007] Thus, it is interesting to predict the functional lifetime of said material and to observe its impact on said environment, in particular if its degradation causes pollution or toxic effects for the environment. For example, it is important to study the aging and the effects over time of a drug or an implant in a human or animal body. It is also interesting to study the pollution caused by the degradation of drugs [1], plastics and metals, in particular heavy metals, in the environment.

[0008] Furthermore, monitoring of pollution caused by potentially toxic substances is governed by precise directives [2].

[0009] The aging and / or degradation of a material in a given environment is multifactorial. They are notably a function of light, temperature, humidity, pH, and / or interactions with other components of the environment, for example microorganisms. Thus, studies monitoring the aging and / or degradation of a material of interest are generally long, complex, and may require independent, varied and numerous equipment.

[0010] It is known to use aging chambers using UV, IR and / or visible light, temperature, humidity or pressure to study the degradation of a material of interest, including paint, resin, plastic, or metal, as a function of a chosen environmental parameter. These aging chambers are generally bulky and suitable for testing a single environmental variable. There are also methods for bringing a material of interest into contact with microorganisms, for example, gel deposition in a Petri dish. These methods may include static or agitated oven placement to control the temperature, or glove box placement to control the atmosphere, or chamber placement with a simulated day / night cycle. However, it is usually not possible in these cases to monitor in situ the interactions of the material of interest with the microorganisms.Furthermore, these methods only allow the study of the aging and / or degradation of a material of interest according to a simplified model in which the experimental conditions remain far from the target environment.

[0011] Mesocosms are also known for studying the aging or degradation of a material of interest in a simulated environment. These are generally artificial ecosystems placed in natural environmental conditions for the study of the ecotoxicology of various potential environmental contaminants. They can also be laboratory mesocosms to control different parameters, but they often neglect part of the environmental conditions of the target environment and do not allow for sufficiently long study times. Known mesocosms are complex to implement in order to properly control the experimental conditions and they are cumbersome.

[0012] CN2016 / 62570 U describes a device for simulating terrestrial soil. Similarly, W02016 / 103152 A1 describes a device for simulating an environment suitable for plant growth. However, these devices are not suitable for simulating a plurality of varied environments. In addition, they are difficult to transport due to their size and weight.

[0013] There is therefore a need for a device for monitoring the aging or degradation of a material of interest in a simulated environment overcoming the aforementioned drawbacks.

[0014] In particular, there is a need for a device for monitoring the aging or degradation of a material of interest in a simulated environment, which is compact and suitable for exposing the material of interest to environmental conditions while simultaneously controlling different experimental parameters.

[0015] The aim of the invention is to meet, at least in part, this(these) need(s). Statement of the invention

[0016] To this end, the invention relates to a microfluidic platform for monitoring the degradation and / or aging of a material of interest in a simulated environment, comprising:

[0017] - a microfluidic chip delimited by two plates stacked on top of each other, delimiting a fluid circuit comprising:

[0018] • a microfluidic inlet channel,

[0019] • a microfluidic chamber connected downstream to the inlet microfluidic channel, and comprising a housing for the material of interest,

[0020] • an outlet microfluidic channel connected downstream to the microfluidic chamber;

[0021] - a box comprising:

[0022] • two blocks, at least one of which includes a cavity, the two blocks being assembled together to house the microfluidic chip in a sealed manner,

[0023] • a fluidic inlet through which a fluid is intended to be injected, which is connected upstream to the microfluidic inlet channel, when the microfluidic chip is housed in the housing,

[0024] • a fluid outlet through which the fluid is intended to be evacuated, which is connected downstream to the microfluidic outlet channel, when the microfluidic chip is housed in the housing.

[0025] By “material of interest” is meant here and within the framework of the invention, a single-piece solid of which at least one of its dimensions is greater than or equal to 1 mm.

[0026] According to one embodiment, the housing for the material of interest may be an imprint within a recess of one of the two plates, said recess being intended to form the microfluidic chamber.

[0027] According to another embodiment, the housing for the material of interest may comprise at least one holding relief projecting into a recess of one of the plates, said recess being intended to form the microfluidic chamber. Preferably, the microfluidic platform comprises at least one insertion guide for inserting the material of interest therein, which opens onto one of the sides of one of the plates and into the recess opposite the holding relief.

[0028] Preferably, the plates of the microfluidic chip are made of a material transparent to ultraviolet and / or visible and / or infrared radiation, preferably polydimethylsiloxane or photopolymerized transparent resin.

[0029] Preferably, the plates of the microfluidic chip include one or more magnets to keep them stacked on top of each other.

[0030] Preferably, the microfluidic platform comprises a seal arranged in the microfluidic chip around the fluid circuit.

[0031] Preferably, the housing blocks include one or more magnets to hold them together.

[0032] Preferably, the microfluidic platform comprises a seal arranged in the housing around the microfluidic chip.

[0033] Preferably, the microfluidic platform comprises at least one internal sensor housed in one of the blocks so as to be opposite the microfluidic chamber when the microfluidic chip is housed in the housing, in order to measure at least one environmental parameter of the microfluidic chamber, chosen from temperature, pressure, pH, gas concentration, magnetic field, humidity and speed of the microfluidic chamber.

[0034] The internal sensor(s) may be a gas detector, an accelerometer, a pressure sensor, a magnetometer, a thermal sensor and / or a humidity sensor. Preferably, the accelerometer is coupled with a gyroscope.

[0035] Preferably, the microfluidic platform comprises an internal imaging system housed in one of the blocks so as to face the microfluidic chamber when the microfluidic chip is housed in the housing, in order to capture images of the material of interest in the housing of the microfluidic chamber.

[0036] Preferably, the microfluidic platform comprises a wireless communication system connected to the internal sensor and / or the internal imaging system in order to transmit the parameters measured by the internal sensor and / or the images captured by the internal imaging system to a receiver external to the microfluidic platform. The transmission of the wireless communication system can be carried out by Bluetooth or by WIFI.

[0037] Preferably, the microfluidic platform comprises at least one external sensor configured to determine an environmental parameter of the fluid circuit from a measurement taken outside the fluid circuit, the environmental parameter being chosen from temperature, an oxidation-reduction potential, in particular pH, or the presence, or even the quantity, of a substance in the fluid circulating in the fluid circuit.

[0038] Preferably, the microfluidic platform further comprises a thermal regulation device for heating and / or cooling the housing, preferably in the form of a Peltier module and / or an infrared radiation source and / or a heat exchanger.

[0039] Preferably, the Peltier module is coupled with a metal shell, preferably aluminum, intended to be in contact with the housing. The metal shell can be clipped around the housing.

[0040] Preferably, the fluid circuit is made in at least one of the blocks of the housing. Preferably, the fluid circuit surrounds the cavity intended to house the microfluidic chip. This advantageously makes it possible to bring the heat transfer fluid as close as possible to the fluid circuit.

[0041] Preferably, one of the plates includes a viewing window through which the microfluidic chamber can be viewed when the plates are stacked, and one of the blocks includes a viewing porthole superimposed with the viewing window, when the microfluidic chip is housed in the housing.

[0042] Preferably, the window is made of silicon nitride or single crystal quartz.

[0043] The invention also relates to an installation for monitoring the degradation and / or aging of a material of interest in a simulated environment, the installation comprising:

[0044] - a platform according to the invention,

[0045] - an infusion device for injecting a fluid at a given pressure into the fluid inlet.

[0046] Preferably, the installation comprises a flow regulator connected downstream to the fluid outlet to regulate the flow of fluid in the fluid circuit at a determined flow rate. Preferably, the installation comprises a fluid collector connected downstream of the fluid outlet to recover and store the effluents at the outlet of the fluid circuit.

[0047] Preferably, the installation comprises a light source, preferably at least one LED, adapted to emit radiation in the infrared and / or in the visible and / or in the ultraviolet, to illuminate the housing.

[0048] Preferably, the installation comprises at least one visualization device for visualizing the material of interest in the housing of the microfluidic chamber.

[0049] Preferably, the viewing device is arranged with the viewing window in its field of vision.

[0050] Preferably, the viewing device is chosen from a camera, for example a CCD or CMOS camera, a spectroscope, for example an ultraviolet spectroscope or a Raman spectroscope, and a microscope, for example a digital microscope or a scanning electron microscope.

[0051] The invention therefore essentially consists of a microfluidic platform adapted to house in a sealed manner a material of interest in a microfluidic chamber of a fluid circuit whose properties simulate a medium / environment. The material of interest can thus be exposed to microorganisms and / or substances of the target medium in conditions closest to the latter, while limiting external influences as much as possible.

[0052] The present invention can be used for monitoring pollution caused by medicines, plastics, in particular microplastics, or metals in nature, for example in marine or freshwater environments.

[0053] In addition, it is possible to study in real time the behavior of the material of interest in the simulated environment, in particular its degradation and / or its aging. In particular, the microfluidic platform is suitable for regular data sampling of the environment of the microfluidic chamber. In particular, the integration of an internal sensor in the microfluidic platform and / or an external sensor makes it possible to collect physical and / or chemical data of the environment of the microfluidic chamber in real time. Similarly, the installation according to the present invention comprises different elements allowing the observation of the behavior of the material of interest in the microfluidic chamber in real time.

[0054] The microfluidic platform according to the invention is compact and lightweight, which makes it easily transportable and suitable for various locations of use, both indoors and outdoors. In particular, the microfluidic platform can be centimeter-sized when the microfluidic chip is housed in the assembled housing, i.e. its largest dimension can be of the order of a centimeter.

[0055] The same applies to the installation according to the present invention, which is small in size compared to the mesocosms according to the prior art. In particular, due to the small dimensions of the microfluidic platform, the size of the installation depends mainly on the size of the perfusion device and, where appropriate, the flow regulator, the fluid collector, the light source and / or the visualization device. The installation is also easily transportable due to its modular aspect.

[0056] Furthermore, the microfluidic platform according to the invention is simple to manufacture and inexpensive.

[0057] Other advantages and characteristics will become more apparent upon reading the detailed description, given for illustrative and non-limiting purposes, with reference to the following figures.

[0058] Brief description of the drawings

[0059] [Fig 1] Figure 1 is a perspective view of an installation for monitoring the degradation and / or aging of a material of interest according to the present invention.

[0060] [Fig 2] Figure 2 is a perspective view of a microfluidic platform according to the invention intended to be used in an installation for monitoring the degradation and / or aging of a material of interest.

[0061] [Fig 3a], [Fig 3b], [Fig 3c], [Fig 3d] and [Fig 3e] Figures 3a to 3e are each a perspective view of a first plate intended to constitute a part of a microfluidic chip of the microfluidic platform according to the present invention.

[0062] [Fig 4a] and [Fig 4b] Figures 4a and 4b are each a perspective view of a second plate intended to constitute a part of a microfluidic chip of a microfluidic platform according to the present invention. [Fig 5a] Figure 5a is a perspective view of a first block of the housing of a microfluidic platform according to the present invention, the point of view being from the side of the external face of said first block.

[0063] [Fig 5b] Figure 5b is a perspective view of the first block according to Figure 5a, the point of view being from the side of the internal face of said first block.

[0064] [Fig 6a] Figure 6a is a perspective view of a second block of the housing of a microfluidic platform according to the present invention, the point of view being from the side of the internal face of said second block.

[0065] [Fig 6b] Figure 6b is a perspective view of the second block according to Figure 6a, the point of view being from the side of the external face of said second block.

[0066] [Fig 7a] Figure 7a is a perspective view of a syringe pump type infusion device for an installation according to the present invention.

[0067] [Fig 7b] Figure 7b is a perspective view of a pressure controller type infusion device for an installation according to the present invention.

[0068] [Fig 8] Figure 8 is a perspective view of an installation for monitoring the degradation and / or aging of a material of interest according to the present invention, the installation comprising a gravity-type perfusion device.

[0069] Detailed description

[0070] Figure 1 illustrates an installation 1 according to the invention for monitoring the degradation and / or aging of a material of interest.

[0071] The installation 1 comprises a microfluidic platform 2, a perfusion device 3 supplying fluid to the platform 2, a flow regulator 4 for the fluid circulating in the platform 2, a fluid collector 5 for collecting the effluents coming from the platform 2, a light source 6 for illuminating the platform, a display device 7 for the platform 2 connected to a computer 8.

[0072] The microfluidic platform 2 of the installation 1 is illustrated in detail in Figure 2. It comprises a microfluidic chip 9 integrating a fluid circuit 10, and a housing 11 formed by two blocks, called first 11a and second 11b blocks, assembled together to house the microfluidic chip 9 in a sealed manner. The fluid circuit 10 consists of an inlet microfluidic channel 10a, a microfluidic chamber 10b which houses a material of interest and an outlet microfluidic channel 10c communicating with each other. The inlet microfluidic channel 10a is connected upstream to the microfluidic chamber 10b. The outlet microfluidic channel 10c is connected downstream to the microfluidic chamber 10b.

[0073] The housing 11 comprises a fluid inlet 12 and a fluid outlet 13 arranged in the first block 11a. The fluid inlet 12 is connected to the fluid circuit 10 and upstream of it, when the microfluidic chip 9 is housed in a sealed manner in the housing 11. The fluid outlet 13 is connected to the fluid circuit 10 and downstream of it, when the microfluidic chip 9 is housed in a sealed manner in the housing 11.

[0074] The perfusion device 3 is connected to the fluid inlet 12 by a supply conduit 14. This perfusion device 3 is configured to inject a fluid continuously at a given pressure and flow rate into the fluid circuit 10 via the fluid inlet 12. The injected fluid corresponds to that of the fluid medium of interest for which the degradation and / or aging of the material of interest is monitored.

[0075] The flow regulator 4 is connected to the fluid outlet 13 by a discharge conduit 15. The flow regulator 4 is preferably passive, and makes it possible to control, preferably manually, the flow rate of the fluid in the fluid circuit 10. The flow regulator 4 comprises a plurality of tubes 16 of different calibers. Thus, the flow rate of the fluid in the fluid circuit 10 is modified according to the caliber of the tube 16 to which the discharge conduit 15 is connected. Preferably, the tubes 16 are made by etching in polydimethylsiloxane.

[0076] Thus, the invention makes it possible to study the aging and / or degradation of the material of interest in a target medium. For this, the material of interest is housed in the microfluidic chamber 10b and a fluid whose properties and components correspond to the target medium is injected by the perfusion device 3 into the fluid circuit 10 at a controlled flow rate and pressure, in particular by the flow regulator 4.

[0077] Furthermore, in order to best simulate the target medium, the light source 6 makes it possible to control the brightness to which the material of interest is exposed in the microfluidic chamber 10b. The light source 6 is therefore arranged to illuminate the housing 11 and the microfluidic chip 9. The housing 11 and the microfluidic chip 9 are transparent to the radiation emitted by the light source 16. The light source 6 can emit radiation in the infrared and / or in the visible and / or in the ultraviolet. The type of radiation is chosen according to the medium of interest whose simulation is desired. Advantageously, infrared radiation also makes it possible to heat the housing 11 and the microfluidic chip 9.

[0078] The light source 6 may be a lamp external to the housing 11, as illustrated in FIG. 1. Preferably, the light source 6 is arranged so that the angle of incidence of the radiation that it emits on the first block 11a of the housing 11 is less than 45°.

[0079] Alternatively, the light source 6 can be integrated into the housing 11, in particular into the second block 11b.

[0080] On the other hand, installation 1 includes different elements making it possible to collect information regarding the aging and / or degradation of the material of interest under the fluid flow in the microfluidic chamber 10b.

[0081] For this, the installation 1 comprises the fluid collector 5 for collecting the effluents at the outlet of the fluid circuit 10. The fluid collector 5 is connected to the outlet of the flow regulator 4 by a recovery conduit 17. The fluid collector 5 comprises at least one sterile bottle 18 for storing the effluents at the outlet of the fluid circuit 10. The bottle 18 is closed by a stopper 19 pierced in sterile conditions. To collect the effluents, a tube 20, previously cleaned with ethanol, is inserted into the hole of the stopper 19 with one of its ends arranged in the bottle 18 and the other of its ends connected to the recovery conduit 17. The fluid collector 5 may comprise several bottles 18 closed by stoppers 19 pierced as described previously. The bottles 18 may be of different volumes from each other.

[0082] The installation 1 also comprises one or more viewing devices 7 arranged to view the material of interest in the fluid circuit 10. In particular, the second block 11b comprises a viewing window 21 arranged to be superimposed with the housing of the material of interest in the fluid circuit 10. The viewing device(s) 7 is (are) arranged with the viewing window 21 in its (their) field of view. The viewing device(s) 7 may comprise a camera, preferably a CCP or CMOS camera, and / or a spectroscope, preferably for ultraviolet spectroscopy or Raman spectroscopy. The camera may be equipped with a microscope objective.

[0083] The microfluidic platform 2 also comprises at least one internal sensor 22 integrated into the housing 11 and at least one sensor 23 external to the housing 11.

[0084] The internal sensor(s) 22 is (are) configured to measure at least one environmental parameter of the fluid circuit 10, in particular of the microfluidic chamber. The environmental parameter(s) may be the temperature, pressure, pH, gas concentration, humidity and / or speed of the microfluidic chamber.

[0085] The internal sensor 22 is housed in the first block 11a so as to be opposite the microfluidic chip 9, in particular closest to the microfluidic chamber 10b. The microfluidic platform 2 may comprise a plurality of different internal sensors each housed in one of the blocks 11a, 11b of the housing 11.

[0086] In particular, the microfluidic platform 2 may comprise a plurality of internal sensors 22, each of the internal sensors 22 being chosen from:

[0087] - an accelerometer, for example the smart sensor “BHI260AP” sold by the company “Bosch Sensortec”,

[0088] - a pressure sensor, for example the digital pressure sensor “BMP390” sold by the company “Bosch Sensortec”,

[0089] - a magnetometer, for example the “BMM 150” magnetometer sold by the company “Bosch Sensortec”,

[0090] - a thermal sensor, for example a Pt100 temperature probe,

[0091] - a gas detector and / or a hygrometric sensor, in particular a smart sensor capable of measuring gas concentration, humidity, pressure and temperature simultaneously while being controlled by artificial intelligence, for example the smart sensor “BME688” sold by the company “Bosch Sensortec”.

[0092] The microfluidic platform 2 may also comprise an internal imaging system integrated into the housing 11. The internal imaging system is opposite the microfluidic chamber 10b and can thus capture images of the material of interest within said microfluidic chamber 10b. The internal imaging system may comprise a camera, for example a “Nicla Vision” camera developed by Arduino Pro. A battery may be integrated into the housing 11 in order to power the internal sensor(s) and / or the internal imaging system. The sensor(s) 23 external to the housing 11 is (are) configured to measure an environmental parameter of the fluid circuit 10 from a measurement taken outside the latter. For example, an external sensor 23 can measure the temperature of the housing 11 and thereby determine the temperature in the microfluidic chamber 10b.An external sensor 23 may include a Pt100 type probe in contact with the housing 11, and / or an rH meter, in particular a pH meter, arranged to measure the oxidation-reduction potential, where appropriate the pH, of the fluid upstream and / or downstream of the fluid circuit 10. In particular, an rH meter may comprise a measuring probe housed in the supply conduit 14 and / or in the discharge conduit 15. An external sensor 23 may further comprise a liquid chromatograph and / or a spectrometer, in particular a mass spectrometer and / or a Fourier transform infrared spectrometer and / or a magnetic resonance spectrometer, each being arranged to identify and / or quantify different substances of the fluid at the outlet of the fluid circuit 10.

[0093] The internal sensor(s) 22 and the external sensor(s) 23 are connected to a microcontroller 24, preferably of the Arduino type, for example the microcontroller 24 is a “Nicla Sense ME” card developed by Arduino Pro. The microcontroller 24 records the information measured by each of the internal 22 and external 23 sensors and controls them.

[0094] Furthermore, the microcontroller 24 is also connected to the computer 8 itself connected to the display device 7. The computer 8 acquires and records the data collected by the microcontroller 24 and by the display device 7 and transmits instructions to these codes. It is also possible to connect the computer 8 to the light source 6 and / or to the perfusion device 3 in order to control them.

[0095] The microcontroller 24 can communicate via Bluetooth, WIFI or USB with the internal sensors 22 and / or external sensors 23 and / or with the internal imaging system and / or with the computer 8. Where appropriate, the microcontroller 24 is thus a wireless communication system for the microfluidic platform 2.

[0096] 3a illustrates a first plate 9a delimiting the microfluidic chip 9. The first plate 9a has the shape of a rectangular parallelepiped with a length equal to 3.5 mm, and / or a width equal to 1.5 mm, and / or a thickness of between 5 and 10 mm. The first plate 9a comprises an injection groove 25, a recess 26 and a discharge groove 27. The injection groove 25 opens at one end onto an injection orifice 28, passing right through the plate 9a, and opens at the other end into the recess 26. The injection orifice 28 has an opening diameter of between 0.5 and 1.5 mm. The discharge groove 27 opens at one end into the recess 26 and opens at the other end into a discharge orifice 29, passing right through the plate 9a. The discharge orifice 29 has an opening diameter of between 0.5 and 1.5 mm. The injection groove 25 and discharge groove 27 each have a length equal to 5 mm.The sections of the injection grooves 25 and evacuation grooves 27 are rectangular, preferably square, with sides of micrometric sizes, in particular less than 500 μm.

[0097] Figure 4a shows a second plate 9b delimiting the microfluidic chip 9. The second plate 9b has the shape of a rectangular parallelepiped with a length equal to 3.5 mm, and / or a width equal to 1.5 mm, and / or a thickness between 1 and 2.5 mm. The second plate 9b comprises a glazed window 30 made of silicon nitride or monocrystalline quartz.

[0098] Thus, the microfluidic chip 9 is delimited by the first plate 9a and the second plate 9b stacked on top of each other. Once the stacking is completed, the injection orifice 28 and the injection groove 25 form the inlet microfluidic channel 10a, the recess 26 forms the microfluidic chamber 10b, and the discharge orifice 29 and the discharge groove 27 form the outlet microfluidic channel 10c. Furthermore, the viewing window 30 is opposite the microfluidic chamber 10b.

[0099] Figure 3b illustrates a first alternative plate 9a, according to which an imprint 31 has been made in the recess 26. The imprint 31 thus forms a housing for the material of interest. The shape of the imprint 31 is complementary to the shape of the material of interest. For example, the imprint 31 may have the shape of a rectangular parallelepiped, in particular of length equal to 10 mm, and / or of width equal to 10 mm, and / or of height equal to 1 mm.

[0100] Figure 3c illustrates a second alternative plate 9a, according to which two holding reliefs 32 projecting into the recess 26 and insertion guides 33 have been produced. The holding reliefs 32 each have the shape of a tongue extending in the direction of the flow of the fluid between the inlet microfluidic channel 10a and the outlet microfluidic channel 10c, that is to say parallel to the straight line connecting the end of the injection groove 25 opening into the recess 26 with the end of the discharge groove 27 opening into the recess 26. The holding reliefs 32 form supports for the material of interest which can be housed in the microfluidic chamber formed by the recess 26 in the microfluidic chip 9.

[0101] The insertion guides 33 are conduits opening out pierced in the thickness of the plate 9a with one of their ends opening into the recess 26, opposite one of the holding reliefs 32, and the other of the ends opening onto one of the longitudinal sides of the plate 9a. Alternatively, the insertion guides 33 may be notches made in the plate 9a with one end opening into the recess 26, opposite one of the holding reliefs 32, and the other end opening onto one of the longitudinal sides of the plate 9a. These insertion guides 33 are particularly suitable for inserting and holding a material of interest in the form of a fiber.In this case, the material of interest is housed in the recess 26 with one end inserted into a first insertion guide 33 and the other end inserted into a second insertion guide 33 opposite the first, the material of interest being supported along its length by the holding reliefs 32. This embodiment, suitable for materials of interest in the form of a fiber, is particularly interesting for the study of the aging and / or degradation of polymers, in particular plastics, in a simulated environment.

[0102] Figures 3d and 3e illustrate a third alternative plate 9a in which a recess 34 is made and magnets 35 are arranged. The recess 34 surrounds the fluid circuit 10 in the microfluidic chip 9 and is intended to accommodate a seal. The magnets 35 are housed in the thickness of the first plate 9a.

[0103] Figure 4b illustrates a second plate 9b complementary to the first plate 9a illustrated in figures 3d and 3e. The second plate 9b also comprises a recess 36 and magnets 37. The recess 36 is arranged so as to be opposite the recess 34 of the first plate 9a. Thus, a seal can be arranged in the space delimited by the recesses 34 and 36 surrounding the fluid circuit 10. The magnets 37 are housed in the thickness of the second plate 9b so as to be opposite the magnets 35 of the first plate 9a. Thus, the magnets 35 and 37 make it possible to keep the two plates 9a and 9b stacked on top of each other. The magnets 35 and 37 are cylindrical in shape with a diameter of between 2 and 3 mm and a height of between 0.7 and 10 mm. Preferably, the magnets 35 and 37 are of the NdFeB type, preferably of N45 magnetization. The adhesive force of the magnets 35 and 37 is between 74 g and 390 g.Advantageously, the magnets 35 and 37 allow simple, sealed and reversible stacking of the plates 9a and 9b on top of each other. It is thus possible to disassemble the plates 9a, 9b and thereby reuse the microfluidic chip 9.

[0104] The second plate 9b comprises a notch 38 for manual gripping in order to be able to easily separate the second plate 9b from the first plate 9a, in particular by lever effect.

[0105] Once the microfluidic chip 9 is produced, it is inserted between the first 11a and second 11b blocks of the housing 11.

[0106] Figures 5a and 5b illustrate a first block 11a of the housing 11. The first block 11a has the shape of a rectangular parallelepiped, for example of length equal to 6 cm and / or width equal to 4 cm. The first block 11a comprises a cavity 39 hollowed out in one of its faces, called the internal face 40. The cavity 39 is adapted to house a part of the microfluidic chip 9. The internal face 40 is intended to bear against the second block 11b. The first block 11a also comprises holes passing right through the first block 11a to open into the cavity 39, said holes thus forming the fluid inlet 12 and the fluid outlet 13. The supply conduit 14 can be inserted into the hole forming the fluid inlet 12. The discharge conduit 15 can be inserted into the hole forming the fluid outlet 13.The first block 11a comprises a recess 41 hollowed out in the internal face 40 and surrounding the cavity 39, the recess 41 being intended to house a seal, called the second seal.

[0107] The first block 11a comprises an external face 42 opposite the internal face 40, the external face 42 being hollowed out to form a housing 43 intended to accommodate an internal sensor 22. The housing 43 comprises a window 44 communicating with the cavity 39. The internal sensor 22 can then be in fluidic contact with the microfluidic chip 9. In particular, the microfluidic chip 9 can be permeable to gases and the internal sensor 22 can be a gas detector. Thus, if there are gas releases during the study of the aging and / or degradation of the material of interest in the microfluidic chip 9, a gaseous layer of these releases is formed in the window 44, and the internal sensor 22 can identify and / or quantify at least a portion of the gases present in this gaseous layer. For example, window 44 may be sized so that the gas layer has a thickness of 500 μm and / or a length of 8 mm and / or a width of 5 mm.

[0108] Figures 6a and 6b illustrate a second block 11b of the housing 11. The second block 11b has the shape of a rectangular parallelepiped, for example of length equal to 6 cm and / or width equal to 4 cm. The second block 11b comprises a cavity 45 hollowed out in one of its faces, called the internal face 46. The cavity 45 is adapted to house a part of the microfluidic chip 9. The internal face 46 is intended to bear against the first block 11a with the cavity 45 of the second block 11b facing the cavity 45 of the first block 11a in order to entirely house the microfluidic chip 9 in the space formed by the superposition of these cavities 39 and 45. The second block 11b comprises a recess 47 hollowed out in the internal face 46 and surrounding the cavity 45, the recess 47 being intended to be facing the recess 41 of the first block 11a when the blocks 11a and 11b are assembled together.Thus the second seal can be arranged in the space formed by the recesses 41 and 47 surrounding the cavities 39 and 45.

[0109] The second block 11b also comprises in its external face 48, opposite its internal face 46, the viewing window 21 overlooking the cavity 45. When studying the aging and / or degradation of the material of interest, the microfluidic chip 9 is housed in the cavity 45 with its glass window 30 facing the viewing window 21. It is thus possible to observe the material of interest in the microfluidic chamber. In particular, the viewing device 7 is arranged so as to be able to view the material of interest in the fluid circuit 10 through the viewing window 21 and the glass window 30.

[0110] Alternatively, the light source 6 can be integrated into the second block 11b instead of the viewing window 21. If necessary, the viewing device 7 observes the material of interest in the microfluidic chamber 10b through the first block 11a or the second block 11b, said block then being made of a material transparent in the wavelengths measured by the viewing device 7.

[0111] As illustrated in Figures 5a and 5b, magnets 49 are housed in the first block 11a. Similarly, as illustrated in Figures 6a and 6b, magnets 50 are inserted into the second block 11b. The magnets 49 and 50 ensure the assembly of the first block 11a with the second block 11b is maintained. The magnets 49 and 50 are cylindrical in shape with a diameter of between 2 and 3 mm and a height of between 0.7 and 10 mm. Preferably, the magnets 49 and 50 are of the NdFeB type, preferably of N45 magnetization. The adhesive force of the magnets 49 and 50 is between 74 g and 390 g. Advantageously, the magnets 49 and 50 allow a simple, sealed and reversible assembly of the first block 11a with the second block 11b. It is thus possible to disassemble the blocks 11a, 11b from each other and reuse the housing 11.

[0112] The second block 11b comprises a notch 51 for manual gripping to easily separate the second block 11b from the first block 11a, in particular by lever effect.

[0113] Alternatively, the first 11a and second 11b blocks can be assembled together and held with their internal faces 40 and 46 pressing against each other by gluing, in particular by oxygen plasma gluing.

[0114] Figure 7a illustrates a syringe pump type infusion device 3 for the installation 1. It comprises a syringe 52 containing the fluid, intended to circulate in the fluid circuit 10, and an infusion pump 53. The syringe 52 is connected to the supply conduit 14. The infusion pump 53 is adapted to press the syringe 52 at at least a given pressure, thus making it possible to administer the fluid into the circuit 10 with a precise flow rate.

[0115] Figure 7b illustrates a perfusion device 3 of the pressure controller type for the installation 1. It comprises a reservoir 54 containing the fluid, intended to circulate in the fluid circuit 10, and a pressure controller 55. The reservoir 54 is connected to the supply conduit 14 by a perfusion tube 56. The pressure controller 55 is connected downstream to a gas inlet 57, and is connected upstream to a gas outlet 58. The gas can be nitrogen or compressed air. The pressure controller 55 is configured to inject the gas from the gas inlet 57 into the gas outlet 58 at a pressure set by the pressure controller 55. The gas outlet 58 is inserted into the reservoir 54. Thus, the pressure controller 55 can modify the pressure within the reservoir 54, and thereby inject the fluid contained in the reservoir 54 into the perfusion tube 56, thus supplying the supply conduit 14 and the fluid circuit 10 with said fluid.

[0116] Figure 8 illustrates a variant of the installation 1 according to the invention for monitoring the degradation and / or aging of a material of interest. According to this variant, the perfusion device 3 is of the gravity type. The perfusion device 3 comprises a reservoir 59 arranged at a height relative to the microfluidic platform 2. The reservoir 59 contains the fluid intended to circulate in the circuit 10. The supply conduit 14 is connected to the bottom of the reservoir 59. Thus, the fluid contained in the reservoir 59 flows by gravity into the supply conduit 14 and circulates in the circuit 10.

[0117] Advantageously, a gravity-type perfusion device 3 is simple to implement, compact and inexpensive. Furthermore, it does not require any energy input other than the potential energy of gravity. It is therefore particularly suitable for use outside the laboratory.

[0118] The reservoir 59 may be a Falcon-type tube, for example 50 mL, or a can, for example 5L. The reservoir 59 is pierced at its lower base with a hole, for example 1.5 mm in diameter. The supply conduit 14 is inserted into said hole, for example the inserted length may be 5 mm. Preferably, the supply conduit 14 has an external diameter equal to that of said hole. Preferably, the passage of the supply conduit 14 in the hole is sealed by depositing an adhesive, preferably of the cyanoacrylate type.

[0119] The reservoir 59 may be arranged a few centimeters, for example 20 cm, above the microfluidic platform 2. For this, the reservoir 59 may be held by a reservoir holder. Preferably, the supply conduit 14 is sized so as to be stretched between the reservoir 59 and the microfluidic platform 2.

[0120] Furthermore, the flow rate of the fluid in the fluid circuit 10 is proportional to the internal diameter of the supply duct 14. Preferably, the internal diameter of the supply duct 14 is between 250 μm and 500 μm. Thus, for an internal diameter of the discharge duct 15 equal to 500 μm, it is possible to vary the flow rate of the fluid in the fluid circuit 10 as a function of the flow regulator 4 between 50 μm / min and 200 μl / min.

[0121] Preferably, the reservoir 59 has been sterilized before being filled with the fluid intended to circulate in the fluid circuit 10. The sterilization can be carried out by rinsing with ethanol and / or ultrapure water. In addition, starting the gravity-type perfusion device 3 can include a priming step to induce the flow of fluid from the reservoir 59 to the supply conduit 14. The priming step can include siphoning the reservoir 59 through the supply conduit 14. A method for manufacturing a microfluidic platform 2 according to the invention is now described. manufacturing the first 9a and second 9b plates intended to constitute the microfluidic chip 9; manufacturing the first 11a and second blocks 11b intended to constitute the housing

[0122] H; optionally, placing a material of interest in a recess 26 of the first plate 9a or the second plate 9b intended to form the microfluidic chamber 10b; stacking the first 9a and second 9b plates one on top of the other, so as to produce the microfluidic chip 9, preferably with the material of interest housed in the microfluidic chamber 10b; placing the microfluidic chip 9 in the cavity of the first plate 11a or the second plate 11b; assembling the block 11a with the second block 11b, so as to produce the housing

[0123] 11 with the microfluidic chip 9 housed tightly inside.

[0124] Steps 3 / and 4 / can be done before or after step 2 / .

[0125] The manufacture of the first 9a and second 9b plates may comprise a sub-step of casting in molds, additive manufacturing and / or micromachining.

[0126] According to a first alternative, step 1 / may comprise manufacturing molds, said molds being negatives of the first 9a and second 9b plates, followed by casting a mixture comprising an elastomer into said molds, crosslinking said mixture and then demolding the first 9a and second 9b plates. Preferably, the molds are manufactured by 3D printing, preferably by photopolymerization of a resin. Such molds are advantageously strong and simple to handle. The elastomer is preferably polydimethylsiloxane. Advantageously, the polydimethylsiloxane is transparent to daylight and is permeable to gases. Preferably, the cast elastomer mixture is degassed and comprises a crosslinking agent. For example, the cast mixture is a degassed mixture of polydimethylsiloxane comprising a crosslinking agent with a weight ratio of 10:1, and the crosslinking is carried out at 67°C in an oven for at least 2 hours.The injection orifice 28 and the discharge orifice 29 can be pierced after the demolding of the first and second plates 9a and 9b, in particular using a punch.

[0127] The insertion guide(s) 33 can be made by incisions after demolding.

[0128] The manufacture of the first 9a and second 9b plates according to this first alternative is simple to implement and requires few sub-steps compared to other usual manufacturing methods for microfluidic chips according to the state of the art. This first alternative is particularly suitable for obtaining a first plate 9a according to figures 3b and 3c and a second plate 9b according to figure 4a. The viewing window 30 can then be in one piece with the rest of the second plate 9b and made of polydimethylsiloxane.

[0129] According to a second alternative, step 1 / may comprise 3D printing by photopolymerization of a resin, preferably transparent, of a first blank and a second blank, the first blank being a plate with the dimensions of the first plate 9a and comprising a recess 26 intended to form the microfluidic chamber 10b, an injection groove 25 opening upstream into the recess 26 and an evacuation groove 27 opening downstream into the recess 26, the second blank being a plate with the dimensions of the second plate 9b. The first blank may comprise an imprint 31 in the recess 26 or at least one holding relief 32 projecting into the recess 26. The first blank may comprise at least one insertion guide 33 opening onto one of the sides of the first blank on the one hand and into the recess 26 opposite the holding relief 32 on the other hand.

[0130] Preferably, the first blank comprises a recess 34 for housing a seal, which surrounds the recess 26, the injection groove 25 and the discharge groove 27. The second blank may comprise a recess 36 arranged so as to face the recess 34 of the first blank when the first and second blanks are stacked against each other.

[0131] The first and second blanks may form, respectively, the first and second plates upon completion of the 3D printing or this may be followed by one or more sub-steps for transforming the first blank and / or the second blank into the first plate 9a, respectively into the second plate 9b. In particular, the 3D printing may be followed by a sub-step of drilling in the first blank an injection orifice 28 and an evacuation orifice 29 passing right through the first blank and arranged so that the injection groove 25, respectively the evacuation groove 27, opens at one end onto the injection orifice 28, respectively onto the evacuation orifice 29.

[0132] The second blank may comprise an open window, the 3D printing being followed by a sub-step of inserting a window into the open window so as to fill it and thereby form the glazed window 30 of the second plate 9b. Preferably, the second blank comprises an insertion slot, hollowed out in its thickness, through which the window is intended to be inserted into the open window. Preferably, the periphery of the window is coated with an adhesive, preferably of the cyanoacrylate type. Advantageously, the adhesive improves the sealing of the microfluidic chip 9.

[0133] The 3D printing may also be followed by a micromachining sub-step for boring blind holes in each of the first and second blanks, and then a sub-step for fixing the magnets 35 and 37 in said blind holes. The fixing of the magnets 35 and 37 may be done by insertion and gluing in the blind holes.

[0134] Furthermore, 3D printing can be followed by a sub-step of polishing the first and second blanks. Advantageously, this improves the transparency of the first and second blanks.

[0135] The manufacture of the first 9a and second 9b plates according to this second alternative is particularly suitable for obtaining a first plate 9a according to figures 3d and 3e and a second plate 9b according to figure 4b.

[0136] According to a third alternative, the first plate 9a can be manufactured by micromachining the injection groove 25, the recess 26, the discharge groove 27, the injection orifice 28 and the discharge orifice 29 directly in the material of interest, the second plate 9b being manufactured according to one of the methods described previously. The first plate 9a is then itself the material of interest and there is no need to carry out step 3 / of the method. The first plate 9a can also be free of the imprint 31 and the holding relief 32. Preferably, the first plate 9a is similar to the first plate illustrated in FIG. 3a. The micromachining can be carried out by micro-milling or by laser cutting, preferably by CCb laser cutting. Preferably, step 2 / of manufacturing the first 11a and second blocks 11b is carried out by 3D printing, preferably by photopolymerization of a resin, preferably transparent.3D printing may be followed by polishing the first 11a and second 11b blocks. Advantageously, this improves their transparency. 3D printing may also be followed by integration of the magnets 49 and 50 into the first 11a and second 11b blocks. The integration of the magnets 49 and 50 may be done by insertion (plugging) and / or by gluing into dedicated blind holes.

[0137] Step 3 / of placing the material of interest may comprise bonding the material of interest in the imprint 31. Preferably, the bonding comprises the deposition of a non-crosslinked elastomer, preferably polydimethylsiloxane, at the bottom of the imprint 31, followed by insertion of the material of interest into the imprint in contact with the elastomer, then crosslinking of the elastomer. The crosslinking may be an oven setting, for example an oven setting at 67°C for at least 1 hour.

[0138] Alternatively, step 3 / of placing a material of interest in the form of a fiber in the recess 26 is carried out by sliding said material of interest into one of the insertion guides 33. The material of interest may be previously soaked in ethanol in order to facilitate its sliding along the insertion guide. Once the material of interest is housed in the recess 26, the insertion guides 33 may be sealed, in particular with the same material as that constituting the plate 9a. Advantageously, this guarantees good sealing of the microfluidic chamber during the study of the aging and / or degradation of the material of interest. The sealing may comprise crosslinking of an elastomer, preferably polydimethylsiloxane. The crosslinking may be an oven setting, for example an oven setting at 67°C for at least 1 hour.

[0139] Step 4 / of stacking the first 9a and second 9b plates may comprise placing the seal between them, so as to surround the fluid circuit 10 in the microfluidic chip 9. The seal may be a commercially available O-ring. Alternatively, the seal may be manufactured by cutting, preferably by laser cutting, a plate comprising a substrate on which an elastomer layer has been deposited and then crosslinked, the cutting being followed by separation of the substrate and the elastomer, the cut elastomer forming the first seal. Preferably, the substrate is made of plexiglass. Preferably, the elastomer is polydimethylsiloxane.

[0140] Step 4 / of stacking the first 9a and second 9b plates may comprise bonding them together. Preferably, the bonding is oxygen plasma bonding. Such bonding improves the sealing of the fluid circuit 10 and the mechanical strength of the microfluidic chip 9.

[0141] Step 5 / and / or step 6 / may be preceded by a step of placing the internal sensor(s) 22 and / or a seal in the first block 11a and / or the second block 11b. This seal between blocks 11a, 11b may be a standard O-ring. Other variants and improvements may be envisaged without departing from the scope of the invention.

[0142] List of cited references

[0143] [1] Sheree A. Pagsuyoin et al.: “Effects of sewer biofilm on the degradation of drugs in sewage: A microcosm study”, Journal of Hazardous Materials, Vol. 424, Part D, 2022, 127666.

[0144] [2] EPA, Ecological Effects Test Guidelines OPPTS 850.1900 Generic Freshwater Microcosm Test, Laboratory.

Claims

Claims 1. Microfluidic platform (2) for monitoring the degradation and / or aging of a material of interest in a simulated environment, comprising: - a microfluidic chip (9) delimited by two plates (9a, 9b) stacked on top of each other, delimiting a fluid circuit (10) comprising: •a microfluidic inlet channel (10a), • a microfluidic chamber (10b) connected downstream to the inlet microfluidic channel, and comprising a housing for the material of interest, • an outlet microfluidic channel (10c) connected downstream to the microfluidic chamber; - a housing (11) comprising: • two blocks (11a, 11b) at least one of which comprises a cavity (39, 45), the two blocks being assembled together to house the microfluidic chip in a sealed manner, • a fluidic inlet (12) through which a fluid is intended to be injected, which is connected upstream to the microfluidic inlet channel, when the microfluidic chip is housed in the housing, • a fluid outlet (13) through which the fluid is intended to be evacuated, which is connected downstream to the microfluidic outlet channel, when the microfluidic chip is housed in the housing.

2. Platform according to claim 1, the housing for the material of interest being an imprint (31) within a recess (26) of one of the two plates, said recess being intended to form the microfluidic chamber.

3. Platform according to claim 1, the housing for the material of interest comprising at least one holding relief (32) projecting into a recess (26) of one of the plates, said recess being intended to form the microfluidic chamber.

4. Platform according to claim 3, comprising at least one insertion guide (33) for inserting the material of interest, which opens onto one of the sides of one of the plates and into the recess opposite the holding relief.

5. Platform according to one of the preceding claims, the plates of the microfluidic chip being made of a material transparent to ultraviolet radiation and / or visible and / or infrared, preferably in polydimethylsiloxane or photo-polymerized transparent resin.

6. Platform according to one of the preceding claims, the plates of the microfluidic chip comprising one or more magnets (35, 37) to keep them stacked on top of each other.

7. Platform according to one of the preceding claims, comprising a seal arranged in the microfluidic chip around the fluid circuit.

8. Platform according to one of the preceding claims, the blocks of the housing comprising one or more magnets (49, 50) to keep them assembled.

9. Platform according to one of the preceding claims, comprising a seal arranged in the housing around the microfluidic chip.

10. Platform according to one of the preceding claims, comprising at least one internal sensor (22) housed in one of the blocks so as to be opposite the microfluidic chamber when the microfluidic chip is housed in the housing, in order to measure at least one environmental parameter of the microfluidic chamber, chosen from temperature, pressure, pH or gas concentration, magnetic field, humidity and speed of the microfluidic chamber.

11. Platform according to one of the preceding claims, comprising at least one external sensor (23) configured to determine an environmental parameter of the fluid circuit from a measurement taken outside the fluid circuit, the environmental parameter being chosen from temperature, an oxidation-reduction potential, in particular pH, or the presence, or even the quantity, of a substance in the fluid circulating in the fluid circuit.

12. Platform according to one of the preceding claims, further comprising a thermal regulation device for heating and / or cooling the housing, preferably in the form of a Peltier module and / or an infrared radiation source and / or a heat exchanger.

13. Platform according to one of the preceding claims, one of the plates comprising a viewing window (30) through which the microfluidic chamber can be viewed when the plates are stacked, and one of the blocks comprising a viewing porthole (21) superimposed with the viewing window, when the microfluidic chip is housed in the housing.

14. Installation (1) for monitoring the degradation and / or aging of a material of interest in a simulated environment, the installation comprising: - a platform (2) according to one of the preceding claims, - an infusion device (3) for injecting a fluid at a given pressure into the fluid inlet.

15. Installation according to claim 14, comprising a flow regulator (4) connected downstream to the fluid outlet to regulate the flow of fluid in the fluid circuit at a determined flow rate.

16. Installation according to claim 14 or 15, comprising a fluid collector (5) connected downstream of the fluid outlet to recover and store the effluents at the outlet of the fluid circuit.

17. Installation according to one of claims 14 to 16, comprising a light source (6), preferably at least one LED, adapted to emit radiation in the infrared and / or in the visible and / or in the ultraviolet, to illuminate the housing.

18. Installation according to one of claims 14 to 17, comprising at least one viewing device (7) for viewing the material of interest in the housing of the microfluidic chamber, preferably the microfluidic platform being according to claim 13 and the viewing device being arranged with the viewing porthole in its field of vision.

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