FLUIDIC COMPONENT AND FLUID VALVE DEVICE FOR ISOLATION

Description

Technical field of the invention

[0001] The present invention relates to a fluidic component and to a fluidic valve device. The device may in particular comprise a reaction chamber which can be isolated by a fluidic valve mechanism. The invention also relates to an analysis method implemented in said device. State of the art

[0002] It is known from documents US2012 / 064597A1 , US2013 / 130262A1 , US2007 / 166199A1 AndUS2006 / 076068A1 microfluidic devices formed from a microfluidic network of microfluidic capsules and channels connecting the capsules to each other. Each microfluidic capsule comprises a chamber into which an inlet channel opens and from which an outlet channel emerges. A deformable membrane is controlled between two positions to confer two distinct states to the capsule, a first state in which the inlet channel communicates with the outlet channel via the chamber allowing a transfer of fluid, and a second state in which the membrane blocks the communication between the two channels, preventing the flow of fluid and the filling of the chamber of the capsule. The membrane is controlled between its two states using pneumatic means, for example by exerting a positive pressure or a negative pressure on it.

[0003] To realize these devices, the known solutions are realized by a multilayer assembly in which the deformable membrane forms an intermediate layer taken between two substrates. The membrane is often glued, pinched between two layers or fixed by pre-cut double-sided adhesive. In these documents, the microfluidic capsules are integrated into microfluidic cards or cartridges which have pneumatic connectors so as to be connected to external pressure sources and regulators. A disadvantage of these solutions is having to ensure a connection without air or fluid leakage between the microfluidic card integrating the capsules and the pressure sources. Another disadvantage is the noise produced by the pumps or compressors generally used as pressure sources.

[0004] An alternative to pumps and compressors is the use of a gas cartridge, but the pressure produced must be regulated and, moreover, the use of such pressure sources may be subject to regulations, such as during transport by air.

[0005] Patent application EP3326717A1 proposes another solution in which the valve is created by adding a liquid to a cavity intended to form an element made of deformable material. The actuation mechanism of the invention is controlled by a control and processing unit to deform the element made of deformable material of each capsule, for example by exerting pressure or a pressure pulse by means of a pressure fluid, and in particular a pressure gas via the actuation holes of each capsule. The control and processing unit is managed by a plurality of software modules, each software module corresponding to one or more of the steps of the method. In this invention the pressure source is not described but the control by a plurality of modules proves to be complex.

[0006] These various valve solutions are pneumatically actuated and require complex external means to be actuated. These means generally include external pumps or compressors as pressure sources, pressure regulators and sometimes also solenoid valves. These means are external to the microfluidic devices so that sealed pneumatic connections must be ensured. In addition, these means must be controlled and regulated by dedicated mechanisms or even controlled by electronic circuits and possibly software.

[0007] It can be advantageous to have a valve mechanism that is simple and reliable to operate, without resorting to complex means that must be controlled or regulated.

[0008] An interesting solution for embedding a pressure source in the fluidic component has been described by means of chemical compounds in the referenced publication "Charlotte Parent, Nicolas Verplanck, Jean-Luc Achard, Yves Fouillet. Validation and integration of an effervescent reaction for fluid actuation in a microfluidic device. MicroTAS 2016 Conference, Oct 2016, Dublin, Ireland and". But this solution requires the loading of reagents in perfectly adjusted quantities to have a pressure level that is both useful and does not risk damaging the component. Another disadvantage is the need for manipulation to perforate the membrane that initially separates the chemical compounds. Documents US 2012 / 275929 A1, US 2010 / 252124 A1 and US2012 / 273077 A1 disclose devices according to the preamble of claim 1.

[0009] It therefore remains relevant to have a fluidic component integrating a fluidic valve mechanism, which can be quickly deployed in the field, using actuation means already present and easily available.

[0010] The aim of the invention is to propose a fluidic valve type device comprising a fluidic component and having simple and reliable means for actuating the fluidic valve mechanism of the component. Statement of the invention

[0011] This aim is achieved by a fluidic valve type device comprising a fluidic component according to claim 1, in which a fluidic circuit is produced which comprises an inlet channel and an outlet channel, said fluidic component comprising: A fluidic valve mechanism comprising: ∘ A sealed reservoir, intended to be filled with a volume of gas capable of expanding, ∘ A deformable membrane closing said reservoir in a sealed manner, said membrane being capable of deforming by expansion of said gas volume between a first position in which it forms a passage between said inlet channel and said outlet channel to allow a fluid to pass, and a second position in which it closes said passage.

[0012] According to one feature, the component comprises at least a first substrate in which said inlet channel and said outlet channel are made, and a second substrate in which a cavity forming said reservoir is hollowed out, opposite the inlet channel and the outlet channel, said membrane being interposed between the first substrate and said second substrate to cover said cavity.

[0013] According to another feature, the membrane is made of an elastomer type material.

[0014] According to another feature, the component is produced in the form of a single-piece element integrating said fluid circuit and said fluid valve mechanism.

[0015] The fluidic valve type device also includes: A fluidic component as defined above, A heating module arranged to heat said volume of gas contained in said reservoir and controlled to heat it to a temperature sufficient to expand said volume of gas present in the reservoir, causing a deformation of the membrane from its first position to its second position.

[0016] According to a particular embodiment, said component is produced in the form of a single-piece element capable of adapting to a support including said heating module.

[0017] According to another particular embodiment, said component is produced in the form of a single-block element, the heating module being integrated into said single-block element.

[0018] According to the invention, the fluid circuit comprises a reaction chamber, and said fluid valve mechanism is arranged on the fluid circuit opening into said reaction chamber, the heating module being arranged to provide both heating of: Said reaction chamber for carrying out a detection reaction, and of the reservoir of said fluidic valve mechanism for expanding the volume of gas, causing the membrane to move towards its closed position in order to isolate the chamber during said reaction.

[0019] The invention also relates to an analysis method implemented in a device as defined above, the method consisting of activating the heating module up to a temperature sufficient to both implement a detection reaction in said reaction chamber and actuate the membrane towards its closed position to isolate the reaction chamber during said detection reaction.

[0020] It should be noted that splitting the heating module into at least two resistive branches advantageously makes it possible to supply at least two distinct thermal powers to the different components of the device, and thus to better sequence the process. Brief description of the figures

[0021] Other features and advantages will appear in the detailed description which follows, given with reference to the attached drawings in which: There Figure 1represents a known device of the fluidic valve type, which is not part of the invention in top view. The Figure 2 illustrates the operating principle of a known fluidic valve type device, not forming part of the invention, respectively with its fluidic valve mechanism in the open position and in the closed position. Figure 3 shows a fluidic component using the device according to the invention to control fluidic access to a reaction chamber of the component. The Figure 4 shows an advantageous embodiment of the heating module used in the fluidic valve type device of the invention. Detailed description of at least one embodiment

[0022] In the following description, the terms "upstream" and "downstream" are to be understood taking into account the direction of circulation of the fluid in the fluid circuit considered.

[0023] In the following description, in a fluidic valve mechanism, a valve in the open state lets the fluid pass (state 1 or ON) and a valve in the closed state blocks the passage of the fluid (state 0 or OFF).

[0024] The invention relates in particular to a fluidic valve mechanism 33 integrated into a fluidic component 1.

[0025] It should be noted that the fluidic valve mechanism 33 of the invention has a reversible operation in the sense that it can be actuated from its first position to its second position and from its second position to its first position, infinitely (within its mechanical limits).

[0026] Fluidic component 1 can in particular be used for an analysis requiring heating.

[0027] The fluidic component 1 can be presented in the form of a single monobloc element. This element can be made by superimposing several layers. Component 1 advantageously incorporates the entire fluidic part of the device.

[0028] In reference to the Figure 1 , the fluidic valve mechanism 33 is intended to be arranged on a fluidic circuit produced in the component 1 to control the passage of a fluid F in this fluidic circuit. In a simplified manner, the fluidic valve mechanism 33 is arranged between an inlet channel 36 and an outlet channel 37 of the fluidic circuit.

[0029] The fluidic valve mechanism 33 comprises at least one sealed reservoir 32 intended to contain a volume of gas, advantageously a volume of air 38.

[0030] The fluidic valve mechanism 33 comprises a space 34 into which the inlet channel 36 opens and from which the outlet channel 37 emerges, the volume of the space 34 being variable according to the position of a deformable membrane 35 of the mechanism.

[0031] The membrane 35 is able to deform between a first open position in which the space 34 forms a passage for the fluid F between the inlet channel 36 and the outlet channel 37 of the controlled fluid circuit ( Figure 2 - P1 ) and a closed position in which it blocks the passage of fluid F in the controlled fluid circuit ( Figure 2 - P2 ). In its closed position P2, the volume of the space 34 is thus zero or almost zero, the membrane 35 being pressed against a surface of an upper substrate, onto which the two channels open. Depending on its position, the membrane 35 therefore makes it possible to modulate the volume of the space 34 of the fluidic valve mechanism 33.

[0032] To move the membrane 35 of the mechanism between its first position and its second position, the device comprises a heating module M1. The heating module M1 is arranged and configured to heat the volume of air 38 placed in the reservoir 32 in order to expand this volume of air. By expanding in the reservoir 32, the air pushes the membrane 35, deforming it towards its second closing position (P2). The membrane 35 then closes the inlet of the two channels 36, 37 to close the fluid circuit by applying pressure.

[0033] It should be noted that the reservoir 32 is sealed in the component.

[0034] The M1 heating module advantageously integrates a power supply source and uses an M2 control module.

[0035] It should also be noted that the heating module M1 can be integrated into a support on which said fluidic component 1 is fitted, so that the component 1 is in the form of a removable consumable in relation to the support, easily replaceable. The support is then a mechanically distinct assembly from the component 1.

[0036] Alternatively, the heating module M1 may at least partly be integrated into said element forming the component 1. In the latter case, for example, a resistor may be integrated into the body of the component 1, said component 1 being adapted to a support for connecting said resistor to an external electrical power source.

[0037] The control module M2 is configured to control the heating module M1 to adjust and regulate the applied temperature.

[0038] According to a particular aspect of the invention, it is possible to produce a fully autonomous beacon, the heating module M1 being able to be external, or integrated into the component or assembled on it. The same applies to the control module M2.

[0039] In reference to the Figure 3 , component 1 can in particular be used to implement a detection reaction, requiring heating of a reaction chamber 30.

[0040] The fluid circuit can in particular open, via the outlet channel 37, into said reaction chamber 30 in order to be able to supply it with fluid F.

[0041] Under certain conditions, it is necessary to isolate the reaction chamber 30, in particular when it is heated to prevent evaporation of the liquid present in the microfluidic chamber.

[0042] Advantageously, the activation of the heating module M1, necessary for implementing the chemical or biochemical detection reaction in the reaction chamber 30, is thus used to also actuate the membrane 35 of the fluidic valve mechanism 33 to its closed position and thus isolate the chamber 30 by closing the fluidic circuit. In other words, by a single command of the heating module M1, both hot insulation of the reaction chamber 30 is obtained using the fluidic valve mechanism 33, and the implementation of the chemical or biochemical detection reaction in the chamber 30.

[0043] More concretely, the operating principle of the device is as follows: At low temperature, the chamber 30 and the fluid circuit are at similar pressures. The membrane 35 is in its open position (P1), and the fluid can thus pass freely. When the heating module M1 is activated, the air contained inside the reservoir 32 expands. If the deformation of the membrane 35 leads to a very small variation in the volume of fluid 38, as a first approximation, the increase in pressure is directly proportional to the increase in temperature (in K). Thus, when going from 25°C to 65°C (298K to 338K), the pressure increases by 13% (around 100 mbar), which deforms the membrane 35 of the fluid valve mechanism 33. The deformed membrane 35 then blocks the two channels of the fluid circuit, isolating the reaction chamber 30 from the outside (P2).

[0044] The deformation rate of the membrane 35 depends on the material used and its geometric characteristics such as its thickness and surface area.

[0045] A very interesting advantage of this device is to compensate for a possible expansion of the air bubbles that may be in the reaction chamber 30. Indeed, as a first approximation, a bubble in the reaction chamber 30 will see the same increase in pressure as the membrane 35, because it will also see the same increase in temperature. With such a device, the size of the bubble in the chamber will therefore not be able to vary significantly during heating, not interfering with any detection means put in place to monitor the progress of the reaction.

[0046] This device, by closing the fluid circuit leading to the reaction chamber 30, also makes it possible to greatly limit evaporation. Thus, thirty-minute analyses can be carried out without significant loss of liquid.

[0047] When the temperature drops, the pressures between the reservoir 32 and the fluid circuits balance out and the membrane 35 returns to its original opening position (P1).

[0048] In a non-limiting manner, the membrane 35 is capable of deforming elastically between its two positions. For example, it can undergo a deformation of more than 100% compared to its initial shape.

[0049] For example, the membrane can be made from materials such as elastomers from the silicone family such as MQ (Methyl-Polysiloxanes), VMQ (Vinyl-Methyl-Polysiloxanes), PVMQ (Phenyl-Vynil-Methyl-Polysiloxanes) or thermoplastic elastomers (TPE), for example TPE-S, TPS, TPE-E, TPC.

[0050] The reaction chamber 30 is advantageously produced in the component 1. This reaction chamber 30 can carry at least part of the reagents necessary for carrying out the reaction. These reagents may, for example, have been dried in the chamber or lyophilized.

[0051] In a non-limiting manner, the detection reaction carried out in the chamber can be of the biomolecular amplification type (PCR, LAMP, etc.) or of the immuno-enzymatic type (ELISA type).

[0052] For example, for biomolecular amplification by LAMP which is carried out at 65°C + / - 1°C, the elastomer membrane can be made with Ecoflex with the following geometric characteristics to isolate the reaction chamber 30: a thickness less than 0.2 mm and a diameter between 2 and 3 mm.

[0053] It should be noted that an analysis by biomolecular amplification of microorganisms generally presupposes an extraction of the genomic material of the microorganisms. Different technical solutions can of course be implemented for this. An interesting and advantageous solution consists of carrying out a thermal lysis of the microorganisms in the chamber 30. If the reagents necessary for the biomolecular amplification are present in the chamber 30 then it is possible with the same heating module M1 to close the valve 33 which thus isolates the chamber 30 from the external environment and prevents the evaporation of the liquid, to carry out the thermal lysis of the microorganisms and to obtain the biomolecular amplification of the extracted DNA or RNA.

[0054] The component can integrate several fluid circuits, leading to the same reaction chamber 30. It can for example also include a fluid circuit comprising a vent, sometimes necessary to ensure fluid filling of the reaction chamber 30. To isolate the chamber during the reaction, this second fluid circuit must also be closed. For this, a fluid valve mechanism 33 identical to that described above can be used. Advantageously, it is then possible to use only a single reservoir 32, common to several mechanisms. The heating module M1 can also be common to all the mechanisms operating according to the principle of the invention. In this context, the heating module M1 is thus intended to heat: The reaction chamber 30; The air volume 38 used for the actuation of the valve 33;

[0055] While retaining only one heating module M1, it may be useful to allow the valve 33 to close before reaching the temperature necessary for the reaction in the chamber 30, in order to avoid any pollution of the environment (by accidental spillage of the component) and to avoid the start of evaporation of the solution present in the reaction chamber 30 during the temperature rise.

[0056] With a single heating source, operation can be optimized by changing the distribution of energy dissipation.

[0057] This involves dividing the heating module into two resistive branches arranged in parallel or in series.

[0058] There Figure 4 illustrates this principle of splitting the M1 heating module into two resistive branches placed in parallel.

[0059] The two branches B1, B2 form two separate resistors in parallel with a power source U. If the material and thickness of each branch are the same, which is simpler for manufacturing, their width varies, allowing two separate resistors to be obtained (the wider the track, the lower the resistance). The current in the first branch is written as I 1 =IxR 2 / (R 1 +R 2 ) with: I the current injected into the assembly; I 1 the current which crosses the first branch; R 1 the resistance of the first branch; R 2 the resistance of the second branch;

[0060] The dissipated power (Joule effect) in the first branch B1 is written P 1 =UxI 1 =UxR 2 / (R 1 +R 2 ) with U the voltage supplied by the control module M2. If the resistance R 1 is different from the resistance R 2 this power is different for the two branches and therefore the heating power is different for the two branches of the heating means M1.

[0061] By varying the resistance values, it is therefore possible to obtain more thermal power in one branch than in the other. With constant materials and material thicknesses, it is possible to increase the power dissipated in the wider branch, as shown in the figure. Figure 4 . On the Figure 4, we can see that the thermal power P1 emitted by the first branch B1 is higher than that (P2) emitted by the second branch B2 of the module. The activation temperature of the valve 33 to seal the chamber 30 is thus reached more quickly than that necessary for the reaction in the reaction chamber 30.

[0062] The same principle can be applied to two resistive branches in series.

[0063] This principle can of course be adapted to several branches in series or parallel or even in series / parallel, by playing each time on the width of each track.

[0064] It is particularly advantageous to produce the M1 heating module on a thin film by deposition (spraying, screen printing, stencil). This makes it possible to precisely align the different branches with the elements of the component to be heated and to choose the thermal power dissipated at each of the branches.

[0065] The device may also comprise a control module M2 configured to control the heating module M1 in order to adjust and regulate the applied temperature, this control module M2 being able to be integrated with the heating module.

[0066] The heating module M1 is advantageously part of an instrument / support on which the component 1 can be fitted.

[0067] Likewise, the M1 control module is advantageously part of the instrument mentioned above.

[0068] In order to create a fully autonomous beacon, the heating module M1 can, however, at least in part, be integrated into the component or assembled on it. The same applies to the control module M2. In this case, the device must include a power source such as an on-board battery.

[0069] The solution of the invention differs from previous solutions in that it is based solely on polymer materials, avoids the use of chemicals for the production of a gas inside the fluidic component, avoids pneumatic connections between the fluidic component and an instrument and does not use external pneumatic solutions for operation. The heating module can also be fully integrated into the component, thus obtaining a completely autonomous and easily transportable device.

Claims

1. Device of fluidic valve type, comprising: - a fluidic component in which there is formed a fluidic circuit which comprises an inlet channel (36) and an outlet channel (37), said fluidic component comprising: ∘ a fluidic valve mechanism (33), comprising: ■ a fluidtight reservoir (32) intended to be filled with a volume of gas (38) capable of expanding, ■ a deformable membrane (35) closing said reservoir (32) in a fluidtight manner, said membrane (35) being able to deform by expansion of said volume of gas (38), between a first position in which it forms a passage between said inlet channel and said outlet channel so as to allow a fluid (F) to pass, and a second position in which it obstructs said passage; - a heating module (M1) designed to heat said volume of gas contained in said reservoir (32) and commanded to heat it to a temperature sufficient to expand said volume of gas (38) present in the reservoir, causing the membrane (35) to deform from its first position toward its second position, characterized in that: - the fluidic circuit comprises a reaction chamber (30), said fluidic valve mechanism being arranged on the fluidic circuit opening into said reaction chamber, and in that the heating module (M1) is designed to heat both: ∘ said reaction chamber (30) in order to perform a detection reaction, and ∘ the reservoir (32) of said fluidic valve mechanism so as to expand the volume of gas, causing the membrane (35) to move toward its closure position with a view to isolating the chamber during said reaction.

2. Device according to Claim 1, characterized in that said component is produced in the form of a one-piece element able to be fitted onto a support including said heating module (M1).

3. Device according to Claim 1, characterized in that said component is produced in the form of a one-piece element and in that the heating module (M1) is incorporated into said one-piece element.

4. Device according to one of Claims 1 to 3, characterized in that the fluidic component comprises at least a first substrate in which said inlet channel and said outlet channel are produced, and a second substrate into which there is hollowed a cavity forming said reservoir (32), facing the inlet channel and the outlet channel, said membrane (35) being interposed between the first substrate and said second substrate in order to cover said cavity.

5. Device according to one of Claims 1 to 4, characterized in that the membrane (35) is produced from a material of elastomer type.

6. Device according to one of Claims 1 to 5, characterized in that the fluidic component is produced in the form of a one-piece element incorporating said fluidic circuit and said fluidic valve mechanism (33).

7. Analysis method implemented in a device as defined in Claim 1, characterized in that it consists in activating the heating module (M1) to a temperature sufficient to both implement a detection reaction in said reaction chamber (30) and actuate the membrane toward its closure position so as to isolate the reaction chamber (30) during said detection reaction.