Device for controlling the movement of a fluid

Abstract

The invention relates to a device for controlling the movement of a fluid (F) comprising: A microfluidic capsule (1) which comprises a microfluidic chamber (10), at least one microfluidic channel (11) opening into said microfluidic chamber (10), and a membrane (13) deformable inside said microfluidic chamber to move a volume of fluid outside the chamber towards said microfluidic channel or to suck a volume of fluid towards the inside of the microfluidic chamber, A device for actuating the membrane (13), the actuating device comprising an actuating channel (20) opening opposite the membrane,The actuating device comprising an actuating liquid (L) placed in the actuating channel (20) and pneumatic actuating means (2) connected to the actuating channel (20) and configured to inject an actuating gas (G) into said actuating channel (20) in order to pressurize said actuating liquid against the membrane (13) and deform it. Figure to be published with the abstract: Figure 2,

Description

Title of the invention: Device for controlling the movement of a fluid Technical field of the invention

[0001] The present invention relates to a device for controlling the movement of a fluid, using a microfluidic component. State of the art

[0002] In a known manner, a microfluidic component, also called a microfluidic device or microfluidic card, comprises a support, often made of a material of the COC, PMMA or equivalent type.

[0003] The component may in particular integrate at least one microfluidic capsule. A microfluidic capsule comprises a chamber into which at least one microfluidic channel opens. The microfluidic capsule also comprises a membrane deformable under the action of pneumatic means. By applying a positive or negative pressure in a dedicated actuation channel, the membrane deforms in the chamber between at least two extreme positions.

[0004] The change from negative pressure to positive pressure, and vice versa, causes the chamber to be filled or emptied. During its movement, the membrane thus modulates the volume of fluid present in the chamber and therefore the volume of fluid that it displaces out of the chamber or that it sucks into the chamber.

[0005] In certain applications, it may be useful to know the volume of fluid delivered or aspirated by the microfluidic capsule, and thus control volumes of fluid to be displaced.

[0006] Patent EP3148696B1 describes in particular a solution which comprises means for measuring the deformation of the membrane, these measuring means being able to be of the optical type and / or of the electrical type. For example, the electrical measuring means can comprise a strain gauge integrated in the membrane. And the optical measuring means are for example configured to determine the angle that the membrane makes in relation to the support during its deformation. Depending on the position of the membrane, the system deduces the volume of liquid that has been displaced by the movement of the membrane.

[0007] In the case of electrical measuring means, this prior solution, however, has the major drawback of requiring the use of a specific instrumented membrane integrating the strain gauge. As regards optical type measurement, this proves difficult to implement because the visualization must be carried out perpendicularly through several layers of the component.

[0008] There is therefore a need to have a device capable of precisely controlling the movement of a fluid within a microfluidic component, and which is: - Easy to implement using readily available means, without requiring the creation of a specific membrane; - Reliable and precise in the volume of fluid displaced; Statement of the invention

[0009] This aim is achieved by a device for controlling the movement of a fluid comprising: - A microfluidic capsule which comprises a microfluidic chamber, at least one microfluidic channel opening into said microfluidic chamber, and a deformable membrane inside said microfluidic chamber for moving a volume of fluid out of the chamber into said microfluidic channel or sucking a volume of fluid into the microfluidic chamber, - A membrane actuating device, the actuating device comprising an actuating channel opening opposite the membrane, - The actuating device comprising an actuating liquid placed in the actuating channel and pneumatic actuating means connected to the actuating channel and configured to inject an actuating gas into said actuating channel in order to pressurize said actuating liquid against the membrane and deform it, - A gas / liquid interface being present in said actuation channel with a variable position depending on the pressure of the actuation gas injected against the actuation liquid, - The control device comprising monitoring means configured to track a displacement in length of said gas / liquid interface along the actuation channel, and control means configured to determine the volume of fluid displaced by the membrane as a function of said displacement in length of the gas / liquid interface tracked.

[0010] According to a particular feature, the control means are configured to compare the measured volume of displaced fluid with a set value and to send a pressure command to the pneumatic actuation means in order to adapt the pressure of the injected actuation gas taking into account the difference between the measured volume of displaced fluid and the set value.

[0011] According to another feature, the control means are configured to determine the pressure to be applied to the actuating gas by taking into account the difference between the measured volume of displaced fluid and the set value.

[0012] According to another feature, the control means are configured to control the pneumatic actuation means by controlling the flow rate of fluid displaced by the membrane.

[0013] According to another feature, the monitoring means comprise a camera positioned to capture images of the actuation channel in which the gas / liquid interface moves.

[0014] According to another feature, the actuation channel comprises a coil in which the gas / liquid interface is able to move.

[0015] According to another feature, the camera comprises an image capture surface and the coil is configured to be adjusted in length and section, to be covered over its entire length by said capture surface.

[0016] According to another feature, the coil defines a volume corresponding at least to the maximum volume of fluid present in the chamber when the membrane is in an extreme position called open.

[0017] According to another feature, the monitoring means are of the capacitive, resistive or inductive type, and the movement of the gas / liquid interface in the actuation channel has the effect of modifying the value of a capacitance, a resistance or an inductance. Brief description of the figures

[0018] Other characteristics and advantages will appear in the detailed description which follows, in connection with the figures listed below: - Figures 1A to 1C represent the principle of production of a microfluidic capsule used in the invention and illustrate the operating principle of the invention; - [Fig.2] schematically represents the principle of production of the device of the invention; - Figures 3A and 3B show an exemplary embodiment of the actuation channel used in the device of the invention; - [Fig.4] shows an example of application of the device of the invention;

[0019] Detailed description of at least one embodiment

[0020] For the remainder of the description, an orthonormal reference frame X, Y, Z is defined, the Z axis being oriented in the vertical direction. The terms "upper", "lower", "above" and "below" or equivalent are to be understood as following the Z axis. Microfluidic card and fluidic valve

[0021] [Fig.lA]

[0022] [Fig.lB]

[0023] [Fig.lC]

[0024] The invention applies to a microfluidic capsule 1 conventionally used in a microfluidic component.

[0025] Such a microfluidic component is notably used in the medical field to analyze a fluid, such as a liquid sample (blood for example) by connecting to an analysis machine. The microfluidic component can thus integrate an entire microfluidic network composed of microfluidic elements such as valves, chambers and microfluidic channels. The microfluidic network is for example produced by machining or by molding.

[0026] A microfluidic component can be made in a single layer or by assembling several layers together. Its layers are for example assembled together by thermal sealing. Each layer can be machined or molded so as to create at least part of the microfluidic network of the card, the assembly of the layers by stacking making it possible to form the entire microfluidic network of the microfluidic card.

[0027] The microfluidic component has two opposite faces, each extending in the two dimensions X, Y, and often has a smaller thickness (a few mm for example) along Z compared to the other two dimensions.

[0028] The microfluidic component is advantageously made of a transparent material of the COP (Cyclo-Olefin Polymer), COC (Cyclo-Olefin Copolymer), PMMA (Polymethyl Acrylic Methacrylate), PDMS (Polydimethyl Siloxane), Silicon type, etc.

[0029] The microfluidic network of the microfluidic component may comprise one or more microfluidic capsules 1.

[0030] A microfluidic capsule 1 conventionally comprises a chamber 10 into which at least one fluidic channel opens, advantageously two fluidic channels, designated inlet fluidic channel 11 and outlet fluidic channel 12. The microfluidic capsule also comprises a deformable membrane 13 inside the chamber. Depending on its position, the membrane 13 modulates the volume of fluid F present in the chamber. It can take two extreme positions: - A so-called open position in which the chamber 10 is full ([Fig.lA]); - A closed position, in which the chamber 10 is empty ([Fig.lC]);

[0031] The movement of the membrane 13 inside the chamber 10 causes a movement of fluid F outside the chamber or towards the inside of the chamber, depending on its direction of movement.

[0032] In order for the principle of the invention to operate reliably, the fluid F displaced by the membrane 13 is advantageously incompressible and therefore formed of a liquid.

[0033] [Fig. 1B] shows the microfluidic capsule 1 with the membrane 13 in an intermediate position, located between its open position and its closed position. In an intermediate position, the membrane 13 separates the chamber 10 into two separate spaces, a so-called upper space containing the fluid to be displaced and a lower space pressurized by the actuating liquid L of the device for actuating the membrane 13 (see below).

[0034] The membrane 13 is for example interposed between two layers of the microfluidic component and is sealed between these two layers.

[0035] Currently the deformable membrane 13 is often made of a silicone-based hyperelastic material, such as polydimethylsiloxane (PDMS), or elastomer such as Ecoflex (registered trademark). Other materials having similar mechanical properties or suitable for the application could be considered.

[0036] To actuate the membrane 13 between its two positions, the microfluidic component integrates an actuation channel 20 opening opposite the membrane 13. This actuation channel 20 is part of an actuation device of the fluidic system. Like the microfluidic circuit of the component, the actuation channel 20 is advantageously produced at least in part in the body of the microfluidic component, in a similar manner to the other channels of the microfluidic network of the component. Actuating device

[0037] [Fig.lA]

[0038] [Fig.lB]

[0039] [Fig.lC]

[0040] [Fig.2]

[0041] In the context of the invention, the actuating device comprises an actuating liquid L placed in the actuating channel 20 and pneumatic actuating means 2 connected to the actuating channel and configured to inject an actuating gas G (for example air) into said actuating channel 20 in order to pressurize said actuating liquid L against the membrane 13 to deform it.

[0042] The actuating liquid L comes directly into contact with the membrane 13 to move it by pressurizing the lower space of the chamber 10 of the capsule.

[0043] The actuation channel 20 advantageously has a constant section over its entire length. This section is, for example, rectangular.

[0044] The membrane 13 is actuated between its two positions using the actuating liquid L pressurizing the lower space of the chamber, and the actuating liquid L is moved by the pneumatic means, by application of a positive or negative pressure using the actuating gas G injected into the actuating channel 20.

[0045] It should be noted that the pneumatic actuation means 2 are connected directly to the actuation channel 20 in which the actuation liquid L is placed. The injected actuation gas G therefore comes directly into contact with the actuation liquid L. By the term “directly”, it is meant that the gas G injected into the actuation channel 20 comes into physical contact with the actuation liquid L present in the channel and that there is no intermediate wall, specific membrane or physical barrier separating them.

[0046] In the context of the invention, we are interested in the gas / liquid interface INT present in the actuation channel 20.

[0047] According to the invention, the displacement of the gas / liquid interface INT is directly proportional to the volume of fluid F displaced by the membrane 13 in the microfluidic capsule. This principle applies in particular because the actuating liquid L and the fluid F displaced by the membrane 13 are incompressible. Means of surveillance and control

[0048] [Fig.lA]

[0049] [Fig.lB]

[0050] [Fig.lC]

[0051] [Fig.2]

[0052] By following the displacement of the gas / liquid interface INT inside the actuation channel 20, it is thus possible to deduce the volume of fluid displaced by the membrane 13 in the microfluidic capsule 1.

[0053] By gas / liquid interface INT, it should be understood that it can be a meniscus or a line moving along the actuation channel 20 depending on the pressure level of the gas G injected by the pneumatic actuation means 2.

[0054] The monitoring means advantageously comprise a camera 3 configured to monitor the movement of the gas / liquid interface INT inside the actuation channel 20.

[0055] The camera 3 is coupled to control means 4 responsible for processing the images acquired by the camera 3. The control means 4 are advantageously those already used for controlling the microfluidic component.

[0056] The camera 3 is configured to acquire several images at successive times.

[0057] If the pressure of the actuating gas G injected by the pneumatic actuating means 2 is modified, the gas / liquid interface INT moves. From the acquired images, the control means 4 are configured to determine, at each instant, the position of the gas / liquid interface INT and to deduce therefrom a direction of movement of the gas / liquid interface and a displacement in length of this gas / liquid interface. along the actuation channel 20 when the position of the gas / liquid interface varies over time.

[0058] Alternatively, it would be possible to use other means for monitoring the movement of the gas / liquid interface INT. For example, these could be electrical systems, using capacitive, inductive or resistive measurements. These means require electrodes to be positioned on the internal surface of the actuation channel 20. During the movement of the gas / liquid interface INT, a variation in the capacitance, inductance or resistance is thus observed. Depending on this variation, the control means 4 can deduce a displacement in length of the gas / liquid interface INT in the actuation channel and therefore, ultimately, the volume of fluid displaced by the membrane 13 in the microfluidic capsule 1.The electrodes are for example deposited on the internal surface of the actuation channel 20 and electrical connection points are created on the microfluidic component to connect them to means for measuring the parameter considered (capacitance, inductance, resistance).

[0059] The volume of the actuating liquid L displaced in the actuating channel 20 (taking into account the section of the actuating channel and the length between two positions of the gas / liquid interface) varies as a function of the direction of displacement and the length of displacement of the gas / liquid interface INT along the actuating channel 20.

[0060] Considering that the section of the actuation channel 20 is constant, the length of the displacement of the gas / liquid interface INT is then directly proportional to the volume of fluid displaced by the membrane 13. By monitoring the displacement in length of the gas / liquid interface INT, the control means 4 can implement a control of the volume of fluid displaced by the membrane 13 in the microfluidic capsule 1.

[0061] Advantageously, the control means are configured to regulate the volume of fluid displaced by the membrane 13 using a control loop. With reference to [Fig. 2], the operation is for example as follows: - A set value V_cons of volume to be moved by the microfluidic capsule 1 is injected at the input of the control means 4; - To move this volume, the control means 4 control the pneumatic actuation means 2; - When controlling the pneumatic actuation means 2, the gas / liquid interface INT moves along the actuation channel 20; - The monitoring means (for example the camera 3 via its capture surface 30) measure at least two distinct positions taken by the gas / liquid interface INT during its movement and send data D to the means of control 4; - From the received data D, a software module Ml of the control means 4 determines the displacement in length of the gas / liquid interface INT and deduces therefrom the volume V_r of actual fluid F displaced by the membrane 13 in the microfluidic capsule; - Using a comparison module M2, the control means 4 compare the volume V_r of fluid actually displaced by the membrane 13 with the setpoint value V_cons received at the input; - Taking into account the difference V_x between the actual volume V_r and the set value V_cons, the control means 4 determine the pressure command P to be sent to the pneumatic actuation means 2 to converge the actual volume V_r moved towards the set value V_cons; - The control loop is repeated as long as the actual injected volume V_r does not correspond to the set value V_cons;

[0062] Furthermore, since the flow rate of a fluid corresponds to the volume as a function of time, it should be noted that it would also be possible to control the flow rate of fluid delivered by the microfluidic capsule 1. For this, the control means 4 can control the pneumatic actuation means 2 in flow rate and no longer in volume. It would in particular be possible to control the microfluidic capsule to ensure that it delivers the fluid F at a constant flow rate. For this, the control means 4 are configured to execute a flow rate regulation loop. The principle of regulation would be similar to that described above for volume regulation. Actuation channel architecture

[0063] [Fig.3A]

[0064] [Fig.3B]

[0065] Advantageously, the actuation channel 20 is produced in the form of a serpentine.

[0066] The production in the form of a serpentine makes it possible to take into account the constraint linked to the capture surface 30 of the camera 3. The gas / liquid interface INT to be monitored must in fact remain in the field of the capture surface 30 of the camera. In addition, this capture surface 30 being limited in size, it may be relevant to have an actuation channel that is sufficiently long to be able to move a total volume that is as large as possible. Furthermore, the resolution linked to the volume moved by the membrane can be optimized by adjusting the section of the channel.

[0067] Depending on the section of the actuation channel 20, the extent of the capture surface 30 of the camera and the maximum volume of fluid to be displaced by the membrane 13 in the microfluidic capsule, it is then possible to determine the length that the actuation channel 20 must have in order to always remain in the field of the camera 3.

[0068] As an example, with a capture surface 30 of 4x6 mm2 (length X and width Y in [Fig.3A]) and an actuation channel 20 having a rectangular section of 400pm wide (yl in [Fig.3B]) and 500pm deep (zl in [Fig.3B]), a serpentine actuation channel 20 of 34.2mm will make it possible to follow the displacement of a volume of fluid of 6.8pl. Depending on the level of resolution of the camera 3, it will then be possible to monitor more or less precisely the volume of fluid F displaced.

[0069] For example, with a camera resolution of 100 pm, the precision in measuring the volume of fluid displaced by the membrane will be 0.02 pl (0.30%) and with a camera resolution of 50 pm, the precision in measuring the volume of fluid displaced by the membrane will be 0.01 pl (0.15%).

[0070] Another configuration is for example the following: - Actuating channel having a rectangular section of 500pm in width yl and 800pm in depth zl: - A 28.5mm coil enters the field of view of the capture surface (4x6mm2) of camera 3 and allows the movement of a fluid volume of 11.4pl to be followed. - With a camera resolution of 100pm, the volume measurement accuracy is 0.08pl (0.36%); - With a camera resolution of 50pm, the accuracy of volume measurement is 0.04pl (0.18%);

[0071] It should be noted that it would also be possible to vary the length of the actuation channel 20 and therefore of the coil by using a diverging lens, by using a wide-field camera, i.e. one with a larger capture surface 30, and / or possibly by using several juxtaposed cameras. Applications

[0072] [Fig.4]

[0073] Controlling the volume of fluid displaced by the membrane 13 in the microfluidic capsule may prove useful in certain applications.

[0074] A first application may be in the field of organoids on chips, typically for perfusing organoids with low and controlled flow rates. Thus, for the perfusion of a biological object, a flow of culture medium at a very low flow rate (of the order of 1 pl / min) is allowed to pass near the biological object, in order to provide it with nutrients and evacuate its secretions.

[0075] Another application, illustrated by [Fig. 4], may consist of the creation of concentration profiles by mixing two aqueous compounds. Two microfluidic capsules 1a, 1b are placed in parallel and at least one of them is volume-controlled according to the principle of the invention described above. In [Fig. 4], each capsule is for example controlled via a separate actuation channel 20a, 20b, made in serpentine. From the images acquired (via the two capture surfaces 30a, 30b), the control means 3 control the flow rate of fluid delivered by each capsule 1a, 1b by controlling the pneumatic actuation means 2. Each capsule 1a, 1b delivers its fluid to a common channel 21. Depending on the volume delivered by each capsule, a fluid having a particular concentration profile is formed in this common channel 21.

[0076] A third application using an architecture similar to that of [Fig.4] is for example the creation of drops using two immiscible compounds (oil + water for example). A first capsule is used with water and a second capsule with oil, the outlets of each capsule converging towards a common channel. The device of the invention is adapted to each capsule and the volume of fluid delivered by each capsule is controlled using the principle of the invention towards the common channel. By regulating the pressure in each capsule, drops are formed in the common channel.

[0077] As indicated above, the principle of the invention makes it possible to control a volume of fluid displaced by the membrane 13 but it is also possible to carry out a flow rate control. In the latter case, by monitoring the movement of the gas / liquid interface INT, it is possible to envisage controlling the movement of the membrane 13 to deliver the fluid at a constant flow rate. Benefits

[0078] The invention is therefore a simple solution for effectively monitoring the volume of fluid F displaced by a membrane 13 of a microfluidic capsule 1.

[0079] In the case of using a camera 3, this solution makes it possible in particular to avoid having to profoundly modify the structure of the microfluidic component and to avoid generating additional costs for the component. The means implemented are simple and often already available for controlling the microfluidic component. The microfluidic component can in particular be directly mounted on an instrumented support carrying the pneumatic actuation means 2 and the camera 3.

[0080] The solution of the invention is moreover easily implementable in already known applications.

Claims

Claims

1. Device for controlling the movement of a fluid (F) comprising: - A microfluidic capsule (1) which comprises a microfluidic chamber (10), at least one microfluidic channel (11) opening into said microfluidic chamber (10), and a membrane (13) deformable inside said microfluidic chamber to move a volume of fluid outside the chamber towards said microfluidic channel or to suck a volume of fluid towards the inside of the microfluidic chamber, - A device for actuating the membrane (13), the actuating device comprising an actuating channel (20) opening opposite the membrane,- Characterized in that: - The actuating device comprises an actuating liquid (L) placed in the actuating channel (20) and pneumatic actuating means (2) connected to the actuating channel (20) and configured to inject an actuating gas (G) into said actuating channel (20) in order to pressurize said actuating liquid against the membrane (13) and deform it, - A gas / liquid interface (INT) being present in said actuating channel (20) with a variable position depending on the pressure of the actuating gas (G) injected against the actuating liquid, - The control device comprises monitoring means configured to follow a displacement in length of said gas / liquid interface (INT) along the actuating channel (20),and control means (4) configured to determine the volume of fluid displaced by the membrane as a function of said displacement in length of the gas / liquid interface (INT) monitored.,

2. Device according to claim 1, characterized in that the control means (4) are configured to compare the measured displaced fluid volume (V_r) with a set value (V_cons) and to send a pressure command (P) to the pneumatic actuation means. matics (2) in order to adapt the pressure of the actuating gas (G) injected taking into account the difference between the measured displaced fluid volume (V_r) and the set value (V_cons).

3. Device according to claim 2, characterized in that the control means (4) are configured to determine the pressure to be applied to the actuating gas taking into account the difference between the measured volume of displaced fluid (V_r) and the set value (V_cons).

4. Device according to one of claims 1 to 3, characterized in that the control means (4) are configured to control the pneumatic actuating means (2) by controlling the flow rate of fluid (F) displaced by the membrane (13).

5. Device according to one of claims 1 to 4, characterized in that the monitoring means comprise a camera (3) positioned to capture images of the actuation channel (20) in which the gas / liquid interface (INT) moves.

6. Device according to claim 5, characterized in that the actuating channel (20) comprises a coil in which the gas / liquid interface (INT) is capable of moving.

7. Device according to claim 6, characterized in that the camera (3) comprises an image capture surface (30) and in that the coil is configured to be adjusted in length and section, to be covered over its entire length by said capture surface (30).

8. Device according to claim 7, characterized in that the coil defines a volume corresponding at least to the maximum volume of fluid present in the chamber when the membrane (13) is in an extreme position called open.

9. Device according to one of claims 1 to 4, characterized in that the monitoring means are of the capacitive, resistive or inductive type, and in that the movement of the gas / liquid interface (INT) in the actuation channel (20) has the effect of modifying the value of a capacitance, a resistance or an inductance.

Images