Distributor for microfluidic system
The radial flow distributor addresses the unbalanced flow issues in parallelized microfluidic systems by providing balanced fluid distribution and collection, enhancing productivity and stability for high-throughput applications.
Patent Information
- Application Number
- FR2023011055
- Authority / Receiving Office
- FR · FR
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-10-13
- Publication Date
- 2025-04-18
- Estimated Expiration
- 2043-10-13
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Abstract
Description
Title of the invention: Dispenser for microfluidic system TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to the field of flow distributors. The invention finds applications in particular in the distribution and collection of flows in microfluidic systems. STATE OF THE ART
[0002] Microfluidics is a technology that manipulates fluids in systems incorporating channels of which at least one dimension is of the order of a micrometer or close to it. In the field of liquid-liquid extraction, microfluidic channels allow two or more immiscible liquids to flow side by side in a laminar regime, and to obtain extraction by diffusion of molecules at the interphase between the liquids. This results in an extraction system that maximizes the contact surface between the liquids and allows extraction yields to be increased with reduced solvent use.
[0003] In addition, this extraction process can be operated at room temperature, and therefore have a more favorable ecological footprint than conventional extraction processes, such as molecular distillation, or conventional liquid-liquid extraction. Application WO2021 / 058806 gives an example of a microfluidic extraction process for the refining of vegetable oils and the extraction of biomolecules of cosmetic interest at room temperature and with a high extraction yield.
[0004] The disadvantage of microfluidic systems is the small amount of liquid that can be processed inside the microfluidic circuits. In order to increase productivity, it is common to use microfluidic chips integrating several microfluidic circuits operating side by side on the same substrate. However, the production capacity of these microfluidic chips is still insufficient to consider use at an industrial or semi-industrial level. The parallelization of microfluidic chips has therefore been suggested as a solution to significantly increase their production capacity.
[0005] The operation of a parallelized microfluidic system involves feeding and collecting a plurality of microfluidic chips, each chip also integrating several microfluidic circuits. In a conventional fluid distribution approach, for a linear arrangement of microfluidic chips, the main inlet of a fluid is divided by a first connector with three openings, to divide the main inlet into two channels. Then each channel is brought closer to the microfluidic chip and the microfluidic channels to be fed by means of the pipes straight, possibly with connectors to direct the pipe to the microfluidic chip to be supplied, or additional branches to create more outlets and supply more microfluidic chips. This results in a system of pipes with variable length and / or branches depending on the positioning of the microfluidic chip with respect to the main fluid inlet. The flow rates at the outlets will therefore depend on the outlet of the pipe, and will not be homogeneous between them.
[0006] Radial flow distributors have therefore been proposed as a means of feeding and collecting microfluidic chips, so as to be able to more precisely balance the feed and collection flow rates of microfluidic systems. In this type of distributors, a central flow is divided homogeneously and radially into a plurality of outlets arranged circularly and being connected to the central opening by pipes of similar characteristics.
[0007] Patent EP 1 391 237 B1 gives an example of a chemical installation with five parallel microfluidic chips for the production of droplets, and implementing a radial flow distributor. In this system, each microfluidic chip integrates a plurality of “Y” type microfluidic channels, distributed circularly on a support disc to have a horizontal flow plane, but being supplied and collected along a vertical plane. In particular, the microfluidic channel disc is sandwiched on one side by two distribution discs and on the other side by a collection disc. These distribution and collection discs make it possible to radially share a central flow into several peripheral outlets, or to collect it by reverse routing.The microfluidic circuits are fed and collected by means of vertical conduits formed by superimposed perforations in the outlets of distributor / collector discs, and in the inlets and outlets of the microfluidic channels.
[0008] The latter system allows balanced flow sharing according to the number of inlets and outlets of a single disc integrating a plurality of microfluidic channels. However, to increase the productivity of the microfluidic chip, it is suggested to stack several microfluidic channel discs. This results in unbalanced flow sharing because several microfluidic channels are supplied and collected by means of the same peripheral outlets and shared vertical conduits. This type of distribution would therefore not be suitable for supplying and collecting a high number of microfluidic channels requiring high operating stability, such as in a laminar flow liquid-liquid extraction process.
[0009] It is therefore desirable to have flow distributors suitable for supplying and collecting a microfluidic system comprising several microfluidic chips operating in parallel, and requiring high operating stability. Statement of the invention
[0010] The object of the present invention is to provide a flow distributor for a parallel microfluidic system with laminar flow and being suitable for the individual supply of a large number of microfluidic channels. Another object of the invention is to have a distributor facilitating the design and installation of a supply and collection system for a parallel microfluidic chip system.
[0011] To this end, the invention proposes a distributor comprising at least one radial flow distribution pipe, said pipe having a central opening opening into peripheral openings distributed circularly along a radius around an axial center of said distributor. The distributor of the invention is particular in that:
[0012] -the distributor comprises a support in the form of a regular cylinder, preferably of circular shape, in which said at least one radial distribution pipe is integrated, and so that
[0013] -the peripheral openings are distributed on a cylindrical face of said support to convey a flow into or out of said distributor according to a horizontal flow plane.
[0014] Advantageously, this distributor makes it possible to divide a central flow into a large number of peripheral openings, and so that it allows the individual and perfectly balanced supply and / or collection of a large number of microfluidic channels in a parallel microfluidic chip system. In addition, this distributor is designed to facilitate the installation and integration of said pipes in such a microfluidic system.
[0015] In order to secure the connection to the microfluidic channels, and prevent the risk of leaks, the peripheral openings are respectively provided with hose connectors with fixing means.
[0016] The dispenser is also designed to facilitate central feeding and collection. In particular, the central opening is provided with a connector opening onto an upper or lower face of said support and defining a central connection side 31 of said dispenser.
[0017] The invention also proposes to control a fluid resistance within said distributor. To this end, said at least one pipe (21a, 21b) has a first diameter DI at the central opening, and a second diameter D2 at the peripheral openings (22a, 22b), said second diameter being approximately one millimeter, such as a diameter between 800 pm and 1500 pm,
[0018] and wherein said first diameter DI is greater than the second diameter D2 and decreases along said pipeline up to the level of the peripheral openings, and said second diameter D2.
[0019] The distributor of the invention may also comprise one or all of the following features, in any technically operable combination: - Said at least one pipe comprises a series of regular branches making it possible to divide the flow homogeneously in said plurality of peripheral openings, and each peripheral opening is connected to the central opening by means of a pipe circuit of identical length in said series of branches; - Said central opening is located in the center of a single conduit dividing in a first branch into two identical paths at each of its ends, and said plurality of peripheral openings is defined by said series of regular and successive branches of each of the ends resulting in two paths; - The distributor comprises two pipes superimposed at different heights of said support, and said pipes are superimposed in the distributor in a horizontal position with an angular offset, allowing the peripheral openings of said two pipes to be offset between them; - Said distributor comprises two pipes 21a, 21b superimposed at different heights of said support, and said pipes 21a, 21b are superimposed in the distributor in a horizontal position with an angular offset, making it possible to offset the positioning of the peripheral openings of said two pipes; - The two pipes comprise a connector on an upper or lower face of said support defining a central connection side 31 of said distributor.
[0020] The invention also relates to a distribution assembly comprising two or more superimposed distributors, said distributors being optionally raised by a lower support element.
[0021] Finally, the invention also relates to a microfluidic system comprising a plurality of microfluidic channels and a distributor according to the invention, said distributor being configured to supply and / or collect in parallel said plurality of microfluidic channels, and in which the peripheral openings of said distributor are connected by means of tubing and individually with inlets and / or outlets of said microfluidic channels. BRIEF DESCRIPTION OF THE FIGURES
[0022] Other advantages, aims and particular characteristics of the present invention res will emerge from the following non-limiting description of at least one particular embodiment of the devices, with reference to the appended drawings, in which: • [Fig.l] illustrates a distributor according to the invention integrating two pipes integrated into a circular cylindrical support; • [Fig.2] shows the detail of the pipes integrated inside the distributor of [Fig.l]. • [Fig.3] shows two distributors stacked to form a central supply and collection system for a circularly parallelized microfluidic chip system. • [Fig.4] shows an example of a microfluidic chip system with circular parallelization and integrating the central feeding and collection system of [Fig.3].
[0023] The present invention aims to propose a flow distributor for a system with parallel microfluidic chips. The distributor of the invention has been designed to feed and / or collect in a centralized manner, and under optimal conditions, a series of microfluidic chips distributed circularly.
[0024] The invention relates in particular to a distributor 200 ([Fig.l]) comprising at least one radial flow distribution pipe, said pipe having a central opening opening into peripheral openings 22a, 22b distributed circularly along a radius around an axial center C of said distributor. This distributor is particular in that it comprises a cylindrical support 3 of regular shape, preferably circular, in which said series of radial distribution pipes is integrated, and so that the peripheral openings 22a, 22b are distributed on a cylindrical face 32 of said support 3 to convey a flow at the outlet of said distributor according to a horizontal flow plane.
[0025] This distributor 200 is specially designed for a microfluidic system requiring a central supply and collection system positioned at the center of a series of microfluidic chips distributed circularly, that is to say for a microfluidic system with circular parallelization. Advantageously, the distributor of the invention is designed so that the peripheral openings 22a, 22b define outlets (or flow inlets) positioned on the cylindrical face 32 of said support and according to a circular radius, which makes it possible to individually connect each opening with one of the inlets or outlets of the microfluidic channels which are opposite said peripheral openings.
[0026] The cylindrical support 3 of the distributor makes it possible to facilitate the integration of several pipes according to a predefined arrangement, and to distribute all of the peripheral openings 22a, 22b at the level of the same circular radius of said support. The integration of each pipe 21a, 21b is done easily by the posi operation of the latter at a desired height H in said cylindrical support 3. Each distributor can thus integrate several pipes 21a, 21b in the same support, simplifying the number of parts necessary for the installation of a central supply and collection system.
[0027] [Fig.l] and [Fig.2] illustrate a preferred embodiment in which a distributor 200 integrates two superimposed radial flow distribution pipes 21a, 21b (visible in [Fig.2]). As illustrated in a simplified manner in [Fig.l], the distributor 200 comprises a cylindrical support 3 with a circular base in which two superimposed radial flow distribution pipes 21a, 21b are integrated, at different heights H of said support 3. Each pipe 21a, 21b is designed to have a number n of peripheral openings 22a, 22b equal to the total number of peripheral openings necessary to individually supply or collect all the microfluidic channels of a parallel microfluidic system.Advantageously, this high number of peripheral openings is distributed at the level of a cylindrical face 32 of said support and corresponding to a vertical and lateral wall of said support 3 in the position of use (according to said horizontal flow). In particular, the peripheral openings of each pipe are positioned in two rows at different heights of said support 3 and so that the distribution and flow of flow takes place according to a horizontal plane, including at the level of the peripheral openings 22a, 22b.
[0028] In the illustrated embodiment, the pipes are superimposed with an offset of approximately 5 degrees (360 / 64) for example, so as to offset the positioning of the peripheral openings of the upper pipe 21a and the lower pipe 21b relative to the positioning of the inlets of the double Y type microfluidic channels, and thus facilitate their connection with the latter.
[0029] On the other hand, the cylindrical support 3 has a central connection side 31, corresponding to its circular lower or upper face, and integrating central connection connectors 3a; 3b connected with the central openings of the pipes 21a, 21b. The pipes 21a, 21b can thus be supplied or collected from a single side of the distributor. In particular, the central opening 20a of the first pipe 21a, located at the axial center of said distributor 200 and being closest to the central connection side 31, implements a straight connection (not shown) with the connector 3a. For its part, the central opening 20b of the second pipe, positioned below the first pipe, implements an elbow connection between the connector 3b being offset from the axial center C of said support.
[0030] Each pipe 21a, 21b is completely independent of the other, so that the distributor can be used to supply two different fluids. [Fig.2] shows the detail of the configuration of the pipes according to a preferred embodiment, wherein each pipe 21a, 21b defines a circuit of conduits comprising a central opening 20a, 20b located at the axial center C of said support, and opening into a single conduit, which divides radially into a series of progressive branches until it opens into a plurality of peripheral openings 22, 22b. Advantageously, each pipe 21a, 21b is configured to homogeneously divide the central flow into said plurality of peripheral openings, so as to be able to provide an identical flow rate on each peripheral opening 22a, 22b.
[0031] To this end, the single conduit, of straight shape and short length, branches at its first branch into two ways at each end, each way having the shape of an arc of a circle and being connected by the apex to said single conduit. Then each end of the ways branches again into two ways also in the shape of an arc of a circle, and whose ends branch again according to the same principle of branching into two ways respectively, and so on until the desired number of peripheral openings 22a, 22b is defined. In the example illustrated, each pipe has five series of branches in the shape of an arc of a circle from the single straight conduit, all the branches being connected to the previous end at its apex, and so that the ends of the final branches define sixty-four peripheral openings 22a, 22b. The shape of the branches is not limiting.
[0032] The branches of the pipes being made in a perfectly regular manner, each peripheral opening (22a, 22b) will be connected to the central opening with a pipe of the same length compared to the other peripheral openings. The fluidic resistances are therefore equivalent whatever the path of the flow at the branches. Very fine control of the flow rates can thus be obtained to supply or collect several microfluidic circuits simultaneously.
[0033] As illustrated in [Fig.2], the peripheral openings 22a, 22b have connectors for pipes or tubing, making it possible to connect the microfluidic circuits to the distributor 200 in a sealed manner by means of the dedicated pipes or tubing. Advantageously, the connections comprise fixing means, making it possible to secure the connection with said pipes or tubing, and to be able to increase the working pressures without risk of leakage. In one embodiment, the connectors are provided with a thread making it possible to screw a pipe or connectors for polymer tubing. The connectors are made of metallic material, or of inert polymer material of the fluorinated type, such as inert polymer such as silicone, or fluorinated polymer type FEP (fluorinated ethylene propylene), PFA (perfluoroalkoxy), PEAK (polyaryletherketones), or PTFE (polytetrafluoroethylene).For its part, the dispenser is preferably made of inert plastic material, such as PMMA, or glass or metal. Depending on the material chosen, the dis . The tributor will be manufactured using a suitable microfluidic manufacturing process, such as: deposition and electrodeposition, etching, bonding, injection molding, embossing and photolithography.
[0034] The invention also proposes to adapt the fluid resistance at the level of the pipes 21a, 21b to gradually reduce it towards the peripheral openings 22a, 22b. The fluid resistances within a conduit or a micro conduit depend on the dimensions of said conduit and the viscosities of the fluids. In particular, the fluid resistance is calculated as a function of the dynamic viscosity of the fluid (p), the length of the pipe (L) and the internal diameter of the conduit (R) for a conduit with a circular section, or the height (h) and width (w) dimensions for a rectangular section:
[0035] Fluid resistance for a pipe of spherical section = 8qL / (irR4 )
[0036] Fluid resistance for a rectangular section pipe = (12pL) / (l-0.63(h / w) h3 w)
[0037] Whatever the viscosity of the fluid to be distributed, the dimensions of the distributor pipes will make it possible to influence the fluidic resistances obtained. The invention therefore proposes to gradually reduce a first initial diameter DI of the pipes 21a, 21b, preferably at each branch, and to have a second final diameter close to one millimeter at the peripheral openings. For its part, the first initial diameter will be a few millimeters, for example between 3 and 10 mm. It is thus possible to adjust the fluidic resistance to have a fluidic resistance close to that of the supply of the micro-fluidic circuits, and so as to prevent a sudden increase in fluidic resistance which could generate backflow phenomena.
[0038] In a non-limiting embodiment of the invention, the single conduit and the first series of branches have a diameter of 6 mm, then reduce at each branch to 4 mm, 3 mm, 2 mm and 1 mm at the peripheral openings. According to the illustrated embodiment, the pipes have a circular section, but they can be made with a square or rectangular section.
[0039] As illustrated in [Fig. 3], the dispenser 200 of the invention can be easily stacked with another dispenser 200' thanks to its cylindrical support whose circular upper and lower faces are flat, with solid or partially hollowed surfaces as illustrated in the figures. Optionally, an additional support element S can be used to raise the dispensers 200, 200' to a desired height. The superposition of two dispensers respectively integrating two pipes forms a distribution assembly making it possible to implement a central supply and collection system for a microfluidic system incorporating double Y channels. Two pipes are intended for the supply and collection of a first fluid, and two pipes are intended for the supply and collection of a second fluid, as desired in a liquid-liquid microfluidic extraction system with double "Y" type microfluidic channels. Of course, it will be possible to produce distributors with more or fewer pipes and depending on the number of fluids to be supplied or collected from a certain microfluidic system and the type of integrated microfluidic channels
[0040] [Fig. 4] shows an example of a distribution assembly obtained by superimposing two distributors 200, 200' according to the invention, and its integration into a circularly parallel microfluidic system 1 as a central supply and collection system. In this parallel microfluidic system 1, a plurality of microfluidic chips 10, 10' of the double Y type are arranged circularly around said central supply and collection system. Each microfluidic chip integrates microfluidic channels which are individually connected with the peripheral openings 22a, 22b of distributors by means of the tubes 4. The connectors at the peripheral openings 22a, 22b make it possible to guarantee the sealing of these connections and to work at relatively high pressures of up to more than 10 bars.In this example, the upper distributor 200 is used to distribute a hydroalcoholic solution by means of its first pipe 21a, and an oil to be refined by means of the second pipe 21b. The lower distributor is used to collect these two fluids at the outlet of microfluidic channels by means of its two pipes 21a, 22b.
[0041] Advantageously, the supply and central collection are made from a central connection side 31 of the distributors 200, 200', the latter being able to be oriented as desired in order to facilitate the necessary connections. In the example illustrated, the central connection sides 31 are arranged with opposite orientations, and so as to make the supply connections via an upper part of the system 1, and the collection connections via a lower part of said system.
[0042] The dispenser of the invention thus allows central supply and / or collection of a parallel microfluidic chip system, and in this dispenser all the microfluidic channels can be supplied and collected individually and under identical conditions of flow rate and fluid resistance.
Claims
Claims
1. Distributor (200) comprising at least one pipe (21a, 21b) for radial flow distribution, said pipe (21a, 21b) having a central opening (20a, 20b) opening into peripheral openings (22a, 22b) distributed circularly along a radius around an axial center (C) of said distributor, characterized in that: -the distributor (200) comprises a cylindrical support (3) of regular shape, preferably circular, in which said at least one pipe (21a, 21b) for radial distribution is integrated, and so that -the peripheral openings (22a, 22b) are distributed on a cylindrical face (32) of said support (3) to convey a flow into or out of said distributor along a horizontal flow plane.
2. A dispenser according to claim 1, wherein the peripheral openings are respectively provided with hose connectors with fixing means.
3. Dispenser according to claim 1 or 2, wherein said central opening (20a, 20b) is connected to a central connection connector (3a, 3b) opening onto an upper or lower face of said support and defining a central connection side (31) of said dispenser.
4. Distributor according to one of the preceding claims, wherein said at least one pipe (21a, 21b) has a first diameter DI at the central opening (20a, 20b), and a second diameter D2 at the peripheral openings (22a, 22b), said second diameter being approximately one millimeter, such as a diameter between 800 pm and 1500 pm, and wherein said first diameter DI is greater than the second diameter D2 and decreases along said pipe (21a, 21b) up to the peripheral openings (22a, 22b), and said second diameter D2.
5. Distributor according to one of the preceding claims, in which said at least one pipe (21a, 21b) comprises a series of regular branches making it possible to divide the flow homogeneously in said plurality of peripheral openings, and in which each peripheral opening (22a, 22b) is connected to the central opening (20a, 20b) by means of a pipe circuit of identical length in said series of branches.
6. A dispenser according to claim 5, wherein said opening central (20a, 20b) is located in the center of a single conduit dividing in a first branch into two identical paths at each of its ends, and said plurality of peripheral openings (22a, 22b) is generated by said series of regular and successive branches of each of the resulting ends into two paths.
7. Distributor according to one of the preceding claims, in which said distributor comprises two pipes (21a, 21b) superimposed at different heights (H) of said support, and said pipes (21a, 21b) are superimposed in the distributor in a horizontal position with an angular offset, making it possible to offset the respective peripheral openings (20a, 20b) of said two pipes (21a, 21b) between them.
8. A dispenser according to claim 7, wherein the two pipes (21a, 21b) comprise central openings (20a, 20b) connected respectively to a central connection connector (3a, 3b) on an upper or lower face of said support, and defining a central connection side (31) of said dispenser.
9. Dispensing assembly comprising two or more superimposed dispensers (200, 200') according to one of claims 1 to 7, said dispensers being optionally raised by a lower support element (S).
10. Microfluidic system (1) comprising a plurality of microfluidic channels and a distributor (200) according to one of claims 1 to 8, said distributor (200) being configured to supply and / or collect in parallel said plurality of microfluidic channels, and in which the peripheral openings of said distributor are connected by means of tubing and individually with inlets and / or outlets of said microfluidic channels.
Citation Information
Patent Citations
Fine channel device, desksize chemical plant and fine particle producing apparatus employing them
EP1391237B1
Method for microfluidic extraction from vegetable oil
WO2021058806A1
Device, system and method for fluid delivery for sequencing
WO2020243404A1