Dispenser for a microfluidic system

Abstract

The invention relates to a flow distributor for parallelizing a microfluidic chip system, which is suitable for individually supplying a large number of microfluidic channels. In particular, the invention proposes a distributor comprising at least one radial flow distribution duct, which has a central opening which opens into peripheral openings which are distributed in a circular manner along a radius around an axial center of the distributor, characterized in that the distributor comprises a support in the shape of a regular cylinder, preferably a circular cylinder, into which the at least one radial distribution duct is integrated, and in that the peripheral openings are distributed on the vertical wall of the support to deliver the flow according to a horizontal flow plane at the inlet or at the outlet of the distributor.

Description

Technical Field

[0001] This invention relates to the field of flow distributors. Specifically, it is applied to the distribution and collection of flow in microfluidic systems. Background Technology

[0002] Microfluidics is a technique for manipulating fluids in a system that integrates at least one channel with a size at or near the micrometer level. In the field of liquid-liquid extraction, microfluidic channels allow two or more immiscible solutions to flow side-by-side in laminar flow mode, and extraction occurs through molecular diffusion at the phase interface between the liquids. This allows the extraction system to maximize the contact surface between the liquids and enables increased extraction yields with reduced solvent usage.

[0003] Furthermore, this extraction process can be carried out at ambient temperatures, thus offering a superior eco-footprint compared to conventional extraction processes such as molecular distillation or conventional liquid-liquid extraction. Application WO 2021 / 058806 provides an example of a microfluidic extraction method for refining vegetable oils at ambient temperatures and extracting cosmetic biomolecules with high yields.

[0004] A drawback of microfluidic systems is the limited volume of liquid that can be handled within a microfluidic loop. To improve productivity, microfluidic chips are typically used, which integrate multiple microfluidic loops operating in parallel on the same substrate. However, the production capacity of these microfluidic chips is usually insufficient for industrial or semi-industrial applications. Therefore, parallelizing microfluidic chips has been proposed as a solution to significantly improve their production capacity.

[0005] The operation of a parallelized microfluidic system involves the supply and collection of multiple microfluidic chips, each integrating multiple microfluidic loops. In a conventional fluid distribution scheme, for a linear arrangement of microfluidic chips, the main fluid inlet is branched by a first connector with three openings, splitting the main inlet into two paths. Each path is then directed to the microfluidic chips to be supplied and microfluidic channels via straight pipes, which may optionally have connectors to guide the pipes toward the microfluidic chips to be supplied, or additional branches to create more outlets, thereby supplying more microfluidic chips. This forms a piping system with variable lengths and / or branches depending on the positioning of the microfluidic chips relative to the main fluid inlet. Consequently, the flow rate at the outlets will vary with the pipe outlets and will be non-uniform to each other.

[0006] Therefore, a radial flow distributor has been proposed for supplying and collecting microfluidic chips to more accurately balance the supply and collection flow rates of the microfluidic system. In this type of distributor, the central flow is uniformly split radially to multiple outlets arranged in a circular manner and connected to the central opening via pipes with similar characteristics.

[0007] Patent EP 1 391 237 B1 provides an example of a chemical facility with five parallelized microfluidic chips for droplet generation and a radial flow distributor. In this system, each microfluidic chip integrates multiple Y-shaped microfluidic channels distributed circularly on a support disk, thus having a horizontal flow plane but with supply and collection in a vertical plane. Specifically, the disk with the microfluidic channels is clamped on one side by two distribution disks and on the other side by a collection disk. These distribution and collection disks allow the central flow to be radially diverted to multiple peripheral outlets, i.e., the central flow is collected by reverse delivery. The microfluidic loop is supplied and collected by means of vertical conduits formed by stacked perforations in the outlets of the distribution / collection disks and in the inlets and outlets of the microfluidic channels.

[0008] This system allows for balanced flow splitting based on the number of inlets and outlets of a single disk integrating multiple microfluidic channels. However, to improve the productivity of microfluidic chips, it is recommended to stack multiple microfluidic channel disks. This results in unbalanced flow splitting because multiple microfluidic channels are supplied and collected via the same peripheral outlet and a shared vertical conduit. Therefore, this type of distribution is unsuitable for supplying and collecting a large number of microfluidic channels that require high operational stability, such as in laminar flow liquid-liquid extraction processes.

[0009] Therefore, there is a need for a flow distributor that is suitable for supplying and collecting data from microfluidic chips that include multiple parallel operations and require high operational stability in microfluidic systems. Summary of the Invention

[0010] The object of this invention is to provide a flow distributor for laminar parallel microfluidic systems, which is suitable for individually supplying a large number of microfluidic channels. Another object of this invention is to provide a distributor that facilitates the design and installation of systems for supplying and collecting data from systems with parallel microfluidic chips.

[0011] Therefore, the present invention proposes a distributor comprising at least one radial flow distribution conduit having a central opening leading to peripheral openings distributed in a circular pattern around an axial center of the distributor. The distributor of the present invention is characterized by: - The dispenser includes a support member in a regular cylindrical shape, preferably a circular shape, wherein the at least one radial dispensing conduit is integrated into the support member, and - The peripheral openings are distributed on the cylindrical surface of the support to deliver flow at the inlet or outlet of the distributor in a horizontal flow plane.

[0012] Advantageously, the distributor allows the central flow to be diverted into a large number of peripheral openings, enabling individual and uniformly balanced supply and / or collection of numerous microfluidic channels in a system with parallelized microfluidic chips. Additionally, the distributor is designed to facilitate the mounting and integration of the tubing into such microfluidic systems.

[0013] To secure the connection to the microfluidic channel and prevent the risk of leakage, the outer openings are equipped with pipe connectors with fixing devices.

[0014] The dispenser is also designed to facilitate centralized supply and collection. Specifically, a connector is provided in the center opening, which opens onto the upper or lower surface of the support and defines the central connection side 31 of the dispenser.

[0015] The present invention also proposes controlling the fluid resistance within the distributor. To this end, the at least one conduit (21a, 21b) has a first diameter D1 at its central opening and a second diameter D2 at its peripheral openings (22a, 22b), the second diameter being approximately one millimeter, such that the diameter of the at least one conduit is between 800 µm and 1500 µm. Furthermore, the first diameter D1 is larger than the second diameter D2, and the diameter decreases to the level of the second diameter D2 as it opens outwards along the pipe.

[0016] The dispenser of the present invention may also have one or all of the following features in any technically operable combination: - The at least one pipe includes a series of regular branches for uniformly distributing the flow into the plurality of peripheral openings, and each peripheral opening is connected to the central opening by means of a pipe loop of equal length in the series of branches; - The central opening is located at the center of a single catheter, which splits into two identical paths at each end in a first branch, and the plurality of peripheral openings are defined by the series of regular and successive branches at each end of the two paths; - The distributor includes two pipes stacked at different heights of the support, and the pipes are stacked horizontally in the distributor with an angular offset, such that the outer openings of the two pipes can be offset relative to each other; - The distributor includes two pipes 21a and 21b stacked at different heights of the support, and the pipes 21a and 21b are stacked horizontally in the distributor with an angular offset, such that the outer openings of the two pipes can be offset from each other. - These two pipes include connectors on the upper or lower surface of the support, which define the central connection side 31 of the dispenser.

[0017] The present invention also relates to a dispensing assembly comprising two or more stacked dispensers, which may optionally be raised by a lower support element.

[0018] Finally, the present invention also relates to a microfluidic system comprising a plurality of microfluidic channels and a dispenser according to the invention, the dispenser being configured to supply and / or collect the plurality of microfluidic channels in parallel, wherein a peripheral opening of the dispenser is individually connected to the inlet and / or outlet of the microfluidic channels by means of a tube. Attached Figure Description

[0019] Other advantages, objects and specific features of the invention will become clear from the following non-limiting description of at least one specific embodiment of the device with reference to the accompanying drawings.

[0020] Figure 1 A distributor integrated into a cylindrical support member according to the present invention is shown.

[0021] Figure 2 It shows integration in Figure 1 Details of the piping inside the distributor.

[0022] Figure 3 Two stacked dispensers are shown to form a central supply and collection system for a system with a circularly parallelized microfluidic chip.

[0023] Figure 4 This demonstrates a microfluidic chip with circular parallelization and integrated with Figure 3 An example of a central supply and collection system. Detailed Implementation

[0024] The object of this invention is to provide a flow distributor for systems with parallelized microfluidic chips. The distributor of this invention is designed to supply and / or collect a series of microfluidic chips distributed in a circular manner, under optimal conditions, in a centralized manner.

[0025] This invention specifically relates to a distributor 200 ( Figure 1The distributor includes at least one radial flow distribution conduit having a central opening leading to peripheral openings 22a and 22b distributed in a circular pattern around an axial center C of the distributor. The distributor is characterized by including a regularly shaped, preferably circular, cylindrical support 3, in which the series of radial distribution conduits are integrated, such that the peripheral openings 22a and 22b are distributed on the cylindrical surface 32 of the support 3 to deliver flow at the outlet of the distributor in a horizontal flow plane.

[0026] The dispenser 200 is specifically designed for microfluidic systems requiring a central supply and collection system positioned at the center of a series of circularly distributed microfluidic chips, i.e., for microfluidic systems with circular parallelization. Advantageously, the dispenser of the present invention is designed such that the peripheral openings 22a, 22b define outlets (or inlets) located on the cylindrical surface 32 of the support and along the circular radius, which allows each opening to be individually connected to one of the inlets or outlets of the microfluidic channel facing the peripheral opening.

[0027] The cylindrical support 3 of the distributor facilitates the integration of multiple pipes according to a predefined arrangement, with all peripheral openings 22a, 22b distributed at the same circular radius of the support. Integration is facilitated by positioning each pipe 21a, 21b at a desired height H within the cylindrical support 3. Therefore, each distributor can integrate multiple pipes 21a, 21b within the same support, thus simplifying the number of parts required for installing a central supply and collection system.

[0028] Figure 1 and Figure 2 A preferred embodiment is shown, wherein the distributor 200 integrates two stacked radial flow distribution pipes 21a, 21b (in... Figure 2 (See in the image). For example... Figure 1 As shown in a simplified manner, the distributor 200 includes a cylindrical support 3 with a circular base in which two radial flow distribution conduits 21a, 21b are integrated at different heights H of the support 3. Each conduit 21a, 21b is designed to have n peripheral openings 22a, 22b, the number of which equals the total number of peripheral openings required for individual supply or collection of all microfluidic channels in the parallelized microfluidic system. Advantageously, this larger number of peripheral openings is distributed at the cylindrical surface 32 of the support, which corresponds to the vertical sidewall of the support 3 in the position of use (along the horizontal flow). Specifically, the peripheral openings of each conduit are positioned in two rows at different heights of the support 3 in such a way that distribution and flow (including at the peripheral openings 22a, 22b) occur in the horizontal plane.

[0029] In the illustrated embodiment, the pipes are stacked and have an offset of, for example, about 5 degrees (360 / 64) so ​​that the positioning of the peripheral openings of the upper pipe 21a and the lower pipe 21b is offset relative to the positioning of the inlet of the double Y-shaped microfluidic channel, thus facilitating the connection of the peripheral openings to the inlet of the double Y-shaped microfluidic channel.

[0030] On the other hand, the columnar support 3 has a central connecting side 31, which corresponds to its circular lower or upper surface, and integrates central connecting connectors 3a and 3b, which connect to the central openings of pipes 21a and 21b. Therefore, pipes 21a and 21b can be supplied or collected from one side of the distributor. Specifically, the central opening 20a of the first pipe 21a is located at the axial center of the distributor 200 and is closest to the central connecting side 31, and is vertically connected to connector 3a (not shown). The central opening 20b of the second pipe, located below the first pipe, is bently connected to connector 3b, which is offset from the axial center C of the support.

[0031] Each pipe 21a, 21b is completely independent of each other, allowing the distributor to be used to supply two different fluids. Figure 2 Details of the piping configuration according to a preferred embodiment are shown, wherein each pipe 21a, 21b defines a conduit loop including a central opening 20a, 20b located at the axial center C of the support member, the central opening leading to a single conduit that radially branches into a series of progressively diverging branches until it leads to a plurality of peripheral openings 22, 22b. Advantageously, each pipe 21a, 21b is configured to uniformly distribute the central flow into the plurality of peripheral openings so as to provide the same flow rate at each peripheral opening 22a, 22b.

[0032] To this end, a single, straight, and relatively short conduit branches into two paths at each end of its first branch. Each path has an arc shape and connects to the single conduit via a vertex. Then, each end of a path branches again into two paths, also in an arc shape, and its ends branch again according to the same principle as branching into two paths, and so on, until a desired number of peripheral openings 22a, 22b are defined. In the example shown, each conduit has five series of arc-shaped branches starting from a single straight conduit, all branches connecting to the previous stage end at their vertices, such that the ends of the final branches define sixty-four peripheral openings 22a, 22b. The shape of the branches is not limiting.

[0033] Because the branching of the pipes is made in a completely regular manner, each peripheral opening 22a, 22b will be connected to the central opening via a pipe of the same length relative to the other peripheral openings. Therefore, the fluid resistance is equivalent regardless of the flow path at the branch. This allows for very fine control of the flow rate, enabling the simultaneous supply or collection of multiple microfluidic loops.

[0034] like Figure 2 As shown, the peripheral openings 22a, 22b have connectors for conduits or tubes, allowing the microfluidic circuit to be connected to the dispenser 200 in a sealed manner via a dedicated conduit or tube. Advantageously, the connector includes a securing device that allows the connection to the conduit or tube to be secured and enables increased operating pressure without the risk of leakage. In one embodiment, the connector is provided with internal threads for screwing into conduits or tubes made of polymer. The connector is made of materials such as metals, or fluorinated inert polymers (e.g., inert polymers such as silicone), or fluoropolymers such as FEP (fluorinated ethylene propylene), PFA (perfluoroalkoxy), PAEK (polyaryletherketone), or PTFE (polytetrafluoroethylene).

[0035] The dispenser is preferably made of an inert plastic material (such as PMMA), or of glass or metal. Depending on the material chosen, the dispenser will be manufactured using a suitable microfluidic manufacturing process, such as deposition and electrodeposition, etching, bonding, injection molding, imprinting, and photolithography.

[0036] This invention also proposes an adaptive adjustment of the fluid resistance at pipes 21a and 21b to gradually reduce the fluid resistance towards the peripheral openings 22a and 22b. The fluid resistance within the conduit or microcatheter depends on the size of the conduit and the viscosity of the fluid. Specifically, the fluid resistance is calculated based on the following: the dynamic viscosity of the fluid (µ); the length of the conduit (L); and for a conduit with a circular cross-section, the inner diameter (R), or for a conduit with a rectangular cross-section, the dimensions of the height (h) and width (w): The fluid resistance of a pipe with a spherical cross-section is 8 µL / (πR⁴). The fluid resistance of a rectangular cross-section pipe = (12 µL) / (1-0.63(h / w) h³w) Regardless of the viscosity of the fluid to be dispensed, the dimensions of the dispenser's conduits will affect the resulting fluid resistance. Therefore, this invention proposes gradually reducing the initial first diameter D1 of the conduits 21a, 21b, preferably at each branch, so that the final second diameter at the peripheral opening approaches one millimeter. The initial first diameter is several millimeters, for example, between 3 mm and 10 mm. Thus, the fluid resistance can be adjusted to approximate the fluid resistance supplying the microfluidic circuit, thereby preventing backflow that could occur due to a sudden increase in fluid resistance.

[0037] In a non-limiting embodiment of the invention, the diameter of a single conduit and the first series of branches is 6 mm, then decreases to 4 mm, 3 mm, 2 mm at each branch, and to 1 mm at the peripheral opening. According to the illustrated embodiment, the conduit has a circular cross-section, but the conduit can be manufactured with a square or rectangular cross-section.

[0038] like Figure 3 As shown, the dispenser 200 of the present invention can be easily stacked with another dispenser 200' by means of its cylindrical support, the circular upper and lower surfaces of which are flat and have solid or partially recessed surfaces, as illustrated in the figures. Optionally, additional support elements S can be used to raise the dispensers 200, 200' to a desired height. Stacking two dispensers, each integrating two channels, forms a dispensing assembly, enabling the implementation of a central supply and collection system for a microfluidic system with integrated dual Y-channels. Two channels are intended for supplying and collecting a first fluid, and two channels are intended for supplying and collecting a second fluid, as desired in a liquid-liquid microfluidic extraction system with dual Y-channels. Of course, it will be possible to produce dispensers with more or fewer channels, depending on the amount of fluid to be supplied or collected from a particular microfluidic system and the type of integrated microfluidic channels.

[0039] Figure 4An example of a dispensing assembly according to the invention, obtained by stacking two dispensers 200, 200', is shown, and this dispensing assembly is integrated as a central supply and collection system into a circular parallel microfluidic system 1. In this parallel microfluidic system 1, a plurality of double-Y-shaped microfluidic chips 10, 10' are arranged in a circular manner around the central supply and collection system. Each microfluidic chip integrates a microfluidic channel, which is individually connected to the peripheral openings 22a, 22b of the dispenser by means of a tube 4. Connectors at the peripheral openings 22a, 22b ensure that these connections are sealed and can operate at relatively high pressures of up to 10 bar or more. In this example, the upper dispenser 200 is used to dispense an aqueous alcohol solution by means of its first conduit 21a and to dispense an oil to be refined by means of its second conduit 21b. The lower dispenser is used to collect both fluids at the outlet of the microfluidic channels by means of its two conduits 21a, 22b.

[0040] Advantageously, central supply and collection are performed from the central connection side 31 of the distributors 200, 200', which can be oriented as needed to facilitate the required connection. In the example shown, the central connection side 31 is arranged with opposite orientations to achieve a supply connection via the upper portion of the system 1 and a collection connection via the lower portion of the system.

[0041] Therefore, the dispenser of the present invention allows for centralized supply and / or collection of systems with parallelized microfluidic chips, and in this dispenser, all microfluidic channels can be individually supplied and collected under the same flow rate and fluid resistance conditions.

Claims

1. A distributor (200) comprising at least one radial flow distribution conduit (21a, 21b), the conduit (21a, 21b) having a central opening (20a, 20b) leading to peripheral openings (22a, 22b) distributed in a circular manner around an axial center (C) of the distributor, characterized in that: - The distributor (200) includes a cylindrical support (3) of a regular shape, preferably a circular shape, wherein at least one radial distribution conduit (21a, 21b) is integrated into the cylindrical support, and - The peripheral openings (22a, 22b) are distributed on the cylindrical surface (32) of the support (3) to deliver flow at the inlet or outlet of the distributor in a horizontal flow plane.

2. The dispenser as claimed in claim 1, wherein, The outer openings are each equipped with a pipe connector with a fastening device.

3. The dispenser as claimed in claim 1 or 2, wherein, The central opening (20a, 20b) is connected to the central connector (3a, 3b), which opens on the upper or lower surface of the support and defines the central connection side (31) of the distributor.

4. The dispenser as claimed in any one of the preceding claims, wherein, The at least one conduit (21a, 21b) has a first diameter D1 at the central opening (20a, 20b) and a second diameter D2 at the peripheral opening (22a, 22b), the second diameter being approximately one millimeter, such that the diameter of the at least one conduit is between 800 µm and 1500 µm. Furthermore, the first diameter D1 is larger than the second diameter D2, and decreases along the pipe (21a, 21b) toward the peripheral opening (22a, 22b) to the level of the second diameter D2.

5. The dispenser as claimed in any one of the preceding claims, wherein, The at least one conduit (21a, 21b) includes a series of regular branches for uniformly distributing the flow into the plurality of peripheral openings, wherein each peripheral opening (22a, 22b) is connected to the central opening (20a, 20b) by means of a conduit loop of equal length in the series of branches.

6. The dispenser as claimed in claim 5, wherein, The central opening (20a, 20b) is located at the center of a single catheter, which splits into two identical paths at each end in a first branch, and the plurality of peripheral openings (22a, 22b) are generated by the series of regular and successive branches at each end of the two paths.

7. The dispenser as claimed in any one of the preceding claims, wherein, The distributor includes two pipes (21a, 21b) stacked at different heights (H) of the support, and the pipes (21a, 21b) are stacked horizontally in the distributor with an angular offset, such that the corresponding peripheral openings (20a, 20b) of the two pipes (21a, 21b) can be offset from each other.

8. The dispenser as claimed in claim 7, wherein, The two pipes (21a, 21b) include central openings (20a, 20b) that are respectively connected to central connecting connectors (3a, 3b) on the upper or lower surface of the support, and the central connecting connectors define the central connecting side (31) of the distributor.

9. A dispensing assembly comprising two or more stacked dispensers (200, 200') as described in any one of claims 1 to 7, the dispensers optionally being raised by a lower support element (S).

10. A microfluidic system (1), the microfluidic system comprising a plurality of microfluidic channels and a dispenser (200) as claimed in any one of claims 1 to 8, the dispenser (200) being configured to supply and / or collect the plurality of microfluidic channels in parallel, and wherein, The peripheral opening of the dispenser is connected separately to the inlet and / or outlet of the microfluidic channel via a tube.

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