Microfluidic Mixer

Abstract

A microfluidic mixer, formed by two parts, a first part being a substrate having formations defining fluid channels on an outer surface that is directed towards a second part, which is a flexible layer. The flexile layer has formations defining a fluid channel which, when the flexible layer is positioned over the substrate so as to cover the fluid channels of the substrate provides a fluid communication path. A section of said communication path comprises at least first and second fluid channels for providing first and second fluids. The first and second fluid channels merge before an inlet of a mixing chamber. The mixing chamber comprises perturbation formations. An outlet of the mixing chamber is connected to an outlet fluid channel. The flexible layer comprises points for compression at the inlet and outlet of the mixing chamber for closing the merged fluid channel. The perturbation formations of the mixing chamber are vertically arranged vertically with respect to an inner surface.

Claims

1. A microfluidic mixer, formed by two parts, a first part being a substrate having formations defining fluid channels on an outer surface that is directed towards a second part, the second part being a flexible layer, wherein the flexible layer has formations defining fluid channels which, when the flexible layer is positioned over the substrate, cover the fluid channels of the substrate to provide a fluid communication path, wherein a section of said fluid communication path comprises at least a first and a second fluid channel for providing a first and a second fluid, wherein the first and second fluid channels merge before an inlet of a mixing chamber into a merged fluid channel, wherein the mixing chamber comprises perturbation formations, and an outlet of the mixing chamber is connected to an outlet fluid channel, wherein the flexible layer comprises points for compression at the inlet and outlet of the mixing chamber for closing the merged fluid channel and the outlet fluid channel connected to inlet and outlet of the mixing chamber, wherein perturbation formations of the mixing chamber are vertically arranged walls, pillars, or tubes with respect to an inner surface of the mixing chamber.

2. The microfluidic mixer of claim 1, wherein the perturbation formations in the mixing chamber are arranged perpendicularly with respect to the flow direction of a fluid and the formations are connected to at least one inner surface of the mixing chamber.

3. The microfluidic mixer of claim 1, wherein the section comprising the mixing chamber has on both sides actuation member for deforming the flexible layer.

4. The microfluidic mixer of claim 1, wherein further channels formed by substrate and flexible layer merge before the inlet of the mixing chamber into the merged fluid channel.

5. The microfluidic mixer of claim 1, wherein the outlet fluid channel diverges into a plurality of channels.

6. The microfluidic mixer of claim 1, wherein the substrate is made of a rigid material.

7. A microfluidic device comprising at least one microfluidic mixer according to claim 1.

8. A system comprising a microfluidic device according to claim 7 and at least one mechanical actuator which are arranged above the points of compression of a microfluidic mixer at its inlet and outlet.

9. A method for mixing a fluid in a microfluidic device, comprising the steps of: introducing at least two different liquids for mixing in a first and a second fluid channel in a microfluidic mixer, formed by two parts, a first part being a substrate having formations defining fluid channels on an outer surface that is directed towards a second part, which is a flexible layer, wherein the flexile layer has formations defining first and second fluid channel which, when the flexible layer is positioned over the substrate so as to cover the fluid channels of the substrate to provide a fluid communication path, wherein in a section of said communication path the first and second fluid channel merge before an inlet of a mixing chamber into a merged fluid channel, wherein the mixing chamber comprises perturbation formations, characterized in that perturbation formations of the mixing chamber are vertically arranged walls, pillars, or tubes with respect to an inner surface, and an outlet of the mixing chamber is connected to an outlet fluid channel, applying at least once a mechanical pressure at points for compression at the inlet and outlet of the mixing chamber for closing the channels connected to inlet and outlet of the mixing chamber and mixing of the fluids; and releasing the mechanical pressure so that the mixed fluids can leave the mixing chamber through the outlet.

10. The method of claim 9, wherein the mechanical force to the points of compression is applied in parallel to both points of compression.

11. The method of claim 9, wherein a mechanical actuator is used for applying the mechanical force to the points of compression.

12. The methods of claim 9, wherein the points of compression are sidewise actuated after applying the mechanical force.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0031] A more complete appreciation of the disclosure and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description of embodiments, when considered in connection with the accompanying drawings, wherein:

[0032] FIG. 1 shows a schematic top view onto merging channels before a mixing chamber.

[0033] FIG. 2 shows schematically a sectional view with agitators on both sides of a mixing chamber.

[0034] FIG. 3 shows the same view as FIG. 2, wherein the dashed line in FIG. 3 indicates that the arrangement of pusher and connector can be moved sidewise.

[0035] FIG. 4 shows an embodiment of the mixing chamber with perturbation structures.

[0036] FIG. 5 shows an embodiment with a mixing chamber that extends only laterally but does not have an increased diameter.

[0037] FIG. 6 shows an embodiment of the mixing chamber that is mainly formed in flexible layer.

[0038] FIG. 7 shows an embodiment where the mixing chamber does not have an increased diameter in any direction.

[0039] FIG. 8 shows an embodiment where the mixing chamber is simply a part of the channel system.

DETAILED DESCRIPTION OF THE INVENTION

[0040] The technical problem is solved by the independent claims. The dependent claims cover further specific embodiments of the invention.

[0041] The microfluidic device according to the present disclosure relates to the channels of a microfluidic device which are formed in a flexible layer, which can be mechanically closed by a pair of actuators for example to enclose the two liquids that should be mixed in a section between the two points of closure which can be a mixing chamber.

[0042] By moving the pair of actuators horizontally along or into the flexible channels, a “peristaltic” movement is generated, that will agitate the liquid. Perturbation structures in the mixing channel or chamber, together with the movement, will enable a fast and efficient mixing.

[0043] In addition, in an aspect of the device according to the present disclosure, the structure can be manufactured in high volume by injection molding, because only two layers are required.

[0044] A microfluidic device according to the present disclosure thus comprises a microfluidic mixer which is formed between two layers: a bottom layer, which can be of rigid or flexible material, and a top layer, which is made of a flexible material. Between the layers, channels and optional chambers are formed. Via two channels, two or more liquids that should be mixed are delivered and merged into one channel. A larger chamber can be formed in this single channel, with or without perturbation structures (e.g., pillars, tubes etc.).

[0045] Before and after the mixing volume in a mixing chamber, sections are provided for mechanical actuation. The actuation shall squeeze the channels and thereby enclose the liquid plug (containing the liquids to be mixed). By horizontal movement at the sections for mechanical movement, e.g., by rolling back and forth, a movement is introduced in the liquids to be mixed which enables faster and more efficient mixing, rather than relying only on diffusion or passive mixing.

[0046] Any elastomeric material can be used for the flexible layer, as long as it fulfils all related requirements for the dedicated application. Examples include elastomer, silicone or natural or synthetic rubber. Depending on the material the manufacturing process for the elastomeric layer could be casting (curing/hardening by time, temperature, light, ...), injection molding (e.g., for TPEs) or reactive injection molding (e.g., for polyurethanes). Examples include thermoplastic elastomer (TPE) such as thermoplastic polyolefine (TPO), thermoplastic vulcanisate (TPV), thermoplastic rubber (TPR), styrene based thermoplastic (TPS), amid based thermoplastic (TPA), ester based thermoplastic (TPC), urethane based thermoplastic (TPU), any kind of silicone such as ploymethylsiloxan or any kind of natural or synthetic rubber such as nitrile butadiene rubber (NBR), fluorine rubber (FKM), ethylene propylene diene monomer rubber (EPDM), styrene ethylene butadiene styrene (SEBS) or the like.

[0047] The substrate may be formed of, for example, at least one of: a polymeric material; a material selected from glass, quartz, silicon nitride, and silicon oxide, polyolefins, polyethers, polyesters, polyamides, polyimides, polyvinylchlorides, polyacrylates; including their modifications, derivatives and copolymers; more specifically (by way of example) one of the list containing acrylnitril-butadien-styrole (ABS), cyclo-olefin-polymers and copolymers (COC/COP), Polymethylene-methacrylate (PMMA), Polycarbonate (PC), Polystyrole (PS), Polypropylene (PP), Polyvinylchloride (PVC), Polyamide (PA), Polyethylene (PE), Polyethylene-terephthalate (PET), Polytetrafluorethylene-ethylene (PTFE), Polyoxymethylene (POM), Thermoplastic elastomers (TPE), thermoplastic polyurethane (TPU), Polyimide (PI), Polyether-ether-ketone (PEEK), Polylactic acid (PLA), polymethyl pentene (PMP) or the like.

[0048] The arrangement shown in the top part of FIG. 1 shows a first fluid channel 1 for delivering a first fluid and a second fluid channel 2 for delivering a second fluid, wherein first and second fluid channel 1, 2 merge into a single channel 5 before a mixing chamber 10 with an inlet 9 and an outlet 11. The mixing chamber 10 comprises perturbation structures 12. An outlet fluid channel 13 is arranged behind outlet 11 of the mixing chamber 10 for providing the mixed fluids for further processing in a microfluidic device.

[0049] The lower part of FIG. 1 shows a central sectional view of the top part of FIG. 1 beginning with the merged fluid channel 5 on the left side. The microfluidic device is formed by two parts, a flexible layer 20 which is arranged on top of a substrate 30. Formations between the two parts define fluid channels like the merged fluid channel 5 which is connected to the inlet 9 of the mixing chamber 10 with perturbation structures 12. An outlet fluid channel 13 is connected to the outlet 11 of the mixing chamber 10 for guiding the mixed liquids away from the mixing chamber 10.

[0050] FIG. 2 shows the sectional view comparable to the lower part of FIG. 1 with a mechanical actuator 40. The mixing chamber 10 with perturbation structures 12 is arranged between the merged fluid channel 5 and the outlet fluid channel 13. A mechanical force can be applied to the upper flexible layer 20 by a mechanical actuator 40 so as to deform the flexible layer 20 and thus compress the merged fluid channel 5 and the outlet fluid channel 13 such that a fluid flow between the two points of compression 41, 42 is either inhibited to flow or leave the volume between the points of compression 41, 42 or enter the volume between the points of compression 41, 42.

[0051] The mechanical actuator 40 in FIG. 2 is having two rounded pusher 45 which are linked by a connector 47. It is not necessary that pusher 45 are rounded or linked by a connector 47 but if both pushers shall be pressed in parallel into the flexible layer 20, the mechanical actuator 40 will allow to apply a force only to the connector 47 for moving the pushers 45 into the flexible layer 20. It is also within the scope of the present disclosure that the pushers 45 can be actuated independently from another.

[0052] FIG. 3 shows the same view as FIG. 2, wherein the dashed line in FIG. 3 indicates that the arrangement of pusher 45 and connector 47 can be moved sidewise so that a movement in the liquid is initiated which is comprised between the first and second point of compression 41, 42. Even the compression of the flexible layer 20 will result in a kind of a peristaltic pressure on the liquid between the two points of compression 41, 42. A repeated sidewise movement or swinging of pusher 45 and connector 47 will enhance the movement of the liquid and thus improve mixing of different liquids forming the liquid between the points of compression 41, 42. The movement of a single one of the pushers 45 alone will also result in a movement of the fluid comprised between the points of compression 41, 42.

[0053] FIG. 4 shows an embodiment of the mixing chamber 10 with inlet and outlet 9, 11 and surrounding channels 1, 2, 5, 13. The mixing chamber 10 in FIG. 4 comprises perturbation structures. Mixing will be achieved by compressing flexible layer 20 and possibly moving the actuator (not shown) sidewise. The mixing chamber 10 in FIG. 4 is mainly formed in substrate 30.

[0054] FIG. 5 shows an embodiment of the mixing chamber 10 with inlet and outlet 9, 11 and surrounding channels 1, 2, 5, 13 with a mixing chamber 10 that extends laterally but does not have an increased diameter as can be seen in the lower part of FIG. 5.

[0055] FIG. 6 shows an embodiment of the mixing chamber 10 with inlet and outlet 9, 11 and surrounding channels 1, 2, 5, 13. The mixing chamber 10 in FIG. 6 comprises perturbation structures. Mixing will be achieved by compressing flexible layer 20 and possibly moving the actuator (not shown) sidewise. The mixing chamber 10 in FIG. 6 is mainly formed in flexible layer 20.

[0056] FIG. 7 shows an embodiment where the mixing chamber 10 with inlet and outlet 9, 11 and surrounding channels 1, 2, 5, 13 with a mixing chamber 10 is simply a part of the channel and does not have an increased diameter in any direction compared to merged fluid channel 5 and outlet fluid channel 13 as can be seen in the lower part of FIG. 7.

[0057] FIG. 8 shows an embodiment where the mixing chamber 10 with inlet and outlet 9, 11 and surrounding channels 1, 2, 5, 13 with a mixing chamber 10 is simply a part of the channel and comprises perturbation structure 12 but does not have an increased diameter in any direction compared to merged fluid channel 5 and outlet fluid channel 13 as can be seen in the lower part of FIG. 8.

[0058] The perturbation structures in the mixing chamber are intended to impede the fluid flow. For that reason, formations are envisaged which are arranged perpendicular to the fluid flow direction. The perturbation structures comprise pillars, walls or tubes which are connected to the upper or lower inner surface of the mixing chamber.

[0059] The advantages of the invention can be summarized as follows: [0060] a. Easy to manufacture: Elastic materials (e.g., thermoplastic elastomers TPE) can be injection molded, also featuring micro-channels, chambers, and perturbation structures. [0061] b. Only two layers are needed to form the mixing chamber. [0062] c. Simple actuation: the actuation is performed mechanically, which is simple to implement into an instrument that drives the microfluidic device (in contrast to e.g., thermal interfaces). Means for actuation do not require a very precise alignment. [0063] d. Mixing efficiency improved over passive structures: Mixing structures with the same footprint will enable more efficient mixing by the means of agitation. In other terms, for the same mixing efficiency, less footprint will be needed, enabling smaller devices, resulting in saving cost. [0064] e. Minimal dead volume: In contrast to many other implementations of mixers (e.g., with side channels), a device according to the present disclosure has basically no dead volume. [0065] f. Liquids completely enclosed: during the mixing, the liquids are completely isolated and have no direct contact to the outside environment or other parts of the instrument, which provides a good containment, and reduces thus the risk of contamination.

[0066] Alternative approaches may relate to other actuation methods employing pumps or pressure pulses, which can be used to achieve the same effect. However, such measures usually need more complicated actuators or have dead volume, or need outside contact (e.g., pressure driven systems). The most direct comparable solution are two peristaltic pump elements before and after a mixing volume or the mixing chamber, respectively.

[0067] The foregoing description of the preferred embodiment of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The embodiment was chosen and described in order to explain the principles of the invention and its practical application to enable one skilled in the art to utilize the invention in various embodiments as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto, and their equivalents. The entirety of each of the aforementioned documents is incorporated by reference herein.

Reference Numeral

[0068] 1 first fluid channel [0069] 2 second fluid channel [0070] 5 merges channel [0071] 9 inlet mixing chamber [0072] 10 mixing chamber [0073] 11 outlet mixing chamber [0074] 12 perturbation structures [0075] 13 outlet fluid channel [0076] 20 flexible layer [0077] 30 substrate [0078] 40 mechanical actuator [0079] 41 first point for compression [0080] 42 second point for compression [0081] 45 pusher [0082] 47 connector