Patent Application
20230122655
The present application claims priority to Luxembourg Patent Application No. LU 102865 filed on Oct. 14, 2021. The aforementioned application is hereby incorporated by reference in its entirety.
The invention relates to a mixer for fluids in a microfluidic device.
Microfluidic devices for use in clinical diagnostics and life sciences are produced by a number of companies. For example, STRATEC® Consumables GmbH, Anif, Austria, produces a number of devices for specimen handling and detection for use in automated analyser systems and other laboratory instrumentation.
Microfluidic devices are used for fluid manipulation at a small scale, typically characterised by fluid volumes measured in µL (microlitres). In a microfluidic device, fluids are manipulated within microfluidic channels or other formations, typically being formations provided in a structure of one or more layers by an etching, moulding, laser cutting, milling, hot embossing or lithographic process.
Microfluidic devices comprise a system of microfluidic channel. In such a microfluidic channel system, mixing two liquids may be challenging, because the laminar flow is prevalent, and liquids that are joined by a Y-junction from separate inlets for instance may not mix but remain adjacent in the channel, even if structures are present in the channels and/or chambers that are supposed to perturb the laminar flow.
Lee and colleagues (Lee et al., Int J Mol Sci, 2011, 12(5), p. 3263-3287) describe in their review relating to microfluidic mixing that the aim of microfluidic mixing is to achieve a thorough and rapid mixing of multiple samples in microscale devices. In known devices, sample mixing is essentially achieved by enhancing the diffusion effect between the different species flows. Broadly speaking, microfluidic mixing schemes can be categorized as either “active”, where an external energy force is applied to perturb the sample species, or “passive”, where the contact area and contact time of the species samples are increased through specifically designed microchannel configurations.
If the mixing should be performed “passively,” i.e., only driven by the liquid flow and the geometric structure of the channels and chambers, the needed mixing length is usually rather large, which needs large footprint on the device. In order to shorten the mixing length, more complicated structures and 3D structures are being proposed, which are more difficult to manufacture. Some structures need multiple layer lamination for the manufacturing.
Other mixing techniques rely on external actuation. Several actuation methods are described, but most of them need special actuators. Active mixers typically use acoustic/ultrasonic, dielectrophoretic, electrokinetic time-pulse, pressure perturbation, electro-hydrodynamic, magnetic or thermal techniques to enhance the mixing performance (comp.
Flexible materials were usually either casted (e.g., polydimethylsiloxane (PDMS)) or hot embossed, both methods do not scale well for mass manufacturing (i.e., high cost). With the use of injection molding of flexible materials e.g., thermoplastic elastomers (TPE), this can be scaled into mass manufacturing.
Published European Patent application EP 3 270 018 A1 discloses a micro fluidic flow controller which comprises a substrate having formations defining two or more fluid channels having channel fluid ports which are open at an outer surface of the substrate; and a flexible layer having formations defining a fluid channel which, when the flexible layer is positioned over the substrate so as to cover at least the channel fluid ports, provides a fluid communication path between the channel fluid ports but which, when a force is applied to press the flexible layer towards the substrate, deforms so as to inhibit fluid communication between the channel fluid ports. The disclosed device provides only means for flow control but not for mixing fluids.
Published U.S. Pat. Application US 2013/264205 A1 relates to a the microfluidic device which comprises a first chamber with at least one inlet and at least one outlet; a second chamber operatively connected with a pressure supply unit; and an elastic membrane disposed between the first chamber and the second chamber and forming a wall of at least part of the first and second chambers, wherein the first chamber comprises or contains a material that binds to a target material.
Published International patent application WO 2004/073863 A2 discloses Method and apparatus for performing controlled performance of reactions, the apparatus comprising at least one channel for receiving a substance, the channel having a first end and a second end, and at least one treatment zone intermediates the first end and second end of the channel, for performing a treatment on substance in the channel(s). Means are provided for applying a pump action to the channel(s), the pump action in use causing substance within the channel(s) to pass back and forth over the treatment zone(s).
Published U.S. Pat. Application US 2003/107946 A1 teaches a cover slip mixing apparatus having a support and a flexible cover slip positioned over and forming a chamber between the support and the cover slip. A device is positioned with respect to the support and cover slip for applying a force on the cover slip and flexing the cover slip toward the support, the flexing cover slip providing a mixing action of a material located in the chamber. A microfluidic device includes a substrate with a fluid path disposed in the substrate. A flexible cover is positioned over the substrate and the fluid path, and a device is positioned with respect to the substrate and the cover. The device is operable to apply forces to the cover and flex the cover to act on fluid in the fluid path.
It is therefore the object of this invention to provide a device and a method for improving mixing of fluids in a microfluidic device.
The present invention provides 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 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 a section of said communication path comprises at least a first and a second fluid channel for providing a first and a second fluid, wherein 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, 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 characterized in that perturbation formations of the mixing chamber are vertically arranged walls, pillars, or tubes with respect to an inner surface.
Another aspect of the invention relates to perturbation formations in the mixing chamber which 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.
It may further be intended that the section comprising the mixing chamber has on both sides actuation member for deforming the flexible layer.
In another aspect of the present invention, further channels formed by substrate and flexible layer may merge before the inlet of the mixing chamber into the merged fluid channel.
The microfluidic mixer according to the present invention may also comprise an outlet fluid channel that diverges into a plurality of channels.
Another embodiment of a microfluidic mixer according to the present invention may comprise a substrate that is made of a rigid material.
Another object of the present invention is a microfluidic device comprising at least one microfluidic mixer as described above.
A further object of the present invention relates to a system comprising a microfluidic device comprising a microfluidic mixer as described in more detail above and at least one mechanical actuator which are arranged above the points of compression of a microfluidic mixer at its inlet and outlet.
Another object of the present invention is a method for mixing a fluid in a microfluidic device, comprising the steps of
The method may further encompass that the mechanical force to the points of compression is applied in parallel to both points of compression.
In another aspect of the method according to the present invention, a mechanical actuator is used for applying the mechanical force to the points of compression.
The methods may also comprise a step, wherein the points of compression are sidewise actuated after applying the mechanical force.
Still other aspects, features, and advantages of the present invention are readily apparent from the following detailed description, simply by illustrating preferable embodiments and implementations. The present invention is also capable of other and different embodiments and its several details can be modified in various obvious respects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and descriptions are to be regarded as illustrative in nature, and not as restrictive. Additional objects and advantages of the invention will be set forth in part in the description which follows and in part will be obvious from the description or may be learned by practice of the invention.
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:
The technical problem is solved by the independent claims. The dependent claims cover further specific embodiments of the invention.
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.
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.
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.
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.).
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.
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.
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.
The arrangement shown in the top part of
The lower part of
The mechanical actuator 40 in
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.
The advantages of the invention can be summarized as follows:
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.
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.
| Number | Date | Country | Kind |
|---|---|---|---|
| 102865 | Oct 2021 | LU | national |
