Droplet generation device, chip, reaction device for multi-component substrate mixing

Abstract

This invention discloses a droplet generation device for mixing multi-component substrates, comprising a solution injection zone, a droplet forming and mixing zone, and a droplet buffer collection zone. The solution injection zone includes a first continuous phase injection microchannel, a second continuous phase injection microchannel, multiple dispersed phase injection microchannels, and a junction. A break exists between the inlet of the first continuous phase injection microchannel and the inlet of the second continuous phase injection microchannel. The first continuous phase injection microchannel and / or the second continuous phase injection microchannel are selectively opened by the position of the chip continuous phase opening. One or more of the multiple dispersed phase injection microchannels are selectively opened by the position of the chip dispersed phase opening. The continuous phase solution in the first continuous phase injection microchannel and / or the second continuous phase injection microchannel cuts the dispersed phase solution in one or more of the multiple dispersed phase injection microchannels into droplets. This invention has broad application prospects in the generation of multi-component substrate microdroplets.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and in particular to a droplet generation device for mixing multi-component substrates, as well as a droplet flow control chip and a droplet reaction device including the droplet generation device for mixing multi-component substrates. Background Technology

[0002] Microfluidics technology has been developing for over 30 years. It utilizes microfabrication techniques to fabricate functional components such as microchannels, microvalves, micropumps, micromixers, microstorage units, and microdetectors onto microfluidic chips. The main characteristic of microfluidic chips is that they use fluids as a medium to manipulate the transport, surface modification, mixing, reaction, storage, or detection of biochemical components carried in the fluid medium within microchannels. It's like shrinking large-scale laboratory experiments to a tiny chip only a centimeter in size. Compared to traditional experiments, its advantages include high throughput, speed, reduced cost of using expensive compounds, and portability.

[0003] In recent years, droplet generation microfluidic chips have developed rapidly. Their main characteristic is the use of two immiscible fluids, a continuous phase and a dispersed phase, to generate droplets through the uniform cutting of the continuous phase, leading to a series of applications. In droplet generation microfluidic chips, droplets are formed by the combined effects of surface tension and shear force at the interface between the continuous and mobile phases. They are generally classified as water-phase droplets in an oil phase (W / O) and oil-phase droplets in an aqueous phase (O / W). Droplets obtained by controlling the microchannel structure and the flow rate ratio of the two phases are called passive droplet generation methods. This contrasts with active droplet generation methods, which drive and control droplets through an external driving force.

[0004] There are three common methods for passive droplet generation: the T-channel method, the flow focusing method, and the coaxial flow focusing method. However, current passive droplet generation chips typically only use one of these methods in their design. But in certain types of droplet generation (e.g., protein hydrogel reactions), there are often many different combinations of reaction substrates. Therefore, to be applicable to various protein hydrogel reactions, a droplet generation chip is needed that allows for the selection of the number of chip openings based on the amount of reaction components, thus adapting to different reactions. Summary of the Invention

[0005] The purpose of this invention is to provide a droplet generation device for mixing multi-component substrates, as well as a droplet flow control chip and a droplet reaction device including the droplet generation device for mixing multi-component substrates.

[0006] To achieve the above objectives, the present invention provides a droplet generation device for mixing multi-component substrates, comprising a solution injection region, a droplet forming and mixing region, and a droplet buffering and collecting region. The solution injection region includes a first continuous phase injection microchannel, a second continuous phase injection microchannel, multiple dispersed phase injection microchannels, and a junction. The multiple dispersed phase injection microchannels are disposed within the region surrounded by the first and second continuous phase injection microchannels. A break exists between the inlet of the first continuous phase injection microchannel and the inlet of the second continuous phase injection microchannel. The first continuous phase injection microchannel is selectively activated by the location of the chip continuous phase opening. The continuous phase injection microchannel and / or the second continuous phase injection microchannel are selectively opened by the chip dispersed phase opening position. The output ports of the first continuous phase injection microchannel, the second continuous phase injection microchannel, and the output ports of the multiple dispersed phase injection microchannels are connected at the junction. The continuous phase solution in the first continuous phase injection microchannel and / or the second continuous phase injection microchannel cuts the dispersed phase solution in one or more of the multiple dispersed phase injection microchannels into droplets, which then enter the droplet forming mixing zone and the droplet buffer collection zone.

[0007] In the droplet generation device for mixing multi-component substrates provided by the present invention, the cross-sections of the first continuous phase injection microchannel, the second continuous phase injection microchannel, and the plurality of dispersed phase injection microchannels are square, with a width of 200μm-400μm and a height of 150μm; the cross-section of the confluence portion is square, with a width of 100μm-200μm.

[0008] In the droplet generation device for mixing multi-component substrates provided by the present invention, the droplet forming mixing zone is composed of a connecting channel and a plurality of alternating semi-circular channels, and the connecting channel is connected to the outlet of the solution injection zone.

[0009] In the droplet generation device for mixing multi-component substrates provided by the present invention, the cross-section of the connecting channel and the plurality of semi-circular arc-shaped channels is square, with a width of 50μm-250μm and a height of 150μm; the length of the connecting channel is 150μm, and the length of the semi-circular arc-shaped channels is 3mm-9m, with an outer diameter of 150μm-350μm and an inner diameter of 100µm.

[0010] In the droplet generation device for mixing multi-component substrates provided by the present invention, the droplet buffer collection area includes multiple vertical straight channels, multiple semi-circular arc-shaped connecting channels, a turning connecting channel, and a horizontal straight channel. The multiple vertical straight channels are connected through the multiple semi-circular arc-shaped connecting channels, and the last vertical straight channel is connected to the horizontal straight channel through the turning connecting channel.

[0011] In the droplet generation device for mixing multi-component substrates provided by the present invention, the cross-sections of the plurality of vertical straight channels, the plurality of semi-circular arc-shaped connecting channels, the directional connecting channel, and the horizontal straight channel are square, with a width of 200μm-400μm and a height of 150μm; the outer diameter of the plurality of semi-circular arc-shaped connecting channels and the directional connecting channel is 800μm, and the length of the horizontal straight channel is 3mm-5mm.

[0012] In addition, to achieve the above objectives, the present invention also provides a droplet flow control chip, the droplet flow control chip comprising a substrate and a reaction fluid channel layer disposed on the substrate; the reaction fluid channel layer is provided with a droplet generation device, a continuous phase injection port, and one or more dispersed phase injection ports as described above.

[0013] In the droplet flow control chip provided by this invention, the substrate is a glass plate, and the reaction fluid channel layer is an elastic silicone PDMS layer. In the droplet flow control chip provided by this invention, the substrate and the reaction fluid channel layer are integrally formed.

[0014] The present invention also provides a droplet reaction apparatus, including the droplet generation apparatus for mixing multi-component substrates as described above.

[0015] The droplet generation device for multi-component substrate mixing provided by this invention has the following advantages: The droplet generation device for multi-component substrate mixing includes three functional areas, integrating droplet multi-component substrate mixing, droplet generation, and droplet collection. By selectively opening the first continuous phase injection microchannel and / or the second continuous phase injection microchannel through the chip continuous phase opening position, both the T-channel method and the flow focusing method can be simultaneously implemented, reducing costs. By setting multiple dispersed phase injection microchannels and selectively opening one or more of these microchannels through the chip dispersed phase opening position, multi-substrate mixing can be achieved. The curved droplet forming mixing zone effectively and passively mixes different substrates in the droplet uniformly through the channel geometry during droplet flow. The droplet buffer collection zone, formed by continuous S-shaped channels, further mixes the droplets, forming droplets output from the mixing zone and smoothly guiding them to a droplet collection device connected outside the device. This droplet generation device can rapidly and efficiently generate uniform microdroplets, is easy to manufacture, and has a reasonable structural design, showing broad application prospects in the generation of multi-component substrate microdroplets. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort:

[0017] Figure 1 The diagram shown is a schematic representation of a droplet generation device for mixing multi-component substrates according to an embodiment of the present invention.

[0018] Figure 2 The diagram shown is a schematic diagram of the solution injection region of a droplet generation device for mixing multi-component substrates according to an embodiment of the present invention.

[0019] Figure 3 The diagram shown is a schematic representation of the droplet forming and mixing zone of a droplet generating apparatus for mixing multi-component substrates according to an embodiment of the present invention.

[0020] Figure 4 The diagram shown is a schematic representation of the droplet buffer collection region of a droplet generation device for mixing multi-component substrates according to an embodiment of the present invention.

[0021] Figure 5 The image shown is an actual effect diagram of the droplet flow control chip provided in an embodiment of the present invention;

[0022] Figure 6 The figure shown is a droplet generation effect diagram of a droplet generation device for multi-component substrate mixing provided in an embodiment of the present invention when only one solution is used as the dispersed phase solution;

[0023] Figure 7 The image shown is a droplet generation effect diagram of a droplet generation device for multi-component substrate mixing provided in an embodiment of the present invention when two solutions are used as the dispersed phase solution.

[0024] Figure 8 The image shows the droplet generation effect of a droplet generation device for mixing multi-component substrates provided in an embodiment of the present invention when three solutions are used as the dispersed phase solutions. Detailed Implementation

[0025] To facilitate understanding of the present invention, a more complete description will be given below with reference to the accompanying drawings. Typical embodiments of the invention are shown in the drawings. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0027] The general idea of ​​this invention is to address the problem that existing droplet generation devices cannot be applied to various protein hydrogel reactions, and to provide a droplet generation device for mixing multi-component substrates. By setting up a solution injection area including a first continuous phase injection microchannel, a second continuous phase injection microchannel, multiple dispersed phase injection microchannels, and a junction, the first continuous phase injection microchannel and / or the second continuous phase injection microchannel can be selectively opened by the position of the chip continuous phase opening, and one or more of the multiple dispersed phase injection microchannels can be selected to be opened by the position of the chip dispersed phase opening, thereby achieving simultaneous mixing of dispersed phase solutions of multiple substrates.

[0028] To better understand the above technical solutions, the following will describe the above technical solutions in detail with reference to the accompanying drawings and specific embodiments. It should be understood that the embodiments of the present invention and the specific features in the embodiments are detailed descriptions of the technical solutions of this application, rather than limitations on the technical solutions of this application. In the absence of conflict, the embodiments of the present invention and the technical features in the embodiments can be combined with each other.

[0029] Reference Figure 1 , Figure 1 The diagram shown is a schematic representation of a droplet generation device for mixing multi-component substrates according to an embodiment of the present invention. Figure 1 As shown, the droplet generation device for mixing multi-component substrates provided by this invention includes a solution injection zone 1, a droplet forming and mixing zone 2, and a droplet buffer collection zone 3. Continuous phase solution and dispersed phase solution are injected into the microchannels of the solution injection zone via an externally connected injection pump, and then pass through the droplet forming and mixing zone and the droplet buffer collection zone. In the solution injection zone 1, the continuous phase injection microchannels converge from the upper and lower sides with multiple dispersed phase injection microchannels in the center. The continuous phase solution is responsible for cutting the dispersed phase solution to form droplets. The upper and lower continuous phase injection microchannels are disconnected at the input end, and the position of the chip openings can determine whether one or two continuous phase solutions are open. The number of openings in the multiple dispersed phase injection microchannels in the middle can be determined as needed to achieve simultaneous mixing of dispersed phase solutions containing multiple substrates. In the droplet forming and mixing zone 2, a meandering channel is designed to achieve chaotic mixing of the substrates. The droplet buffer collection zone is mainly used for further thorough mixing of the mixed droplets before they enter the collection zone.

[0030] Figure 2 The diagram shown is a schematic representation of the solution injection region of a droplet generation device for mixing multi-component substrates according to an embodiment of the present invention. Figure 2 As shown, the solution injection region 1 includes a first continuous phase injection microchannel 110, a second continuous phase injection microchannel 120, multiple dispersed phase injection microchannels (140, 150, 160), and a junction 130. The multiple dispersed phase injection microchannels are disposed within the area surrounded by the first and second continuous phase injection microchannels. There is a break between the input ports of the first and second continuous phase injection microchannels. The first and / or second continuous phase injection microchannels are selectively opened based on the chip continuous phase opening position, and one or more of the multiple dispersed phase injection microchannels are selectively opened based on the chip dispersed phase opening position. The output ports of the first and second continuous phase injection microchannels are connected to the output ports of the multiple dispersed phase injection microchannels at the junction. The continuous phase solution in the first and / or second continuous phase injection microchannels cuts the dispersed phase solution in one or more of the multiple dispersed phase injection microchannels into droplets, which then enter the droplet forming mixing region and the droplet buffer collection region. Figure 2 The illustrated embodiment includes three dispersed phase injection microchannels, such as Figure 2 As shown, the outer square channel is the first continuous phase injection microchannel 110 and the second continuous phase injection microchannel 120, and the three channels in the middle that are distributed in a dispersed manner and converge at one point are the dispersed phase injection microchannels.

[0031] Furthermore, in one embodiment of the present invention, the location of the opening of the continuous phase injection via on the chip can determine whether one or two continuous phase solutions are activated, i.e., the T-channel method or the flow focusing method is selected to generate droplets. If the opening does not connect to the break in the left continuous phase injection microchannel, it is the T-channel method; if the opening connects to the break in the continuous phase injection microchannel, it is the flow focusing method. During chip fabrication, depending on the needs, if the T-channel method is selected, the opening can be located above or below the break and not overlapping with the break (e.g., ...). Figure 2 Point A or B in the diagram is used as the opening position for the continuous phase injection orifice. A single-fluid continuous phase is used, i.e., the continuous phase fluid solution is injected through the first continuous phase injection microchannel 110 (point A is selected as the opening position for the continuous phase injection orifice) or the second continuous phase injection microchannel 120 (point B is selected as the opening position for the continuous phase injection orifice). If the flow focusing method is selected, a position spanning the fracture surface (e.g., point A or point B in the diagram) needs to be selected. Figure 2Point C in the diagram is used as the opening position of the continuous phase injection aperture to connect the upper and lower continuous phase injection microchannels, forming a two-fluid continuous phase. The injected continuous phase fluid solution is evenly distributed between the upper and lower channels after entering the channel, i.e., injected through the first continuous phase injection microchannel 110 and the second continuous phase injection microchannel 120. Therefore, by selecting the opening position of the first continuous phase injection microchannel and / or the second continuous phase injection microchannel through the chip's continuous phase aperture, both the T-channel method and the flow focusing method can be simultaneously implemented, reducing costs.

[0032] Furthermore, in one embodiment of the present invention, the dispersed phase solution has multiple injection microchannels, and the required number of channels can be selectively opened to mix the multi-component droplet solution. If the dispersed phase requires only one substrate, one injection channel is opened; if the dispersed phase requires mixing two substrates, two channels are opened; and so on. Figure 2 Taking the three dispersed phase injection microchannels shown as an example, if the droplet solution reaction substrate has only one or more substrates that can be pre-mixed into a single solution, then only one opening needs to be selected, for example, only the inlet of the dispersed phase injection microchannel 150 in the middle of the channel needs to be opened; if there are two reaction substrates that cannot be pre-mixed (such as hydrogels), then two openings need to be selected, for example, the inlet of dispersed phase injection microchannel 140 and the inlet of dispersed phase injection microchannel 160; if there are more than two reaction substrates, then all the inlets of dispersed phase injection microchannels 140, 150, and 160 need to be opened. Figure 2 In the illustrated embodiment, depending on the amount of substrate component in the dispersed phase solution, any one, two, or three of the three dispersed phase solution inlets can be perforated, with a minimum of one and a maximum of three perforations. If no perforations are made, in actual fluid operation, the unperforated channel will not affect the fluid flow direction of other connected channels because the channel is blocked. By setting multiple dispersed phase injection microchannels and selecting one or more of the multiple dispersed phase injection microchannels to be opened by the chip dispersed phase perforation positions, multi-substrate mixing can be achieved.

[0033] Furthermore, in one embodiment of the present invention, the cross-sections of the first continuous phase injection microchannel, the second continuous phase injection microchannel, and the plurality of dispersed phase injection microchannels are square, with a width of 200μm-400μm, preferably 300μm, and a height of 150μm; the cross-sections of the junctions are square, with a width of 100μm-200μm, preferably 150μm.

[0034] Figure 3 The diagram shown is a schematic representation of the droplet forming and mixing region of a droplet generating apparatus for mixing multi-component substrates according to an embodiment of the present invention. Figure 3As shown, the droplet forming mixing zone 2 is composed of a connecting channel 210 and multiple alternating semi-circular arc-shaped channels 220. The connecting channel connects to the outlet of the solution injection zone. The dispersed phase solution is cut in the connecting channel and then enters the curved semi-circular arc-shaped channels for passive mixing. The curved droplet forming mixing zone effectively and uniformly mixes different substrates in the droplets through the channel geometry during droplet flow. Further, in one embodiment of the invention, the cross-section of the connecting channel and the multiple semi-circular arc-shaped channels is square, with a width of 50μm-250μm and a height of 150μm; the length of the connecting channel is 150μm, and the length of the semi-circular arc-shaped channels is 3mm-9m, with an outer diameter of 150μm-350μm and an inner diameter of 100µm. Figure 3 In the embodiment shown, the droplet forming mixing zone 2 is composed of a short connecting channel of about 150 μm and 16 alternating semi-circular channels. The outer diameter of the semi-circular channels is 250 µm, the inner diameter is 100 µm, and the length of the meandering channel is 6 mm.

[0035] Figure 4 The diagram shown is a schematic representation of the droplet buffer collection region of a droplet generation device for mixing multi-component substrates according to an embodiment of the present invention. Figure 4 As shown, the droplet buffer collection area 3 includes multiple vertical straight channels 310, multiple semi-circular arc-shaped connecting channels 320, a turning connecting channel 330, and a horizontal straight channel 340. The multiple vertical straight channels are connected through the multiple semi-circular arc-shaped connecting channels, and the last vertical straight channel is connected to the horizontal straight channel through the turning connecting channel. The droplet buffer collection area, formed by continuous S-shaped channels, further mixes the droplets to form droplets output from the mixing region and smoothly guides them into the droplet collection device connected to the outside of the device. The cross-sectional width of the droplet buffer collection area channel is twice the cross-sectional width of the droplet mixing region channel, which is more conducive to the smooth flow of viscous hydrogel droplets. The number of vertical straight channels in the microchannel is adjustable and controlled within the range of 3-5 to maintain the overall chip size. The length is consistent with the vertical width of the solution injection area. The channel width of the semi-circular arc connecting channel, the channel width of the arc-shaped turning channel, and the channel width of the horizontal straight channel are consistent with the width of the vertical straight channel. Further, in one embodiment of the present invention, the cross-sections of the plurality of vertical straight channels, the plurality of semi-circular arc-shaped connecting channels, the turning connecting channel, and the horizontal straight channel are square, with a width of 200μm-400μm and a height of 150μm; the outer diameter of the plurality of semi-circular arc-shaped connecting channels and the turning channel is 800μm, and the length of the horizontal straight channel is 3mm-5mm. Figure 4In the illustrated embodiment, the droplet buffer collection area is composed of three vertical straight channels with a length of 6.3 mm, two vertical straight channels with a length of 3.1 mm, four semi-circular arc-shaped connecting channels with an outer diameter of 800 μm, one turning connecting channel with an outer diameter of 800 μm, and one horizontal straight channel with a length of 4 mm.

[0036] The droplet generation device for multi-component substrate mixing provided by this invention has three functional areas, integrating multi-component substrate mixing, droplet generation, and droplet collection into one unit. It can rapidly and efficiently generate uniform microdroplets. This droplet generation device is simple to manufacture and has a reasonable structural design, showing broad application prospects in the generation of multi-component substrate microdroplets.

[0037] This application also provides a droplet flow control chip, including a substrate and a reaction fluid channel layer disposed on the substrate. The reaction fluid channel layer is provided with the droplet generation device described above, a continuous phase injection port, and one or more dispersed phase injection ports. Figure 5 The image shown is an actual effect diagram of a droplet flow control chip provided in an embodiment of the present invention. This droplet flow control chip is fabricated using a glass substrate and a molded PDMS layer through chemical bonding, and can be used for the preparation and collection of droplets containing various substrates. All microchannels are transferred onto an elastic silicone PDMS (polydimethylsiloxane) layer using soft etching technology, and then bonded to a flat glass plate as a substrate to form a closed microchannel system.

[0038] Furthermore, in one embodiment of the present invention, the selection of all openings can be implemented on the PDMS reaction fluid channel layer. The openings for both the continuous phase injection microchannels and the dispersed phase injection microchannels are completed before the PDMS layer is bonded to the substrate glass layer, according to the actual reaction requirements.

[0039] Furthermore, in one embodiment of the present invention, the substrate and the reaction fluid channel layer are integrally formed, and the substrate and the reaction fluid channel layer are made of a water-proof, oil-proof, gas-proof, and reaction-inert material.

[0040] Furthermore, in one embodiment of the present invention, the fluid control of the droplet flow control chip is achieved by adjusting an externally connected injection pump, and the number of injection pumps is determined according to the number of openings.

[0041] The following describes a method for generating microdroplets using the droplet generation device for multi-component substrate mixing according to the present invention: First, a continuous phase fluid is injected through a continuous phase injection port to fill the entire microfluidic fluid channel layer; then, a dispersed phase fluid is injected through a dispersed phase injection port. The pressure of the continuous phase fluid must be greater than that of the dispersed phase fluid to ensure that the dispersed phase can be continuously and normally cut into droplets, and also to ensure that the continuous phase fluid uniformly separates the dispersed phase fluids, preventing them from merging due to excessive proximity. Further, the dispersed phase fluid can be either an aqueous phase or an oil phase, but the corresponding continuous phase fluid must also be either an oil phase or an aqueous phase, and the continuous phase fluid and dispersed phase fluid are immiscible. This droplet generation method is simple to operate and can handle the generation of droplets from various substrate mixtures, rapidly and efficiently generating a large number of uniformly sized microdroplets under the same conditions in a short time.

[0042] Below, we will demonstrate a specific application example of the multi-component mixed microfluidic chip using a pigment solution as the dispersed phase and mineral oil as the continuous phase.

[0043] like Figure 6 As shown in (A), the red pigment is the dispersed phase. The opening of the continuous phase injection microchannel is located at point B, which is the inlet opening of the dispersed phase injection microchannel 150. Two syringes, one for the continuous phase mineral oil and the other for the dispersed phase red pigment solution, are injected through the pump. The continuous phase solution enters the channel through the second continuous phase injection microchannel, cutting the dispersed phase solution at the intersection, thus forming droplets using the T-channel method. In the droplet formation mixing zone, the dispersed phase is observed to be cut, and in the droplet buffer collection zone, which is twice the width of the initial flow, uniform droplet formation is observed. In this application, the injection flow rates of both the dispersed and continuous phase solutions are 2 µl / min. In the remaining two dispersed phase injection microchannels, the first continuous phase injection microchannel shows a small amount of red pigment solution. This is a normal backflow phenomenon caused by the compressible gas in the channel, and the backflow stops after the pressure in the channel stabilizes.

[0044] like Figure 6 As shown in (B), when the opening position of the continuous phase injection microchannel is point C, the gap between the two continuous phase injection microchannels is 325µm, and the diameter of the punch is 500µm, drilling at point C will connect the first and second continuous phase injection microchannels. That is, if a continuous phase solution is injected at the opening position C after drilling, the solution will be divided into two parts, entering the channels through the first and second continuous phase injection microchannels respectively. Figure 2 The channel intersections shown in the figure simultaneously cut through the dispersed phase solution, which is the flow focusing method used to form droplets. In the droplet formation mixing zone, the dispersed phase is observed to be cut, and uniform droplet formation is seen in the droplet buffer zone, which is twice the width of the dispersed phase. In the application example shown in the figure, the continuous phase flow rate is 2 µl / min, and the dispersed phase flow rate is 2 µl / min.

[0045] like Figure 7 As shown in (A), when two substrates need to be mixed as dispersed phases, two channels can be selected for opening in multiple dispersed phase injection microchannels. In the example, yellow and blue pigments are selected as the two dispersed phase solutions to be mixed. When the opening position of the continuous phase injection microchannel is point B, the continuous phase solution enters the channel through the second continuous phase injection microchannel. At the intersection, the two dispersed phase solutions entering at the same time are cut, forming droplets using a T-channel method. As shown in the figure, the blue and yellow pigment solutions are cut into droplet fragments. After passing through the droplet mixing zone, they are fully mixed to form uniform green droplets, which are further mixed uniformly through the droplet buffer collection zone and collected outside the chip. A small amount of green or yellow pigment solution is seen in both the first continuous phase injection microchannel and the dispersed phase injection microchannel 150. This is a normal solution backflow phenomenon caused by the compressible gas in the channel. The backflow phenomenon stops after the pressure in the channel stabilizes. In the application example shown in the figure, the continuous phase flow rate is 2 µl / min, and the dispersed phase flow rate is 2 µl / min.

[0046] like Figure 7 As shown in (B), with Figure 6 Similar to (B), when the opening position of the continuous phase injection microchannel is point C, the two continuous phase injection microchannels are connected. The mineral oil injection channel, which serves as the continuous phase, is then divided into two, entering the channel through the first continuous phase injection microchannel and the second continuous phase injection microchannel respectively. Figure 2 The channel intersection shown in the figure simultaneously cuts two dispersed phase solutions of yellow and blue pigments to be mixed. The dispersed phase droplets are cut using a flow focusing method. After passing through the mixing zone formed by these droplets, they are thoroughly mixed to form uniform green droplets. These droplets are then further mixed uniformly in the droplet buffer collection zone and collected outside the chip. In the application example shown in the figure, the continuous phase flow rate is 2 µl / min, and the dispersed phase flow rate is 2 µl / min.

[0047] like Figure 8 As shown, the dispersed phase solutions to be mixed here are increased to three types: yellow pigment solution, blue pigment solution, and red pigment solution. All three channels of the dispersed phase injection microchannel are open. When the opening position of the continuous phase injection microchannel is point B, the continuous phase solution enters the channel through the second continuous phase injection microchannel, cutting the three dispersed phase solutions that enter simultaneously at the intersection point. The dispersed phase droplets are cut using a T-tube method. After passing through the mixing zone formed by the droplets, they are fully mixed to form uniform dark green droplets, which are further mixed evenly through the droplet buffer collection zone and collected outside the chip. A small amount of blue pigment solution can be seen in the first continuous phase injection microchannel. This is a normal solution backflow phenomenon caused by the compressible gas in the channel. The backflow phenomenon stops after the pressure in the channel stabilizes. In the application example shown in the figure, the continuous phase flow rate is 4 µl / min, and the dispersed phase flow rate is 2 µl / min.

[0048] like Figure 8 As shown in Figure 7(B), similar to the case shown in Figure 7(B), when the opening position of the continuous phase injection microchannel is C, the two continuous phase injection microchannels are connected. The mineral oil injection channel, which serves as the continuous phase, is then divided into two, entering the channel through the first continuous phase injection microchannel and the second continuous phase injection microchannel respectively. Figure 2 The channel intersection shown in the figure simultaneously cuts three dispersed phase solutions of yellow, blue, and red pigments to be mixed. The dispersed phase droplets are cut using a flow focusing method. After passing through the mixing zone formed by these droplets, they are thoroughly mixed to form uniform dark green droplets. These droplets are then further mixed and collected outside the chip via the droplet buffer collection zone. In the application example shown in the figure, the continuous phase flow rate is 4 µl / min, and the dispersed phase flow rate is 2 µl / min.

[0049] Numerous specific details are set forth in the specification provided herein. However, it will be understood that embodiments of the invention may be practiced without these specific details. In some instances, well-known methods, structures, and techniques have not been shown in detail so as not to obscure the understanding of this specification.

[0050] Similarly, it should be understood that, in order to simplify this disclosure and aid in understanding one or more of the various aspects of the invention, in the above description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof. However, this method of disclosure should not be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as reflected in the following claims, inventive aspects lie in fewer than all features of a single foregoing disclosed embodiment. Therefore, the claims following the detailed description are hereby expressly incorporated into this detailed description, wherein each claim itself is a separate embodiment of the invention.

[0051] Furthermore, those skilled in the art will understand that although some embodiments herein include certain features included in other embodiments but not others, combinations of features from different embodiments are intended to be within the scope of the invention and form different embodiments. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0052] It should be noted that the above embodiments are illustrative of the invention and not restrictive, and that those skilled in the art can devise alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses should not be construed as limiting the claims. The word "comprising" does not exclude the presence of elements or steps not listed in the claims. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. The invention can be implemented by means of hardware comprising several different elements and by means of a suitably programmed computer. In the unit claims enumerating several means, several of these means may be embodied by the same item of hardware. The use of the words first, second, and third, etc., does not indicate any order. These words can be interpreted as names.

Claims

1. A droplet generation device for mixing multi-component substrates, characterized in that, The device includes a solution injection zone, a droplet formation and mixing zone, and a droplet buffer collection zone. The solution injection zone includes a first continuous phase injection microchannel, a second continuous phase injection microchannel, multiple dispersed phase injection microchannels, and a junction. The multiple dispersed phase injection microchannels are located within the area surrounded by the first and second continuous phase injection microchannels. There is a break between the inlet of the first and second continuous phase injection microchannels. The first and / or second continuous phase injection microchannels are selectively opened by the location of the chip continuous phase opening, and one or more of the multiple dispersed phase injection microchannels are selectively opened by the location of the chip dispersed phase opening. The outlets of the first and second continuous phase injection microchannels are connected to the outlets of the multiple dispersed phase injection microchannels at the junction. The continuous phase solution in the first and / or second continuous phase injection microchannels cuts the dispersed phase solution in one or more of the multiple dispersed phase injection microchannels into droplets, which then enter the droplet formation and mixing zone and the droplet buffer collection zone.

2. The droplet generation device for mixing multi-component substrates according to claim 1, characterized in that, The first continuous phase injection microchannel, the second continuous phase injection microchannel, and the plurality of dispersed phase injection microchannels have square cross-sections with a width of 200μm-400μm and a height of 150μm; the cross-section of the junction is square, with a width of 100μm-200μm.

3. The droplet generation device for mixing multi-component substrates according to claim 1, characterized in that, The droplet forming mixing zone is composed of a connecting channel and multiple alternating semi-circular channels, and the connecting channel is connected to the outlet of the solution injection zone.

4. The droplet generation device for mixing multi-component substrates according to claim 3, characterized in that, The cross-section of the connecting channel and the plurality of semi-circular arc-shaped channels is square, with a width of 50μm-250μm and a height of 150μm; the length of the connecting channel is 150μm, the length of the semi-circular arc-shaped channels is 3mm-9m, the outer diameter is 150μm-350μm, and the inner diameter is 100µm.

5. The droplet generation device for mixing multi-component substrates according to claim 1, characterized in that, The droplet buffer collection area includes multiple vertical straight channels, multiple semi-circular arc connecting channels, turning connecting channels, and horizontal straight channels. The multiple vertical straight channels are connected through the multiple semi-circular arc connecting channels, and the last vertical straight channel is connected to the horizontal straight channel through the turning connecting channel.

6. The droplet generation apparatus for mixing multi-component substrates according to claim 5, characterized in that, The cross-sections of the plurality of vertical straight channels, the plurality of semi-circular arc connecting channels, the turning connecting channel, and the horizontal straight channel are square, with a width of 200μm-400μm and a height of 150μm; the outer diameter of the plurality of semi-circular arc connecting channels and the turning connecting channel is 800μm, and the length of the horizontal straight channel is 3mm-5mm.

7. A droplet flow control chip, characterized in that, The droplet flow control chip includes a substrate and a reaction fluid channel layer disposed on the substrate; the reaction fluid channel layer is provided with a droplet generation device, a continuous phase injection port, and one or more dispersed phase injection ports as described in any one of claims 1-6.

8. The droplet flow control chip according to claim 7, characterized in that, The substrate is a glass plate, and the reaction fluid channel layer is an elastic silicone PDMS layer.

9. The droplet flow control chip according to claim 7, characterized in that, The substrate and the reaction fluid channel layer are integrally formed.

10. A droplet reaction apparatus, characterized in that, Includes the droplet generation device for mixing multi-component substrates as described in any one of claims 1-6.

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