Dispersed phase self-propulsion-based micro-fluidic droplet generation method and micro-fluidic chip

Abstract

The invention discloses a micro-fluidic liquid drop generation method based on dispersed phase self-propulsion and a micro-fluidic chip, and relates to the technical field of micro-fluidic chips, and the micro-fluidic chip comprises a micro-channel layer, a liquid drop generation unit and a substrate; the micro-channel layer comprises a micro-channel, a sample inlet and a sample outlet; the liquid drop generation unit comprises a capturing area and a liquid drop generation area; a dispersed phase fluid is injected into the micro-fluidic chip from the sample inlet, the dispersed phase fluid flows through the droplet generation unit, part of the dispersed phase fluid is intercepted to the capture area, and the remaining dispersed phase fluid enters the droplet generation area; continuous-phase fluid is injected into the micro-fluidic chip from the sample injection port, the continuous-phase fluid flows through the droplet generation unit, dispersed-phase fluid captured by the capturing area flows out of the capturing area under the action of Laplace pressure difference and enters the droplet generation area, the dispersed-phase fluid is fractured under extrusion of the continuous-phase fluid, and the droplet generation area generates droplets. One part flows to the sample outlet along with the continuous-phase fluid in the form of liquid drops, and the other part is pressed back into the capturing channel.

Description

Technical Field

[0001] The invention relates to the technical field of microfluidic chips, and in particular to a microfluidic droplet generation method based on self-propulsion of dispersed phase fluid and a microfluidic chip. Background Art

[0002] Microfluidic chip technology is a technology that integrates basic operating units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a tiny chip. Based on a microchannel network, various complex functions are achieved through precise manipulation of fluids at the microscale. Closely integrated with the field of biochemical analysis, in clinical diagnosis, microfluidic detection chips are easy to operate, multifunctional, small and easy to carry, and suitable for the development of bedside diagnosis, such as the detection of markers such as electrolytes, metabolites, nucleic acids, proteins, and cells. However, traditional microfluidic technology still has disadvantages such as large reagent consumption, easy sample contamination, and low detection throughput, which restricts its further development in the field of point-of-care testing (POCT).

[0003] Droplet microfluidics technology uses microfluidic chips as a platform. Through photolithography technology, silicon wafers with fluid channels of tens to hundreds of microns are designed. Two immiscible fluids are introduced to produce monodisperse droplets, which are manipulated and analyzed. The reaction volume is small, which can effectively reduce the reaction time and improve the detection sensitivity. The droplets generated can be divided into water-in-water (two immiscible aqueous solutions), water-in-oil and oil-in-water, among which oil-in-water is more common. According to the different structures of the generated droplets, droplet microfluidics can be divided into four categories: coaxial flow method, T-channel, flow focusing and step emulsification. However, traditional droplet generation technology requires the management of continuous phase fluid (generally oil phase) and dispersed phase fluid (generally water phase). The operation is complicated and requires at least two or more external drive devices to provide power, which increases the complexity of channel design and equipment operation.

[0004] Defects and shortcomings of the existing technology:

[0005] 1. Complex channel design and production: Among the traditional droplet generation methods, coaxial flow, T-channel and flow focusing methods all require specific and complex channel designs, and multiple microchannels are required for droplet generation; step emulsification requires the production of chips with height differences for droplet generation, and chip production is difficult.

[0006] 2. The equipment operation is complex and the cost is high: The traditional droplet generation method has extremely strict requirements on the flow rate of the dispersed phase fluid and the continuous phase fluid. Therefore, more than two precision external drive devices are required to accurately control the flow rate of the dispersed phase fluid and the continuous phase fluid respectively. The operation is complex and the production cost is high.

[0007] 3. The problem of flow velocity fluctuation of the driving device itself: During the operation of the device itself, due to factors such as mechanical resistance and tube deformation, flow velocity fluctuations may occur occasionally, causing the originally constant flow velocity to change. Too many external driving devices will aggravate the occurrence of this phenomenon. In the process of generating droplets at high flow rates, even very small flow velocity fluctuations will cause the generated droplets to be of uneven size.

[0008] 4. There are limitations in the field of droplet multiplexing. It can only rely on adding external driving devices to generate multiple droplets with different properties, or adding fluids of different properties into the chip one by one through micro-tweezers to generate droplets. The operation is complicated and cumbersome, making it difficult to promote in the market. Summary of the invention

[0009] In order to solve the above technical problems, the present invention utilizes the Laplace pressure difference principle to generate droplets through self-propulsion of the water phase. The chip channel design is simple, the flow rate accuracy requirement is low, and only one external driving device is required. It is less affected by the mechanical error interference of the equipment and can realize multi-path droplet generation.

[0010] The present invention proposes a microfluidic chip based on the self-propulsion of dispersed phase fluid to generate droplets, the microfluidic chip comprising: a microchannel layer, a droplet generation unit and a substrate;

[0011] The microchannel layer and the substrate are assembled by bonding and process; the microchannel layer includes a microchannel, an injection port and an outlet; the droplet generation unit includes a capture area and a droplet generation area;

[0012] Inject dispersed phase fluid into the microfluidic chip from the injection port, the dispersed phase fluid flows through the droplet generation unit, part of the dispersed phase fluid is retained in the capture area, and the remaining dispersed phase fluid enters the droplet generation area;

[0013] The continuous phase fluid is injected into the microfluidic chip from the injection port, and the continuous phase fluid flows through the droplet generation unit. The dispersed phase fluid captured in the capture area flows out of the capture area under the action of the Laplace pressure difference and enters the droplet generation area. The dispersed phase fluid breaks under the extrusion of the continuous phase fluid, generating single or multiple droplets and flowing to the sample outlet with the continuous phase.

[0014] In a preferred embodiment, the capture area is trumpet-shaped, the maximum width of the capture area is wider than the maximum width of the droplet generation area, and the narrowest part of the capture area is narrower than the narrowest part of the droplet generation area, so that the dispersed phase fluid enters the capture area first and then enters the droplet generation area.

[0015] In a preferred embodiment, the capture area includes: a connecting channel, a circular chamber, an air plug channel and a capture channel; the droplet generation area includes: a growth channel, a cross-sectional angle and an adjustment channel; the microchannel includes: an injection buffer zone, a main channel and an observation channel.

[0016] In a preferred embodiment, the dispersed phase fluid flows through the injection buffer and reaches the T-shaped intersection connected to the connecting channel and the growth channel. The dispersed phase fluid first fills the circular chamber and then reaches the connection between the circular chamber and the capture channel. Due to the fluid resistance, the dispersed phase fluid fills the growth channel upward and reaches the connection between the growth channel and the adjustment channel. The fluid resistance increases, and the dispersed phase fluid continues to flow downward into the capture channel until it reaches the gas plug channel. The dispersed phase fluid is captured by the capture area due to the existence of the gas plug channel.

[0017] In a preferred embodiment, when the remaining dispersed phase fluid that has not entered the capture channel is completely discharged by the air, a continuous phase fluid is introduced into the microfluidic chip under the action of an external driving device, and the continuous phase fluid enters the connecting channel and the air plug channel to discharge the air in the air plug channel, so that the captured dispersed phase fluid is wrapped by the continuous phase fluid, and the front and rear ends where the dispersed phase fluid contacts the continuous phase fluid both form an arc shape convex outward, the front end of the dispersed phase fluid has a large curvature radius, and the rear end has a small curvature radius, and is suppressed in the capture area under the action of the Laplace pressure difference; the driving device is turned off, the flow rate of the continuous phase fluid is reduced, and the dispersed phase fluid flows out under the action of the Laplace pressure difference, and when the dispersed phase fluid in the capture channel completely flows out to the growth channel and then stops, the external driving device is turned on to drive the continuous phase fluid to flow into the microfluidic chip, and the dispersed phase fluid in the growth channel is cut off at the cross-sectional angle to generate single or multiple droplets and flow to the sample outlet with the continuous phase.

[0018] In a preferred embodiment, circular chamber diameter > growth channel width > capture channel width > regulation channel width > gas plug channel width.

[0019] In a preferred embodiment, the microfluidic chip is a multi-channel droplet generation chip for performing multi-channel droplet generation, including: a plurality of droplet generation units, a dispersed phase fluid outlet, and a continuous phase fluid outlet; each droplet generation unit is used to add different droplets respectively, the continuous phase fluid and droplets flow out of the microfluidic chip through the continuous phase fluid outlet, and the dispersed phase fluid that is not captured flows out through the dispersed phase fluid outlet.

[0020] The present invention also proposes a method for generating droplets using the above-mentioned microfluidic chip based on the self-propulsion of dispersed phase fluid to generate droplets, comprising the following steps:

[0021] S1, dispersed phase fluid capture;

[0022] Inject dispersed phase fluid into the microfluidic chip from the injection port. When the dispersed phase fluid flows through the droplet generation unit, part of the dispersed phase fluid is retained in the capture area, and the remaining dispersed phase fluid flows out from the outlet.

[0023] S2, dispersed phase fluid droplet generation;

[0024] The continuous phase fluid is injected into the microfluidic chip from the injection port, and the continuous phase fluid flows through the droplet generation unit. The dispersed phase fluid captured in the capture area flows out of the capture area under the action of the Laplace pressure difference and enters the droplet generation area. The dispersed phase fluid breaks under the extrusion of the continuous phase fluid, generating single or multiple droplets and flowing to the sample outlet with the continuous phase.

[0025] Compared with the prior art, the present invention has the following beneficial technical effects:

[0026] The device of the present invention adopts the Laplace pressure difference principle to design a microfluidic chip, thereby introducing dispersed phase fluid and continuous phase fluid to generate stable and uniform droplets through self-propulsion, avoiding the complex flow rate control of the continuous phase fluid and the dispersed phase fluid in the traditional droplet generation process, making droplet generation simpler, reducing the requirements for the precision of instruments and equipment, and only requiring an external drive device to achieve droplet generation, which not only reduces equipment cost, but also can reduce the influence of the mechanical error of the equipment itself on the uniformity of droplets. The overall structure is simple and reasonable. In summary, the present invention provides a new method for droplet generation that is simple to operate, easy to integrate, low in cost, and has good uniformity, and has advantages in the field of multiplexing. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 A schematic diagram of the structure of a single-channel droplet generation microfluidic chip based on self-propulsion of dispersed phase fluid provided in an embodiment of the present invention;

[0028] Figure 2 A three-dimensional diagram of a single-channel droplet generation microfluidic chip based on self-propulsion of dispersed phase fluid provided in an embodiment of the present invention;

[0029] Figure 3 A schematic diagram of the structure of a multi-channel droplet generation microfluidic chip based on self-propelled dispersed phase fluid provided in an embodiment of the present invention;

[0030] Figure 4 A three-dimensional diagram of a multi-channel droplet generation microfluidic chip based on self-propulsion of dispersed phase fluid provided in an embodiment of the present invention.

[0031] Figure 5 A result diagram of a multi-path droplet generation process based on self-propulsion of dispersed phase fluid provided in an embodiment of the present invention.

[0032] Figure 6 It is a schematic diagram of the capture area of ​​the present invention;

[0033] Figure 7 It is a schematic diagram of the droplet generation area of ​​the present invention.

[0034] Figure numerals: 100-single-channel droplet generation chip; 101-injection port; 102-injection buffer; 103-connecting channel; 104-circular chamber; 105-capture channel; 106-gas plug channel; 107-growth channel; 108-cross-sectional angle; 109-adjustment channel; 110-main channel; 111-observation channel; 112-outlet; 200-substrate; 300-multi-channel droplet generation chip; 301-injection port; 302-droplet generation unit; 303-dispersed phase fluid outlet; 304-multi-droplet observation channel; 305-continuous phase fluid outlet; 400-capture area; 500-droplet generation area. DETAILED DESCRIPTION

[0035] The technical scheme in the embodiment of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiment of the present invention. Obviously, the described embodiment is only a part of the embodiment of the present invention, not all of the embodiments. Based on the embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0036] The microfluidic chip for generating liquid droplets based on the self-propelled dispersed phase fluid of the present invention comprises: a microchannel layer, a liquid droplet generating unit and a substrate; the microchannel layer and the substrate are assembled by bonding and process.

[0037] The microchannel layer is used for receiving and transporting droplets, and includes: a microchannel, an inlet and an outlet; the inlet and outlet at both ends of the microchannel layer are respectively connected to a driving device and a collecting device for the inflow and discharge of different droplets.

[0038] The droplet generation unit includes a capture area and a droplet generation area; the dispersed phase fluid first enters the fluid capture area and then enters the droplet generation area.

[0039] The capture area is trumpet-shaped, with the maximum width of the capture area being wider than the maximum width of the droplet generation area, and the narrowest part of the capture area being narrower than the narrowest part of the droplet generation area, so that the dispersed phase fluid enters the capture area first and then enters the droplet generation area.

[0040] The capture area includes: a connecting channel, a circular chamber, an air plug channel and a capture channel; the droplet generation area includes: a growth channel, a cross-sectional angle and an adjustment channel; and the microchannel includes: an injection buffer zone, a main channel and an observation channel.

[0041] The dispersed phase fluid flows through the injection buffer and reaches the T-shaped intersection connected to the connecting channel and the growth channel. The dispersed phase fluid first fills the circular chamber and then reaches the connection between the circular chamber and the capture channel. Due to the fluid resistance, the dispersed phase fluid fills the growth channel upward and reaches the connection between the growth channel and the adjustment channel. The fluid resistance increases, and the dispersed phase fluid continues to flow downward into the capture channel until it reaches the gas plug channel. The dispersed phase fluid is captured by the capture area due to the existence of the gas plug channel.

[0042] When the remaining dispersed phase fluid that has not entered the capture channel is completely discharged by the air, the continuous phase fluid is introduced into the microfluidic chip under the action of the external driving device, and the continuous phase fluid enters the connecting channel and the air plug channel to discharge the air in the air plug channel, so that the captured dispersed phase fluid is wrapped by the continuous phase fluid, and the front and rear ends of the dispersed phase fluid in contact with the continuous phase fluid both form an arc shape convex outward, the front end curvature radius of the dispersed phase fluid is large, and the rear end curvature radius is small, and under the action of the Laplace pressure difference, the dispersed phase fluid is suppressed in the capture area; the driving device is closed, the flow rate of the continuous phase fluid is reduced, and the dispersed phase fluid flows out under the action of the Laplace pressure difference. When the dispersed phase fluid in the capture channel completely flows out to the growth channel and then stops, the external driving device is turned on to drive the continuous phase fluid to flow into the microfluidic chip, and the dispersed phase fluid in the growth channel is cut into two parts at the cross-sectional angle, generating a single or multiple droplets and flowing to the sample outlet with the continuous phase.

[0043] In a preferred embodiment, circular chamber diameter > growth channel width > capture channel width > regulation channel width > gas plug channel width.

[0044] In a preferred embodiment, the microfluidic chip is a multi-channel droplet generation chip for performing multi-channel droplet generation, including: a plurality of droplet generation units, a dispersed phase fluid outlet, and a continuous phase fluid outlet; each droplet generation unit is used to add different droplets respectively, the continuous phase fluid and droplets flow out of the microfluidic chip through the continuous phase fluid outlet, and the dispersed phase fluid that is not captured flows out through the dispersed phase fluid outlet.

[0045] Example 1

[0046] This embodiment proposes a single-channel droplet generation microfluidic chip based on self-propelled dispersed phase fluid, such as Figure 1-2 As shown, it is a schematic diagram of the structure of a single-channel droplet generation microfluidic chip based on self-propulsion of dispersed phase fluid.

[0047] The single-channel droplet generation chip 100 includes: an injection port 101; an injection buffer 102; a connecting channel 103; a circular chamber 104; a capture channel 105; an air plug channel 106; a growth channel 107; a cross-sectional angle 108; an adjustment channel 109; a main channel 110; an observation channel 111; and a sample outlet 112.

[0048] The injection buffer 102, the main channel 110, and the observation channel 111 constitute a microchannel. The microchannel, the injection port 101, and the outlet port 112 together constitute a microchannel layer for receiving and transporting droplets.

[0049] like Figure 6 As shown, the connecting channel 103, the circular chamber 104, the capture channel 105, and the gas plug channel 106 together constitute the capture area 400; Figure 7 As shown, the growth channel 107 , the cross-sectional angle 108 , and the adjustment channel 109 together constitute the droplet generation area 500 .

[0050] The capture area and the droplet generation area together constitute a droplet generation unit.

[0051] The microchannel layer and substrate are assembled by bonding process, which can be plasma activated bonding, thermal bonding or UV light curing. The selected bonding method needs to ensure the tight bonding between the various parts of the chip without affecting the structure and function of the microchannel.

[0052] The microchannel layer uses specific materials and processing techniques to ensure stability and efficiency during droplet generation. The specific materials can be materials with biocompatibility, corrosion resistance, high dielectric strength, and easy processing, such as polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polycarbonate (PC), polyethylene glycol diacrylate (PEGDA), or epoxy resin.

[0053] Processing techniques can include soft lithography, hot embossing, 3D printing, laser ablation or injection molding, which can accurately replicate the complex structure of microchannels.

[0054] Preferably, PDMS is selected as the chip material, a glass slide is selected as the substrate 200 material, the chip is manufactured by soft lithography technology, PDMS and the glass slide are bonded by plasma cleaning, and then heated at 80° C. overnight to ensure the bonding strength.

[0055] The injection port 101 and the outlet port 112 are respectively connected to the driving device and the collecting device by PTFE tubes. The dispersed phase fluid is injected into the chip by the gas pressure applied by the driving device. The dispersed phase fluid flows through the injection buffer 102 and reaches the T-shaped intersection connected to the connecting channel 103 and the growth channel 107. The dispersed phase fluid first fills the circular chamber 104 and reaches the connection between the circular chamber 104 and the capture channel 105. Affected by the fluid resistance, the dispersed phase fluid fills the growth channel 107 upward and reaches the connection between the growth channel 107 and the regulating channel 109. The fluid resistance increases, and the dispersed phase fluid continues to flow downward into the capture channel 105 until it reaches the gas plug channel 106. The fluid resistance is greater than the fluid resistance of the regulating channel 109. The dispersed phase fluid passes through the regulating channel 109 and along the main channel 110, and flows out from the outlet port 112 into the collecting device. At this time, the upper and lower interfaces of the gas plug channel 106 are sealed by the dispersed phase fluid, and air exists in the middle to form an air plug.

[0056] After the dispersed phase fluid fills the capture area, the dispersed phase fluid will remain in the connecting channel 103, the circular chamber 104 and the capture channel 105. When droplets are subsequently generated, only the dispersed phase fluid in the capture channel 105 generates droplets and flows out.

[0057] After the dispersed phase fluid fills the capture area, air is introduced into the chip. The dispersed phase fluid that has not entered the capture channel is pushed out of the chip from the sample outlet 112 along the growth channel 107, the adjustment channel 109, and the main channel 110 and enters the collection device; while the dispersed phase fluid that has entered the capture area cannot overcome the fluid resistance and flow out due to the existence of the air plug channel 106, and is therefore captured in the capture area.

[0058] After the remaining dispersed phase fluid that has not entered the capture channel is completely expelled by the air, the continuous phase fluid is introduced into the chip at a relatively high pressure under the action of the external driving device. The continuous phase fluid enters the connecting channel 103 and the air plug channel 106 along the wall, and the air in the air plug channel 106 is expelled, so that the captured dispersed phase fluid is wrapped by the continuous phase fluid. The front and rear ends of the dispersed phase fluid in contact with the continuous phase fluid form an outwardly convex arc shape. The front end of the dispersed phase fluid has a large curvature radius, and the rear end has a small curvature radius. Under the action of the Laplace pressure difference, the dispersed phase fluid The body has a tendency to flow forward, but at a higher continuous phase fluid flow rate, it is suppressed in the capture area; the driving device is turned off, the continuous phase fluid flow rate is reduced, and the dispersed phase fluid flows out under the Laplace pressure difference. When the dispersed phase fluid in the capture channel completely flows out to the growth channel 107 and then stops, the external driving device is turned on to drive the continuous phase fluid into the chip with a higher pressure. The dispersed phase fluid in the growth channel 107 is squeezed by the continuous phase fluid and is cut into two parts at the cross-sectional angle 108, generating a single or multiple droplets and flowing to the sample outlet with the continuous phase. The droplets flowing with the continuous phase fluid pass through the observation channel 111 for various signal observations such as morphological structure, inclusions or fluorescence intensity.

[0059] Circular chamber diameter > growth channel width > capture channel width > regulation channel width > gas plug channel width.

[0060] The formula for fluid resistance R is:

[0061]

[0062] Where μ is the fluid viscosity, and L, w, and h are the length, width, and height of the microchannel, respectively.

[0063] The fluid resistance is related to the channel width. The larger the channel width, the smaller the fluid resistance and the easier it is for the fluid to flow through.

[0064] In a preferred embodiment, the inlet and outlet at both ends of the microchannel layer are designed with through holes for the inflow and discharge of different droplets, thereby realizing the multifunctional application of the microfluidic chip.

[0065] The diameters of the inlet and outlet of the microfluidic chip are slightly larger than the actual through-hole diameter, ensuring that the through-hole can be completely covered by the chip inlet and outlet during the punching process. The diameter of the through-hole is slightly larger than the width of the flow channel, ensuring that the droplets can pass smoothly without breaking or merging.

[0066] The dispersed phase fluid is injected into the chip through a hose connected to the driving device and then exported to the collection tube through the hose. The hose is made of polytetrafluoroethylene (PTFE) tube. The collection device can be a centrifuge tube or a waste liquid cylinder. The driving device adopts a piezoelectric proportional valve control system, including a carbon dioxide cylinder, a DC adjustable power supply, a piezoelectric proportional valve, an airtight liquid storage tank and a PTFE tube. Injection pumps, peristaltic pumps, syringes, etc. can also be used.

[0067] Preferably, the hose is made of polytetrafluoroethylene (PTFE) tube, and the driving device is made of a piezoelectric proportional valve control system.

[0068] Example 2

[0069] This embodiment proposes a multi-channel droplet generation microfluidic chip based on self-propelled dispersed phase fluid. Figure 3 , which is a schematic diagram of the structure of a multi-channel droplet generation chip 300. The multi-channel droplet generation chip 300 includes: an inlet 301, a dispersed phase fluid outlet 303, a plurality of droplet generation units 302, an observation channel 304 and a continuous phase fluid outlet 305.

[0070] Combination Figure 3-5 As shown, multi-path droplet generation is performed. First, the system is pre-buried in the capture area. The system can be biological or chemical components such as dyes, nanoparticles, PCR primers, PCR freeze-dried systems, etc. In this embodiment, four different colors of pigment dyes are used to generate droplets with a volume of about 70nL.

[0071] A multi-channel droplet generation chip made of PDMS was made by soft lithography technology. 1 μL of four different colors of pigment dyes were added to the circular chamber of each droplet generation unit 302 in advance by spotting, and the chip was placed at room temperature or in an oven until the water was completely evaporated. The chip was bonded to the glass slide by plasma cleaning and the chip was kept at 80°C overnight. Before using the chip, first use a rubber plug to seal the continuous phase fluid outlet 305, use a PTFE tube to connect the inlet 301 and the dispersed phase fluid outlet 303, and refer to the above steps to introduce deionized water into the bonded chip for capture. The remaining deionized water that is not captured flows out through the dispersed phase fluid outlet 303, and the deionized water in the capture area dissolves the pigment dye to form four colors of pigment solutions; remove the rubber plug to open the continuous phase fluid outlet 305, use a rubber plug to seal the dispersed phase fluid outlet 303, and then refer to the above steps to generate droplets, and the four colors of droplets flow through the observation channel 304 for observation. The continuous phase fluid and droplets flow out of the chip through the continuous phase fluid outlet 305. When observing the droplets, you can observe with the naked eye, or you can combine with an optical microscope, a fluorescence microscope or other observation devices to perform other forms of droplet observation.

[0072] Example 3

[0073] This embodiment proposes a method for generating droplets using the above-mentioned microfluidic chip based on the self-propulsion of dispersed phase fluid to generate droplets, comprising the following steps:

[0074] S1, dispersed phase fluid capture;

[0075] Inject dispersed phase fluid into the microfluidic chip from the injection port. When the dispersed phase fluid flows through the droplet generation unit, part of the dispersed phase fluid is retained in the capture area, and the remaining dispersed phase fluid flows out from the outlet.

[0076] S2, dispersed phase fluid droplet generation;

[0077] The continuous phase fluid is injected into the microfluidic chip from the injection port. When the continuous phase fluid flows through the droplet generation unit, the captured dispersed phase fluid flows out of the capture area under the action of the Laplace pressure difference and enters the droplet generation area. It breaks and generates droplets under the extrusion of the continuous phase fluid, generating single or multiple droplets and flowing to the outlet with the continuous phase.

[0078] In summary, the device of the present invention adopts the Laplace pressure difference principle for chip design, and generates stable and uniform droplets by self-propulsion by introducing dispersed phase fluid and continuous phase fluid, avoiding the complex flow rate control of continuous phase fluid and dispersed phase fluid in the traditional droplet generation process, making droplet generation simpler, reducing the requirements for the precision of instruments and equipment, and only requiring an external drive device to achieve droplet generation, which not only reduces equipment costs, but also reduces the impact of the mechanical errors of the equipment itself on the uniformity of droplets. The overall structure is simple and reasonable, providing a new method for droplet generation that is simple to operate, easy to integrate, low cost, and has good uniformity, and can be applied to the field of multiplexing.

[0079] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. The embodiments should therefore be considered exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

Claims

1. A microfluidic chip based on self-propelled generation of droplets by dispersed phase fluid, characterized in that: The microfluidic chip includes: a microchannel layer, a droplet generation unit and a substrate; The microchannel layer and the substrate are assembled by bonding and process; the microchannel layer includes a microchannel, an injection port and an outlet; the droplet generation unit includes a capture area and a droplet generation area; Inject dispersed phase fluid into the microfluidic chip from the injection port, the dispersed phase fluid flows through the droplet generation unit, part of the dispersed phase fluid is retained in the capture area, and the remaining dispersed phase fluid enters the droplet generation area; The continuous phase fluid is injected into the microfluidic chip from the injection port, and the continuous phase fluid flows through the droplet generation unit. The dispersed phase fluid captured in the capture area flows out of the capture area under the action of the Laplace pressure difference and enters the droplet generation area. The dispersed phase fluid breaks under the extrusion of the continuous phase fluid, generating single or multiple droplets and flowing to the sample outlet with the continuous phase.

2. The microfluidic chip for generating droplets based on self-propulsion of dispersed phase fluid according to claim 1, characterized in that: The capture area is trumpet-shaped, the maximum width of the capture area is wider than the maximum width of the droplet generation area, and the narrowest part of the capture area is narrower than the narrowest part of the droplet generation area, so that the dispersed phase fluid enters the capture area first and then enters the droplet generation area.

3. The microfluidic chip for generating droplets based on self-propulsion of dispersed phase fluid according to claim 1, characterized in that: The capture area includes: a connecting channel, a circular chamber, an air plug channel and a capture channel; the droplet generation area includes: a growth channel, a cross-sectional angle and an adjustment channel; the microchannel includes: an injection buffer zone, a main channel and an observation channel.

4. The microfluidic chip for generating droplets based on self-propulsion of dispersed phase fluid according to claim 3, characterized in that: The dispersed phase fluid flows through the injection buffer and reaches the T-shaped intersection connected to the connecting channel and the growth channel. The dispersed phase fluid first fills the circular chamber and then reaches the connection between the circular chamber and the capture channel. Due to the fluid resistance, the dispersed phase fluid fills the growth channel upward and reaches the connection between the growth channel and the adjustment channel. The fluid resistance increases, and the dispersed phase fluid continues to flow downward into the capture channel until it reaches the gas plug channel. The dispersed phase fluid is captured by the capture area due to the existence of the gas plug channel.

5. The microfluidic chip for generating droplets based on self-propulsion of dispersed phase fluid according to claim 4, characterized in that: When the remaining dispersed phase fluid that has not entered the capture channel is completely expelled by the air, the continuous phase fluid is introduced into the microfluidic chip under the action of the external driving device, and the continuous phase fluid enters the connecting channel and the air plug channel to expel the air in the air plug channel, so that the captured dispersed phase fluid is wrapped by the continuous phase fluid, and the front and rear ends of the dispersed phase fluid in contact with the continuous phase fluid both form an arc shape convex outward, the front end of the dispersed phase fluid has a large curvature radius, and the rear end has a small curvature radius, and is suppressed in the capture area under the action of the Laplace pressure difference; The driving device is turned off, the flow rate of the continuous phase fluid is reduced, and the dispersed phase fluid flows out under the action of the Laplace pressure difference. When the dispersed phase fluid in the capture channel completely flows out to the growth channel and then stops, the external driving device is turned on to drive the continuous phase fluid to flow into the microfluidic chip, and the dispersed phase fluid in the growth channel is cut off at the cross-sectional angle to generate single or multiple droplets.

6. The microfluidic chip for generating droplets based on self-propulsion of dispersed phase fluid according to claim 2, characterized in that: Circular chamber diameter > growth channel width > capture channel width > regulation channel width > gas plug channel width.

7. The microfluidic chip for generating droplets based on self-propulsion of dispersed phase fluid according to claim 1, characterized in that: The microfluidic chip is a multi-channel droplet generation chip, which is used for multi-channel droplet generation, including: multiple droplet generation units, dispersed phase fluid outlets and continuous phase fluid outlets; each droplet generation unit is used to add different droplets respectively, the continuous phase fluid and droplets flow out of the microfluidic chip through the continuous phase fluid outlet, and the dispersed phase fluid that is not captured flows out through the dispersed phase fluid outlet.

8. A method for generating droplets using a microfluidic chip based on self-propulsion of dispersed phase fluid to generate droplets according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1, dispersed phase fluid capture; Inject dispersed phase fluid into the microfluidic chip from the injection port. When the dispersed phase fluid flows through the droplet generation unit, part of the dispersed phase fluid is retained in the capture area, and the remaining dispersed phase fluid flows out from the outlet. S2, dispersed phase fluid droplet generation; The continuous phase fluid is injected into the microfluidic chip from the injection port, and the continuous phase fluid flows through the droplet generation unit. The dispersed phase fluid captured in the capture area flows out of the capture area under the action of the Laplace pressure difference and enters the droplet generation area. The dispersed phase fluid breaks under the extrusion of the continuous phase fluid, generating single or multiple droplets and flowing to the sample outlet with the continuous phase.

Images