Micro-fluidic chip for capturing liquid drops based on gravity, method and application of micro-fluidic chip

Abstract

The invention provides a micro-fluidic chip for capturing liquid drops based on gravity, a method and application of the micro-fluidic chip. The chip comprises a micro-fluidic chip main body; the micro-channel is located in the micro-fluidic chip main body, two ends of the micro-channel are respectively communicated with the inlet or the outlet of the chip channel, and the inlet or the outlet of the chip channel is used for inflow and outflow of liquid drops; the liquid drop capturing unit is a circular trench unit which is distributed in the micro-channel in an array manner and is used for capturing liquid drops under the action of gravity; the micro-fluidic chip cover plate covers the micro-fluidic chip main body and is tightly attached to the micro-fluidic chip main body to form a closed micro-channel space. In this way, the continuous capturing state of the liquid drops can be maintained without continuously applying external force, high-flux continuous capturing and releasing of the liquid drops can be achieved, and large-scale related research and application of the liquid drops are facilitated.

Description

Technical Field

[0001] The present application relates to the field of microfluidic chip technology, and in particular to a microfluidic chip, method and application thereof for capturing droplets based on gravity. Background Art

[0002] Microfluidic chips, known as "labs on a chip," are the core platform of microfluidic technology and are widely used in numerous fields. They offer advantages such as low sample consumption, ease of operation, compact size, portability, and multifunctional integration. At the micro- and nanoscale, microfluidic chips can manipulate immiscible two-phase solutions to produce minute liquid units, or tiny droplets. They can also generate, split, merge, mix, and capture these droplets, bringing new research and application ideas to fields such as chemical synthesis, biological analysis, drug screening, and materials science.

[0003] In microfluidics, water-in-oil (W / O) and oil-in-water (O / W) droplets are important emulsification systems, playing a key role in industries such as food processing, cosmetics, and pharmaceutical research and development. However, the size distribution of traditionally prepared W / O and O / W droplets is wide and their stability is poor, which greatly limits the development and utilization of droplets. With the development of microfluidics and nanotechnology, related research and development and applications have made significant progress. Microfluidics can not only accurately prepare monodisperse droplets, but also develop emulsification systems with specific functions by adjusting the composition and structure of droplets. The effective capture and manipulation of droplets will help to further study the interfacial behavior of droplets, thereby improving the efficiency of developing stable W / O and O / W droplets.

[0004] Currently, droplet capture technology mainly relies on external force fields, such as electric fields, magnetic fields, or acoustic fields. These technologies achieve droplet capture by applying external energy, but there are many problems in practical applications: Complex and costly operations: Droplet manipulation techniques that rely on external force fields typically require sophisticated and expensive equipment and complex operating procedures. This not only increases experimental difficulty but also limits their application in rapid testing and on-site analysis, making them difficult to promote in resource-limited settings.

[0005] Poor biocompatibility and insufficient stability: Strong electric and magnetic fields can damage biological samples, such as causing cell membrane electroporation or protein denaturation, limiting the application of this technology in the biomedical field. Furthermore, the instability of the external force field can lead to poor reproducibility in the droplet manipulation process, affecting the accuracy and reliability of experimental results.

[0006] Droplets are easily deformed and difficult to capture continuously: When using an external force field to capture droplets, the droplets may be squeezed, and once the external force is removed, the captured droplets will quickly escape from the chip, making it impossible to continuously capture the droplets.

[0007] Therefore, there is an urgent need to develop a new droplet capture and manipulation technology that does not rely on external force fields. Summary of the Invention

[0008] In response to the problem that the current precise capture and manipulation of droplets mainly rely on external force fields, the present application provides a microfluidic chip, method and application based on gravity-based droplet capture, aiming to utilize the microstructure in the chip to achieve the capture, release and in situ observation of droplets in the chip.

[0009] According to a first aspect of the present application, a microfluidic chip for capturing droplets based on gravity is provided, comprising: Microfluidic chip body; A microchannel is located inside the microfluidic chip body, and both ends of the microchannel are connected to the chip flow channel inlet or outlet, respectively, and the chip flow channel inlet or outlet is used for the inflow and outflow of droplets; A droplet capture unit, wherein the droplet capture unit is a circular channel unit distributed in an array in the microfluidic channel and is used to capture droplets under the action of gravity; The microfluidic chip cover plate covers the microfluidic chip body and fits tightly with the microfluidic chip body to form a closed microchannel space.

[0010] Furthermore, the microchannel and the droplet capturing unit are hydrophilic or hydrophobic.

[0011] Furthermore, the material of the chip is selected from one or more combinations of the following categories: Polymer materials: including but not limited to polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polydimethylsiloxane-vinylsiloxane copolymer, polycarbonate (PC), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polypropylene (PP), polyimide (PI), thermoplastic polyurethane (TPU), cyclic olefin copolymer (COC), polystyrene (PS), polyetheretherketone (PEEK), or hydrogel; Inorganic materials: including but not limited to glass, metal, ceramics or their surface functionalized modified materials; Composite materials: including polymer-based nanocomposites, paper-based materials, 3D-printed materials, or metal-polymer laminate structures.

[0012] Furthermore, the microfluidic chip further includes a substrate, which is located at the bottom of the microfluidic chip and is used to support the entire chip.

[0013] Furthermore, the surface properties and structural size of the chip microfluidic channel and droplet capture unit can be customized according to the properties and size of the droplets. When the chip microfluidic channel and droplet capture unit are hydrophilic, they can capture oil-in-water droplets or multiple droplets with an outermost layer of aqueous solution. When the chip microchannels and droplet capture units are hydrophobic, it is possible to capture water-in-oil droplets or multiple droplets whose outermost layer is an organic solution.

[0014] Furthermore, the hydrophobicity of the chip can be obtained by hydrophobic modification, wherein the hydrophobic modification is that the molecular structure of the hydrophobic modifier contains a group that can chemically react with the surface of the substrate and a group that provides hydrophobic properties, and the hydrophobic modifier includes one or more treatments of a silane reagent and a fluorination reagent; Wherein, the silane includes one or more of fluorinated silane, long chain alkyl silane and functional silane; fluorinated silane is a C3~C 18 Silane; long chain alkyl silane is C 12 ~C 18 Alkyl chain silane; functionalized silane is silane containing active groups such as amino, epoxy, and mercapto groups; the fluorination agent includes one or more of fluorocarbon compounds, fluorinated polymers, and fluoride ions.

[0015] Furthermore, the method of making the chip hydrophilic includes one or more of plasma treatment, ultraviolet / ozone treatment, silane coupling agent treatment and physical coating of a hydrophilic layer; The gas used in the plasma treatment includes one or more of oxygen, argon and nitrogen, and the silane coupling agent used in the silane coupling agent treatment is trimethyl[3-(2-methoxy)propyl]silane; The reagent coated in the physical coating hydrophilic layer includes one or more of polyvinyl alcohol, polyethylene glycol, chitosan and polydopamine.

[0016] Furthermore, the microfluidic chip also has multi-scale capture capabilities, and its targets include: fluid substances, solid / semi-solid materials and other micro-nano functional units, among which fluid substances include water-in-oil, oil-in-water type single emulsion droplets and multiple emulsion droplets; solid / semi-solid materials include microgel particles, polymer microspheres, inorganic / organic nanoparticles; other micro-nano functional units other micro-nano functional units.

[0017] According to the second aspect of the present application, a droplet capture method is provided, which uses the above-mentioned microfluidic chip for gravity-based droplet capture, wherein the droplets are oil-in-water droplets, water-in-oil droplets or other multiple droplets that will sink under the action of gravity.

[0018] According to a third aspect of the present application, a droplet release method is provided, using the aforementioned microfluidic chip for gravity-based droplet capture to release captured droplets from a droplet capture unit. The droplets may be water-in-oil droplets, oil-in-water droplets, or other multiple droplets that sink under gravity.

[0019] According to a fourth aspect of the present application, a method for in-situ observation of droplets is provided, which uses the above-mentioned microfluidic chip based on gravity capture of droplets to perform in-situ observation of oil-in-water droplets or water-in-oil droplets.

[0020] According to the fifth aspect of the present application, an application of a microfluidic chip based on gravity-based droplet capture is provided, which is used in the research and development of droplets and microgels in fields including food, medicine, health products, basic scientific research, life sciences, as well as in the fields of droplet microreaction and microdetection.

[0021] Compared with the prior art, the present invention has the following advantages: The present disclosure utilizes the microstructure in a microfluidic chip to capture and release droplets in the chip. The operation is simple and can maintain the continuous capture state of droplets without the need for continuous application of external force. It can also easily achieve in-situ and precise observation of droplets.

[0022] When used in series with other microfluidic chips, precise dynamic observation of droplet generation, splitting, merging, and rupture can be achieved. It can be used for droplet research and development in life sciences or basic scientific research fields such as food, medicine, and health products, and can also be expanded to fields such as droplet micro-reaction and micro-detection.

[0023] At the same time, the structure and surface properties of the microfluidic channels and droplet capture units of the chip described in the present disclosure can also be customized according to the size and type of the captured object, thereby achieving the capture of droplets, gels, and microspheres of different properties and sizes. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The above and other features, advantages and aspects of the embodiments of the present application will become more apparent with reference to the following detailed description in conjunction with the accompanying drawings. The accompanying drawings are provided for a better understanding of the present invention and do not constitute a limitation of the present application. In the accompanying drawings, the same or similar reference numerals represent the same or similar elements, among which: Figure 1 A schematic diagram of the structure of a microfluidic chip for capturing droplets based on gravity according to an embodiment of the present application is shown; Figure 2 A flow chart showing a manufacturing scheme of a microfluidic chip for capturing droplets based on gravity according to an embodiment of the present application is shown; Figure 3 A schematic diagram of the capture result of water-in-oil droplets according to an embodiment of the present application is shown; Figure 4A schematic diagram of in-situ observation results after capture of water-in-oil droplets according to an embodiment of the present application is shown; Figure 5 A schematic diagram showing the capture results of oil-in-water droplets according to an embodiment of the present application is shown; Figure 6 A schematic diagram of in-situ observation results after capture of oil-in-water droplets according to an embodiment of the present application is shown; Among them, 1: substrate; 2: chip flow channel inlet or outlet; 3: droplet capture unit; 4: chip cover; 5: chip microchannel; 6: chip body. DETAILED DESCRIPTION

[0025] To make the purpose, technical solutions, and advantages of the embodiments of this application more clear, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the drawings in the embodiments of this application. Obviously, the described embodiments are part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0026] In this document, the term "and / or" simply describes a relationship between related objects, indicating that three possible relationships exist. For example, "A and / or B" can represent: A exists alone, A and B exist simultaneously, or B exists alone. Furthermore, the character " / " in this document generally indicates that the related objects are in an "or" relationship.

[0027] Example 1: This application proposes a microfluidic chip based on gravity capture of droplets, such as Figure 1 As shown, (A) is a schematic diagram of the 2D structure of the chip, (B) is a partial enlarged diagram of the 2D structure of the chip, (C) is a physical diagram of the chip, and (D) is a simulated diagram of the 3D structure of the chip; The microfluidic chip is composed of a chip flow channel inlet or outlet 2, a droplet capture unit 3, a chip cover 4, a microchannel 5 and a microfluidic chip body 6.

[0028] Among them, the flow channel outlets are distributed at both ends of the microchannel, forming the inlet or outlet of the chip ( Figure 1 (A), (C) and (D)), the droplet capture microstructure is a circular channel unit array distributed in the microfluidic channel ( Figure 1 (B) and (D)).

[0029] Preferably, the microfluidic chip further comprises a substrate 1 located at the bottom of the microfluidic chip 6 for supporting the entire chip.

[0030] Preferably, the material of the chip is: Polymer materials: including but not limited to polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polydimethylsiloxane-vinylsiloxane copolymer, polycarbonate (PC), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polypropylene (PP), polyimide (PI), thermoplastic polyurethane (TPU), cyclic olefin copolymer (COC), polystyrene (PS), polyetheretherketone (PEEK), or hydrogel; Inorganic materials: including but not limited to glass, metal, ceramics or their surface functionalized modified materials; Composite materials: including polymer-based nanocomposites (such as graphene / PDMS), paper-based materials (cellulose materials with hydrophobic treatment), 3D printing materials (photosensitive resins, bio-inks), or metal-polymer laminate structures; Other materials: Other materials with similar processing characteristics, chemical stability or biocompatibility as the above materials, suitable for the manufacture of microfluidic chips.

[0031] As a preferred embodiment, the micro-channel 5 and the droplet capturing unit 3 have hydrophobicity or hydrophilicity.

[0032] Example 2: This example provides a manufacturing solution for a microfluidic chip for capturing droplets based on gravity, as follows: like Figure 2 As shown in FIG, the manufacturing scheme of the microfluidic chip based on gravity-captured droplets includes three steps: soft lithography, chip molding and chip bonding.

[0033] (1) Soft lithography Take a wafer and place it on a spin coater. Pour an appropriate amount of photoresist onto the wafer and run the spin coater according to the set parameters to evenly spin-coat the photoresist onto the wafer surface. After spin coating, transfer the wafer to a hot plate and perform a soft bake (bake the wafer at 95°C in the dark for 5-10 minutes) until the photoresist on the wafer is cured. After the soft bake, transfer the wafer to a photolithography machine and run the photolithography process to etch the chip flow path into the photoresist. After the photolithography process is completed, transfer the wafer to a hot plate and bake the wafer at 95°C in the dark for 5-10 minutes to harden the wafer. After hardening, spin-coat the wafer again with photoresist and perform the soft bake and photolithography process again to etch the microdroplet capture unit into the chip flow path. After the etching process is completed, transfer the wafer to the hot plate again and perform the hardening process. After the hardening film is completed, the photoresist on the wafer is rinsed with a developer to remove excess photoresist, exposing the chip flow channel and droplet capture unit. The wafer is then transferred to a heating table for hard baking (bake the wafer at 95°C in the dark for 5-10 minutes) to obtain a chip template.

[0034] (2) Chip forming According to the introduction of the first embodiment, there are many options for chip materials. According to the different materials selected, an appropriate chip forming process needs to be adopted. Specifically, a. Polymer materials (such as PDMS, PMMA, COC, etc.) Place the engraved chip template in a petri dish. If using PDMS, mix the PDMS and curing agent in a 10:1 mass ratio, then pour the mixture into the petri dish, allowing the PDMS to spread evenly over the chip template. Then, place the petri dish in a vacuum chamber to remove air bubbles. After degassing, place the petri dish in an oven and heat at 65°C until the PDMS is completely hardened. Cut the hardened PDMS from the chip to obtain the main PDMS droplet capture chip template. If using thermoplastic materials (such as PMMA or COC), use an injection molding process, injecting the molten material into the template and then cooling and demolding.

[0035] b. Inorganic materials (such as glass) Using wet etching or laser micromachining technology, microchannels and droplet capture units are directly etched on the material surface according to the template structure.

[0036] c. Composite materials (such as 3D printing materials) 3D printing materials (such as photosensitive resins) can directly build chip structures layer by layer through photocuring 3D printing technology.

[0037] (3) Chip bonding If using PDMS, take a piece of PDMS cover plate of appropriate size without any texture ( Figure 1 In (C), the control is in the droplet capture chip body ( Figure 1 (C)) two flow channels ( Figure 1 A hole is opened at (C) in the center. Then, they and the substrate are placed in an oxygen plasma cleaner. After running the plasma cleaning program, the PDMS cover and the chip body are bonded together, and then bonded together to the substrate to obtain a complete droplet capture chip.

[0038] According to the embodiments of the present application, the following beneficial effects are achieved: (1) The soft lithography process can accurately carve chip flow channels and micro-droplet capture units on the photoresist through multiple steps such as spin coating, photolithography, and baking, ensuring the fineness and accuracy of the microstructure, laying the foundation for subsequent stable droplet capture. For example, the precise microstructure size can be customized according to different droplet sizes to improve capture efficiency.

[0039] (2) During the casting process of the PDMS chip template, the ratio of PDMS to curing agent, vacuum degassing and heating hardening conditions are strictly controlled so that the PDMS can evenly cover the chip template and form a high-quality chip main body template, reducing internal bubbles and defects and improving the physical properties and service life of the chip.

[0040] Example 3: This example provides a hydrophobic or hydrophilic modification scheme for a microfluidic chip for gravity-based droplet capture, as follows: (1) Chip hydrophobic modification scheme The complete droplet capture chip obtained in Example 2 was placed in a plasma cleaner and cleaned. After the cleaning process was complete, a hydrophobic modifier was injected into the chip's microchannels. After a period of reaction, the excess hydrophobic modifier was flushed away. This resulted in a highly hydrophobic droplet capture chip suitable for capturing water-in-oil droplets.

[0041] The hydrophobic modifier includes one or more of a silane agent and a fluorination agent.

[0042] Furthermore, the silane includes one or more of fluorinated silane, long-chain alkyl silane and functionalized silane.

[0043] Furthermore, the fluorinated silane is a C3~C 18 silane (such as tridecafluorooctyl triethoxysilane); fluorinated silane is a C3~C 18 silanes (such as tridecafluorooctyltriethoxysilane); long-chain alkyl silanes are C-containing 12 ~C 18 Alkyl chain silanes (such as octadecyltrimethoxysilane); functionalized silanes are silanes containing active groups such as amino, epoxy, and mercapto groups (such as aminopropyltriethoxysilane).

[0044] Furthermore, the fluorination agent includes one or more of fluorocarbon compounds, fluorinated polymers and fluoride ion liquids.

[0045] (2) Chip hydrophilic modification scheme Plasma treatment: Place the bonded droplet capture chip of Example 2 into a plasma cleaning machine, introduce gas (one or more of oxygen, argon or nitrogen), run the plasma cleaning program, and then inject water into the chip flow channel to make the droplet capture chip hydrophilic, which can be used to capture water-in-oil droplets.

[0046] UV / ozone treatment: Place the droplet capture chip bonded in Example 2 into the sample chamber of the UV / ozone device. After running the device program, inject water into the chip flow channel to make the droplet capture chip hydrophilic and can be used to capture oil-in-water droplets.

[0047] Silane coupling agent treatment: The silane coupling agent trimethyl[3-(2-methoxy)propyl]silane is injected into the chip flow channel treated with oxygen plasma. After a period of reaction in the dark, the droplet capture chip becomes hydrophilic and can be used to capture oil-in-water droplets.

[0048] Physically coating the hydrophilic layer: The bonded droplet capture chip from Example 2 is placed in a plasma cleaner. Gas (one or more of oxygen, argon, or nitrogen) is introduced. After a plasma cleaning process, a hydrophilic solution is injected into the chip's flow channels. After a period of time, the excess hydrophilic solution in the flow channels is flushed away, rendering the droplet capture chip hydrophilic and suitable for capturing oil-in-water droplets. The reagents used in the physical hydrophilic coating include one or more of PVA (polyvinyl alcohol), PEG (polyethylene glycol), chitosan, and polydopamine.

[0049] According to the embodiments of the present application, the following beneficial effects are achieved: By modifying the chip hydrophobicly or hydrophilically, the chip surface properties can be flexibly adjusted based on the type of droplet being captured (water-in-oil or oil-in-water droplets). Hydrophobic modification makes the chip suitable for capturing water-in-oil droplets, while hydrophilic modification is suitable for capturing oil-in-water droplets, significantly expanding the chip's application range. Furthermore, stable hydrophobic or hydrophilic modification ensures that chip performance remains unaffected during multiple capture and release processes, improving experimental reproducibility and reliability.

[0050] Example 4: Figure 3 As shown, this embodiment provides an implementation scheme of a droplet capture microfluidic chip for capturing / releasing water-in-oil droplets, as follows: (1) Preparation and capture of water-in-oil droplets By dissolving an emulsifier in oil as the continuous phase and using a saturated calcium chloride solution as the dispersed phase, W / O droplets of appropriate particle size are prepared on a droplet generation microfluidic chip. The droplets are then transported from any port of the droplet capture microfluidic chip into the chip through a pipeline. When the droplets flow through the microfluidic channel unit, they will fall into the droplet capture microstructure under the action of gravity, thus achieving capture of the droplets.

[0051] (2) Water-in-oil droplet release scheme The chip is inverted, with the droplet-capturing microstructure positioned above the flow channel. Due to gravity, the captured droplets fall from the microstructure and are distributed throughout the chip's flow channels. Flushing the flow channels with a solution can then release the captured droplets. Furthermore, after flushing the flow channels with a detergent and drying any remaining moisture within the chip, the chip can be reused.

[0052] (3) Experimental results like Figure 3As shown in (A), when no droplets are captured, the droplet capture units are neatly arranged in the chip flow channel. When a droplet is captured, it falls into the droplet capture unit ( Figure 3 (B) in the figure). After the droplet is released, the chip microstructure no longer contains the droplet ( Figure 3 (C) in the figure). Compare Figure 3 From (A) and (B) in the figure and Table 1 below (data of water-in-oil droplet capture, and all data are expressed as mean value and standard deviation), we can see that the chip successfully captured droplets, with a droplet capture rate of up to 75%. Figure 2 From (B) and (C) in Figure 1 (water-in-oil droplet capture data), it can be seen that the droplets captured in the chip were successfully released, and the droplet release rate was 100%.

[0053] Table 1

[0054] In summary, according to this embodiment, the microfluidic chip successfully achieves the capture and release of water-in-oil droplets, and after the droplets are released, the chip can be reused.

[0055] Example 5: This example provides a specific solution for the application of a microfluidic chip based on droplet capture in in-situ observation of water-in-oil droplets, as follows: in, Figure 4 (A) in the middle: the state of the captured droplet at 0 min; Figure 4 (B) The state of the captured droplet at 20 min; Figure 4 (C) The state of the captured droplet at 40 min; Figure 4 (D) The state of the captured droplet at 60 min; Figure 4 (E) The state of the captured droplet at 80 min; Figure 4 (F) The captured droplet shape at 100 min; Figure 4 (G) Changes in the number of captured droplets from 0 to 100 min; Figure 4 (H) Particle size change of captured droplets from 0 to 100 min.

[0056] (1) Preparation, capture and in situ observation of water-in-oil droplets Due to gravity or material factors, droplets often shift, deform, or rupture when observed using substrates or plastic well plates, affecting the observation results and making it difficult to accurately observe the droplets in situ. However, the droplet capture chip of the present invention, because PDMS is an inert material, avoids direct reaction with the droplets. Furthermore, the arrayed microstructures within the chip prevent droplet displacement, enabling in situ observation of the droplets.

[0057] Based on this, this experiment will prepare droplets in the manner of Example 4. After capturing the droplets, the state of the droplets in the same field of view at different time periods will be photographed at a fixed position under a microscope, and the number of droplets captured and the change in particle size in the field of view will be analyzed.

[0058] (2) Experimental results like Figure 4 As shown in (A)-(F) in the figure, the droplets captured in the same field of view are stable in the chip capture unit from 0 to 100 minutes. The number of droplet captures did not change significantly from 0 to 100 minutes ( Figure 4 (G) and Table 2 below (in situ observation results after capture of water-in-oil droplets), the particle size of the captured droplets did not change significantly within 0-100 min ( Figure 4 (H) and Table 2 below).

[0059] Table 2

[0060] Note: ns: compared with the 0 min group, p>0.05, all data are expressed as mean standard deviation.

[0061] Furthermore, the oil includes corn oil, olive oil, soybean oil, peanut oil, rapeseed oil, sunflower oil, linseed oil, grape seed oil, sesame oil, salad oil, blended oil, fish oil, algae oil and white oil, and can be one or more of them.

[0062] Furthermore, the emulsifier includes, but is not limited to, one or more of soy lecithin, Span20, Span40, Span60, Span80, Span85, monoglycerol fatty acid glyceride, diglycerol fatty acid glyceride, citric acid fatty acid glyceride, lactic acid glycerol fatty acid glyceride, polyglycerol ricinoleate (PGPR), sucrose fatty acid ester, xylitol monostearate, polyglycerol fatty acid ester, polyoxyethylene lauryl ether, polyoxyethylene stearyl ether, polyoxyethylene stearate, polyoxyethylene stearamide and polyoxyethylene stearic acid glyceride.

[0063] In summary, the chip provided by the present invention successfully achieves the capture and in-situ observation of water-in-oil droplets.

[0064] Example 6: This example provides an implementation scheme for a droplet capture chip to capture / release oil-in-water droplets, as follows: like Figure 5 As shown, Figure 5 (A) in the middle: Micrograph of the chip when unloaded; Figure 5 (B): Micrograph of the chip after capturing the droplet. Figure 5 Middle (C): Micrograph of the chip after droplet release.

[0065] (1) Preparation and capture of oil-in-water droplets Polyvinyl alcohol was dissolved in water to form a 2% (W / V) solution, which served as the continuous phase. Polycaprolactone was dissolved in dimethyl carbonate to form a 3% (W / V) solution, which served as the dispersed phase. O / W droplets of appropriate particle size were prepared on a droplet generation microfluidic chip. These droplets were then piped into the chip from any port of a hydrophilic-modified droplet capture microfluidic chip. As the droplets flowed through the microfluidic channel unit, they fell into the droplet capture microstructure under the action of gravity, achieving capture.

[0066] (2) Oil-in-water droplet release scheme The chip is inverted, with the droplet-capturing microstructure positioned above the flow channel. Due to gravity, the captured droplets fall from the microstructure and are distributed throughout the chip's flow channels. Flushing the flow channels with aqueous solution flushes the captured droplets out of the chip, releasing them. Furthermore, rinsing the flow channels with pure water allows the chip to be reused.

[0067] (3) Experimental results like Figure 5 As shown in (A), when no droplets are captured, the droplet capture units are neatly arranged in the chip flow channel, and there is no foreign matter in the channel. When a droplet is captured, the droplet falls into the droplet capture unit ( Figure 5 (B) in the figure). After the droplet is released, the chip microstructure no longer contains the droplet ( Figure 5 (C) in the figure). Compare Figure 5 From (A) and (B) in the figure and Table 3 below (Oil-in-water droplet capture data), we can see that the chip successfully captured OIL droplets, with a droplet capture rate of 91.7%. Figure 5 As shown in (B) and (C) and Table 3 below, the droplets captured in the chip were successfully released, with a droplet release rate of 100%.

[0068] Table 3

[0069] Note: All data are expressed as mean ± standard deviation.

[0070] Furthermore, the oil phase used in the oil-in-water droplets includes dimethyl carbonate, dichloromethane, ethyl acetate, etc., which can be one or more of them.

[0071] Furthermore, the emulsifier used in the oil-in-water droplets includes polyvinyl alcohol, Tween 80, Tween 20, sodium dodecylbenzenesulfonate, etc., which can be one or more of them.

[0072] Furthermore, the oil phase solute used in the oil-in-water droplets includes polycaprolactone, polylactic acid, polylactic acid-glycolic acid copolymer, etc., and can be one or more of them.

[0073] In summary, the chip provided by the present invention successfully captures and releases oil-in-water droplets, and the chip can be reused after the droplets are released.

[0074] Example 7: Figure 6 As shown, this embodiment provides an application of a microfluidic chip based on droplet capture in in-situ observation of oil-in-water droplets, as follows: like Figure 6 , Figure 6 (A) in the middle: the state of the captured droplet at 0 min; Figure 6 (B) in the middle: the state of the captured droplet at 2 min; Figure 6 (C) in the middle: Change in particle size of the captured droplets from 0 to 2 minutes.

[0075] Polymer microspheres are a general term for a class of polymer material systems, which are widely used in the medical beauty industry. The main way to prepare polymer microspheres is to use emulsification technology using a single solvent evaporation system, that is, to dissolve the starting materials in a volatile solvent, and then disperse them in another solvent that is immiscible with the previous solvent to form water-in-oil droplets. Polymer microspheres can be obtained by evaporating the dispersed phase solvent of the droplets. However, since the size of the droplets and microspheres changes greatly after the solvent evaporates, this poses a challenge to the industrial production of microspheres of a specified particle size. To this end, this embodiment provides an application based on a droplet capture chip in the in-situ observation of water-in-oil droplets, which will help to obtain information on the size changes of the microspheres. The specific experimental plan is as follows: (1) Preparation, capture, and in situ observation of oil-in-water droplets Polyvinyl alcohol was dissolved in water to form a 2% (W / V) solution, which was used as the continuous phase. A polymer was dissolved in a dimethyl carbonate solution to form a 3% (W / V) solution, which was used as the dispersed phase. O / W droplets of appropriate particle size were prepared on a droplet generation microfluidic chip. The droplets were then transported into the chip through a pipeline from any port of a droplet capture microfluidic chip (hydrophilic modification). As the droplets flowed through the microfluidic channel unit, they fell into the droplet capture microstructure under the action of gravity, achieving capture of the droplets. As the observation time increased, the dimethyl carbonate in the droplets gradually evaporated, and the droplets eventually transformed into polymer microspheres.

[0076] After the droplets are captured, the state of the droplets in the same field of view at different time periods is photographed at a fixed position under a microscope, and the change information of the droplet particle size in the field of view is analyzed.

[0077] (2) Experimental results like Figure 6 As shown in (A), the polymer oil-in-water droplets are captured by the chip, with an average of 3 droplets captured in each channel, and the droplets are colorless. Figure 6 As shown in (B), when dimethyl carbonate evaporates, polymer microspheres are formed and appear black. This phenomenon shows that the droplet capture chip successfully records the entire process of the transformation of polymer microspheres from droplets to microspheres ( Figure 6 (A) and (B) in the figure).

[0078] Further analysis of the particle size shows that ( Figure 6 (C) in the figure and Table 4 below (in situ observation results after capture of oil-in-water droplets), the average particle size of the polymer microspheres in the oil-in-water droplet state is 35.6, the particle size after forming microspheres is 16.2, and the shrinkage rate is 54.53%, that is, compared with the oil-in-water droplets, the particle size of the polymer microspheres is significantly reduced.

[0079] Table 4

[0080] Note: ns: compared with the 0 min group, p>0.05; compared with the 0 min group, p<0.001, all data are expressed as mean ± standard deviation.

[0081] Furthermore, the polymer includes polycaprolactone, polylactic acid, polylactic acid-glycolic acid copolymer, etc., and can be one or more of them.

[0082] In summary, the chip provided by the present invention successfully achieved the capture of oil-in-water droplets and in-situ observation of polymer microspheres, and successfully obtained the shrinkage rate information of droplets to microspheres, which will provide data support for the industrial production of microspheres of specified particle sizes.

[0083] According to the above embodiments, the present disclosure achieves the following technical effects: 1. The present invention has a patterned microstructure chip design with a simple structural design. The microstructure size within the chip can be arbitrarily adjusted to achieve the capture of droplets of any size; 2. The present invention can achieve high-throughput continuous capture and release of droplets based on a patterned droplet capture array; 3. The present invention is based on patterned microstructure chip design, and the microstructure can be adjusted individually, which reduces the difficulty of chip design and facilitates personalized large-scale production.

[0084] In the technical solution of this application, the acquisition, storage and application of user personal information involved are in compliance with the provisions of relevant laws and regulations and do not violate public order and good morals.

[0085] It should be understood that the various forms of the processes shown above can be used to reorder, add, or delete steps. For example, the steps described in this application can be performed in parallel, sequentially, or in a different order, as long as the desired results of the technical solutions disclosed in this application can be achieved. This is not a limitation herein.

[0086] The above specific embodiments do not constitute a limitation on the scope of protection of this application. Those skilled in the art will appreciate that various modifications, combinations, sub-combinations, and substitutions may be made based on design requirements and other factors. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application shall be included within the scope of protection of this application.

Claims

1. A microfluidic chip for capturing droplets based on gravity, characterized in that: The microfluidic chip comprises: Microfluidic chip body (6); A microchannel (5) is located inside the microfluidic chip body (6), and both ends of the microchannel (5) are respectively connected to the chip flow channel inlet or outlet (2), and the chip flow channel inlet or outlet (2) is used for the inflow and outflow of droplets; A droplet capturing unit (3), wherein the droplet capturing unit (3) is a circular channel unit distributed in an array in the microchannel (5), and is used to capture droplets under the action of gravity; A microfluidic chip cover plate (4) is covered on the microfluidic chip body (6) and is tightly fitted with the microfluidic chip body (6), together forming a closed microchannel space.

2. The microfluidic chip for capturing droplets based on gravity according to claim 1, characterized in that: The microchannel (5) and the droplet capturing unit (3) are hydrophilic or hydrophobic.

3. The microfluidic chip for capturing droplets based on gravity according to claim 1, characterized in that: The material of the chip is selected from one or more combinations of the following categories: Polymer materials: including but not limited to polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polydimethylsiloxane-vinylsiloxane copolymer, polycarbonate (PC), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polypropylene (PP), polyimide (PI), thermoplastic polyurethane (TPU), cyclic olefin copolymer (COC), polystyrene (PS), polyetheretherketone (PEEK), or hydrogel; Inorganic materials: including but not limited to glass, metal, ceramics or their surface functionalized modified materials; Composite materials: including polymer-based nanocomposites, paper-based materials, 3D-printed materials, or metal-polymer laminate structures.

4. The microfluidic chip for capturing droplets based on gravity according to claim 1, characterized in that: The microfluidic chip further includes a substrate located at the bottom of the microfluidic chip for supporting the entire chip.

5. The microfluidic chip for capturing droplets based on gravity according to claim 1, characterized in that: The surface properties and structural size of the chip microfluidic channel and droplet capture unit can be customized according to the properties and size of the droplets. When the chip microfluidic channel and droplet capture unit are hydrophilic, they can capture oil-in-water droplets or multiple droplets with an outermost layer of aqueous solution. When the chip microchannels and droplet capture units are hydrophobic, it is possible to capture water-in-oil droplets or multiple droplets whose outermost layer is an organic solution.

6. The microfluidic chip for capturing droplets based on gravity according to claim 5, characterized in that: The hydrophobicity of the chip can be obtained by hydrophobic modification, wherein the hydrophobic modification is that the molecular structure of the hydrophobic modifier contains a group that can chemically react with the surface of the substrate and a group that provides hydrophobic properties, and the hydrophobic modifier is processed by one or more silane reagents and fluorination reagents; Wherein, the silane includes one or more of fluorinated silane, long chain alkyl silane and functional silane; fluorinated silane is a C3~C 18 Silane; long chain alkyl silane is C 12 ~C 18 Alkyl chain silane; functionalized silane is silane containing active groups such as amino, epoxy, and mercapto groups; the fluorination agent includes one or more of fluorocarbon compounds, fluorinated polymers, and fluoride ions.

7. The microfluidic chip for capturing droplets based on gravity according to claim 5, characterized in that: Methods for making the chip hydrophilic include one or more of plasma treatment, ultraviolet / ozone treatment, silane coupling agent treatment, and physical coating of a hydrophilic layer; The gas used in the plasma treatment includes one or more of oxygen, argon and nitrogen, and the silane coupling agent used in the silane coupling agent treatment is trimethyl[3-(2-methoxy)propyl]silane; The reagent coated in the physical coating hydrophilic layer includes one or more of polyvinyl alcohol, polyethylene glycol, chitosan and polydopamine.

8. The microfluidic chip for capturing droplets based on gravity according to claim 7, characterized in that: The microfluidic chip also has multi-scale capture capabilities, and its targets include: fluid substances, solid / semi-solid materials and other micro-nano functional units, among which fluid substances include water-in-oil, oil-in-water type single emulsion droplets and multiple emulsion droplets; solid / semi-solid materials include microgel particles, polymer microspheres, inorganic / organic nanoparticles; other micro-nano functional units and other micro-nano functional units.

9. A droplet capture method, characterized in that: A microfluidic chip for capturing droplets based on gravity as described in any one of claims 1 to 8 is used, wherein the droplets are water-in-oil droplets, oil-in-water droplets, or other multiple droplets that sink under the action of gravity.

10. A droplet release method, characterized in that: A microfluidic chip for capturing droplets based on gravity as described in any one of claims 1 to 8 is used, wherein the droplets are water-in-oil droplets, oil-in-water droplets, or other multiple droplets that sink under the action of gravity.

11. A method for in-situ observation of droplets, characterized in that: The microfluidic chip for capturing droplets based on gravity as described in any one of claims 1 to 8 is used to perform in situ observation of water-in-oil droplets or oil-in-water droplets.

12. Application of a microfluidic chip for capturing droplets based on gravity, characterized in that: It is used in the research and development of droplets and microgels in fields including food, medicine, health products, basic scientific research, life sciences, as well as in the fields of droplet microreaction and microdetection.

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