Micro-fluidic chip, manufacturing method therefor, and method for generating micro-droplets

Abstract

A micro-fluidic chip, a manufacturing method therefor, and a method for generating micro-droplets (8). The micro-fluidic chip comprises a flexible cover plate (6) and a substrate (7). A bonding passivation area (5) is provided on the flexible cover plate (6) and / or the substrate (7). The flexible cover plate (6) and the substrate (7) are connected by bonding. The bonding passivation area (5) forms a liquid channel (3). The method for manufacturing the micro-fluidic chip comprises: forming the bonding passivation area (5) on the flexible cover plate (6) and / or the substrate (7); and connecting the substrate (7) and the flexible cover plate (6) by bonding, such that the liquid channel (3) is formed at the bonding passivation area (5). The method for generating micro-droplets (8) comprises: a liquid passes through the liquid channel (3), and the flexible cover plate (6) generates an oscillation force on micro-droplets (8) at an outlet of the liquid channel (3), so as to form micro-droplets (8) with a micron-scale diameter. The liquid reaching the outlet forms micro-droplets (8) under interfacial tension. The flexible cover plate (6) oscillates, and the micro-droplets (8) are affected by the oscillation force generated by the flexible cover plate (6), so that the generation of the micro-droplets (8) can be accelerated, and the micro-droplets (8) with uniform and satisfactory diameters can be generated.

Description

Microfluidic chip, manufacturing method and microdroplet generation method

[0001] Citation of Related Applications

[0002] This application claims priority to Chinese patent application CN2023112038066 filed on September 18, 2023, and the contents of the above patent application are incorporated into this application in their entirety by reference and for all purposes. Technical Field

[0003] The present application belongs to the field of droplet microfluidics technology, and in particular relates to a microfluidic chip, a manufacturing method, and a microdroplet generation method. Background Art

[0004] Droplet microfluidics technology is widely used in single-cell sequencing, single-cell secretion research, digital PCCP30298SWU, and single-molecule detection due to its unique advantages, including sensitive response, precise control, simple equipment, low reagent consumption, and effective two-phase interface to prevent cross-contamination of reactants. As the most fundamental unit of droplet microfluidics, uniformity and high-throughput production of droplets are prerequisites for its commercialization. Compared with active droplet generation methods such as electricity, magnetism, centrifugation, light, heat, and mechanical force, passive droplet generation does not require the addition of an additional field and relies solely on the inherent properties of the fluid. The generation mechanism is essentially a competitive balance between capillary, viscous, and inertial forces.

[0005] Passive droplet generation structures mainly include T-shaped channels, coaxial flow, and flow focusing. The T-shaped channel has a slow droplet generation speed, coaxial flow has difficulty generating small droplets, and flow focusing requires two-way injection, especially when generating small droplets, which requires human intervention. Small droplets are difficult to achieve parallelization within the channel. In other words, even if multiple branch pipes are set up on a main pipe, and a main pipe is connected to multiple branch pipes in parallel, each branch pipe is equivalent to a branch channel, but it is difficult for multiple branch pipes to evenly divide the droplets, and multiple branch pipes are difficult to run in parallel, resulting in low flux.

[0006] In addition, in these mainstream structure droplet generation, the size and uniformity of the droplets are heavily dependent on the flow rate of the fluid. Slight fluctuations in the flow rate will result in the generation of polydisperse droplets, and the dead volume in the entire droplet generation process will inevitably lead to sample waste. That is, when the liquid channel is in the initial debugging process or the end process of generating liquid, no qualified micro-droplets can be generated. The diameter size of the micro-droplets generated in the above stage is unqualified and cannot be used. When using a T-channel structure to generate micro-droplets, air pressure or a flow pump is generally used to push the liquid into the liquid channel, and the micro-droplets are generated by the shearing effect of the oil on the water at the outlet of the liquid channel. When the liquid pressed into the liquid channel by air pressure is about to be squeezed out, the speed at which the liquid in the liquid channel is pushed becomes faster and faster. During the debugging process and the end process of generating micro-droplets from the sample liquid, the diameter size of the generated micro-droplets will be unstable, resulting in inability to use.

[0007] The interfacial tension-driven stepped droplet generation structure perfectly avoids these shortcomings, generating uniformly sized droplets solely through variations in channel wall constraints. However, the diameter of the droplets produced by conventional stepped droplet generation structures is often only slightly smaller than the liquid channel size, and especially at high throughput, the droplet size can be several times larger than the channel.

[0008] Existing oscillation methods all rely on external vibrating structures to achieve oscillation and generate droplets. The generation of microdroplets in the liquid channel requires that the frequency of the external vibrating structure matches the generation frequency of the microdroplets. During the debugging process at the beginning and end of the microdroplet generation, the size of the generated microdroplets is unqualified.

[0009] Traditional droplet generation channels are primarily formed by creating grooves in a substrate. The resulting grooves have micron-scale thickness and width. After the substrate and a cover plate are stacked and connected, the resulting liquid channel has micron-scale height and width. This micron-scale liquid channel can only produce microdroplets using traditional droplet generation methods, and the diameter of the resulting microdroplets is the same as the liquid channel size, only slightly smaller than the channel size. This prevents the generation of uniform microdroplets much smaller than the channel size, and results in a low throughput. Furthermore, existing methods for creating liquid channels by creating grooves in substrates are costly and difficult to manufacture. Furthermore, fabricating nanoscale grooves is nearly impossible and extremely costly.

[0010] Summary of the Invention

[0011] In view of the shortcomings of the existing technology, the purpose of this application is to provide a microfluidic chip that at least solves one of the above technical problems.

[0012] To achieve this goal, this application adopts the following technical solutions:

[0013] A microfluidic chip comprises a flexible cover plate and a substrate. A bonding passivation area is provided on the flexible cover plate and / or the substrate. The flexible cover plate and the substrate are bonded to each other, and the bonding passivation area forms a liquid channel.

[0014] Optionally, the bonding surface between the flexible cover and the substrate is a plane.

[0015] Optionally, the bonding passivation area is a passivation coating with a thickness of nanometer level or molecular level provided on the flexible cover plate and / or the substrate.

[0016] Optionally, the passivation coating is processed by using any one of SU8 photoresist technology, vapor deposition technology or sputtering technology.

[0017] Optionally, the cross-sectional shape of the liquid channel includes at least one of a regular quadrilateral, a U-shape, a circle or an ellipse.

[0018] Optionally, the cross section of the liquid channel is rectangular, and the dimension of the liquid channel along the width direction is not greater than 250 μm. If the dimension is greater than this, non-uniform small droplets may be generated.

[0019] Optionally, the flexible cover plate is made of any one of polydimethylsiloxane and silicone plate.

[0020] Optionally, a liquid injection component is further included, which is connected to the liquid channel and can inject liquid into the liquid channel.

[0021] Optionally, the liquid injection assembly is arranged on the flexible cover and / or the substrate.

[0022] Optionally, the liquid injection assembly includes a fluid inlet opened on the flexible cover or the substrate, and the fluid inlet is connected to the liquid channel.

[0023] Optionally, an alignment pool is provided between the fluid inlet and the liquid channel, and a cross-sectional area of ​​the alignment pool where it connects to the liquid channel is larger than a maximum cross-sectional area of ​​the fluid inlet.

[0024] Optionally, the alignment pool is any one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity.

[0025] Optionally, there is at least one liquid channel.

[0026] Optionally, at least two of the liquid channels are arranged in parallel or distributed radially.

[0027] Optionally, the device further comprises a droplet collecting assembly disposed at the outlet of the liquid channel, wherein the droplet collecting assembly is used to collect micro-droplets generated by the liquid channel.

[0028] Optionally, the droplet collecting assembly includes a hydrophobic modified oil pool connected to the external atmosphere, and the hydrophobic modified oil pool is connected to the outlet of the liquid channel.

[0029] Optionally, the hydrophobically modified oil pool is opened on the flexible cover plate and / or the substrate.

[0030] Optionally, the hydrophobic modified oil pool is opened on the flexible cover plate, and the bottom surface or the top surface of the hydrophobic modified oil pool is flush with the surface of the substrate at the micro-droplet outlet.

[0031] Optionally, the inner surface of the hydrophobically modified oil pool is coated with a nano-hydrophobic coating.

[0032] Optionally, the wall thickness of the hydrophobically modified oil pool ranges from 200 μm to 10 cm.

[0033] Optionally, the hydrophobically modified oil pool is any one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity.

[0034] Another object of the present application is to provide a method for manufacturing a microfluidic chip to at least solve one of the above technical problems.

[0035] To achieve this goal, this application adopts the following technical solutions:

[0036] A method for manufacturing a microfluidic chip, comprising:

[0037] Processing bonding passivation areas on the flexible cover and / or substrate;

[0038] The substrate is bonded to the flexible cover, and the liquid channel is formed at the bonding passivation area.

[0039] Optionally include:

[0040] The flexible cover and the substrate are connected by chemical bonding or physical bonding.

[0041] Optionally, SUS8 photoresist technology is used on the smooth flexible cover and / or the substrate as a base, and a layer of SUS8 photoresist with a height of nanometers is photoetched on the base using soft lithography technology to form a bonding passivation area with a thickness of nanometers.

[0042] Optionally, by using vapor deposition technology, the bonding passivation area to be prepared is exposed on the flexible cover and / or the substrate, and a mask is set at other positions, and the substrate is placed in a confined space. Alkyl chloride is introduced into the confined space, and the alkanol chloride evaporates to cover the area not covered by the mask to form the bonding passivation area with a thickness of the molecular level.

[0043] Optionally, using sputtering technology, the flexible cover and / or the substrate where the bonding passivation area needs to be prepared is covered with a mask and bombarded with oxygen ions to mask out the unbombarded areas to form a bonding passivation area with a thickness of molecular level.

[0044] Another object of the present application is to provide a method for generating micro-droplets to at least solve one of the above-mentioned technical problems.

[0045] To achieve this goal, this application adopts the following technical solutions:

[0046] A method for generating microdroplets, using the microfluidic chip, comprising:

[0047] When the liquid passes through the liquid channel, the flexible cover plate generates an oscillating force on the micro-droplets at the outlet of the liquid channel to form micro-droplets with a diameter of micrometer level.

[0048] Compared with the prior art, the present application has the following beneficial effects: the bonding passivation area on the flexible cover plate and / or the substrate forms a liquid channel, the liquid channel is formed by the bonding passivation area that is not bonded, the size of the liquid channel along the height direction is close to zero, when the liquid passes through the liquid channel, the liquid channel is squeezed and expanded, the liquid enters the liquid channel into a flat structure, and produces extrusion deformation on the flexible cover plate in the liquid channel, when the liquid reaches the outlet to form micro-droplets, the flexible cover plate produces fluctuations, and generates an oscillating force on the liquid at the outlet, and the oscillating force acts as a shear force on the liquid at the outlet, causing the liquid to break and form micro-droplets. At the same time, the micro-droplets are affected by the oscillating force generated by the flexible cover plate, which can accelerate the generation of micro-droplets and produce micro-droplets with uniform diameter and qualified size.

[0049] When the width of the liquid channel is within a certain range, the flow rate of the liquid entering the liquid channel varies. Because the interfacial tension of the flexible cover or substrate dominates the generation of microdroplets, and the generation of microdroplets is achieved by the vibration and shearing effect of the flexible cover on the liquid, changes in the liquid pressure within the liquid channel have little effect on the size change of the diameter of the microdroplets. In this embodiment, microdroplets can be generated without relying on an external vibrating structure. When the flow rate within the liquid channel changes, the diameter of the generated microdroplets is essentially unaffected. Therefore, the diameter of the microdroplets remains essentially unchanged during the initial commissioning process and at the end of the microdroplet generation process, and microdroplets of a qualified diameter size can still be generated, thereby fully utilizing the sample, especially for small and rare samples.

[0050] This microfluidic chip can further break through the minimum size limit of microdroplet generation based on traditional step-by-step droplet generation and realize the generation of small-sized microdroplets.

[0051] Because the microfluidic chip generates microdroplets, the liquid in the liquid channel squeezes the flexible cover, and the flexible cover adaptively generates an oscillating force on the liquid at the liquid channel outlet to shear the liquid at the outlet to form microdroplets. Therefore, high-throughput microdroplet generation can be achieved, thereby reducing the commercial cost of microdroplet microfluidic applications.

[0052] Compared with the various structures of passive droplet generation in the prior art (T-channel, coaxial flow and flow focusing), the microfluidic chip in this embodiment can still produce qualified microdroplets with uniform diameters at high throughput because the liquid channel is close in size in the height direction and under the action of the oscillating force generated by the flexible cover.

[0053] When the alignment pool is connected to the above-mentioned at least two liquid channels at the same time, the alignment pool is set to facilitate liquid filling. The alignment pool is used to achieve parallel liquid flow in the above-mentioned at least two liquid channels, and solves the problem that the liquids in the traditional multiple liquid channels cannot be parallel. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] FIG1 is a schematic diagram of the structure of the microfluidic chip in this application;

[0055] FIG2 is a microscopic magnified image of microdroplets generated when the flow rate Q of the microfluidic chip in this application is 0.1-0.5 μl / min;

[0056] FIG3 a is a microscopic magnified image of the microfluidic chip in the present application when the flow rate Q is 1-10 μl / min and the liquid channel generates microdroplets;

[0057] FIG3 b is an enlarged view of the distribution of microdroplets generated when the flow rate Q of the microfluidic chip in this application is 1-10 μl / min;

[0058] FIG4 a is a microscopic magnified image of the microfluidic chip in the present application when the flow rate Q is 40 μl / min and the liquid channel generates microdroplets;

[0059] FIG4 b is an enlarged view of the microdroplet distribution generated when the flow rate Q of the microfluidic chip in this application is 40 μl / min;

[0060] FIG5 is a top view of the microfluidic chip in this application (multiple liquid channels are arranged in parallel);

[0061] FIG6 is a top view of the microfluidic chip in the present application (multiple liquid channels are arranged radially);

[0062] FIG7 is a schematic diagram of a first relative position structure of the flexible cover plate, the substrate, and the hydrophobically modified oil pool in the present application;

[0063] FIG8 is a schematic diagram of a second relative position structure of the flexible cover plate, the substrate, and the hydrophobically modified oil pool in the present application;

[0064] FIG9 is a schematic diagram of a third relative position structure of the flexible cover plate, substrate, and hydrophobic modified oil pool in the present application;

[0065] FIG10 is a schematic diagram of a fourth relative position structure of the flexible cover plate, substrate, and hydrophobic modified oil pool in the present application;

[0066] FIG11 is a schematic diagram of the fifth relative position structure of the flexible cover plate, substrate and hydrophobic modified oil pool in the present application;

[0067] FIG12 is a schematic diagram of the sixth relative position structure of the flexible cover plate, substrate and hydrophobic modified oil pool in the present application;

[0068] FIG13 is a schematic diagram of the seventh relative position structure of the flexible cover plate, substrate and hydrophobic modified oil pool in this application.

[0069] Among them, 1. fluid inlet; 2. alignment pool; 3. liquid flow channel; 4. hydrophobic modified oil pool; 5. bonding passivation area; 6. flexible cover; 7. substrate; 8. micro droplets. DETAILED DESCRIPTION

[0070] To make the objectives, technical solutions, and advantages of the embodiments of the present application more clear, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the accompanying drawings of the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Generally, the components of the embodiments of the present application described and shown in the drawings herein can be arranged and designed in various different configurations.

[0071] Therefore, the following detailed description of the embodiments of the present application provided in the accompanying drawings is not intended to limit the scope of the present application for protection, but merely represents selected embodiments of the present application. All other embodiments obtained by persons of ordinary skill in the art based on the embodiments in the present application without creative work are within the scope of protection of the present application.

[0072] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, it does not need to be further defined or explained in subsequent drawings.

[0073] In the description of this application, it should be noted that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inside", "outside", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, or are the orientations or positional relationships in which the product of the application is usually placed when in use. They are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on this application. In addition, the terms "first", "second", "third", etc. are only used to distinguish the description and cannot be understood as indicating or implying relative importance. In the description of this application, unless otherwise specified, "multiple" means two or more.

[0074] It should also be noted that, in the description of this application, unless otherwise specified or limited, the terms "disposed" and "connected" should be understood in a broad sense. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections or electrical connections. Those skilled in the art will understand the specific meanings of these terms in this application based on the specific circumstances.

[0075] In this application, unless otherwise expressly specified or limited, a first feature being "above" or "below" a second feature may include the first and second features being in direct contact, or may include the first and second features being in contact not directly but through another feature between them. Moreover, a first feature being "above," "above," and "above" a second feature may include the first feature being directly above or obliquely above the second feature, or may simply mean that the first feature is higher in level than the second feature. A first feature being "below," "below," and "below" a second feature may include the first feature being directly below or obliquely below the second feature, or may simply mean that the first feature is lower in level than the second feature.

[0076] The following describes in detail embodiments of the present application. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present application and are not to be construed as limiting the present application.

[0077] A microfluidic chip is provided in this embodiment. The microfluidic chip can be a microfluidic chip for generating oscillating micro-slit droplets. The microfluidic chip includes a flexible cover plate 6 and a substrate 7. A bonding passivation area 5 is provided on the flexible cover plate 6 and / or the substrate 7. The flexible cover plate 6 and the substrate 7 are bonded to each other, and the bonding passivation area 5 that is not bonded to each other forms a liquid channel 3.

[0078] In this embodiment, the bonded passivation area 5 on the flexible cover plate 6 and / or substrate 7 forms a liquid channel 3. Liquid enters the liquid channel 3, forming a flat structure. This channel 3 squeezes and deforms the flexible cover plate 6. When the liquid reaches the outlet and forms microdroplets 8, the flexible cover plate 6 undulates, generating an oscillating force on the liquid at the outlet. This oscillating force acts as a shear force on the liquid at the outlet, causing the liquid to break and form microdroplets 8. Simultaneously, the oscillating force generated by the flexible cover plate 6 promotes the formation of microdroplets 8.

[0079] Compared to existing methods that rely on the vibration of an external vibrating structure to generate microdroplets, in this embodiment, when the width of the liquid channel 3 is within a certain range, the liquid flow rate into the liquid channel 3 changes. Due to the interfacial tension of the flexible cover plate 6 or substrate 7, the generation of microdroplets 8 is dominated by the interfacial tension. The generation of microdroplets 8 is achieved by the vibration and shearing effect of the flexible cover plate 6 on the liquid. The change in the liquid pressure in the liquid channel 3 has little effect on the size change of the diameter of the microdroplets 8. In this embodiment, microdroplets 8 can be generated without relying on an external vibrating structure. When the flow rate in the liquid channel 3 changes, the diameter of the generated microdroplets 8 is basically unaffected. Therefore, the diameter of the microdroplets 8 remains essentially unchanged during the initial commissioning process and the final commissioning process of generating microdroplets 8. Microdroplets 8 with a qualified diameter size can still be generated, thereby fully utilizing the sample, especially for small and rare samples.

[0080] This microfluidic chip can further break through the minimum size limit of microdroplets 8 generated by traditional step-by-step droplet generation, achieving the generation of small-sized microdroplets. In addition, by controlling the flow rate of the liquid in the liquid channel 3, the size of the prepared microdroplets can be made smaller than the width of the liquid channel 3.

[0081] In addition, because the microfluidic chip generates microdroplets, the liquid in the liquid channel 3 squeezes the flexible cover 6, and the flexible cover 6 adaptively generates an oscillating force on the liquid at the outlet of the liquid channel 3 to shear the liquid at the outlet to form microdroplets 8. Therefore, high-throughput microdroplet generation can be achieved, thereby reducing the commercial cost of microdroplet microfluidic applications.

[0082] Preferably, in this embodiment, the bonding surfaces of the flexible cover plate 6 and the substrate 7 are flat surfaces, so as to reduce the difficulty of machining the bonding surfaces and the difficulty of bonding the two, thereby reducing production costs.

[0083] Preferably, the flexible cover plate 6 is made of any one of polydimethylsiloxane (PDMS) and silicone rubber.

[0084] In the above embodiment, the liquid channel 3 is formed by the bonded passivation area 5 that is not bonded. The size of the liquid channel 3 along the height direction is close to 0, and the size along the width direction is less than 1 mm. For example, the size of the liquid channel 3 along the width direction ranges from a few microns to several hundred microns. When the liquid passes through the liquid channel 3, the liquid channel 3 is squeezed and expanded. Therefore, the cross-sectional shape of the formed liquid channel 3 is at least one of a regular quadrilateral, a circle or an ellipse. The specific shape is determined according to the shape of the bonded passivation area 5 formed on the flexible cover plate 6 and / or the substrate 7.

[0085] Preferably, the cross-section of the entire liquid channel 3 has the same shape. In other embodiments, the cross-section of the liquid channel 3 can also include at least any two of the above cross-sections.

[0086] In this embodiment, the cross section of the liquid channel 3 formed by liquid extrusion is rectangular. The micro-droplets 8 are subjected to the oscillating force of the flexible cover plate 6 at the outlet of the liquid channel 3, and the generated micro-droplets 8 have a uniform flat structure.

[0087] Specifically, as shown in Figures 1 and 2, the cross-section of the liquid channel 3 in this embodiment is rectangular, the dimension along the height direction is close to 0, the dimension along the width direction is 60μm, the thickness of the flexible cover 3 is less than 200μm, (the height direction here refers to the stacking direction of the flexible cover 6 and the substrate 7, and the width direction is perpendicular to the height direction and the length direction of the liquid channel 3), the flow rate Q in the liquid channel 3 is 0.1-0.5μl / min, and two types of micro-droplets with uniform diameters can be generated at the same time. The diameter ranges of the two micro-droplets are 80-85μm and 25-46μm, respectively.

[0088] As shown in FIG3 a and FIG3 b , when the flow rate Q in the liquid channel 3 is 1-10 μl / min, the diameter of the generated micro-droplets ranges from 65 μm to 75 μm.

[0089] As shown in Figures 4a and 4b, when the flow rate Q in the liquid channel 3 is 40 μl / min, the diameter size of the generated microdroplets ranges from 63 μm to 65 μm. The sizes of the microdroplets generated by the liquid channel 3 are very close, and the microdroplets are uniform, which can achieve high-throughput production of microdroplets.

[0090] That is, compared to the various passive droplet generation structures (T-channel, coaxial flow, and flow focusing) in the prior art, the microfluidic chip in this embodiment can still produce uniform and qualified microdroplets at high throughput because the height dimension of the liquid channel 3 is close to zero and the oscillating force generated by the flexible cover 3. In this embodiment, the flow rate Q can be adjusted to achieve the generation of monodisperse droplets of different sizes.

[0091] Compared to the liquid channels formed in the passive droplet generation structures of the prior art, the height dimension of the channels is not close to zero. Therefore, at high flow rates, very uneven droplets are generated. Conventional liquid channel generation methods all use slotting processing. Only under low-throughput conditions, that is, flow rates Q less than 10μl / min, can uniform micro-droplets be generated. The diameter of the generated micro-droplets is relatively large, and micro-droplets with diameters significantly smaller than the liquid channel size cannot be generated. The diameter of the micro-droplets generated using T-shaped channels is basically the same as the size of the T-shaped channel. The diameter of the micro-droplets generated by the stepped droplet generation structure is significantly different from the size of the liquid channel. At high throughput, the diameter of the micro-droplets is several times the size of the liquid channel.

[0092] Preferably, when the cross section of the liquid channel 3 is rectangular, the dimension along the width direction is no greater than 250 μm.

[0093] Preferably, in the above embodiment, the liquid channel 3 can be a straight line or a curve, that is, the path of the liquid in the liquid channel 3 can be a straight line or a curve.

[0094] Preferably, the above-mentioned bonding passivation area 5 is a passivation coating with a thickness of nanometer level or molecular level provided on the flexible cover plate 6 and / or the substrate 7. The passivation coating is tightly adhered to the surface of the flexible cover plate 6 and / or the substrate 7. Because the thickness of the passivation coating is nanometer level or molecular level, after the flexible cover plate 6 and the substrate 7 are bonded and passivated, the size of the liquid channel 3 formed in the height direction is ensured to be close to 0, thereby ensuring that the shock force generated by the flexible cover plate 6 accelerates the generation of micro-droplets, and at the same time, it is also ensured that micro-droplets can be generated under high throughput. When the bonding passivation area 5 is provided on the flexible cover plate 6, it cannot be bonded to the substrate 7 to form a liquid channel 3. When the bonding passivation area 5 is provided on the substrate 7, it cannot be bonded to the flexible cover plate 6 to form a liquid channel 3. When the bonding passivation area 5 is provided at the corresponding positions on the flexible cover plate 6 and the substrate 7, the bonding passivation areas 5 on the two cannot be connected by bonding to form a liquid channel 3.

[0095] Further preferably, the above-mentioned bonding passivation area 5 is processed by any one of SU8 photoresist technology, vapor deposition technology or sputtering technology to form the passivation coating. The passivation coating can be a material that can prevent bonding, such as photoresist, liquid metal, oil or other liquids. The method of preventing bonding can be directly using the nanoscale height of the passivation coating itself, or using the passivation coating itself as a mask to guide local bonding.

[0096] Regarding the number and arrangement of the liquid channels 3 in the above-mentioned microfluidic chip, in this embodiment, there is at least one liquid channel 3. When there are multiple liquid channels 3, by setting up multiple liquid channels 3, each liquid channel 3 can generate microdroplets 8, thereby increasing the generation rate of microdroplets 8.

[0097] In addition, as shown in FIG5 , there are at least two liquid channels 3, and the at least two liquid channels 3 are arranged in parallel, or as shown in FIG6 , the at least two liquid channels 3 are radially distributed, ensuring that the same micro-droplets 8 are simultaneously produced at the outlets of the liquid channels 3. Further preferably, the at least two liquid channels 3 are radially distributed along the circumference, ensuring that the micro-droplets 8 produced by the liquid channels 3 in all directions of the circumference are substantially the same.

[0098] The microfluidic chip further comprises a liquid injection component, which is connected to the liquid channel 3 and can inject liquid into the liquid channel 3 .

[0099] The liquid injection assembly injects liquid into the liquid channel 3 to form micro-droplets 8 in the liquid channel 3. The liquid injection assembly can be arranged on the flexible cover plate 6 and / or the substrate 7, or the liquid injection assembly can also be arranged on the flexible cover plate 6 or the substrate 7.

[0100] Specifically, in this embodiment, the liquid injection assembly is provided on the flexible cover plate 6, which facilitates processing of the liquid injection assembly on the flexible cover plate 6 and facilitates bonding of the flexible cover plate 6 to the substrate 7. When the microfluidic chip is used, the flexible cover plate 6 is positioned above the substrate 7, and the liquid injection assembly is provided on the flexible cover plate 6, facilitating liquid injection into the liquid injection assembly, such as by using a pneumatic pump for pneumatic injection or a flow pump for flow injection.

[0101] Preferably, with respect to the specific structure of the above-mentioned liquid injection assembly, the liquid injection assembly includes a fluid inlet 1 provided on the flexible cover plate 6, and the fluid inlet 1 is connected to the liquid channel 3. When the microfluidic chip is in use, the flexible cover plate 6 is located above the substrate 7. Alternatively, the liquid injection assembly includes a fluid inlet 1 provided on the substrate 7, and the fluid inlet 1 is connected to the liquid channel 3. When the microfluidic chip is in use, the substrate 7 is located above the flexible cover plate 6.

[0102] Further preferably, an alignment pool 2 is provided between the fluid inlet 1 and the liquid channel 3. The cross-sectional area of ​​the alignment pool 2 where it connects to the liquid channel 3 is larger than the maximum cross-sectional area of ​​the fluid inlet 1. The provision of the alignment pool 2 facilitates the injection of fluid into the liquid channel 3, so that the liquid channel 3 is evenly filled with liquid. The alignment pool 2 also facilitates communication between the fluid inlet 1 and the liquid channel 3 formed by the bonded passivation area 5 when the flexible cover 6 and the substrate 7 are bonded together. When the alignment pool 2 is simultaneously connected to the at least two liquid channels 3, the provision of the alignment pool 2 facilitates liquid filling. The alignment pool 2 enables the liquids in the at least two liquid channels 3 to flow in parallel, solving the problem that the liquids in the conventional multiple liquid channels 3 cannot flow in parallel.

[0103] The alignment pool 2 is any one of a cylindrical cavity, a polyhedral cavity, and a special-shaped cavity. That is, when the alignment pool 2 is a cylindrical cavity, the cross section at the connection between the alignment pool 2 and the liquid channel 3 is a circular cross section, and the circular cross section area is larger than the area of ​​the maximum cross section of the fluid inlet 1.

[0104] When the alignment reservoir 2 is a polyhedral or shaped cavity, to ensure that the liquids in at least two liquid channels 3 can flow completely parallel to each other, the cross-sectional area of ​​the connection between the polyhedral or shaped cavity and the liquid channel 3 is greater than the maximum cross-sectional area of ​​the fluid inlet 1. This means that at the end of the alignment reservoir 2 connected to the liquid channel 3, the cross-sectional area of ​​the polyhedral or shaped cavity below the end of the liquid channel 3 is greater than the cross-sectional area of ​​the fluid inlet 1. The cross-sectional area of ​​the shaped cavity can be irregular, as long as the cross-sectional area at the connection between the shaped cavity and the liquid channel 3 is greater than the maximum cross-sectional area of ​​the fluid inlet 1.

[0105] In this embodiment, the fluid inlet 1 is a cylindrical cavity, the alignment pool 2 is a cylindrical cavity, and the cross-sectional area of ​​the alignment pool 2 is larger than the cross-sectional area of ​​the fluid inlet 1. Preferably, the diameter of the alignment pool 2 is in the range of 2mm-10mm, and the height is in the range of 2mm-10mm.

[0106] Preferably, the microfluidic chip further comprises a droplet collection assembly disposed at the outlet of the liquid channel 3, the droplet collection assembly being used to collect the microdroplets 8 generated by the liquid channel 3. When at least two liquid channels 3 are provided, a set of droplet collection assemblies may be disposed at the outlet of each liquid channel 3.

[0107] Regarding the relative position of the droplet collecting assembly and the flexible cover 6 and substrate 7, the droplet collecting assembly can be located outside the flexible cover 6 and substrate 7, and can also be arranged on the flexible cover 6 and / or substrate 7.

[0108] Preferably, the droplet collection assembly includes a hydrophobic modified oil pool 4 that is connected to the outside atmosphere. This pool 4 is connected to the outlet of the liquid channel 3. The droplets 8 generated by the liquid channel 3 fall into and are stored within the pool 4. This connection to the outside atmosphere ensures that the droplets 8 are not trapped by the sealed space within the pool 4. Specifically, a hydrophobic modified oil pool 4 can be provided at the outlet of each liquid channel 3, or a single pool can be shared by at least two liquid channels 3.

[0109] Preferably, the inner surface of the hydrophobically modified oil pool 4 is coated with a nano-hydrophobic coating to promote and ensure the stability of the generated microdroplets 8. The wall thickness of the hydrophobically modified oil pool 4 ranges from 200 μl to 10 cm. It is understood that 200 μl to 10 cm is a continuous range of values, including any value within 200 μl to 10 cm, such as 1.1 cm, 1.111 cm, and so on. Exemplarily, the wall thickness of the hydrophobically modified oil pool 4 is 200 μl, 500 μl, 1 cm, 2 cm, 3 cm, and 10 cm, but the wall thickness of the hydrophobically modified oil pool 4 is not limited to the aforementioned values. For another example, the dimensions of the hydrophobically modified oil pool 4 in all directions are on the centimeter level.

[0110] Further preferably, the hydrophobically modified oil pool 4 is one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity, that is, it is ensured that the hydrophobically modified oil pool 4 can receive the micro-droplets 8 generated by the droplet channel.

[0111] Preferably, in this embodiment, the hydrophobic modified oil pool 4 is a rectangular parallelepiped cavity, and the hydrophobic modified oil pool 4 is provided on the flexible cover plate 6 and / or the base plate 7. Further preferably, the hydrophobic modified oil pool 4 is provided on the flexible cover plate 6.

[0112] Preferably, as shown in FIG7 , when the flexible cover plate 6 is located above the substrate 7, the hydrophobic modified oil pool 4 is provided on the flexible cover plate 6, and the bottom surface of the hydrophobic modified oil pool 4 is flush with the surface of the substrate 7 at the outlet of the micro-droplets 8, that is, the top surface of the substrate 7 serves as the bottom surface of the hydrophobic modified oil pool 4. This arrangement ensures that the micro-droplets 8 are acted upon by the substrate 7 at the outlet of the liquid channel 3, and the micro-droplets 8 at the outlet can only be generated upward. At the outlet, the liquid is subjected to the downward oscillating force of the flexible cover plate 6 as a shear force for generating micro-droplets 8, thereby accelerating the generation rate of the micro-droplets 8. The greater the oscillating force, the greater the shearing effect on the micro-droplets 8, the faster the shearing rate of the micro-droplets 8 at the outlet, the shorter the generation time of the micro-droplets 8, and the faster the generation rate.

[0113] In other embodiments, as shown in FIG8 , when the flexible cover plate 6 is positioned below the substrate 7, the hydrophobic modified oil pool 4 is disposed on the flexible cover plate 6, and the top surface of the hydrophobic modified oil pool 4 is flush with the surface of the substrate 7 at the outlet of the micro-droplets 8. This arrangement ensures that the micro-droplets 8 are acted upon by the substrate 7 at the outlet of the liquid channel 3 and can only be generated downward. The liquid at the outlet is subjected to an upward oscillating force, which shears the liquid upward. The greater the oscillating force, the greater the shearing effect on the micro-droplets 8, which can accelerate the shearing speed of the micro-droplets 8 at the outlet. That is, the generation time of the micro-droplets 8 is shortened and the generation speed is faster. In this embodiment, since the hydrophobic modified oil pool 4 is located on the flexible cover plate 6 and below the substrate 7, in order to ensure that the micro-droplets 8 generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole connected to the outside atmosphere is opened on the upper part of the side wall of the hydrophobic modified oil pool 4, that is, the hole is opened on the side wall of the hydrophobic modified oil pool 4 on the side opposite to the liquid channel 3, or a hole connected to the outside atmosphere is opened on the substrate 7, that is, the hole is opened at the top of the hydrophobic modified oil pool 4.

[0114] In other embodiments, as shown in Figure 9, when the flexible cover plate 6 is positioned above the substrate 7 and the hydrophobic modified oil pool 4 is disposed on the substrate 7, the top surface of the hydrophobic modified oil pool 4 is flush with the bottom surface of the flexible cover plate 6 at the outlet of the micro-droplets 8, i.e., the bottom surface of the flexible cover plate 6 serves as the top surface of the hydrophobic modified oil pool 4. In this embodiment, to ensure that the micro-droplets generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole is provided in the sidewall of the hydrophobic modified oil pool 4 to connect to the atmosphere, i.e., the hole is provided in the upper portion of the sidewall of the hydrophobic modified oil pool 4 on the side opposite the liquid channel 3. Alternatively, a hole is provided in the top of the hydrophobic modified oil pool 4 to connect to the outside atmosphere, i.e., the hole is provided in the flexible cover plate 6.

[0115] As shown in Figures 10 and 11, when the flexible cover plate 6 is located below the substrate 7 and the hydrophobic modified oil pool 4 is opened on the substrate 7, the bottom surface of the hydrophobic modified oil pool 4 is flush with the top surface of the flexible cover plate 6 at the outlet of the micro-droplet 8, that is, the top surface of the flexible cover plate 6 serves as the bottom surface of the hydrophobic modified oil pool 4. In this embodiment, to ensure that the micro-droplets generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole connected to the atmosphere is opened on the side wall of the hydrophobic modified oil pool 4, that is, the hole is opened on the upper part of the side wall of the hydrophobic modified oil pool 4 on the side opposite to the liquid channel 3. Alternatively, as shown in Figure 11, a hole connected to the outside atmosphere is opened on the top of the hydrophobic modified oil pool 4, that is, the hole is opened on the flexible cover plate 6, or the top of the hydrophobic modified oil pool 4 is opened to communicate with the outside atmosphere.

[0116] As shown in FIG12 , the hydrophobic modified oil pool 4 can also be provided on both the flexible cover plate 6 and the substrate 7. The hydrophobic modified oil pool 4 is provided on both the flexible cover plate 6 and the substrate 7, and is located between the flexible cover plate 6 and the substrate 7. To ensure that the droplets generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole is provided on the upper portion of the sidewall of the hydrophobic modified oil pool 4 on the side opposite to the liquid channel 3, that is, a hole is provided on the flexible cover plate 6 or the substrate 7 to connect to the atmosphere. Alternatively, as shown in FIG13 , a hole is provided on the top of the hydrophobic modified oil pool 4 to connect to the atmosphere, or the top opening of the hydrophobic modified oil pool 4 is connected to the atmosphere.

[0117] This embodiment also provides a method for manufacturing a microfluidic chip to manufacture the above-mentioned microfluidic chip, including processing a bonding passivation area 5 on a flexible cover plate 6 and / or a substrate 7. The substrate 7 is bonded to the flexible cover plate 6, and a liquid channel 3 is formed at the bonding passivation area 5. By processing the bonding passivation area 5 on the flexible cover plate 6 and / or the substrate 7, after the two are bonded, the bonding passivation area 5 cannot be bonded, thereby forming a liquid channel 3. The dimension of the liquid channel 3 along the height direction is close to 0. The liquid channel 3 cooperates with the oscillating force generated by the flexible cover plate 6 on the micro-droplets 8 at the outlet of the liquid channel 3 to form micro-droplets 8 with a size much smaller than the size of the liquid channel 3, and can accelerate the generation of micro-droplets 8. At the same time, because the oscillating force of the flexible cover plate 6 on the liquid at the outlet of the liquid channel 3 is an adaptive force generated by the liquid squeezing the flexible cover plate 6 in the liquid channel 3, micro-droplets 8 with uniform diameter can still be produced at high throughput.

[0118] Preferably, the flexible cover 6 and substrate 7 can be connected by chemical bonding or physical bonding, such as chemical bonding by ionic bonding, covalent bonding, metallic bonding, paradigm force, hydrogen bonding, etc., or by physical bonding by thermal bonding, surface modification bonding, ultrasonic bonding, solvent bonding, adhesive bonding, etc.

[0119] Further preferably, in this embodiment, the flexible cover plate 6 and the base plate 7 are connected by oxygen ion bonding, and the dimension of the formed liquid channel in the height direction is close to 0.

[0120] Specifically, the SU8 photoresist technology uses a smooth flexible cover plate 6 and / or substrate 7 as a substrate. Using soft lithography, a layer of SU8 photoresist with a thickness of nanometers is formed on the substrate to form a bonding passivation region 5. The bonding passivation region 5 formed using this technology, and thus the liquid channel 3, is manufactured at a low cost.

[0121] The above-mentioned vapor deposition technology uses a mask to cover the entire flexible cover plate 6 or substrate 7, exposing only the position where the passivation bonding area needs to be prepared, and puts it into a sealed container. Chlorosilane is introduced into the sealed container. The chlorosilane evaporates and covers the area not covered by the mask to form a passivation coating with molecular-level thickness. The passivation coating is the bonding passivation area 5.

[0122] The above-mentioned sputtering technology uses a mask to cover the entire flexible cover 6 or substrate 7 where the bonding passivation area 5 needs to be prepared, and then bombards it with oxygen ions to form a passivation coating with molecular-level thickness in the masked unbombarded area. The passivation coating is the bonding passivation area 5.

[0123] This embodiment also provides a method for generating microdroplets, using the above-mentioned microfluidic chip, including liquid passing through the liquid channel 3, and the flexible cover 6 generating an oscillating force on the microdroplets 8 at the outlet of the liquid channel 3 to form microdroplets 8 with a diameter of micrometer level.

[0124] Obviously, the above embodiments of the present application are merely examples for the purpose of clearly illustrating the present application, and are not intended to limit the embodiments of the present application. For those skilled in the art, other variations or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present application shall be included within the scope of protection of the claims of the present application.

Claims

1. A microfluidic chip, characterized in that: The invention comprises a flexible cover plate (6) and a substrate (7), wherein a bonding passivation area (5) is provided on the flexible cover plate (6) and / or the substrate (7), the flexible cover plate (6) and the substrate (7) are bonded to each other, and the bonding passivation area (5) forms a liquid channel (3).

2. The microfluidic chip according to claim 1, characterized in that: The bonding surfaces of the flexible cover plate (6) and the substrate (7) are planes.

3. The microfluidic chip according to claim 2, characterized in that: The bonding passivation area (5) is a passivation coating with a nanometer-level or molecular-level thickness disposed on the flexible cover plate (6) and / or the substrate (7).

4. The microfluidic chip according to claim 3, characterized in that: The passivation coating is processed by using any one of SU8 photoresist technology, vapor deposition technology or sputtering technology.

5. The microfluidic chip according to any one of claims 1 to 4, characterized in that: The cross-sectional shape of the liquid channel (3) includes at least one of a regular quadrilateral, a U-shape, a circle or an ellipse.

6. The microfluidic chip according to claim 5, characterized in that: The cross section of the liquid channel (3) is rectangular, and the dimension of the liquid channel (3) along the width direction is no greater than 250 μm.

7. The microfluidic chip according to any one of claims 1 to 4, characterized in that: The material of the flexible cover plate (6) is any one of polydimethylsiloxane and silicone plate.

8. The microfluidic chip according to any one of claims 1 to 4, characterized in that: It also comprises a liquid injection component, which is connected to the liquid channel (3) and can inject liquid into the liquid channel (3).

9. The microfluidic chip according to claim 8, characterized in that: The liquid injection assembly is arranged on the flexible cover plate (6) and / or the base plate (7).

10. The microfluidic chip according to claim 9, characterized in that: The liquid injection assembly comprises a fluid inlet (1) opened on the flexible cover plate (6) or the base plate (7), and the fluid inlet (1) is connected to the liquid channel (3).

11. The microfluidic chip according to claim 10, characterized in that: An alignment pool (2) is provided between the fluid inlet (1) and the liquid channel (3), and the cross-sectional area of ​​the alignment pool (2) where it connects to the liquid channel (3) is greater than the maximum cross-sectional area of ​​the fluid inlet (1).

12. The microfluidic chip according to claim 11, characterized in that: The alignment pool (2) is any one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity.

13. The microfluidic chip according to any one of claims 1 to 4, characterized in that: There is at least one liquid channel (3).

14. The microfluidic chip according to claim 13, characterized in that: At least two of the liquid channels (3) are arranged in parallel or distributed radially.

15. The microfluidic chip according to any one of claims 1 to 4, characterized in that: It also comprises a droplet collection component arranged at the outlet of the liquid channel (3), and the droplet collection component is used to collect micro droplets generated by the liquid channel (3).

16. The microfluidic chip according to claim 15, characterized in that: The droplet collection assembly comprises a hydrophobic modified oil pool (4) connected to the external atmosphere, and the hydrophobic modified oil pool (4) is connected to the outlet of the liquid channel (3).

17. The microfluidic chip according to claim 16, characterized in that: The hydrophobic modified oil pool (4) is opened on the flexible cover plate (6) and / or the base plate (7).

18. The microfluidic chip according to claim 17, characterized in that: The hydrophobic modified oil pool (4) is opened on the flexible cover plate (6), and the bottom surface or top surface of the hydrophobic modified oil pool (4) is flush with the surface of the substrate (7) at the outlet of the micro droplet (8).

19. The microfluidic chip according to claim 18, characterized in that: The inner surface of the hydrophobically modified oil pool (4) is coated with a nano-hydrophobic coating.

20. The microfluidic chip according to claim 19, characterized in that: The wall thickness of the hydrophobically modified oil pool (4) ranges from 200 μm to 10 cm.

21. The microfluidic chip according to claim 20, characterized in that: The hydrophobic modified oil pool (4) is any one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity.

22. A method for manufacturing a microfluidic chip, characterized in that: The microfluidic chip according to any one of claims 1 to 21 is manufactured, comprising: Processing a bonding passivation area (5) on a flexible cover plate (6) and / or a substrate (7); The substrate (7) is bonded to the flexible cover plate (6), and the liquid channel (3) is formed at the bonding passivation area (5).

23. The method for manufacturing a microfluidic chip according to claim 22, characterized in that: include: The flexible cover plate (6) and the base plate (7) are connected by chemical bonding or physical bonding.

24. The method for manufacturing a microfluidic chip according to claim 23, characterized in that: Using SUS8 photoresist technology, the smooth flexible cover plate (6) and / or the substrate (7) is used as a substrate, and using soft lithography technology, a layer of SUS8 photoresist with a height of nanometers is photoetched on the substrate to form a bonding passivation area (5) with a thickness of nanometers.

25. The method for manufacturing a microfluidic chip according to claim 23, characterized in that: By using vapor deposition technology, the bonding passivation area (5) to be prepared is exposed on the flexible cover plate (6) and / or the substrate (7), and masks are set at other positions. The substrate is placed in a closed space, and chlorinated alkane is introduced into the closed space. The chlorinated alkane evaporates and covers the area not covered by the mask to form the bonding passivation area (5) with a thickness of molecular level.

26. The method for manufacturing a microfluidic chip according to claim 23, characterized in that: By using the sputtering technology, the flexible cover plate (6) and / or the substrate (7) are covered with a mask where the bonding passivation area (5) is to be prepared, and bombarded with oxygen ions, so that the masked unbombarded area forms a bonding passivation area (5) with a thickness of the molecular level.

27. A method for generating microdroplets, characterized in that: The microfluidic chip according to any one of claims 1 to 21, comprising: The liquid passes through the liquid channel (3), and the flexible cover plate (6) generates an oscillating force on the micro-droplets at the outlet of the liquid channel (3), so as to form micro-droplets with a diameter of micrometer level.

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