Micro-fluidic chip, manufacturing method and micro-droplet generation method

Abstract

The invention relates to a micro-fluidic chip, a manufacturing method and a micro-droplet generation method, the micro-fluidic chip comprises a flexible cover plate and a substrate, the flexible cover plate and / or the substrate are / is provided with a bonding passivation area, the flexible cover plate and the substrate are in bonding connection, and the bonding passivation area forms a liquid channel. The manufacturing method of the micro-fluidic chip comprises the following steps: processing a bonding passivation region on a flexible cover plate and / or a substrate; the substrate is in bonding connection with the flexible cover plate, and a liquid channel is formed in the bonding passivation area. The micro-droplet generation method comprises the steps that liquid passes through the liquid channel, and the flexible cover plate generates oscillation force on the micro-droplets at the outlet of the liquid channel so as to form the micro-droplets with the diameter in the micron order. The liquid reaches the outlet and forms micro-droplets under the leading of interfacial tension. The flexible cover plate fluctuates, the micro-droplets are subjected to the action of the oscillation force generated by the flexible cover plate, the generation of the micro-droplets can be accelerated, and qualified micro-droplets with uniform diameters can be generated.

Description

Technical Field

[0001] The invention belongs to the field of droplet microfluidics technology, and in particular relates to a microfluidics chip, a manufacturing method and a micro droplet generating method. Background Art

[0002] 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 such as sensitive response, precise control, simple equipment, low reagent consumption and two-phase interface that can effectively avoid cross-contamination of reactants. As the most basic unit of droplet microfluidics technology, uniformity and high-throughput preparation are the 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 additional fields and only depends on the inherent characteristics of the fluid. The generation mechanism is essentially a competitive balance between capillary force, viscosity and inertia.

[0003] Passive droplet generation structures mainly include T-channels, coaxial flow and flow focusing. T-channels have slow droplet generation speed, coaxial flow is difficult to generate small droplets, flow focusing requires two-way injection, especially when generating small droplets, human intervention is required, and small droplets are difficult to achieve parallelization in the channel, that is, even if multiple branch pipes are set on a main pipe, a main pipe is connected to multiple branch pipes in parallel at the same time, and each branch pipe is equivalent to a branch channel, but it is difficult for multiple branch pipes to evenly divide the droplets, and it is difficult for multiple branch pipes to be parallel, resulting in low flux.

[0004] In addition, in the generation of droplets in these mainstream structures, the size and uniformity of the droplets are heavily dependent on the flow rate of the fluid. Slight fluctuations in the flow rate will lead to 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, qualified micro-droplets cannot be generated. The diameter size of the micro-droplets generated in the above stage is unqualified and cannot be used. The T-type channel structure is used to generate micro-droplets, generally using air pressure or a flow pump to push the liquid into the liquid channel, and relying on the shearing effect of the oil on the water at the outlet of the liquid channel to generate micro-droplets. When the liquid pressed into the liquid channel by air pressure is about to be pressed out, the speed at which the liquid in the liquid channel is pushed is getting 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.

[0005] The stepped droplet generation structure dominated by interfacial tension can perfectly avoid the above shortcomings, and only uses the changes in the channel wall constraints to generate droplets of uniform size. However, the diameter of the micro-droplets generated by the traditional stepped droplet generation structure can only be slightly smaller than the liquid channel size, especially at high throughput, the droplet size is several times larger than the channel.

[0006] Existing oscillation methods all rely on external vibration structures to achieve oscillation and generate droplets. The generation of micro-droplets in the liquid channel requires that the frequency of the external vibration structure matches the generation frequency of the micro-droplets. During the debugging process and the end process of the micro-droplet generation, the size of the generated micro-droplets is unqualified.

[0007] The traditional method of forming a droplet generation channel is mainly to open a groove on a substrate, and the thickness and width of the formed groove are both in the micron level. After the substrate and the cover plate set thereon are stacked and connected, the height and width dimensions of the formed liquid channel are both in the micron level. The micron-level liquid channel can only generate micro droplets according to the traditional droplet generation method, and the diameter of the generated micro droplets is the same as the size of the liquid channel, only slightly smaller than the size of the channel, and it is impossible to generate micro droplets that are much smaller than the channel size and uniform, and the flux is low. In addition, the existing processing method of preparing a liquid channel by opening a groove on a substrate has high processing cost and difficulty, and it is almost impossible to complete if nano-level grooves are to be processed, and the cost is extremely high. Summary of the invention

[0008] In view of the deficiencies in the prior art, an object of the present invention is to provide a microfluidic chip that at least solves one of the above technical problems.

[0009] To achieve this object, the present invention adopts the following technical solutions:

[0010] A microfluidic chip comprises a flexible cover plate and a substrate. A bonding passivation area is arranged 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.

[0011] Optionally, the bonding surface between the flexible cover plate and the substrate is a plane.

[0012] Optionally, the bonding passivation area is a passivation coating with a nanometer-level or molecular-level thickness disposed on the flexible cover plate and / or the substrate.

[0013] Optionally, the passivation coating is processed by using any one of SU8 photoresist technology, vapor deposition technology or sputtering technology.

[0014] 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.

[0015] 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.

[0016] Optionally, the flexible cover plate is made of any one of polydimethylsiloxane and silicone plate.

[0017] Optionally, it further includes a liquid injection component, which is connected to the liquid channel and can inject liquid into the liquid channel.

[0018] Optionally, the liquid injection assembly is arranged on the flexible cover plate and / or the substrate.

[0019] Optionally, the liquid injection assembly includes a fluid inlet opened on the flexible cover plate or the substrate, and the fluid inlet is connected to the liquid channel.

[0020] 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.

[0021] Optionally, the alignment pool is any one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity.

[0022] Optionally, there is at least one liquid channel.

[0023] Optionally, at least two of the liquid channels are arranged in parallel or distributed radially.

[0024] Optionally, it 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.

[0025] Optionally, the droplet collection assembly comprises 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.

[0026] Optionally, the hydrophobic modified oil pool is opened on the flexible cover plate and / or the substrate.

[0027] 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.

[0028] Optionally, the inner surface of the hydrophobically modified oil pool is coated with a nano-hydrophobic coating.

[0029] Optionally, the wall thickness of the hydrophobically modified oil pool ranges from 200 μm to 10 cm.

[0030] Optionally, the hydrophobically modified oil pool is any one of a cylindrical cavity, a polyhedral cavity or a special-shaped cavity.

[0031] Another object of the present invention is to provide a method for manufacturing a microfluidic chip, which at least solves one of the above technical problems.

[0032] To achieve this object, the present invention adopts the following technical solutions:

[0033] A method for manufacturing a microfluidic chip, to manufacture the microfluidic chip, comprising:

[0034] Processing bonding passivation areas on the flexible cover and / or substrate;

[0035] The substrate is bonded to the flexible cover plate, and the liquid channel is formed at the bonding passivation area.

[0036] Optionally include:

[0037] The flexible cover plate and the substrate are connected by chemical bonding or physical bonding. Optionally, a SUS8 photoresist technology is used on the smooth flexible cover plate and / or the substrate as a substrate, and a layer of SUS8 photoresist with a height of nanometers is photoetched on the substrate by soft lithography technology to form a bonding passivation area with a thickness of nanometers.

[0038] Optionally, by using vapor deposition technology, the bonding passivation area to be prepared is exposed on the flexible cover and / or the substrate, and masks are set at other positions, and placed in a closed space, and alkyl chloride is introduced into the closed space. The alkyl chloride evaporates and covers the area not covered by the mask to form the bonding passivation area with a thickness of the molecular level.

[0039] 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 area to form a bonding passivation area with a molecular-level thickness.

[0040] Another object of the present invention is to provide a method for generating micro-droplets, which at least solves one of the above-mentioned technical problems.

[0041] To achieve this object, the present invention adopts the following technical solutions:

[0042] A method for generating microdroplets, using the microfluidic chip, comprising:

[0043] 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.

[0044] Compared with the prior art, the present invention 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 as a flat structure, and the flexible cover plate is squeezed and deformed in the liquid channel, when the liquid reaches the outlet to form micro-droplets, the flexible cover plate fluctuates, and an oscillating force is generated on the liquid at the outlet, and the oscillating force acts as a shear force of 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 can produce micro-droplets with uniform diameter size and qualified.

[0045] When the size of the liquid channel in the width direction is within a certain range, the liquid flow rate entering the liquid channel changes. Because the interfacial tension of the flexible cover plate or substrate dominates the generation of micro-droplets, and the generation of micro-droplets is achieved by relying on the vibration shearing effect of the flexible cover plate on the liquid, the change in the liquid pressure in the liquid channel has little effect on the size change of the diameter of the micro-droplets. In this embodiment, micro-droplets can be generated without relying on an external vibration structure. When the flow rate in the liquid channel changes, it has basically no effect on the diameter size of the generated micro-droplets. Therefore, the diameter size of the micro-droplets in the initial debugging process of generating micro-droplets and the end process is basically unchanged, and micro-droplets with qualified diameter size can still be generated, thereby making full use of the sample, especially for small and rare samples.

[0046] 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.

[0047] Because the microfluidic chip generates microdroplets, the liquid in the liquid channel squeezes the flexible cover plate, and the flexible cover plate adaptively generates an oscillating force on the liquid at the outlet of the liquid channel to shear the liquid at the outlet to form microdroplets. Therefore, high-throughput microdroplet generation can be achieved, thereby reducing the commercialization cost of microdroplet microfluidic applications.

[0048] 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 diameter under high throughput because the liquid channel is close in size to each other in the height direction and under the action of the shock force generated by the flexible cover.

[0049] When the alignment pool is connected to the at least two liquid channels at the same time, the alignment pool is provided to facilitate liquid filling, and the liquids in the at least two liquid channels are parallelized through the alignment pool, thereby solving the problem that the liquids in the traditional multiple liquid channels cannot be parallelized. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 Schematic diagram of the structure of the microfluidic chip in the present invention;

[0051] Figure 2 This is a microscopic magnified image of microdroplets generated when the flow rate Q of the microfluidic chip in the present invention is 0.1-0.5 μl / min;

[0052] Figure 3a This is a microscopic magnified image of the microfluidic chip in the present invention when the flow rate Q is 1-10 μl / min and the liquid channel generates micro droplets;

[0053] Figure 3b This is an enlarged view of the distribution of microdroplets generated when the flow rate Q of the microfluidic chip in the present invention is 1-10 μl / min;

[0054] Figure 4a This is a microscopic magnified picture of the microfluidic chip in the present invention when the flow rate Q is 40 μl / min and the liquid channel generates micro droplets;

[0055] Figure 4b This is an enlarged view of the micro-droplet distribution generated when the flow rate Q of the microfluidic chip in the present invention is 40 μl / min;

[0056] Figure 5 A top view of the microfluidic chip of the present invention (multiple liquid channels are arranged in parallel);

[0057] Figure 6 A top view of the microfluidic chip of the present invention (multiple liquid channels are arranged radially);

[0058] Figure 7 This is a schematic diagram of the first relative position structure of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention;

[0059] Figure 8 This is a schematic diagram of the second relative position structure of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention;

[0060] Fig. 9 This is a schematic diagram of the third relative position structure of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention;

[0061] Fig.10 This is a schematic diagram of the fourth relative position structure of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention;

[0062] Fig.11 It is a fifth relative position structure schematic diagram of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention;

[0063] Fig.12Schematic diagram of the sixth relative position structure of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention;

[0064] Fig.13 This is a seventh schematic diagram of the relative position structure of the flexible cover plate, the substrate and the hydrophobic modified oil pool in the present invention.

[0065] Among them, 1. fluid inlet; 2. alignment pool; 3. liquid flow channel; 4. hydrophobic modified oil pool; 5. bonding passivation area; 6. flexible cover plate; 7. substrate; 8. micro droplets. DETAILED DESCRIPTION

[0066] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Generally, the components of the embodiments of the present invention described and shown in the drawings here can be arranged and designed in various different configurations.

[0067] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0068] 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, further definition and explanation thereof is not required in subsequent drawings.

[0069] In the description of the present invention, it should be noted that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inside", "outside", etc. indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings, or are the positions or positional relationships in which the inventive product is usually placed when in use. They are only for the convenience of describing the present invention 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 limiting the present invention. 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 the present invention, unless otherwise specified, "multiple" means two or more.

[0070] In the description of the present invention, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "disposed" and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0071] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0072] Embodiments of the present invention are described in detail below, examples of which 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 invention, and cannot be understood as limiting the present invention.

[0073] A microfluidic chip is provided in this embodiment. The microfluidic chip can be an oscillating micro-slit droplet generation microfluidic chip. 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.

[0074] In this embodiment, the bonding passivation area 5 on the flexible cover plate 6 and / or the substrate 7 forms a liquid channel 3, and the liquid enters the liquid channel 3 in a flat structure, and the flexible cover plate 6 is squeezed and deformed in the liquid channel 3. When the liquid reaches the outlet to form micro-droplets 8, the flexible cover plate 6 fluctuates, generating 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 8. At the same time, the micro-droplets 8 are affected by the oscillating force generated by the flexible cover plate 6, which can promote the generation of micro-droplets 8.

[0075] Compared with the existing form of generating micro-droplets by oscillation of an external vibration structure, in this embodiment, when the size of the liquid channel 3 in the width direction is within a certain range, the liquid flow rate entering the liquid channel 3 changes, and the generation of micro-droplets 8 is dominated by the interfacial tension of the flexible cover plate 6 or the substrate 7, and the generation of micro-droplets 8 is achieved by the vibration shearing effect of the flexible cover plate 6 on the liquid. The change of the liquid pressure in the liquid channel 3 has little effect on the size change of the diameter of the micro-droplet 8. In this embodiment, the micro-droplet 8 can be generated without relying on an external vibration structure, and when the flow rate in the liquid channel 3 changes, it has basically no effect on the diameter size of the generated micro-droplet 8. Therefore, the diameter size of the micro-droplet 8 in the initial debugging process and the end process of generating the micro-droplet 8 is basically unchanged, and the micro-droplet 8 with a qualified diameter size can still be generated, so that the sample can be fully utilized, especially for small and rare samples.

[0076] The microfluidic chip can further break through the minimum size limit of the microdroplet 8 generated on the basis of the traditional step-type droplet generation, and realize the generation of small-sized microdroplets. In addition, the size of the prepared microdroplet can be made smaller than the width of the liquid channel 3 by controlling the flow rate of the liquid in the liquid channel 3.

[0077] 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 commercialization cost of microdroplet microfluidic applications.

[0078] Preferably, in this embodiment, the bonding surfaces of the flexible cover plate 6 and the substrate 7 are planes, so as to reduce the difficulty of processing the bonding surfaces of the two and the difficulty of bonding the two, thereby reducing the production cost.

[0079] Preferably, the material of the flexible cover plate 6 is any one of polydimethylsiloxane (PDMS) and silicone plate.

[0080] In the above embodiment, the liquid channel 3 is formed by the bonding passivation area 5 that is not bonded, and 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 bonding passivation area 5 formed on the flexible cover plate 6 and / or the substrate 7.

[0081] Preferably, the cross-section of the entire liquid channel 3 has a consistent shape. In other embodiments, the cross-section of the liquid channel 3 can also include at least any two of the above cross-sections.

[0082] In this embodiment, the cross section of the liquid channel 3 formed by liquid extrusion is rectangular, and the micro-droplets 8 are subjected to the oscillating force of the flexible cover plate 6 at the outlet of the liquid channel 3, so that the generated micro-droplets 8 have a uniform flat structure.

[0083] Specifically, Figure 1 and Figure 2 As shown, in this embodiment, the cross-section of the liquid channel 3 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 plate 3 is less than 200μm, (the height direction here refers to the stacking direction of the flexible cover plate 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 kinds of micro-droplets with uniform diameters can be generated at the same time, and the diameter ranges of the two micro-droplets are 80-85μm and 25-46μm respectively.

[0084] like Figure 3a and Figure 3b As shown, when the flow rate Q in the liquid channel 3 is 1-10 μl / min, the diameter size range of the generated micro droplets is 65 μm-75 μm.

[0085] like Figure 4a and Figure 4b As shown, when the flow rate Q in the liquid channel 3 is 40 μl / min, the diameter size of the generated micro-droplets ranges from 63 μm to 65 μm. The sizes of the micro-droplets generated by the liquid channel 3 are very close, and the micro-droplets are uniform, which can achieve high-throughput production of micro-droplets.

[0086] That is, 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 generate qualified micro droplets with uniform diameter size under high flux because the liquid channel 3 is close to 0 in the height direction and under the action of 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.

[0087] Compared with the liquid channel formed in the passive droplet generation structure in the prior art, the size in the height direction is not close to 0. Therefore, under high flow, very uneven droplets will be generated. The conventional liquid channel generation method adopts the groove processing form. Only under low flux conditions, that is, the flow rate Q is less than 10μl / min, can uniform micro-droplets be generated, and the diameter size of the generated micro-droplets is relatively large, and it is impossible to generate micro-droplets with a diameter size significantly smaller than the liquid channel size. The diameter size of the micro-droplets generated by the T-type channel is basically close to the size of the T-type channel. The diameter of the micro-droplets generated by the stepped droplet generation structure is very different from the size of the liquid channel. The diameter of the micro-droplets under high flux is several times the size of the liquid channel.

[0088] Preferably, when the cross section of the liquid channel 3 is rectangular, the dimension along the width direction is no greater than 250 μm.

[0089] 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.

[0090] Preferably, the above-mentioned bonding passivation area 5 is a passivation coating with a thickness of nanometer or molecular level arranged on the flexible cover plate 6 and / or the substrate 7, and 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 or molecular level, after the flexible cover plate 6 and the substrate 7 are bonded and passivated, the size of the formed liquid channel 3 in the height direction is guaranteed 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 guaranteed that micro-droplets can be generated under high throughput. When the bonding passivation area 5 is arranged 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 arranged 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 arranged at the corresponding positions on the flexible cover plate 6 and the substrate 7, the bonding passivation areas 5 on both cannot be connected by bonding to form a liquid channel 3.

[0091] Further preferably, the above-mentioned bonding passivation area 5 is the passivation coating processed by any one of SU8 photoresist technology, vapor deposition technology or sputtering technology. 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.

[0092] Regarding the number and arrangement of the liquid channels 3 in the above-mentioned microfluidic chip, in this embodiment, the above-mentioned liquid channel 3 is at least one. 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 speed of microdroplets 8.

[0093] In addition, if Figure 5 As shown, the liquid channels 3 are at least two, and the at least two liquid channels 3 are arranged in parallel, or as shown in FIG. Figure 6 As shown, at least two liquid channels 3 are radially distributed to ensure that the same micro-droplets 8 are simultaneously generated at the outlet of the liquid channels 3. Further preferably, the at least two liquid channels 3 are radially evenly distributed along the circumference to ensure that the micro-droplets 8 generated by the liquid channels 3 in all directions of the circumference are substantially the same.

[0094] 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 .

[0095] 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.

[0096] Specifically, in this embodiment, the liquid injection component is provided on the flexible cover plate 6, which is convenient for processing the liquid injection component on the flexible cover plate 6, and convenient for bonding the flexible cover plate 6 to the substrate 7. When the microfluidic chip is used, the flexible cover plate 6 is located above the substrate 7, and the liquid injection component is provided on the flexible cover plate 6, which is convenient for injecting liquid into the liquid injection component, such as using a pneumatic pump to realize pneumatic injection, or using a flow pump to realize flow injection.

[0097] Preferably, with respect to the specific structure of the above-mentioned liquid injection component, the liquid injection component includes a fluid inlet 1 opened on the flexible cover plate 6, and the fluid inlet 1 is connected to the liquid channel 3. When the microfluidic chip is used, the flexible cover plate 6 is located above the substrate 7. Or, the liquid injection component includes a fluid inlet 1 opened on the substrate 7, and the fluid inlet 1 is connected to the liquid channel 3. When the microfluidic chip is used, the substrate 7 is located above the flexible cover plate 6.

[0098] Further preferably, 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 at the point where the liquid channel 3 is connected is larger than the maximum cross-sectional area of ​​the fluid inlet 1. The alignment pool 2 is provided to facilitate the injection of fluid into the liquid channel 3, so that the liquid channel 3 is evenly filled with liquid. The alignment pool 2 facilitates the communication of the liquid channel 3 formed by the fluid inlet 1 and the bonding passivation area 5 when the flexible cover plate 6 and the substrate 7 are bonded. When the alignment pool 2 is connected to the above-mentioned at least two liquid channels 3 at the same time, the alignment pool 2 is provided to facilitate the filling of liquid. The alignment pool 2 is used to realize the parallel flow of liquid in the above-mentioned at least two liquid channels 3, and solves the problem that the liquid in the traditional multiple liquid channels 3 cannot be parallel.

[0099] 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.

[0100] When the alignment pool 2 is a polyhedral cavity or a special-shaped cavity, in order to ensure that the liquids in at least two liquid channels 3 can be completely parallel, the cross-sectional area of ​​the connection between the polyhedral cavity or the special-shaped cavity and the liquid channel 3 is larger than the maximum cross-sectional area of ​​the fluid inlet 1. That is, the cross-sectional area of ​​the space of the polyhedral cavity or the special-shaped cavity below the end of the liquid channel 3 where the alignment pool 2 is connected to the liquid channel 3 is larger than the cross-sectional area of ​​the fluid inlet 1. The cross-sectional area of ​​the special-shaped cavity can be an irregular shape, as long as the cross-sectional area of ​​the connection between the special-shaped cavity and the liquid channel 3 is larger than the maximum cross-sectional area of ​​the fluid inlet 1.

[0101] 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 ranges from 2mm to 10mm, and the height ranges from 2mm to 10mm.

[0102] Preferably, the microfluidic chip further comprises a droplet collecting assembly disposed at the outlet of the liquid channel 3, and the droplet collecting assembly is used to collect the micro droplets 8 generated by the liquid channel 3. When at least two liquid channels 3 are provided, a group of droplet collecting assemblies may be disposed at the outlet of each liquid channel 3.

[0103] Regarding the relative position of the droplet collecting assembly and the flexible cover plate 6 and substrate 7 , the droplet collecting assembly can be located outside the flexible cover plate 6 and substrate 7 , and can also be arranged on the flexible cover plate 6 and / or substrate 7 .

[0104] Preferably, the droplet collection assembly includes a hydrophobic modified oil pool 4 connected to the outside atmosphere, the hydrophobic modified oil pool 4 is connected to the outlet of the liquid channel 3, and the micro-droplets 8 generated by the liquid channel 3 fall and are stored in the hydrophobic modified oil pool 4. The hydrophobic modified oil pool 4 is connected to the outside atmosphere to ensure that the micro-droplets 8 will not be difficult to drip due to the sealed space in the hydrophobic modified oil pool 4 when dripping. That is, a hydrophobic modified oil pool 4 can be set at the outlet of each liquid channel 3, and at least two liquid channels 3 can share one hydrophobic oil pool.

[0105] Preferably, the inner surface of the hydrophobic modified oil pool 4 is coated with a nano-hydrophobic coating to promote and ensure the stability of the generated micro-droplets 8. The wall thickness of the hydrophobic modified oil pool 4 ranges from 200 μl to 10 cm. It can be understood that 200 μl to 10 cm is a continuous range of values, including any value in 200 μl to 10 cm, such as 1.1 cm, 1.111 cm, etc. Exemplarily, the wall thickness of the hydrophobic modified oil pool 4 is 200 μl, 500 μl, 1 cm, 2 cm, 3 cm, 10 cm, but the wall thickness of the hydrophobic modified oil pool 4 is not limited to the above values. For example, the dimensions of the hydrophobic modified oil pool 4 in all directions are in the centimeter level.

[0106] Further preferably, the hydrophobic 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 hydrophobic modified oil pool 4 can receive the micro-droplets 8 generated by the droplet channel.

[0107] 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 substrate 7. Further preferably, the hydrophobic modified oil pool 4 is provided on the flexible cover plate 6.

[0108] Preferably, if Figure 7 As shown, when the flexible cover plate 6 is located above the substrate 7, the hydrophobic modified oil pool 4 is opened 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-droplet 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-droplet 8 is affected by the substrate 7 at the outlet of the liquid channel 3, and the micro-droplet 8 at the outlet can only be generated upward. At the outlet, the liquid is subjected to the oscillating force of the flexible cover plate 6 acting downward as a shear force to generate the micro-droplet 8, so as to accelerate the generation speed of the micro-droplet 8. The greater the oscillating force, the greater the shearing effect on the micro-droplet 8, the faster the shearing speed of the micro-droplet 8 at the outlet, the shorter the generation time of the micro-droplet 8, and the faster the generation speed.

[0109] In other embodiments, Figure 8As shown, when the flexible cover plate 6 is located below the substrate 7, the hydrophobic modified oil pool 4 is opened 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-droplet 8. This arrangement ensures that the micro-droplet 8 is affected by the substrate 7 at the outlet of the liquid channel 3 and can only be generated downward, and the liquid at the outlet is subjected to the upward shock force, which produces an upward shearing effect on the liquid. The greater the shock force, the greater the shearing effect on the micro-droplet 8, which can accelerate the shearing speed of the micro-droplet 8 at the outlet, that is, the generation time of the micro-droplet 8 is shorter 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 on the top of the hydrophobic modified oil pool 4.

[0110] In other embodiments, Fig. 9 As shown, when the flexible cover plate 6 is located above the substrate 7 and the hydrophobic modified oil pool 4 is opened 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-droplet 8, that is, the bottom surface of the flexible cover plate 6 serves as the top surface of the hydrophobic modified oil pool 4. In this embodiment, in order 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, 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.

[0111] like Fig.10 and Fig.11 As shown, 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, in order 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. Or as Fig.11 As shown, 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 opening of the hydrophobic modified oil pool 4 is connected to the outside atmosphere.

[0112] like Fig.12As shown, the hydrophobic modified oil pool 4 can also be opened on the flexible cover plate 6 and the substrate 7 at the same time. The hydrophobic modified oil pool 4 is opened on the flexible cover plate 6 and the substrate 7 at the same time, and the hydrophobic modified oil pool 4 is located inside between the flexible cover plate 6 and the substrate 7. In order 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 outside atmosphere 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, that is, a hole connected to the atmosphere is opened on the flexible cover plate 6 or the substrate 7. Or, as Fig.13 As shown, a hole connected to the outside atmosphere is provided at the top of the hydrophobic modified oil pool 4, or the top opening of the hydrophobic modified oil pool 4 is connected to the outside atmosphere.

[0113] In the present embodiment, a method for manufacturing a microfluidic chip is also provided 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 to form a liquid channel 3, and the size of the liquid channel 3 along the height direction is close to 0. The liquid channel 3 cooperates with the flexible cover plate 6 to generate a shock force on the micro-droplets 8 at the outlet of the liquid channel 3, and can 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 shock 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 size can still be generated under high throughput.

[0114] Preferably, the flexible cover plate 6 and the substrate 7 can be connected by chemical bonding or physical bonding, such as chemical bonding by ionic bonding, covalent bonding, metal bonding, paradigm force, hydrogen bonding, etc., or physical bonding by thermal bonding, surface modification bonding, ultrasonic bonding, solvent bonding, adhesive bonding, etc.

[0115] Further preferably, in this embodiment, the flexible cover plate 6 and the substrate 7 are connected by oxygen ion bonding, and the dimension of the formed liquid channel in the height direction is close to 0.

[0116] Specifically, the SU8 photoresist technology uses a smooth flexible cover plate 6 and / or substrate 7 as a substrate, and uses soft lithography technology to photolithograph a layer of SU8 photoresist with a height of nanometers on the substrate to form a bonding passivation area 5. The bonding passivation area 5 formed by the above technology further forms the liquid channel 3, and its manufacturing cost is low.

[0117] 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.

[0118] 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.

[0119] This embodiment also provides a method for generating micro-droplets, using the above-mentioned microfluidic chip, including liquid passing through the liquid channel 3, and the flexible cover plate 6 generating an oscillating force on the micro-droplets 8 at the outlet of the liquid channel 3 to form micro-droplets 8 with a diameter of micrometer level.

[0120] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes 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 invention should be included in the protection scope of the claims of the present invention.

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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