Microfluidic chips, manufacturing methods, and microdroplet generation methods

Abstract

This invention relates to microfluidic chips, manufacturing methods, and microdroplet generation methods. The microfluidic chip includes a flexible cover plate and a substrate. Bonding passivation regions are formed on the flexible cover plate and / or the substrate. The flexible cover plate and the substrate are bonded together, and the bonding passivation regions form liquid channels. The manufacturing method of the microfluidic chip includes: processing bonding passivation regions on the flexible cover plate and / or the substrate; bonding the substrate to the flexible cover plate, forming liquid channels at the bonding passivation regions. A microdroplet generation method includes: liquid flowing through the liquid channel; and the oscillating force generated by the flexible cover plate on the microdroplets at the outlet of the liquid channel to form microdroplets with a diameter on the micrometer scale. The liquid reaches the outlet and forms microdroplets under the dominance of interfacial tension. The oscillation generated by the flexible cover plate, and the oscillating force on the microdroplets, can accelerate the generation of microdroplets and produce microdroplets with uniform and qualified diameters.

Description

Technical Field

[0001] This invention belongs to the field of droplet microfluidics technology, and particularly relates to microfluidic chips, manufacturing methods, and microdroplet generation methods. Background Technology

[0002] Droplet microfluidics, with its unique advantages such as high responsiveness, precise control, simple equipment requirements, low reagent consumption, and effective prevention of cross-contamination at the two-phase interface, is widely used in single-cell sequencing, single-cell secretion research, digital PCCP30298SWU, and single-molecule detection. As the most fundamental unit of droplet microfluidics, the uniformity and high-throughput preparation of microdroplets are prerequisites for its commercialization. Compared to active droplet generation methods such as electrostatic, magnetic, centrifugal, optical, thermal, and mechanical forces, passive droplet generation requires no additional action field and depends solely on the inherent properties of the fluid. The generation mechanism is essentially a competitive balance among capillary forces, viscous forces, and inertial forces.

[0003] Passive droplet generation structures mainly include T-channels, coaxial flow, and flow focusing. T-channels result in slow droplet generation, coaxial flow struggles to generate small droplets, and flow focusing requires two-way injection, especially when generating small droplets, necessitating human intervention. Furthermore, it's difficult for small droplets to flow in parallel within the channel. Even with multiple branch lines connected to a single main line, each branch line acts as a separate channel, making it difficult to distribute droplets evenly and achieve parallel flow, leading to low throughput.

[0004] Furthermore, in these mainstream droplet generation structures, droplet size and uniformity heavily depend on fluid velocity. Slight fluctuations in flow rate can lead to polydisperse droplets, and the unavoidable dead volume during droplet generation inevitably results in sample waste. In other words, if qualified microdroplets cannot be generated during the initial setup or termination of liquid generation within the liquid channel, the diameter of the microdroplets generated in these stages will be unacceptable and cannot be used. T-channel structures typically use air pressure or a flow pump to push liquid into the channel, relying on the shearing action of the oil against the water at the channel outlet to generate microdroplets. When the air pressure-pumped liquid into the channel is almost depleted, the speed at which the liquid is pushed within the channel increases, causing instability in the diameter of the generated microdroplets during the setup process and the termination of microdroplet generation, rendering them unusable.

[0005] Stepped droplet generation structures, dominated by interfacial tension, perfectly avoid the aforementioned drawbacks, generating uniformly sized droplets solely through variations in channel wall constraints. However, the diameter of microdroplets generated by traditional stepped droplet generation structures is often only slightly smaller than the liquid channel size, especially at high throughput where the droplet size is several times larger than the channel size.

[0006] Existing oscillating systems rely on external vibration structures to generate droplets. The generation of microdroplets within the liquid channel requires the frequency of the external vibration structure to match the generation frequency of the microdroplets. During the initial and final stages of microdroplet generation, the generated microdroplets may not meet the required size specifications.

[0007] Traditional methods for forming droplet generation channels primarily involve creating grooves on a substrate. The thickness and width of these grooves are typically in the micrometer range. After the substrate and a cover plate are stacked and connected, the resulting liquid channel has dimensions in both the height and width directions in the micrometer range. This micrometer-scale liquid channel can only generate microdroplets using traditional droplet generation methods, and the diameter of the generated microdroplets is the same as, or only slightly smaller than, the channel size. It cannot generate much smaller and more uniform microdroplets than the channel size, and the throughput is low. Furthermore, existing methods for fabricating liquid channels by creating grooves on a substrate are costly and difficult to implement; fabricating nanometer-scale grooves is virtually impossible and extremely expensive. Summary of the Invention

[0008] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a microfluidic chip that solves at least one of the above-mentioned technical problems.

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

[0010] A microfluidic chip includes a flexible cover plate and a substrate, wherein the flexible cover plate and / or the substrate are provided with bonding passivation regions, the flexible cover plate and the substrate are bonded together, and the bonding passivation regions form liquid channels.

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

[0012] Optionally, the bonding passivation region is a passivation coating with a thickness of nanometers or molecules disposed on the flexible cover plate and / or the substrate.

[0013] Alternatively, the passivation coating may be processed 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 no greater than 250 μm. If the dimension is greater than this, uneven small droplets may be generated.

[0016] Optionally, the flexible cover plate is made of either polydimethylsiloxane or silicone sheet.

[0017] Optionally, it also includes a liquid injection assembly that is connected to the liquid channel and is capable of injecting liquid into the liquid channel.

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

[0019] Optionally, the liquid injection assembly includes a fluid inlet formed on the flexible cover or the substrate, the fluid inlet communicating with the liquid channel.

[0020] Optionally, an alignment pool is provided between the fluid inlet and the liquid channel, wherein the cross-sectional area of ​​the alignment pool at the point where it connects to the liquid channel is greater than the maximum cross-sectional area of ​​the fluid inlet.

[0021] Optionally, the alignment pool is any one of a cylindrical cavity, a polyhedral cavity, or an irregular cavity.

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

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

[0024] Optionally, it also includes a droplet collection assembly disposed at the outlet of the liquid channel, the droplet collection assembly being used to collect microdroplets generated by the liquid channel.

[0025] Optionally, the droplet collection assembly includes a hydrophobic modified oil pool that is in communication with the outside atmosphere, and the hydrophobic modified oil pool is connected to the outlet of the liquid channel.

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

[0027] Optionally, the hydrophobic modified oil pool is formed on the flexible cover plate, and the bottom or top surface of the hydrophobic modified oil pool is flush with the surface of the substrate at the microdroplet outlet.

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

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

[0030] Optionally, the hydrophobic modified oil bath is any one of a cylindrical cavity, a polyhedral cavity, or an irregular 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-mentioned technical problems.

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

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

[0034] Bonding passivation regions are processed on the flexible cover plate and / or substrate;

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

[0036] Optionally, it includes:

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

[0038] Optionally, using vapor deposition technology, the bonding passivation region to be prepared is exposed on the flexible cover plate and / or the substrate, while masks are placed at other locations and placed in a sealed space. Chlorinated alkane is introduced into the sealed space, and the chlorinated alkane evaporates, covering the areas not covered by the mask to form the bonding passivation region with a thickness at the molecular level.

[0039] Optionally, using sputtering technology, the flexible cover plate and / or the substrate are covered with a mask for areas where bonding passivation regions need to be formed, and bombarded with oxygen ions to form bonding passivation regions with molecular-level thickness in the masked areas that were not bombarded.

[0040] Another object of the present invention is to provide a method for generating microdroplets, 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, utilizing the aforementioned microfluidic chip, includes:

[0043] As the liquid passes through the liquid channel, the flexible cover exerts an oscillating force on the microdroplets at the outlet of the liquid channel, forming microdroplets with a diameter of micrometers.

[0044] Compared with the prior art, the present invention has the following beneficial effects: A liquid channel is formed by the bonding passivation region on the flexible cover plate and / or the substrate. The liquid channel is formed by the unbonded bonding passivation region, and the dimension of the liquid channel along the height direction is close to zero. When liquid passes through the liquid channel, the liquid channel is squeezed and expanded. The liquid enters the liquid channel with a flat structure and undergoes compression deformation on the flexible cover plate within the liquid channel. When the liquid reaches the outlet and forms microdroplets, the flexible cover plate fluctuates, generating an oscillating force on the liquid at the outlet. This oscillating force acts as a shear force for the liquid at the outlet, causing the liquid to break and form microdroplets. Simultaneously, the oscillating force generated by the flexible cover plate accelerates the formation of microdroplets and produces microdroplets with uniform and qualified diameters.

[0045] When the width of the liquid channel is within a certain range, changes in the liquid flow rate within the channel lead to the generation of microdroplets due to the interfacial tension of the flexible cover or substrate. The generation of microdroplets is achieved through the vibrational shearing action of the flexible cover on the liquid. Changes in liquid pressure within the channel have little impact on the diameter of the microdroplets. In this embodiment, microdroplets can be generated without relying on an external vibration structure. Changes in the flow rate within the liquid channel have virtually no effect on the diameter of the generated microdroplets. Therefore, the diameter of the microdroplets remains essentially unchanged during the initial and final stages of microdroplet generation, ensuring the generation of microdroplets with acceptable diameters. This allows for full utilization 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 the traditional stepped droplet generation, and realize the generation of small-sized microdroplets.

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

[0048] Compared to existing passive droplet generation structures (T-channel, coaxial flow, and flow focusing), the microfluidic chip in this embodiment can still generate uniform and qualified microdroplets at high throughput because the liquid channel has a similar size in the height direction and is subjected to the oscillation force generated by the flexible cover plate.

[0049] When the alignment pool is connected to at least two liquid channels, the alignment pool facilitates liquid filling. The alignment pool enables the parallel flow of liquids in the at least two liquid channels and solves the problem that liquids in traditional multiple liquid channels cannot flow in parallel. Attached Figure Description

[0050] Figure 1 This is a schematic diagram of the microfluidic chip in this invention;

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

[0052] Figure 3a This is a magnified microscopic image of the microfluidic chip in this invention when the flow rate Q is 1-10 μl / min and microdroplets are generated in the liquid channel.

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

[0054] Figure 4a This is a magnified microscopic image of the microfluidic chip in this invention when the flow rate Q is 40 μl / min and microdroplets are generated in the liquid channel.

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

[0056] Figure 5 This is a top view of the microfluidic chip in this invention (multiple liquid channels arranged side by side);

[0057] Figure 6 This is a top view of the microfluidic chip in this 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 tank in this 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 tank in this invention;

[0060] Figure 9 This is a schematic diagram of the third relative position structure of the flexible cover plate, the substrate, and the hydrophobic modified oil tank in this invention.

[0061] Figure 10 This is a schematic diagram of the fourth relative position structure of the flexible cover plate, the substrate, and the hydrophobic modified oil tank in this invention;

[0062] Figure 11 This is a schematic diagram of the fifth relative position structure of the flexible cover plate, the substrate, and the hydrophobic modified oil tank in this invention;

[0063] Figure 12This is a schematic diagram of the sixth relative position structure of the flexible cover plate, the substrate, and the hydrophobic modified oil tank in this invention;

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

[0065] Among them, 1. fluid inlet; 2. alignment pool; 3. liquid flow channel; 4. hydrophobic modified oil pool; 5. bonding passivation zone; 6. flexible cover plate; 7. substrate; 8. microdroplet. Detailed Implementation

[0066] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0067] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the 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, it does not need to be further defined or explained in subsequent drawings.

[0069] In the description of this invention, it should be noted that the terms "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product of this invention is in use. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0070] In the description of this invention, it should also be noted that, unless otherwise explicitly specified and limited, the terms "set" and "connection" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0071] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0072] Embodiments of the present invention are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0073] This embodiment provides a microfluidic chip that can generate microfluidic droplets in an oscillating microslit. The microfluidic chip includes a flexible cover plate 6 and a substrate 7. The flexible cover plate 6 and / or the substrate 7 are provided with bonding passivation regions 5. The flexible cover plate 6 and the substrate 7 are bonded together. The unbonded bonding passivation regions 5 form liquid channels 3.

[0074] In this embodiment, a liquid channel 3 is formed in the bonding passivation region 5 on the flexible cover plate 6 and / or the substrate 7. The liquid entering the liquid channel 3 has a flat structure and exerts a squeezing deformation on the flexible cover plate 6 within the liquid channel 3. When the liquid reaches the outlet and forms microdroplets 8, the flexible cover plate 6 fluctuates, 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. At the same time, the oscillating force generated by the flexible cover plate 6 promotes the formation of microdroplets 8.

[0075] Compared to existing methods that rely on external vibration structures to generate microdroplets, in this embodiment, when the width of the liquid channel 3 is within a certain range, changes in the liquid flow rate within the liquid channel 3 are primarily driven by the interfacial tension of the flexible cover plate 6 or the substrate 7 to generate microdroplets 8. The generation of microdroplets 8 is achieved through the vibrational shearing effect of the flexible cover plate 6 on the liquid. Changes in the liquid pressure within the liquid channel 3 have little impact on the diameter of the microdroplets 8. This embodiment generates microdroplets 8 without relying on an external vibration structure, and changes in the flow rate within the liquid channel 3 have virtually no effect on the diameter of the generated microdroplets 8. Therefore, the diameter of the microdroplets 8 remains essentially unchanged during the initial and final stages of microdroplet generation, ensuring the generation of microdroplets 8 with acceptable diameters. This allows for full utilization of the sample, especially for small and rare samples.

[0076] This microfluidic chip can further overcome the minimum size limitation of microdroplet generation based on traditional stepped droplet generation, realizing the generation of small-sized microdroplets. In addition, by controlling the flow rate of liquid in liquid channel 3, the size of the prepared microdroplets can be made smaller than the width of liquid channel 3.

[0077] Furthermore, because the microfluidic chip generates microdroplets, the liquid in the liquid channel 3 squeezes the flexible cover plate 6, and the flexible cover plate 6 adaptively generates an oscillating force on the liquid at the outlet of the liquid channel 3 to shear the liquid at the outlet and 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 planar, so as to reduce the processing difficulty of the bonding surfaces and the bonding difficulty of the two, thereby reducing production costs.

[0079] Preferably, the flexible cover plate 6 is made of either polydimethylsiloxane (PDMS) or silicone sheet.

[0080] In the above embodiments, the liquid channel 3 is formed by the unbonded passivation region 5. The dimension of the liquid channel 3 along the height direction is close to 0, and the dimension along the width direction is less than 1 mm. For example, the dimension of the liquid channel 3 along the width direction ranges from a few micrometers to several hundred micrometers. 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 region 5 formed on the flexible cover plate 6 and / or the substrate 7.

[0081] Preferably, the cross-sectional shape of the entire liquid channel 3 is uniform. In other embodiments, the cross-section of the liquid channel 3 may also include at least any two of the aforementioned cross-sections.

[0082] In this embodiment, the cross-section of the liquid channel 3 formed after liquid extrusion is rectangular. The microdroplets 8 are subjected to the vibration force of the flexible cover plate 6 at the outlet of the liquid channel 3, and the generated microdroplets 8 have a uniform flat structure.

[0083] Specifically, if Figure 1 and Figure 2 As shown, in this embodiment, the cross-section of the liquid channel 3 is rectangular, with a dimension close to 0 along the height direction and a dimension of 60 μm along the width direction. The thickness of the flexible cover plate 3 is less than 200 μm. (Here, the height direction 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 0.1-0.5 μl / min, which can simultaneously generate two types of microdroplets with uniform diameters. The diameter ranges of the two microdroplets are 80-85 μm and 25-46 μm, 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 of the generated microdroplets ranges from 65 μm to 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 of the generated microdroplets ranges from 63 μm to 65 μm. The microdroplets generated by the liquid channel 3 are very close in size and uniform, which enables high-throughput production of microdroplets.

[0086] In this embodiment, compared to existing passive droplet generation structures (T-channel, coaxial flow, and flow focusing), the microfluidic chip can still generate uniform and qualified microdroplets at high throughput because the phase size of the liquid channel 3 in the height direction is close to 0, and under the oscillating force generated by the flexible cover plate 3. In this embodiment, the generation of monodisperse droplets of different sizes can be achieved by adjusting the flow rate Q.

[0087] Compared to existing passive droplet generation structures, where the liquid channel's height dimension is not close to zero, resulting in highly non-uniform droplets at high flow rates, conventional liquid channel generation methods employ slotted processing. Uniform microdroplets can only be generated at low flow rates (Q less than 10 μl / min), and even then, the generated microdroplets have relatively large diameters, failing to produce droplets with diameters significantly smaller than the liquid channel size. In contrast, the diameter of microdroplets generated using a T-channel is close to the T-channel's size, while the diameter of microdroplets generated by a stepped droplet generation structure differs greatly from the liquid channel size, with droplet diameters several times larger than the liquid channel size at high flow rates.

[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 embodiments, 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 aforementioned bonding passivation region 5 is a passivation coating with a thickness of nanometer or molecular level disposed on the flexible cover plate 6 and / or substrate 7. This passivation coating adheres tightly to the surface of the flexible cover plate 6 and / or substrate 7. Because the thickness of this passivation coating is nanometer or molecular level, after the flexible cover plate 6 and substrate 7 are bonded and passivated, the dimension of the formed liquid channel 3 in the height direction is close to 0, thereby ensuring that the oscillation force generated by the flexible cover plate 6 accelerates the generation of microdroplets, and also ensuring that microdroplets can be generated at high throughput. When the bonding passivation region 5 is disposed on the flexible cover plate 6, it cannot be bonded to the substrate 7 to form the liquid channel 3. When the bonding passivation region 5 is disposed on the substrate 7, it cannot be bonded to the flexible cover plate 6 to form the liquid channel 3. When bonding passivation regions 5 are disposed at corresponding positions on both the flexible cover plate 6 and substrate 7, the bonding passivation regions 5 on both cannot be bonded together to form the liquid channel 3.

[0091] More preferably, the aforementioned bonding passivation region 5 is processed using any one of SU8 photoresist technology, vapor deposition technology, or sputtering technology to form the passivation coating. The passivation coating can be a photoresist, liquid metal, oil, or other liquid material that can prevent bonding. The method of preventing bonding can be by directly utilizing the nanoscale height of the passivation coating itself, or by using the passivation coating itself as a mask to guide local bonding.

[0092] Regarding the number and arrangement of liquid channels 3 in the microfluidic chip, in this embodiment, there is at least one liquid channel 3. When there are multiple liquid channels 3, each liquid channel 3 can generate microdroplets 8 by setting multiple liquid channels 3, thereby increasing the generation speed of microdroplets 8.

[0093] In addition, such as Figure 5 As shown, there are at least two liquid channels 3, and the at least two liquid channels 3 are arranged in parallel, or as shown in the diagram. Figure 6 As shown, at least two liquid channels 3 are radially distributed to ensure that the same microdroplets 8 are generated simultaneously at the outlet of the liquid channels 3. More preferably, the above-mentioned at least two liquid channels 3 are radially distributed along the circumference to ensure that the microdroplets 8 generated by the liquid channels 3 in all directions of the circumference are substantially the same.

[0094] The microfluidic chip also includes a liquid injection component, which is connected to the liquid channel 3 and is capable of injecting liquid into the liquid channel 3.

[0095] The aforementioned liquid injection assembly injects liquid into the liquid channel 3 to facilitate the formation of microdroplets 8 within the liquid channel 3. This liquid injection assembly can be disposed on the flexible cover plate 6 and / or the substrate 7, or it can be disposed elsewhere without being on the flexible cover plate 6 or the substrate 7.

[0096] Specifically, in this embodiment, the liquid injection component is disposed on the flexible cover plate 6, which facilitates the fabrication of the liquid injection component on the flexible cover plate 6 and also facilitates the bonding connection between the flexible cover plate 6 and the substrate 7. When using this microfluidic chip, the flexible cover plate 6 is located above the substrate 7, and the liquid injection component is disposed on the flexible cover plate 6, which facilitates the injection of liquid into the liquid injection component, such as by using a pneumatic pump to achieve pneumatic injection, or by using a flow pump to achieve flow injection.

[0097] Preferably, regarding the specific structure of the above-mentioned liquid injection assembly, the liquid injection assembly includes a fluid inlet 1 formed on the flexible cover plate 6, and the fluid inlet 1 communicates with the liquid channel 3. When using this microfluidic chip, the flexible cover plate 6 is located above the substrate 7. Alternatively, the liquid injection assembly includes a fluid inlet 1 formed on the substrate 7, and the fluid inlet 1 communicates with the liquid channel 3; when using this microfluidic chip, the substrate 7 is located above the flexible cover plate 6.

[0098] More 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 where it connects to the liquid channel 3 is larger than the maximum cross-sectional area of ​​the fluid inlet 1. The alignment pool 2 facilitates fluid injection into the liquid channel 3, ensuring uniform filling of the liquid channel 3. The alignment pool 2 also facilitates communication between the fluid inlet 1 and the liquid channel 3 formed by the bonding passivation region 5 when the flexible cover plate 6 and the substrate 7 are bonded together. When the alignment pool 2 connects to at least two liquid channels 3 simultaneously, it facilitates liquid filling and enables parallel liquid flow in at least two liquid channels 3, solving the problem of the inability to flow in parallel within traditional multiple liquid channels 3.

[0099] The alignment pool 2 described above can be any one of a cylindrical cavity, a polyhedral cavity, or an irregularly 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 area of ​​this circular cross-section 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 an irregularly shaped cavity, to ensure that the liquids in at least two liquid channels 3 can flow in parallel, the cross-sectional area of ​​the connection between the polyhedral cavity or irregularly shaped cavity and the liquid channel 3 must be greater than the maximum cross-sectional area of ​​the fluid inlet 1. That is, the cross-sectional area of ​​the polyhedral cavity or irregularly shaped cavity located below the port of the liquid channel 3 at one end of the alignment pool 2 is greater than the cross-sectional area of ​​the fluid inlet 1. The cross-section of the irregularly shaped cavity can be irregular in shape, as long as the cross-sectional area of ​​the connection between the irregularly shaped cavity and the liquid channel 3 is greater than the maximum cross-sectional area of ​​the fluid inlet 1.

[0101] In this embodiment, the fluid inlet 1 is a cylindrical cavity, and the alignment pool 2 is a cylindrical cavity, with the cross-sectional area of ​​the alignment pool 2 being larger than that 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.

[0102] Preferably, the microfluidic chip further includes a droplet collection component disposed at the outlet of the liquid channel 3, the droplet collection component being used to collect microdroplets 8 generated by the liquid channel 3. When at least two liquid channels 3 are provided, a set of droplet collection components can be provided at the outlet of each liquid channel 3.

[0103] Regarding the relative positions of the droplet collection component with the flexible cover plate 6 and the substrate 7, the droplet collection component can be located outside the flexible cover plate 6 and the substrate 7, or it can be disposed on the flexible cover plate 6 and / or the substrate 7.

[0104] Preferably, the droplet collection assembly includes a hydrophobic modified oil tank 4 connected to the outside atmosphere. This hydrophobic modified oil tank 4 is connected to the outlet of the liquid channel 3. Microdroplets 8 generated by the liquid channel 3 fall and are stored in the hydrophobic modified oil tank 4. The connection between the hydrophobic modified oil tank 4 and the outside atmosphere ensures that the microdroplets 8 will not be unable to drip due to the sealed space within the hydrophobic modified oil tank 4. That is, one hydrophobic modified oil tank 4 can be provided at the outlet of each liquid channel 3, or at least two liquid channels 3 can share one hydrophobic oil tank.

[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 microdroplets 8. The wall thickness of the hydrophobic modified oil pool 4 ranges from 200 μl to 10 cm. This range is understood to be a continuous numerical range, including any value within this range, such as 1.1 cm, 1.111 cm, etc. For example, the wall thickness of the hydrophobic modified oil pool 4 may be 200 μl, 500 μl, 1 cm, 2 cm, 3 cm, or 10 cm, but the wall thickness is not limited to these values. Furthermore, the dimensions of the hydrophobic modified oil pool 4 in all directions may be on the order of centimeters.

[0106] More preferably, the hydrophobic modified oil pool 4 is one of a cylindrical cavity, a polyhedral cavity, or an irregular cavity, that is, to ensure that the hydrophobic modified oil pool 4 can receive microdroplets 8 generated by the droplet channel.

[0107] Preferably, in this embodiment, the hydrophobic modified oil tank 4 is a cuboid cavity, and the hydrophobic modified oil tank 4 is formed on the flexible cover plate 6 and / or the substrate 7. More preferably, the hydrophobic modified oil tank 4 is formed on the flexible cover plate 6.

[0108] Preferably, such as Figure 7 As shown, when the flexible cover plate 6 is located above the substrate 7, the hydrophobic modified oil pool 4 is formed on the flexible cover plate 6. The bottom surface of the hydrophobic modified oil pool 4 is flush with the surface of the substrate 7 at the outlet of the microdroplets 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 microdroplets 8 are acted upon by the substrate 7 at the outlet of the liquid channel 3, and the microdroplets 8 at the outlet can only be generated upwards. The liquid at the outlet is subjected to the downward oscillating force of the flexible cover plate 6, which serves as the shear force for generating the microdroplets 8, thereby accelerating the generation speed of the microdroplets 8. The greater the oscillating force, the greater the shearing effect on the microdroplets 8, the faster the shearing speed of the microdroplets 8 at the outlet, the shorter the generation time of the microdroplets 8, and the faster the generation speed.

[0109] In other embodiments, such as Figure 8As shown, when the flexible cover plate 6 is located below the substrate 7, the aforementioned hydrophobic modified oil pool 4 is formed on the flexible cover plate 6. The top surface of the hydrophobic modified oil pool 4 is flush with the surface of the substrate 7 at the outlet of the microdroplet 8. This arrangement ensures that the microdroplet 8, under the influence of the substrate 7 at the outlet of the liquid channel 3, can only be generated downwards. The liquid at the outlet is subjected to an upward oscillating force, which generates an upward shearing effect on the liquid. The greater the oscillating force, the greater the shearing effect on the microdroplet 8, which can accelerate the shearing speed of the microdroplet 8 at the outlet, that is, the generation time of the microdroplet 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 microdroplets 8 generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole communicating with 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 communicating with 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, such as Figure 9 As shown, when the flexible cover plate 6 is located above the substrate 7 and the hydrophobic modified oil pool 4 is formed 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 microdroplets 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, to ensure that the microdroplets generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole communicating with the atmosphere is formed on the side wall of the hydrophobic modified oil pool 4, that is, the hole is formed 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 communicating with the outside atmosphere is formed on the top of the hydrophobic modified oil pool 4, that is, the hole is formed on the flexible cover plate 6.

[0111] like Figure 10 and Figure 11 As shown, when the flexible cover plate 6 is located below the substrate 7 and the hydrophobic modified oil pool 4 is formed 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 microdroplets 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 microdroplets generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil pool 4, a hole communicating with the atmosphere is formed on the side wall of the hydrophobic modified oil pool 4, that is, the hole is formed 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... Figure 11 As shown, a hole is made at the top of the hydrophobic modified oil tank 4 to connect with the outside atmosphere, that is, the hole is made on the flexible cover plate 6, or the top opening of the hydrophobic modified oil tank 4 is connected to the outside atmosphere.

[0112] like Figure 12As shown, the aforementioned hydrophobic modified oil tank 4 can also be simultaneously formed on the flexible cover plate 6 and the substrate 7. The hydrophobic modified oil tank 4 is simultaneously formed on the flexible cover plate 6 and the substrate 7, and is located inside between the flexible cover plate 6 and the substrate 7. To ensure that the microdroplets generated by the liquid channel 3 can smoothly enter the hydrophobic modified oil tank 4, a hole communicating with the outside atmosphere is formed on the upper part of the sidewall of the hydrophobic modified oil tank 4 on the side opposite to the liquid channel 3, that is, a hole communicating with the atmosphere is formed on the flexible cover plate 6 or the substrate 7. Or, as... Figure 13 As shown, the top of the hydrophobic modified oil tank 4 has a hole that connects to the outside atmosphere, or the top opening of the hydrophobic modified oil tank 4 is connected to the outside atmosphere.

[0113] This embodiment also provides a method for manufacturing a microfluidic chip, including processing a bonding passivation region 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 region 5. By processing the bonding passivation region 5 on the flexible cover plate 6 and / or the substrate 7, after the two are bonded together, the bonding passivation region 5 cannot be bonded, thus forming a liquid channel 3. The dimension of the liquid channel 3 along the height direction is close to 0. The liquid channel 3, in conjunction with the oscillating force generated by the flexible cover plate 6 on the microdroplets 8 at the outlet of the liquid channel 3, can form microdroplets 8 with a size much smaller than the size of the liquid channel 3, and can accelerate the generation of microdroplets 8. At the same time, since 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 squeezing of the liquid on the flexible cover plate 6 within the liquid channel 3, microdroplets 8 with uniform diameter 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 through ionic bonds, covalent bonds, metallic bonds, paradigm forces, hydrogen bonding, etc., or by physical bonding through thermal bonding, surface modification bonding, ultrasonic bonding, solvent bonding, adhesive bonding, etc.

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

[0116] Specifically, the aforementioned SU8 photoresist technology uses a smooth, flexible cover plate 6 and / or substrate 7 as a base. A layer of SU8 photoresist with a height at the nanometer scale is photolithographically formed on the substrate using soft photolithography to create a bonding passivation region 5. The bonding passivation region 5 formed using this technology then forms the liquid channel 3, resulting in low manufacturing costs.

[0117] The aforementioned vapor deposition technique involves using a mask to cover the entire flexible cover plate 6 or substrate 7, exposing only the area where the passivation bonding region needs to be prepared. The substrate is then placed in a sealed container, and chlorosilane is introduced into the sealed container. The chlorosilane evaporates and covers the area not covered by the mask, forming a passivation coating with a molecular-level thickness. This passivation coating is the bonding passivation region 5.

[0118] The above sputtering technique involves using a mask to cover the entire area of ​​the flexible cover plate 6 or substrate 7 where the bonding passivation region 5 needs to be prepared, and then bombarding it with oxygen ions to form a passivation coating with molecular-level thickness in the unbombarded area. This passivation coating is the bonding passivation region 5.

[0119] This embodiment also provides a method for generating microdroplets, which utilizes the microfluidic chip described above, including the liquid passing through the liquid channel 3 and the oscillation force generated by the flexible cover plate 6 on the microdroplets 8 at the outlet of the liquid channel 3 to form microdroplets 8 with a diameter of micrometers.

[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 implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A microfluidic chip, characterized in that, It includes a flexible cover plate (6) and a substrate (7), wherein the flexible cover plate (6) and / or the substrate (7) are provided with bonding passivation regions (5), the flexible cover plate (6) and the substrate (7) are bonded together, and the bonding passivation regions (5) form liquid channels (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 planar.

3. The microfluidic chip according to claim 2, characterized in that, The bonding passivation region (5) is a passivation coating with a thickness of nanometer or molecular level 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 using any one of SU8 photoresist technology, vapor deposition technology, or sputtering technology.

5. The microfluidic chip according to any one of claims 1-4, 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 liquid channel (3) has a rectangular cross-section, 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 1-4, characterized in that, The flexible cover plate (6) is made of either polydimethylsiloxane or silicone sheet.

8. The microfluidic chip according to any one of claims 1-4, characterized in that, It also includes a liquid injection assembly that is connected to the liquid channel (3) and is capable of injecting liquid into the liquid channel (3).

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

10. The microfluidic chip according to claim 9, characterized in that, The liquid injection assembly includes a fluid inlet (1) formed on the flexible cover plate (6) or the substrate (7), and the fluid inlet (1) communicates with 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) at the point 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 non-circular cavity.

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

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

15. The microfluidic chip according to any one of claims 1-4, characterized in that, It also includes a droplet collection assembly disposed at the outlet of the liquid channel (3), the droplet collection assembly being used to collect microdroplets generated by the liquid channel (3).

16. The microfluidic chip according to claim 15, characterized in that, The droplet collection assembly includes a hydrophobic modified oil pool (4) that is connected to the outside 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 bath (4) is formed on the flexible cover plate (6) and / or the substrate (7).

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

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

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

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

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

23. The method for manufacturing a microfluidic chip according to claim 22, characterized in that, include: The flexible cover plate (6) and the substrate (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, a layer of SUS8 photoresist with a height of nanometers is photolithographically formed on the smooth flexible cover plate (6) and / or the substrate (7) as a substrate, in order to form a bonding passivation region (5) with a thickness of nanometers.

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

26. The method for manufacturing a microfluidic chip according to claim 23, characterized in that, Using sputtering technology, the flexible cover plate (6) and / or the substrate (7) are covered by a mask to form a bonding passivation region (5). The masked area is bombarded with oxygen ions to form a bonding passivation region (5) with a thickness of molecular level.

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

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