Droplet-based biological detection microfluidic chip and control method thereof

Abstract

The application relates to a droplet biological detection microfluidic chip and a control method thereof, which comprises a storage pool, a focusing flow channel and a detection channel. The storage pool is used for connecting a droplet generation module and an inlet end of the focusing flow channel. The droplet generation module is used for generating droplets. The inlet end of the detection channel is communicated with the outlet end of the focusing flow channel. The focusing flow channel is provided with an interdigital transducer on at least one side in the extending direction. The inlet end of the focusing flow channel and the inlet end of the detection channel can be communicated or closed. The detection channel is provided with a light source on at least one side in the extending direction. The droplets move along a first path in the detection channel. The light emitted by the light source is projected on the detection point of the first path. The path length L of the first path between the inlet end of the detection channel and the detection point satisfies the condition of nS2<L≤(n+1)S2-(V1+V2)S1 / V1. According to the droplet biological detection microfluidic chip, the accuracy and resolution of optical detection of the droplets can be improved.

Description

Technical Field

[0001] This application relates to the field of microfluidics, and in particular to a droplet-type biodetection microfluidic chip and its control method. Background Technology

[0002] The term "microfluidic chip" originated in the 1990s when Manz and Widmer proposed the Micrototal Analysis System (μTAS). Professor Manz successfully applied MEMS technology to analytical chemistry and soon after achieved high-speed capillary electrophoresis on a microchip. His findings were published in journals such as *Science*, and this field quickly gained attention from the academic community, becoming one of the most cutting-edge technological fields in the world today. Lab on a chip and microfluidic chip are both different names coined for this field. However, as its applications have expanded from initial analytical chemistry to multiple research and application areas, and as researchers have gained a deeper understanding of the discipline, "microfluidic chip" has become the general term for this field. Microfluidics is the science and technology of handling and manipulating minute amounts (10⁻⁹ to 10⁻¹⁸ liters) of fluid within channel systems on the scale of tens to hundreds of micrometers. The key characteristic of microfluidic chip technology is the manipulation of fluids within micrometer-scale channels. It is precisely because the micron-scale structure of microfluidic chips significantly increases the specific surface area of ​​fluids, that is, the ratio of surface area to volume, that a series of special surface-related effects are generated, such as laminar flow effect, surface tension, capillary effect, rapid heat conduction effect, diffusion effect, etc., thus bringing them superior performance that macroscopic laboratory devices do not have, making them burst with vitality.

[0003] Droplet microfluidics, an important branch of microfluidic chip research, is a discontinuous flow microfluidic technology developed in the last two years based on traditional continuous flow microfluidic systems. It utilizes incompatible microfluidics to generate dispersed microdroplets for experimental manipulation. Droplet microfluidics combines the characteristics of droplets and microfluidics, offering advantages such as small size, rapid generation rate, uniform size, closed system, and good monodispersity. It enables flow control of droplets within microchannels, providing a novel platform for biological and medical research and has been widely applied in the analysis and detection of biomolecules such as DNA, proteins, and enzymes, as well as drug delivery and other biomedical fields.

[0004] Combining droplet microfluidics with fluorescence analysis enables rapid detection and quantitative analysis of biomarker characteristics from biological samples, thereby guiding disease diagnosis and treatment. Meanwhile, it can be used to detect and control the quality of food or environmental samples. Currently, the application of droplet microfluidic chips in the biomedical field is still in its initial stage, and multi-functionalization, integration, and intelligence are the development trends. Droplet microfluidics still faces a series of challenges, among which how to achieve rapid and accurate detection and analysis of a large number of droplets is a difficult point in the popularization of this technology. The droplet generation speed is very fast, and the too-fast formation speed and the short distance between droplets affect the accuracy and resolution of later optical detection. Summary of the Invention

[0005] The present invention aims to solve at least one of the technical problems existing in the prior art. For this purpose, the present invention provides a droplet-based biological detection microfluidic chip, enabling droplets to have sufficient flow space so that their speeds can meet the requirements of detection speed and detection time when flowing through the detection point, thereby improving the accuracy and resolution of optical detection of droplets.

[0006] The droplet-based biological detection microfluidic chip according to an embodiment of the present invention includes: a storage pool, a focusing channel, and a detection channel. The storage pool is used to connect the droplet generation module and the inlet end of the focusing channel. The droplet generation module is used to generate droplets. The inlet end of the detection channel is connected to the outlet end of the focusing channel. The focusing channel is provided with interdigital transducers on at least one side in its extending direction. The inlet ends of the focusing channel and the detection channel can be both turned on or off. The detection channel is provided with a light source on at least one side in its extending direction. The droplets move along a first path in the detection channel. The position where the light emitted by the light source is projected on the first path is the detection point. The path length L between the inlet end of the detection channel and the detection point on the first path satisfies: nS2 < L ≤ (n + 1)S2 - (V1 + V2)S1 / V1, where n is a positive integer greater than or equal to 1, S1 is the distance between the focused droplets in the focusing channel, V1 is the flow velocity of the focused droplets, S2 is the minimum distance between the droplets required for detection, and V2 is the maximum flow velocity of the droplets in the detection channel that meets the detection speed requirement.

[0007] According to an embodiment of the present invention, the droplet-type bio-detection microfluidic chip is placed in the field of view of the detector during use. The droplets generated by the droplet generation module are stored in a storage pool. When the inlet end of the focusing channel is open, the droplets in the storage pool can enter the focusing channel. When the inlet end of the focusing channel is closed, the droplets are stored in the storage pool to prevent the droplets from being generated too quickly and entering the focusing channel at the same time, which could lead to inaccurate subsequent detection. When the droplets enter the focusing channel, the surface acoustic waves generated by the interdigital transducer act on the droplets in the focusing channel, causing the droplets to be focused and arranged in a row. Then, they enter the detection channel. The sheath fluid input by the sheath fluid delivery device drives the focused droplets to continue to move forward into the detection channel. The light source is focused at a position in the detection channel as a detection point to detect the droplets passing through this point. By limiting the path length of the droplets from the inlet end of the detection channel to the detection point, the droplets have enough flow space so that their speed can meet the requirements of detection speed and detection time when flowing through the detection point, thereby improving the accuracy and resolution of optical detection of droplets.

[0008] According to an embodiment of the present invention, in a droplet-type biodetection microfluidic chip, the multiple interdigital electrodes of the interdigital transducer are curved in an arc shape in the same direction.

[0009] According to an embodiment of the present invention, the droplet-type biodetection microfluidic chip has a focusing channel extending along a first direction, the length of the focusing channel being L1, and a first position on the focusing channel along the first direction. The distance D between the first position and the inlet end of the focusing channel satisfies: D = 2 / 3L1. The projection of the interdigital transducer on the focusing channel is located between the inlet end of the focusing channel and the first position.

[0010] Optionally, interdigital transducers are provided on both sides of the focusing channel along the first direction, and the multiple interdigital electrodes of the two interdigital transducers are bent toward the focusing channel.

[0011] Optionally, the center line of symmetry of each interdigital transducer and the midpoint of the focusing channel along the first direction are collinear.

[0012] Optionally, the linewidth d1 and spacing d2 of the interdigital transducer's interdigital electrodes satisfy: d1=d2=1 / 4λ, where λ is the wavelength of the sound wave, and / or, the multiple interdigital electrodes of the interdigital transducer have the same central angle α, where α satisfies: 30°≤α≤40°.

[0013] According to an embodiment of the present invention, in a droplet-type biodetection microfluidic chip, the distances between the two interdigital transducers and the sidewalls of the adjacent focusing channels are equal.

[0014] According to an embodiment of the present invention, the droplet-type biodetection microfluidic chip further includes: a detector, which is disposed on one side of the detection channel in the third direction and spaced apart from the detection channel, and the projection of the detector in the third direction covers the detection point, with the first direction, the second direction and the third direction being perpendicular to each other.

[0015] According to an embodiment of the present invention, the droplet-type biodetection microfluidic chip has a detection channel with an inlet end including a first inlet end and a second inlet end. The first inlet end is connected to the outlet end of the focusing channel, and the second inlet end is used to connect to a sheath fluid delivery device, which is used to deliver sheath fluid to the detection channel.

[0016] According to an embodiment of the present invention, a control method is used in the above-mentioned droplet-type biodetection microfluidic chip. The droplet-type biodetection microfluidic chip includes a first switch and a second switch, both of which are polydimethylsiloxane membrane pneumatic valves. The first switch is located between the storage pool and the focusing channel to open or close the inlet end of the focusing channel, and the second switch is located at the inlet end of the detection channel to open or close the inlet end of the detection channel. The control method includes: simultaneously opening or closing the first switch and the second switch, with the opening duration t1 = S1 / V1 and the closing duration t2 ≥ (S2 - (V1 + V2)t1) / V2; when the first droplet flows out of the focusing channel, the first switch and the second switch are controlled alternately with a closing duration of t2 and an opening duration of t1, wherein S1 is the distance between the focused droplets in the focusing channel, V1 is the flow velocity of the focused droplets, S2 is the minimum distance between the droplets required for detection, and V2 is the maximum flow velocity of the droplets in the detection channel to meet the detection velocity requirements. Attached Figure Description

[0017] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, those skilled in the art can obtain other drawings based on these drawings without creative effort.

[0019] Figure 1 A cross-sectional view of a droplet-type biodetection microfluidic chip according to an embodiment of the present invention;

[0020] Figure 2 This is a schematic diagram of a droplet-type biodetection microfluidic chip according to an embodiment of the present invention;

[0021] Figure 3 for Figure 2Cross-sectional view at point AA;

[0022] Figure 4 for Figure 2 Cross-sectional view at point BB;

[0023] Figure 5 This is a schematic diagram of the cover plate of a droplet-type biodetection microfluidic chip according to an embodiment of the present invention.

[0024] Figure label:

[0025] Cover plate 1a, substrate 1b, storage tank 10, sample inlet 11, focusing channel 20, first switch 21, second switch 22, detection channel 30, first inlet end 31, second inlet end 32, waste liquid outlet 33, interdigital transducer 40, light source 50, detector 60, blind hole 61, optical focusing channel 70.

[0026] Droplet generation module 2, third switch 201,

[0027] Detection point a. Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0029] like Figure 1 As shown, the droplet-type biodetection microfluidic chip according to an embodiment of the present invention includes: a storage pool 10, a focusing channel 20, a detection channel 30, an interdigital transducer 40, and a light source 50.

[0030] Specifically, the storage pool 10 is used to connect the droplet generation module 2 and the inlet end of the focusing channel 20. The droplet generation module 2 is used to generate droplets. The inlet end of the detection channel 30 is connected to the outlet end of the focusing channel 20. The focusing channel 20 is provided with interdigital transducers 40 on at least one side in its extending direction. The inlet end of the focusing channel 20 and the inlet end of the detection channel 30 can be导通 or closed. The detection channel 30 is provided with a light source 50 on at least one side in its extending direction. The droplets move along a first path in the detection channel 30. The position where the light emitted by the light source 50 is projected on the first path is the detection point a. The path length L between the inlet end of the detection channel 30 and the detection point a on the first path satisfies: nS2 < L ≤ (n + 1)S2 - (V1 + V2)S1 / V1, where n is a positive integer greater than or equal to 1, S1 is the distance between the focused droplets in the focusing channel 20, V1 is the flow velocity of the focused droplets, S2 is the minimum distance between the droplets required for detection, and V2 is the maximum flow velocity of the droplets in the detection channel 30 that satisfies the detection velocity requirement.

[0031] It should be noted that the detection channel 30 can be a straight channel extending in the first direction, as Figure 1 shown, or a curved channel, which is not limited in this application. When the detection channel 30 is a straight channel extending in the first direction, the distance between the light source 50 and the inlet end of the detection channel 30 in the first direction is equal to the path length L between the inlet end of the detection channel 30 and the detection point a on the first path.

[0032] In use, the droplet-based biological detection microfluidic chip is placed in the field of view of the detector 60. The droplets generated by the droplet generation module 2 are stored in the storage pool 10. When the inlet end of the focusing channel 20 is导通, the droplets in the storage pool 10 can enter the focusing channel 20. When the inlet end of the focusing channel 20 is closed, the droplets are stored in the storage pool 10 to prevent the possibility that the droplets are generated too fast and enter the focusing channel 20 simultaneously, resulting in inaccurate subsequent detection. The droplets enter the focusing channel 20, and the surface acoustic wave generated by the interdigital transducer 40 acts on the droplets in the focusing channel 20 to make the droplets focus and arrange in a row, and then enter the detection channel 30. The droplets move along the first path, and the light emitted by the light source 50 is focused on a position in the detection channel 30 as the detection point a. The detector 60 is focused on the detection point a to detect the droplets flowing through here. By限定 the path length of the droplets moving from the inlet end of the detection channel 30 to the detection point a, the droplets passing through the detection point a are detected, so that the droplets can have enough flow space to make their speed meet the requirements of detection speed and detection time when flowing through the detection point a, thereby improving the accuracy and resolution of optical detection of droplets. Among them, the detector 60 can be内置 in the droplet-based microfluidic chip or an external optical device.

[0033] It should be noted that the Chinese character "导通" in the original text may not be an accurate English expression. Here, it is tentatively translated as "conducted", but it may need to be adjusted according to the specific context. Also, the term "内置" is tentatively translated as "built-in", which may also need to be refined.The inlet ends of the focusing channel 20 and the detection channel 30 can be opened or closed via a first switch 21 and a second switch 22. Both the first switch 21 and the second switch 22 are polydimethylsiloxane membrane pneumatic valves. The first switch 21 is located between the droplet generation module 2 and the focusing channel 20 to open or close the inlet end of the focusing channel, and the second switch 22 is located at the inlet end of the detection channel 30 to open or close the inlet end of the detection channel 30.

[0034] It is understandable that the width of the focusing channel 20 is greater than the diameter of the droplet, and the length of the focusing channel 20 along the first direction is greater than the length of the interdigital transducer 40.

[0035] According to the droplet-type biodetection microfluidic chip of the present invention, the distance between the light source 50 and the inlet end of the detection channel 30 in the first direction allows the droplet to have sufficient flow space so that its speed can meet the requirements of detection speed and detection time when flowing through the detection point a, thereby improving the accuracy and resolution of optical detection of droplets.

[0036] like Figure 1 and Figure 5 As shown, the storage tank 10 is also provided with an inlet 11, through which a buffer solution can be introduced, thereby driving the droplets in the storage tank 10 to flow out into the focusing channel 20. The outlet end of the droplet generation module 2 is provided with a third switch 201, which can control the generated droplets to enter the storage tank 10 by turning the third switch 201 on or off.

[0037] In some embodiments, the droplet-type biodetection microfluidic chip further includes a detector 60, meaning that the droplet-type biodetection microfluidic chip has a built-in detector 60. The detector 60 is disposed on one side of the detection channel 30 in the third direction. Along the third direction, the detector 60 is disposed above the detection channel 30 and spaced apart from it, or the detector 60 is disposed below the detection channel 30 and spaced apart from it. The projection of the detector 60 in the third direction covers the detection point a, wherein the first direction, the second direction, and the third direction are perpendicular to each other.

[0038] In some embodiments, the droplet-type biosensing microfluidic chip further includes an optical focusing channel 70, in which a light source 50 is disposed. The optical focusing channel 70 is perpendicular to and spaced apart from the detection channel 30 in a second direction, and light is transmitted between the optical focusing channel 70 and the detection channel 30. The light source 50 may be an LED light source. In some embodiments, the light source 50 is provided on one of the two opposite sides of the detection channel 30 along the second direction; in other embodiments, the light source 50 is provided on both opposite sides of the detection channel 30 along the second direction.

[0039] In some embodiments, the droplet-type biosensing microfluidic chip is fabricated as follows:

[0040] like Figure 5 As shown, the cover plate 1a is fabricated using etching / photolithography injection molding technology to create the related gas path chamber structure and through-hole structure of the first switch 21 and the second switch 22. This includes an inlet 11, a second inlet end 32, a waste liquid outlet 33 for discharging detected droplets, and a blind hole 61 for housing the detector 60. The blind hole 61 is transparent to the detection channel 30 so that the detector 60 can capture images. Figures 2-4 As shown, a polydimethylsiloxane (PDMS) film is bonded on substrate 1b using plasma technology. The PDMS film is commonly referred to as a PDMS film. The focusing channel 20 is integrated by spin-coating on substrate 1b with parameters of 30 kPa, 300 rpm, and 10 s. The soft-bake parameters are 90°C and 120 s, followed by two repeated exposures, development for 100 s, and post-bake at 230°C for 30 min. The interdigital transducer 40 is integrated by depositing interdigital electrodes on a LiNbO3 piezoelectric substrate. The data line etching temperature is 125°C. The interdigital electrode layer is formed by photolithography using a molybdenum-aluminum-molybdenum (Mo-Al-Mo) composite film with the following parameters: The substrate 1b and the cover plate 1a are then hot-pressed or encapsulated with UV adhesive. An interdigital transducer 40 is disposed on one side of the focusing channel 20 on the substrate 1b.

[0041] In other embodiments, such as Figure 1 As shown, the detection channel 30 includes a first inlet end 31 and a second inlet end 32, which can be opened or closed. The outlet end of the focusing channel 20 is connected to the first inlet end 31, and the second inlet end 32 is used to connect to the sheath fluid delivery device. The inlet end and outlet end of the focusing channel 20 are arranged along a first direction. The sheath fluid delivery device is used to input sheath fluid into the detection channel 30 to drive the focused droplets to move, so that the droplets can continue to advance into the detection channel 30 at a certain speed. One end of the second switch 22 is connected to the sheath fluid delivery device and the focusing channel 20, and the other end of the second switch 22 is connected to the detection channel 30. The second switch 22 is used to close the inlet end of the detection channel 30.

[0042] The first inlet end 31 is located between the two second inlet ends 32. The droplet enters the detection channel 30 through the first inlet end 31 located in the middle, and is then squeezed and pushed to the detection point a by the sheath flow on both sides. In addition, since the acoustic radiation force experienced by the particles in the focusing channel 20 has a component in the direction perpendicular to the interdigital transducer 40, the height of the focusing channel 20 along the third direction is set to 50-100 μm in order to limit the displacement of the particles along its vertical direction. For example, the height of the focusing channel 20 is 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, and 100 μm, etc. Among them, the first direction, the second direction, and the third direction are perpendicular to each other.

[0043] According to an embodiment of the droplet-type biodetection microfluidic chip of the present invention, the multiple interdigital electrodes of the interdigital transducer 40 are curved in the same direction in an arc shape. The curved interdigital electrodes enable the surface acoustic wave field formed by them to exhibit a non-uniform fan-shaped arc. In the acoustic field, particles of different sizes are subjected to different acoustic radiation forces, thereby enabling better separation and focusing of sample droplets.

[0044] According to an embodiment of the droplet-type biodetection microfluidic chip of the present invention, a focusing channel 20 extends along a first direction. The focusing channel 20 is a straight channel with a length of L1. A first position is located on the focusing channel 20 along the first direction. The distance D between the first position and the inlet end of the focusing channel 20 satisfies: D = 2 / 3L1. The projection of the interdigital transducer 40 on the focusing channel 20 is located between the inlet end of the focusing channel 20 and the first position. This allows the droplet to be fully focused while ensuring that the droplet flows out of the focusing channel 20 after the focusing is stable.

[0045] According to an embodiment of the present invention, the droplet-type biodetection microfluidic chip has interdigital transducers 40 on both sides of the focusing channel 20 along the first direction. The multiple interdigital electrodes of the two interdigital transducers 40 are bent toward the focusing channel 20. This utilizes the focusing characteristics of the focusing interdigital transducers 40. Before focusing, the oscillation of the surface acoustic wave slows down. After focusing, the attenuation of the sound field energy gradually slows down, thereby enabling better focusing of the sample droplet.

[0046] Optionally, the center line of symmetry of each interdigital transducer 40 and the midpoint of the focusing channel 20 along the first direction are collinear. This allows the droplets to be fully focused while ensuring that the droplets flow out of the focusing channel 20 after the focusing is stable.

[0047] Optionally, the linewidth d1 and spacing d2 of the interdigital electrodes of the interdigital transducer 40 satisfy: d1=d2=1 / 4λ, where λ is the wavelength of the sound wave.

[0048] Optionally, the multiple interdigital electrodes of the interdigital transducer 40 have the same central angle α, where α satisfies: 30° ≤ α ≤ 40°. For example, α can be 32°, 34°, 36°, 38°, and 40°, etc.

[0049] The larger the focusing angle, i.e., the central angle, of the interdigital transducer 40, the better its focusing performance. When the focusing angle increases to a certain extent, its amplitude is approximately constant and the focusing area is relatively concentrated, but the insertion loss is also large at this point. Therefore, the focusing angle cannot be too large. In addition, the focusing angle cannot be too small either, as a too small focusing angle will lead to unstable and unconcentrated focusing energy.

[0050] According to an embodiment of the droplet-type biosensing microfluidic chip of the present invention, the distances between the two interdigital transducers 40 and the sidewalls of the adjacent focusing channels 20 are equal. This ensures that the droplets flowing through the focusing centers of the two interdigital transducers 40 are subjected to uniform force, preventing deflection.

[0051] According to the control method of the present invention, for the above-mentioned droplet-type biodetection microfluidic chip, the control method includes: simultaneously opening or closing the first switch 21 and the second switch 22, with the opening duration t1 = S1 / V1 and the closing duration t2 ≥ (S2 - (V1 + V2)t1) / V2; when the first droplet flows out of the focusing channel 20, controlling the first switch 21 and the second switch 22 to alternately control the closing duration t2 and the opening duration t1, wherein S1 is the distance between the focused droplets in the focusing channel 20, V1 is the flow velocity of the focused droplets, S2 is the minimum distance between the droplets required for detection, and V2 is the maximum flow velocity of the droplets in the detection channel 30 to meet the detection speed requirements. When the first droplet, after being focused by the focusing channel 20, flows out of the outlet of the focusing channel 20, the first switch 21 and the second switch 22 are controlled to be closed for a duration of t2. The sheath fluid carries the focused droplet to the detection point a at a certain speed. After the first droplet has traveled a certain distance, the first switch 21 and the second switch 22 are controlled to be opened, releasing the second focused droplet into the detection channel 30. The sheath fluid carries the second droplet to the detection point a at the same speed, and so on. This ensures that the distance between the two droplets that pass through the detection point a successively is greater than or equal to S2, thereby improving the accuracy and precision of the detection.

[0052] According to the control method of the present invention, the speed and spacing of the droplet flowing through the detection point a can be guaranteed to meet the requirements of optical detection, eliminate the interference of the droplet flow speed on optical detection, and improve the accuracy and resolution of optical detection of droplets.

[0053] Optionally, the sheath fluid delivery device controls the sheath fluid flow rate of the input detection channel 30 to be less than or equal to V2, so that the speed at which the focused droplet flows through the detection point a meets the requirement of not exceeding V2, preventing the droplet from flowing too fast and reducing the detection accuracy.

[0054] In the description of this invention, it should be understood that the terms "upper," "lower," "left," "right," "inner," "outer," "axial," "radial," and "circumferential," etc., indicating orientation or positional relationships, are based on the orientation or positional relationships shown in the accompanying drawings and are only for the convenience of describing the invention and 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, and therefore should not be construed as a limitation of the invention. Furthermore, features defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0055] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" 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; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0056] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

Claims

1. A droplet bio-detection microfluidic chip, characterized in that, The microfluidic chip comprises: a storage pool, a focusing flow channel and a detection channel, the storage pool is used for connecting a droplet generating module and an inlet end of the focusing flow channel, the droplet generating module is used for generating droplets, an inlet end of the detection channel is connected with an outlet end of the focusing flow channel, the focusing flow channel is provided with an interdigital transducer on at least one side in the extension direction of the focusing flow channel, the inlet end of the focusing flow channel and the inlet end of the detection channel are both openable or closable, and the detection channel is provided with a light source on at least one side in the extension direction of the detection channel, the droplets move along a first path in the detection channel, a detection point is formed by the light emitted by the light source on the position of the first path, and the path length L of the first path between the inlet end of the detection channel and the detection point satisfies: nS2 < L ≤ (n+1)S2-(V1+V2)S1 / V1, wherein n is a positive integer greater than or equal to 1, S1 is the distance between the focused droplets in the focusing flow channel, V1 is the flow velocity of the focused droplets, S2 is the minimum distance required for detecting the droplets, and V2 is the maximum flow velocity of the droplets in the detection channel that meets the detection velocity requirement; the droplet biological detection microfluidic chip comprises a first switch and a second switch, the first switch and the second switch are both polydimethylsiloxane film pneumatic valves, the first switch is arranged between the storage pool and the focusing flow channel and is used for opening or closing the inlet end of the focusing flow channel, and the second switch is arranged at the inlet end of the detection channel and is used for opening or closing the inlet end of the detection channel.

2. The droplet-based bio-detection microfluidic chip according to claim 1, wherein, The plurality of interdigital electrodes of the interdigital transducer are curved in a circular arc shape towards the same direction.

3. The droplet-based bio-detection microfluidic chip according to claim 1, wherein, The focusing flow channel extends along a first direction, the length of the focusing flow channel is L1, the focusing flow channel has a first position along the first direction, the distance D between the first position and the inlet end of the focusing flow channel satisfies: D = 2 / 3L1, and the projection of the interdigital transducer on the focusing flow channel is located between the inlet end of the focusing flow channel and the first position.

4. The droplet-based bio-detection microfluidic chip according to claim 3, wherein, The focusing flow channel is provided with the interdigital transducer on both sides along the first direction, and the plurality of interdigital electrodes of the two interdigital transducers are curved towards the focusing flow channel.

5. The droplet-based bio-detection microfluidic chip according to claim 4, wherein, The center lines of symmetry of the interdigital transducers and the midpoint of the focusing flow channel along the first direction are collinear.

6. The droplet-based bio-detection microfluidic chip according to claim 4, wherein, The line width d1 and the pitch d2 of the interdigital electrodes of the interdigital transducer satisfy: d1 = d2 = 1 / 4λ, wherein λ is the wavelength of the acoustic wave, and / or The plurality of interdigital electrodes of the interdigital transducer have the same central angle degree α, and α satisfies: 30° ≤ α ≤ 40°.

7. The droplet-based bio-detection microfluidic chip according to claim 1, wherein, The distance between the two interdigital transducers and the side walls of the adjacent focusing flow channels is equal.

8. The droplet-based bio-detection microfluidic chip according to claim 1, wherein, Further comprising: a detector arranged on one side of the detection channel in a third direction and spaced from the detection channel, the projection of the detector on the third direction covers the detection point, and the first direction, the second direction and the third direction are perpendicular to each other.

9. The droplet-based bio-detection microfluidic chip of claim 1, wherein the inlet end of the detection channel comprises a first inlet end and a second inlet end, the first inlet end is in communication with the outlet end of the focusing flow channel, and the second inlet end is configured to be in communication with a sheath fluid delivery device configured to deliver sheath fluid to the detection channel.

10. A control method for controlling the droplet bio-detection microfluidic chip according to any one of claims 1-9, characterized in that, The droplet-based bio-detection microfluidic chip comprises a first switch and a second switch, both of which are polydimethylsiloxane membrane pneumatic valves, the first switch is disposed between the reservoir and the focusing flow channel and configured to open or close the inlet end of the focusing flow channel, and the second switch is disposed at the inlet end of the detection channel and configured to open or close the inlet end of the detection channel, and the control method comprises: opening or closing the first switch and the second switch at the same time, the opening maintaining time t1=S1 / V1, and the closing maintaining time t2≥(S2-(V1+V2)t1) / V2; controlling the first switch and the second switch to be closed for t2 and opened for t1 in turn and alternately when the first droplet flows out of the focusing flow channel, wherein S1 is the distance between the focused droplets in the focusing flow channel, V1 is the flow velocity of the focused droplets, S2 is the minimum distance required for the detection between the droplets, and V2 is the maximum flow velocity of the droplets in the detection channel to meet the detection velocity requirement.

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