Microfluidic chip and related devices and methods

Abstract

The present application relates to display technical field, provide a kind of microfluidic chip and the detection device comprising the microfluidic chip, microfluidic chip at least includes the substrate and sensing device of relative arrangement, the substrate is provided with driving electrode, the substrate with the sensing device forms the channel of containing droplet to be measured between it;The sensing device includes mutually connected control component and sensing component, the control component can control at least one of the sensing component and the substrate relative motion in the direction of approaching or moving away each other, to make the sensing component pass through the droplet to be measured and the driving electrode form electric connection passage.The detection device provided by the present application can accurately control the spacing between sensing component and different size droplet to be measured, thereby improving the accuracy of test data;And when the microfluidic chip in the present application adopts sealing structure, the evaporation rate of droplet can be effectively slowed down.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of display, in particular to a microfluidic chip, a detection device comprising the same and a detection method. BACKGROUND

[0002] Gene sequencing is a hot spot in the current biological medical field, and it is particularly important to study single cell or biochemical droplet system in sequencing engineering. The existing water droplet angle detection device can detect the water droplet angle or dynamic water droplet angle of water droplets or droplets on different substrates, so as to quantitatively evaluate the hydrophilic and hydrophobic performance, which is widely used in the testing and research of silicon crystal, liquid crystal, glass, fiber, synthetic material and other fields. Compared with traditional microarray and microfluidic system, the digital microfluidic device has stronger operability, does not need external air path device, can realize automation and miniaturization, and is widely used in the above-mentioned water droplet angle detection device.

[0003] The existing digital microfluidic device is mostly open single-pole plate type and single condition double-pole plate type. The single-pole plate type is driven by a metal wire with surface treatment as an electrode, and the water droplet or droplet on the chip electrode moves, which is recorded by a camera, so as to evaluate the moving performance of the water droplet or droplet. The double-pole plate type is monitored by a camera, so as to evaluate the moving performance of the water droplet or droplet, and obtain the water droplet angle size of the droplet. However, whether the digital microfluidic device of the single-pole plate type or the double-pole plate type, the upper electrode is fixedly arranged, and the position thereof cannot be adjusted, so that the spacing between the upper electrode and the droplet of different sizes is difficult to guarantee, which is not conducive to improving the precision of test data.

[0004] Therefore, the present application is proposed. SUMMARY

[0005] The present application provides a continuous dynamic detection device for digital droplets of a sequencer, so as to solve the problem in the prior art that the fixed position of the upper electrode leads to the difficulty in guaranteeing the spacing between the upper electrode and the droplet of different sizes, which is not conducive to improving the precision of test data.

[0006] To solve the above problems, the present application provides a microfluidic chip in a first aspect, which at least comprises a substrate and a sensing device arranged oppositely, the substrate is provided with a driving electrode; the substrate and the sensing device form a channel for accommodating a to-be-tested droplet; the sensing device comprises a control component and a sensing component connected with each other, the control component can control at least one of the sensing component and the substrate to move towards each other or away from each other, so that the sensing component forms an electrical connection path with the driving electrode through the to-be-tested droplet.

[0007] The microfluidic chip provided by the scheme comprises at least a substrate and a sensing device, the substrate is provided with a driving electrode, a channel for accommodating a to-be-tested droplet is formed between the substrate and the sensing device, and different to-be-tested droplets in different morphologies and components can be added dropwise in the channel above the driving electrode; the sensing device comprises a control component and a sensing component connected with each other, the control component can control at least one of the sensing component and the substrate to move in a direction of approaching or moving away from each other, that is, the control component can control the sensing component to move or control the substrate to move, or both the sensing component and the substrate can move, so that the sensing component forms an electrical connection path with the driving electrode through the to-be-tested droplet, the sensing component can sense the morphology and size of the to-be-tested droplet, and feedback the sensed information (such as the distance between the to-be-tested droplet and the sensing component) to the control component, and the control component adjusts the position of the sensing component (or the substrate) accordingly to accurately control the distance between the sensing component (that is, the upper electrode) and the to-be-tested droplet in different sizes, thereby improving the accuracy of test data.

[0008] In other preferred embodiments, the microfluidic chip further comprises a side wall connected with the top plate and extending towards the substrate; the sensing component comprises a top plate and at least one sensing electrode arranged on the top plate; the side wall, the top plate and the substrate form a sealed cavity, and when the control component controls the top plate to drive the sensing electrode to move, the top plate changes position relative to the substrate in the height direction of the side wall; and the driving electrode is at least partially located in the sealed cavity.

[0009] In specific use, the side wall, the top plate and the substrate form a sealed cavity, and the to-be-tested droplet is in a sealed environment, which can effectively solve the volatilization problem of the droplet, especially in the variable voltage detection of the droplet volatilizing rapidly, and the volatilization effect of the scheme is more obvious. The top plate is provided with at least one sensing electrode, the number of working sensing electrodes is matched with the number and position of to-be-tested droplets one by one, when the control component controls the top plate to drive the sensing electrode to move, the top plate changes position relative to the substrate in the height direction of the side wall, the vertical distance between the sensing electrode and the to-be-tested droplet can be adjusted, the distance between the upper electrode (that is, the sensing electrode) and the to-be-tested droplet in different sizes can be accurately controlled, and the driving electrode is at least partially located in the sealed cavity, so that the to-be-tested droplet can be placed above the part of the driving electrode located in the sealed cavity, and the sensing electrode can form an electrical connection path with the driving electrode through the to-be-tested droplet.

[0010] In other preferred embodiments, the upper surface of the substrate is provided with at least one driving electrode, and the upper surface of the driving electrode is provided with at least one detection area in which at least one droplet to be detected can be dropped, and the sensing electrode corresponds to the droplet to be detected in the detection area below; the sensing electrode is arranged corresponding to the detection area, and the sensing electrode is generally located above the corresponding detection area, and the microfluidic chip further comprises a positioning device for positioning the side of the sensing electrode close to the detection area, so as to monitor the distance between the sensing electrode and the droplet through the positioning device, and facilitate the adjustment of the distance between the sensing electrode and the droplet to be detected of different sizes.

[0011] In other preferred embodiments, all sensing electrodes are movably arranged on the top plate and are connected with the control component; the control component further controls the movement of the sensing electrode relative to the top plate towards the direction of approaching or moving away from the droplet to be detected on the basis of the movement of the top plate relative to the substrate.

[0012] In particular detection, after dropping the droplet to be detected in a certain detection area, the control component can control the sensing electrode at the corresponding position of the droplet to be detected to extend, and then the control component controls the movement of the top plate relative to the substrate (i.e. only the top plate can move), and when the top plate reaches the initially determined position (coarse adjustment), the control component further controls the movement of the sensing electrode relative to the top plate towards the direction of approaching or moving away from the droplet to be detected (fine adjustment), so as to make the tip of the sensing electrode contact the droplet to be detected through the cooperation of the above-mentioned coarse adjustment and fine adjustment, and facilitate the detection of the contact angle of the droplet.

[0013] In other preferred embodiments, the side wall is provided with a light-transmitting portion for transmitting light, and the light-transmitting rate of the light-transmitting portion is greater than or equal to 0.8, so as to ensure better light-transmitting effect, and the external light source can transmit light into the sealed cavity through the light-transmitting portion, and the light-transmitting portion is highly transparent, so as to facilitate the penetration of light and image acquisition.

[0014] In other preferred embodiments, the side wall comprises an inner wall made of transparent material and an outer wall made of non-transparent material, and the light-transmitting portion is arranged on the outer wall.

[0015] The inner wall and the outer wall in the present scheme can be directly attached, or can have a gap, and the light-transmitting portion is arranged on the non-transparent outer wall, so that the external light source can transmit light into the sealed cavity through the light-transmitting portion and the transparent inner wall, and facilitate the normal performance of subsequent image acquisition work.

[0016] In other preferred embodiments, the sensing electrode comprises an electrode wire and a shaft sleeve axially sleeved on the outer periphery of the electrode wire, and the shaft sleeve drives the electrode wire to be movably connected relative to the top plate, and the shaft sleeve can effectively protect the electrode wire embedded therein, so that the electrode wire can normally and stably perform sensing function.

[0017] In other preferred embodiments, the driving electrode comprises a patterned electrode sheet and a first protective layer disposed on the side of the electrode sheet close to the top plate; the first protective layer comprises at least a first dielectric layer and a first hydrophobic layer, and the driving electrode is used to control the movement of the droplet. The upper surface of the electrode sheet needs to be structured with a dielectric layer and a hydrophobic layer, or a two-in-one dielectric hydrophobic layer, which can be achieved by means of film pasting, spraying, deposition, etc. The dielectric layer is used to maintain the insulation between the lines and the layers.

[0018] In another preferred aspect, a second protective layer is disposed on the side of the top plate close to the substrate; the second protective layer comprises at least a conductive layer and a second hydrophobic layer disposed on the side of the conductive layer close to the substrate. The lower surface of the top plate needs to be structured with a conductive layer, such as by spraying, deposition, sputtering, etc., or by using a conductive material, and a hydrophobic layer needs to be structured outside the conductive layer, or a conductive and hydrophobic material is used.

[0019] In other preferred embodiments, a temperature control component connected to the substrate is further included, which is used to adjust the temperature of the substrate to control the temperature in the sealed cavity at 4-97℃, thereby solving the volatilization problem existing in the existing droplet contact angle testing device and enabling the evaluation and detection of droplets in the heating state and PCR process.

[0020] The second aspect of the present application provides a detection device comprising the microfluidic chip, the detection device further comprising a light source; and

[0021] an output module comprising a first output end connected to the driving electrode and a second output end connected to the sensing component; the output module can output different voltage driving signals to the electrical connection path;

[0022] an image processing module for collecting the morphology of the droplet in the channel under different voltage driving signals and detecting the contact angle size of the droplet.

[0023] In the specific application of the detection device to detect the contact angle of the droplet to be tested, the light source is first aligned with the light-transmitting part to make the light enter the cavity, and is then aligned with the droplet to be tested, so as to facilitate the detection of the contact angle. The position of the sensing electrode is adjusted to make it contact with the droplet to be tested, and then the output module is turned on to supply voltage to the driving electrode and the sensing electrode. Different voltage driving signals are provided to the electrical connection path, and finally the morphology of the droplet in the channel under different voltage driving signals is collected by the image processing module, and the contact angle size of the droplet to be tested is detected.

[0024] In other preferred embodiments, the driving electrodes are arranged in a pattern on the substrate, and each driving electrode in each interval part is provided with a detection area capable of accommodating the droplet to be detected above it, and the control component further controls the output module to output corresponding voltage signals to the driving electrodes to control the movement of the droplet, and in specific applications, the movement, splitting and merging of the droplet can be realized by energizing different electrodes in the patterned electrodes based on the principle of dielectric wetting.

[0025] In other preferred embodiments, the image processing module comprises a camera for acquiring the droplet morphology, and a host device connected with the camera and used for analyzing and processing the image data.

[0026] In specific applications, the morphology of the droplet is first acquired by the camera, and the image data is analyzed and processed by the host device to detect the contact angle of droplets of different sizes and shapes in real time.

[0027] The third aspect of the present application provides a detection method using the detection device, wherein the sensing component comprises a top plate movably arranged on the substrate, and at least one sensing electrode arranged on the top plate, and the channel is formed between the top plate and the substrate; the detection method comprises at least the following steps:

[0028] a. providing a droplet to be detected into the channel;

[0029] b. driving the top plate to move to an initial position relative to the substrate by the control device, then detecting the position information of the sensing electrode by the positioning device and feeding back to the control component, and the control component further adjusts the position of the sensing electrode based on the position information, so that the end of the sensing electrode contacts the droplet to be detected, so that the sensing electrode forms an electrical connection path with the driving electrode through the droplet to be detected;

[0030] c. applying voltage to the driving electrode and the sensing component by the output module, and acquiring the droplet angle and the morphology change diagram of the droplet to be detected under the corresponding condition by the image processing module.

[0031] The present application provides a method for detecting the droplet angle and the morphology change of the droplet under a sealed state, which can not only avoid the volatilization of the droplet, but also automatically control the end of the sensing electrode to contact the droplet to be detected of different sizes by the control device, so that the sensing electrode forms an electrical connection path with the driving electrode through the droplet to be detected, which is convenient for subsequent electrical detection.

[0032] In other preferred embodiments, at least two droplets to be detected with different sizes are located in the channel in step a, and step b further comprises adjusting the distance between the sensing electrode corresponding to each droplet to be detected and the corresponding droplet to be detected, respectively.

[0033] In the embodiment, the morphology and the water drop angle size of at least two different sizes of the droplets to be detected can be detected simultaneously, and it is understood that, under the condition of one-to-one control of the control device, the detection device and the detection method provided by the application can be completely applied to simultaneously detect more different sizes of droplets, and the morphology and the water drop angle size of each droplet can be obtained in real time.

[0034] The fourth aspect of the application provides a sequencing device comprising the microfluidic chip, which adopts a sealed chip device, can prevent volatilization, can accurately control the contact between the upper electrode (the end of the sensing electrode) and droplets of different sizes, is automatically configured in a full process, greatly reduces the manual operation time, and can effectively improve the test data precision.

[0035] The fifth aspect of the application provides a manufacturing method of a droplet control chip for a sequencer, the manufacturing method comprising determining process parameters of the droplet control chip by using the detection device, the process parameters at least comprising position information and voltage control parameters; the sensing component comprises a top plate movably arranged with the substrate and at least one sensing electrode arranged on the top plate, and the channel is formed between the top plate and the substrate; the process parameters of the droplet control chip are determined by:

[0036] selecting droplets to be detected of a specified size, and applying the droplets to be detected into the channel;

[0037] adjusting the relative distance between the top plate and the substrate, and further adjusting the position between the sensing electrode and the droplets to be detected, to obtain the position information corresponding to the top plate, the substrate, the sensing electrode and the driving electrode when the end of the sensing electrode contacts the droplets to be detected;

[0038] adjusting the output module to output different voltage driving signals to the electrical connection path, to obtain the voltage control information corresponding to the droplets to be detected;

[0039] determining the optimal voltage control parameters based on the morphology and the contact angle size of the droplets to be detected under different voltage driving signals detected by the image processing module.

[0040] Compared with the prior art, the application has the following beneficial effects:

[0041] The microfluidic chip provided in the first aspect of the present application can sense the shape and size of the liquid droplet to be measured by the sensing component, and feed back the sensed information (such as the distance between the liquid droplet to be measured and the sensing component) to the control component, and the control component adjusts the position of the sensing component accordingly, so as to accurately control the distance between the sensing component (i.e. the upper electrode) and the liquid droplet to be measured of different sizes, thereby improving the accuracy of the test data; and when the microfluidic chip in the present application adopts a sealed structure, the evaporation rate of the liquid droplet can be effectively slowed down.

[0042] The detection device provided in the second aspect of the present application comprises the microfluidic chip, and the light is first aligned to the liquid droplet to be measured, the position of the sensing electrode is adjusted to make it contact with the liquid droplet to be measured, then different voltage driving signals are provided to the electrical connection channel, and finally the shape of the liquid droplet in the channel under different voltage driving signals is collected by the image processing module, and the contact angle of the liquid droplet to be measured is detected, the whole process is automatically configured, the operation time is greatly reduced, and the accuracy of the test data is improved.

[0043] The method for detecting the contact angle and shape change of a liquid droplet in a sealed state provided in the third aspect of the present application can not only avoid the evaporation of the liquid droplet, but also automatically control the end of the sensing electrode to contact with the liquid droplet to be measured of different sizes by the control device, so that the sensing electrode forms an electrical connection channel through the liquid droplet to be measured and the driving electrode, which is automatic control, convenient, fast and high in accuracy.

[0044] The sequencing device provided in the fourth aspect of the present application comprises the microfluidic chip, and the sealed chip device can not only prevent evaporation, but also accurately control the contact between the upper electrode (the end of the sensing electrode) and the liquid droplet of different sizes.

[0045] The manufacturing method of the liquid droplet control chip for a sequencer provided in the fifth aspect of the present application utilizes the microfluidic chip with a controllable distance between the substrate and the top plate, can quickly and conveniently obtain a plurality of process parameters suitable for the target liquid droplet, accurately prepares the corresponding liquid droplet control chip combined with the obtained process parameters, and is suitable for rapid detection of a multi-channel and complex system, rapid positioning of the optimized process parameters and conditions, and saving of process groping time and cost. BRIEF DESCRIPTION OF DRAWINGS

[0046] In order to more clearly illustrate the specific embodiments of the present application or the technical solutions in the prior art, the drawings needed in the following specific embodiments or prior art description will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0047] Figure 1 The structural schematic diagram of the microfluidic chip provided in one of the embodiments of the present application;

[0048] Figure 2 A structural schematic diagram of a detection device provided by one embodiment of the present application;

[0049] Figure 3 A structural schematic diagram of a detection device provided by another embodiment of the present application;

[0050] Figure 4 One of the morphological diagrams of a droplet to be detected on a driving electrode provided by the present application;

[0051] Figure 5 One of the morphological diagrams of a droplet to be detected on a driving electrode provided by the present application;

[0052] Figure 6 A schematic diagram of the state of a droplet in a detection process of an existing device;

[0053] Figure 7 A schematic diagram of the state of a droplet when a detection process of a sequencing device of the present application is completed;

[0054] Figure 8 A trend diagram of the contact angle of an EB liquid droplet with respect to voltage in a detection process of an existing device;

[0055] Figure 9 A trend diagram of the contact angle of an ultrapure water droplet with respect to voltage in a detection process of an existing device;

[0056] Figure 10 A trend diagram of the contact angle of an ultrapure water droplet and an EB liquid droplet with respect to voltage in a detection process of a sequencing device of the present application;

[0057] Figure 11 A real-time feedback diagram of voltage parameters in a specific embodiment of the present application.

[0058] Reference signs

[0059] 101, substrate; 102, driving motor; 103, temperature control component;

[0060] 200, sensing component; 201, top plate; 202, sensing electrode;

[0061] 300, side wall; 301, inner wall; 302, outer wall;

[0062] 400, driving electrode;

[0063] 500, droplet to be detected;

[0064] 600, light source;

[0065] 700, output module;

[0066] 800, image processing module; 801, camera device; 802, master device. DETAILED DESCRIPTION

[0067] In order to make the above and other features and advantages of the present application more comprehensible, the present application will be further described below with reference to the drawings. It should be understood that the specific embodiments given herein are by way of example only and are not to be construed in a limiting sense.

[0068] In the description of the present application, it should be understood that the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like are used to indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application.

[0069] In addition, the terms "first", "second", "third", etc. are only used for the purpose of description and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the technical features indicated. Therefore, the features defined with "first", "second", etc. can explicitly or implicitly include at least one of the features. In the description of the present application, the meaning of "a plurality of" is at least two, for example, two, three, etc., unless otherwise explicitly specified and limited.

[0070] In the present application, unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connecting", "fixing" and the like should be understood in a broad sense, for example, can be fixedly connected, or can be detachably connected, or can be integrated; can be mechanically connected, or can be electrically connected; can be directly connected, or can be indirectly connected through an intermediate medium; can be the internal communication of two elements or the interaction relationship between two elements, unless otherwise explicitly limited. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0071] In the present application, unless otherwise explicitly specified and limited, the first feature is "on" or "under" the second feature can be that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature is "over", "above" and "on" the second feature can be that the first feature is directly above or obliquely above the second feature, or only indicates that the first feature is horizontally higher than the second feature. The first feature is "under", "below" and "under" the second feature can be that the first feature is directly below or obliquely below the second feature, or only indicates that the first feature is horizontally lower than the second feature.

[0072] In the description of the present application, the description of the terms "one embodiment", "some embodiments", "an example", "a specific example" or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present application, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any suitable manner in any one or more embodiments or examples. In addition, the skilled in the art can combine and combine the different embodiments or examples described in the present application and the features of the different embodiments or examples without contradiction.

[0073] As shown in Figure 1 The present application provides a microfluidic chip in a first aspect, which comprises at least a substrate 101 and a sensing device arranged oppositely, the substrate 101 is provided with a driving electrode 400, the driving electrode 400 is arranged on the side of the substrate 101 opposite to the sensing device, and liquid droplets can be added above the driving electrode 400; the substrate 101 and the sensing device form a channel for accommodating the to-be-tested liquid droplets 500, the number and form of the channel are not limited here, and a plurality of to-be-tested liquid droplets 500 with different forms and sizes can be accommodated; the sensing device comprises a control component and a sensing component 200 connected to each other, the control component can control at least one of the sensing component 200 and the substrate 101 to move towards each other or away from each other, so that the sensing component 200 forms an electrical connection path with the driving electrode 400 through the to-be-tested liquid droplets 500, and then the detection of the water droplet angle of the to-be-tested liquid droplets 500 is realized.

[0074] During the specific implementation process, droplets 500 to be tested with different morphologies and compositions can be dripped into the channel above the driving electrode 400, and the water drop angles of multiple droplets with different morphologies can be detected simultaneously; the control component can control at least one of the sensing component 200 and the substrate 101 to move relative to each other in a direction of approaching or moving away from each other, that is, it can control the movement of the sensing component 200 or the movement of the substrate 101, or it can control the movement of both, so that the end of the sensing component 200 can contact droplets of different sizes and morphologies, which is convenient for accurately detecting the water drop angle. The sensing component 200 can sense the morphology and size of the droplet 500 to be tested, and feed back the sensed distance between the droplet 500 to be tested and the sensing component 200 to the control component. The control component adjusts the position of the sensing component 200 (or the position of the substrate 101) up and down accordingly to accurately control the distance between the sensing component 200 and the droplets 500 to be tested of different sizes, thereby improving the accuracy of the test data.

[0075] In this embodiment, the sensing component 200 can simultaneously sense multiple droplets 500 of different shapes and sizes. It only needs to control different parts of the sensing component 200 to correspond one-to-one with the droplets 500 to be detected, and the application range is wide.

[0076] Furthermore, the microfluidic chip further comprises a side wall 300 connected to the top plate 201 and extending toward the substrate 101; the sensing component 200 comprises a top plate 201 and at least one sensing electrode 202 ( Figure 1 Only one sensing electrode 202 extending therefrom is shown in the figure); the side wall 300, the top plate 201, and the substrate 101 form a sealed cavity. The droplet 500 to be measured is located in the sealed cavity, which can effectively prevent the droplet from volatilizing. When the control component controls the top plate 201 to drive the sensing electrode 202 to move, the top plate 201 changes its position relative to the substrate 101 in the height direction of the side wall 300, that is, the top plate 201 moves up and down; the drive electrode 400 is at least partially located in the sealed cavity.

[0077] In specific use, the side wall 300, the top plate 201 and the base plate 101 form a sealed cavity, the shape of the side wall 300 is not limited herein, and the side wall 300 can be a circular side wall 300 or a side wall 300 composed of multiple planes. The droplet 500 to be tested is in a sealed environment, which can effectively solve the problem of droplet evaporation. The top plate 201 is provided with at least one sensing electrode 202, such as a screw-shaped electrode. The tip of the electrode can be in contact with the top of the droplet 500 to be tested, which can be used to detect the signal of the droplet in the process of manipulating the droplet by the microfluidic chip. The number of sensing electrodes 202 corresponds to the number and position of the droplets 500 to be tested. When the control component controls the top plate 201 to drive the sensing electrode 202 to move, the top plate 201 changes its position up and down relative to the base plate 101 in the height direction of the side wall 300, which can adjust the vertical distance between the sensing electrode 202 and the droplet 500 to be tested. The driving electrode 400 is at least partially located in the sealed cavity. The upper surface area of the base plate 101 should be greater than the bottom area of the sealed cavity so as to be completely sealed. The droplet 500 to be tested is placed above the part of the driving electrode 400 located in the sealed cavity. The sensing electrode 202 can form an electrical connection path with the driving electrode 400 through the droplet 500 to be tested, thereby realizing signal detection of the droplet 500 to be tested.

[0078] Optionally, a liquid adding hole is reserved on the top plate 201. The droplet 500 to be tested can be added dropwise in the channel through the liquid adding hole, without the need to remove the top plate 201, which is convenient for operation.

[0079] Further, the upper surface of the base plate 101 is provided with at least one driving electrode 400, and the upper surface of the driving electrode 400 is provided with at least one detection area. At least one droplet 500 to be tested can be placed in the detection area. The sensing electrode 202 corresponds to the droplet 500 to be tested in the detection area below. The sensing electrode 202 corresponds to the detection area. The sensing electrode 202 is generally located above the corresponding detection area. The distance between the sensing electrode 202 and the droplet 500 to be tested can be adjusted by moving the sensing electrode 202 up and down. The microfluidic chip further comprises a positioning device for positioning the side of the sensing electrode 202 close to the detection area. The distance between the sensing electrode 202 and the droplet can be monitored by the positioning device, which is convenient for adjusting the distance between the sensing electrode 202 and the droplet 500 to be tested of different sizes.

[0080] In other embodiments, the material of the base plate 101 can be PDMS, glass, PC, PMMA, etc. The upper surface of the base plate 101 is provided with a plurality of driving electrodes 400. According to needs, the driving electrodes 400 can be designed in different shapes, such as square, rectangular, crescent and other different patterns. The driving electrodes 400 can also be designed in different spacings, such as equal spacing, unequal spacing, gradient spacing, etc. The driving electrodes 400 are led out to the outside through the internal wiring of the base plate 101 and connected to the external control electrode.

[0081] Further, all the sensing electrodes 202 are movably arranged on the top plate 201 and are connected with the control component; the control component further controls the sensing electrodes 202 to move towards the direction of approaching or moving away from the to-be-tested droplet 500 relative to the top plate 201 on the basis of the movement of the top plate 201 relative to the base plate 101.

[0082] In specific embodiments, in the initial state, all the sensing electrodes 202 are inside the top plate 201, and after the to-be-tested droplet 500 is added in a certain detection area, the control component can control the sensing electrodes 202 at the position corresponding to the to-be-tested droplet 500 to extend, and then the control component further controls the sensing electrodes 202 to move towards the direction of approaching or moving away from the to-be-tested droplet 500 relative to the top plate 201 on the basis of the movement of the top plate 201 relative to the base plate 101, so that the sensing electrodes 202 are in contact with the to-be-tested droplet 500 when the top plate 201 reaches the initially determined position, facilitating the signal detection of the to-be-tested droplet 500.

[0083] In other embodiments, the movement of the base plate 101 or the simultaneous movement of the base plate 101 and the top plate 201 can be controlled to adjust the distance between the sensing electrodes 202 and the to-be-tested droplet 500, so that the top of the to-be-tested droplet 500 is in contact with the tip of the sensing electrode 202.

[0084] Further, the side wall 300 is provided with a light-transmitting portion for transmitting light, and the light transmittance of the light-transmitting portion is greater than or equal to 0.8, so as to ensure a better light transmission effect; the external light source 600 transmits light into the sealed cavity through the light-transmitting portion, and the light-transmitting portion is highly transparent, facilitating the penetration of light and image acquisition.

[0085] The material of the light-transmitting portion is not specifically limited in this embodiment, but the light transmittance thereof needs to be greater than or equal to 0.8 to ensure a better light transmission effect, and the number, shape and size of the light-transmitting portion are also not specifically limited, for example, the light-transmitting portion can be one or more circular light-transmitting pieces, or the entire side of the side wall 300 can be integrally used as the light-transmitting portion.

[0086] Further, the side wall 300 includes an inner wall 301 made of transparent material and an outer wall 302 made of non-transparent material, and the light-transmitting portion is arranged on the outer wall 302.

[0087] The inner wall 301 and the outer wall 302 in the present solution can be directly attached as shown in Figure 1 , or a gap can be left, and the light-transmitting portion is arranged on the non-transparent outer wall 302, and the light-transmitting portion is still in a sealed state; the external light source 600 is aligned with the light-transmitting portion, the light source 600 transmits light into the sealed cavity through the light-transmitting portion and the transparent inner wall 301, and the light is incident on the to-be-tested droplet, facilitating the normal performance of subsequent image acquisition work. In other embodiments, the side of the outer wall 302 opposite to the light source 600 can be integrally used as the light-transmitting portion.

[0088] Further, the sensing electrode 202 comprises an electrode wire and a sleeve axially sleeved outside the electrode wire, the sleeve driving the electrode wire to be movably connected relative to the top plate 201, and the sleeve can effectively protect the electrode wire embedded therein so that the electrode wire can normally and stably play a sensing role.

[0089] The material of the electrode wire can be copper, gold, carbon fiber, etc., and the diameter thereof is 10-500 microns.

[0090] In another embodiment, the electrode wire is a metal wire with a diameter of 10-500 microns, the sleeve has a diameter of 1-10 mm, the metal wire is fixed and embedded in the middle of the sleeve by a fixing glue, the fixing glue can be epoxy resin, acrylic ester, polyurethane, etc., with a molecular weight of 20-200 thousand, the position of the metal wire relative to the liquid drop 500 to be measured on the substrate 101 is adjusted by moving the sleeve up and down, and the position accuracy can be adjusted by a light CMOS.

[0091] In other preferred embodiments, the driving electrode 400 comprises a patterned electrode sheet and a first protective layer arranged on the side of the electrode sheet close to the top plate 201; the first protective layer at least comprises a first dielectric layer and a first hydrophobic layer, and the driving electrode 400 is used to control the movement of the liquid drop. The upper surface of the electrode sheet needs to be structured with a dielectric layer and a hydrophobic layer, or a dielectric-hydrophobic layer, which can be realized by means of film pasting, spraying, deposition, etc. The dielectric layer is used to maintain the insulation between the circuit and each layer, and different dielectric layer thicknesses can be designed according to different design requirements.

[0092] The liquid drop in the microfluidic chip in the present scheme can be in the form of water-in-oil or oil-in-water, mainly depending on the properties of the test liquid drop, so as to solve the problem that the existing water drop angle test technology can only detect the contact angle of water or water dispersion system (including solution) and organic solvent system in air.

[0093] In another preferred scheme, the side of the top plate 201 close to the substrate 101 is provided with a second protective layer; the second protective layer at least comprises a conductive layer and a second hydrophobic layer on the side of the conductive layer close to the substrate 101. The material of the top plate 201 can use PDMS, glass, PC, PMMA, etc., and the lower surface of the top plate 201 needs to be structured with a conductive layer, which can be realized by means of spraying, deposition, sputtering, etc., or by using a conductive material. The conductive layer needs to be structured with a hydrophobic layer outside, or a conductive and hydrophobic material is used.

[0094] In other preferred embodiments, the above-mentioned microfluidic chip also includes a temperature control component 103 connected to the substrate 101. The temperature control component 103 is used to adjust the temperature of the substrate 101 to control the temperature in the sealed cavity at 4 to 97°C. In addition to solving the volatilization problem existing in the existing droplet angle testing device, it can also evaluate and detect the heating status and PCR process of the droplets.

[0095] In another embodiment, the temperature control component 103 is composed of metal electrodes and sensors, and is mainly used to control the temperature inside the chip, and can provide different temperature-time curve controls and different heating and cooling rate controls.

[0096] like Figure 1 As shown, in other embodiments, the outer wall 302 and the inner wall 301 of the microfluidic chip are fitted together, the material used for the outer wall 302 is epoxy resin, etc., the material used for the inner wall 301 is elastic material such as silicone rubber and polydimethylsiloxane, the material of the top plate 201 is one or more of PDMS, PMMA, quartz glass, etc., a patterned electrode is provided on the substrate 101, the area of ​​the patterned electrode is smaller than the upper surface area of ​​the substrate 101, the droplet 500 to be tested is placed in the channel above the patterned electrode, the droplet 500 to be tested contains components such as surfactants and biochemical enzyme reagents, the material used for the substrate 101 is one or more of PC, glass, PCB board, etc., the fine electrode wire is vertically arranged on the lower surface of the top plate 201, and a CMOS sensor that can accurately locate the position of the electrode wire is installed on the outer wall 302.

[0097] In other embodiments, the material of the microfluidic chip is glass or plastic, and the layout design can be realized based on the principle of digital microfluidics to complete the merging and splitting of droplets, such as Figure 4 As shown, the driving electrodes 400 are arranged in an array, and a single driving electrode 400 can be square. The whole is distributed in a grid shape on the substrate. The two droplets 500 to be tested are respectively located in the two detection areas numbered 6 and 7. By adjusting the potential of different detection areas, the two droplets 500 to be tested can be guided to move, split and merge between different areas.

[0098] like Figure 5 As shown, the droplets 500 to be tested of different sizes are located in the detection areas numbered 6-7 and 14-15 respectively. By adjusting the potentials of the detection sites respectively, the droplets 500 to be tested of different sizes can be moved, split and merged.

[0099] Furthermore, the second aspect of the present invention provides a detection device comprising a microfluidic chip, the detection device further comprising a light source 600; and

[0100] The output module 700 includes a first output terminal connected to the driving electrode 400 and a second output terminal connected to the sensing component 200. The output module 700 can output different voltage driving signals to the electrical connection path. The voltage driving signals output by the voltage output module 700 can have different waveforms and frequencies.

[0101] The image processing module 800 is used to collect the morphology of the droplet in the channel under different voltage driving signals and detect the contact angle of the droplet.

[0102] like Figure 3 As shown, when the specific application detection device detects the contact angle of the droplet 500 to be tested, the LED light source 600 is first aligned with the light-transmitting portion to allow the light to enter the cavity and aligned with the droplet 500 to be tested, and the position of the sensing electrode 202 is adjusted so that it contacts the droplet 500 to be tested. Then, the output module 700 is turned on, and pressure is supplied to the driving electrode 400 and the sensing electrode 202. Different voltage driving signals are provided to the electrical connection path. Finally, the image processing module 800 is used to collect the morphology of the droplet in the channel under different voltage driving signals and detect the size of the contact angle of the droplet 500 to be tested. The entire process is automatically carried out in a sealed environment to reduce the volatilization of the droplet.

[0103] It should be added that the main structure of the microfluidic chip in this embodiment is made of a combination of epoxy resin, rubber, glass, etc.

[0104] Furthermore, the driving electrodes 400 are patterned and arranged at intervals on the substrate 101. They can be designed into different shapes, such as squares, rectangles, crescents and other different graphics, and can also be designed with different spacings, such as equal spacing, unequal spacing, gradient spacing, etc. A detection area capable of accommodating the droplets 500 to be tested is correspondingly provided above the driving electrodes 400 of each interval. The control component further controls the output module 700 to output a corresponding voltage signal to the driving electrode 400 to control the movement of the droplets. In specific applications, based on the dielectric wetting principle, different electrodes in the patterned electrodes can be energized to realize the movement, splitting and merging of droplets.

[0105] In specific operations, using the principle of electrowetting, when there is liquid on the driving electrode 400 and a potential is applied to the driving electrode 400, the wettability of the solid-liquid interface at the corresponding position of the driving electrode 400 can be changed, and the contact angle of the interface between the droplet and the driving electrode 400 changes accordingly. If there is a potential difference between the electrodes in the droplet area, resulting in different contact angles, a lateral driving force will be generated, causing the droplet to move laterally on the electrode substrate 101, thereby energizing different electrodes in the patterned electrode to achieve the movement, splitting, and merging of the droplet.

[0106] In other preferred embodiments, the image processing module 800 comprises a camera 801 for acquiring the morphology of the droplet; and a host device 802 connected to the camera 801 and used for analyzing and processing image data.

[0107] In a specific application, the morphology of the droplet is first acquired by the camera 801 (such as a CMOS camera), and the image data is analyzed and processed by the host device 802 to detect the contact angle of droplets of different sizes and shapes in real time.

[0108] The image processing module 800 can take a photo of the morphology of the droplet, then automatically or manually take points for contact angle measurement, output contact angle data, or record and save videos to record the movement, separation, mixing, and other changes of the droplet, etc.

[0109] For example, Figure 2 In a specific embodiment, the above detection device is used to detect the droplet contact angle and morphology change in an open environment, the light source 600 is an LED light, the bottom substrate 101 is one or more of glass, PC or PCB, coated with a PI film, divided into patterned electrodes, the output module 700 is a programmable voltage instrument that can generate -500V~+500V frequency adjustable AC / DC voltage, the CMOS camera and the host computer are arranged on the same side of the droplet, the LED light source 600 is arranged on the other side of the droplet, the first output end of the programmable voltage instrument is connected to the positive electrode, which applies voltage to the corresponding electrode through the solder pad on the biological slide, the second output end is connected to the negative electrode, which is a conductive metal wire with a diameter of 10um~500um, and the detection device can complete the programmed program power supply, test program as needed, automatic recording and feedback functions, etc.

[0110] For example, Figure 3In a specific embodiment, the water drop angle and the morphology change of a plurality of liquid drops in a closed environment are detected simultaneously by using the detection device described above. The driving motor 102 (control component) is only schematically represented and does not represent its structure and connection relationship with other structures. At least two control interfaces are provided on the driving motor 102 (control component). One control interface is used to control the electrode wire corresponding to the position of the liquid drop 500 to be detected to extend out of the top plate 201. The other control interface is used to drive the top plate 201 to make the electrode wire connected thereto contact or leave the liquid drop. The CMOS camera is arranged obliquely above one side of the microfluidic chip, and the LED light source 600 is arranged on the two sides of the liquid drop 500 to be detected, respectively. The position of the electrode wire is calibrated and adjusted by using the CMOS. The material of the top plate 201 is one or more of PDMS, PMMA, quartz glass and the like. The electrode negative pole (i.e. the electrode wire) is a conductive metal wire with a diameter of 10 um to 500 um. The substrate 101 is one or more of glass, PC or PCB, which is coated with a PI film and divided into patterned electrodes (driving electrodes 400). A TEC (semiconductor refrigerator) is arranged on the lower part of the substrate 101 to heat or cool the substrate 101, so as to control the temperature range in the sealed cavity to be 4℃ to 97℃.

[0111] Further, the third aspect of the present application provides a detection method using the detection device. The sensing component 200 includes a top plate 201 movably arranged on the substrate 101, and at least one sensing electrode 202 arranged on the top plate 201. The top plate 201 and the substrate 101 are spaced apart to form a channel, and the channel can accommodate the liquid drop 500 to be detected. The detection method at least includes the following steps:

[0112] a. Providing the liquid drop 500 to be detected in the channel. The liquid drop 500 to be detected can be added through the liquid adding hole on the top plate 201;

[0113] b. Driving the top plate 201 to move to an initial position relative to the substrate 101 by using the control device. Then, the position information of the sensing electrode 202 is detected by using the positioning device and fed back to the control component. The control component further adjusts the position of the sensing electrode 202 based on the position information, so that the end of the sensing electrode 202 contacts the liquid drop 500 to be detected, so that the sensing electrode 202 forms an electrical connection path with the driving electrode 400 through the liquid drop 500 to be detected. In the initial position, the distance between the top plate 201 and the liquid drop 500 to be detected is not greater than 500 um. The movement of the liquid drop 500 to be detected by the microfluidic chip is facilitated, and at the same time, the end of the sensing electrode 202 can be contacted by the liquid drop 500 to be detected, and at the same time, the roughness of the surface of the top plate 201 is avoided to affect the liquid drop 500;

[0114] c.The output module 700 is used to apply voltage to the driving electrode 400 and the sensing component 200, and the image processing module 800 is used to obtain the water drop angle and the morphology change diagram of the liquid drop 500 under the corresponding condition, so as to detect the contact angle of the liquid drop, record the video, and record the movement, separation, mixing and other change processes of the liquid drop.

[0115] The method provided by the present application can detect the water drop angle and the morphology change of the liquid drop under a sealed state, can avoid the volatilization of the liquid drop, and can automatically control the contact between the end of the sensing electrode 202 and the liquid drop 500 of different sizes by the control device, so that the sensing electrode 202 is electrically connected to the driving electrode 400 through the liquid drop 500, and the subsequent power-on detection is facilitated. The voltage generated by the voltage generator (i.e., the output module 700) in the embodiment is time-synchronized with the monitoring picture, so that the image and the voltage waveform can be corresponded.

[0116] It should be noted that the "initial position" in the embodiment refers to that the distance between the top plate 201 and the liquid drop is adjusted to be within 2000 μm after coarse adjustment, and the distance between the sensing electrode 202 and the driving electrode 400 is within 2000 μm. After reaching the initial position, the position information of the sensing electrode 202 is detected by the positioning device and fed back to the control component, and the control component further adjusts the position of the sensing electrode 202 based on the position information, so that the end of the sensing electrode 202 is in contact with the liquid drop 500, that is, the fine adjustment. This step is similar to the operation of observing the specimen by using a microscope.

[0117] Further, the at least two liquid drops 500 of different sizes in step a are located in the channel, and step b further comprises: adjusting the distance between the sensing electrode 202 corresponding to each different liquid drop 500 and the corresponding liquid drop 500.

[0118] In the embodiment, the morphology and the water drop angle of at least two liquid drops 500 of different sizes can be detected simultaneously. It should be understood that under the condition of one-to-one control of the control device, the detection device and the detection method provided by the present application can be completely applied to simultaneously detect liquid drops of more sizes which are different from each other, and the morphology and the water drop angle of each liquid drop can be obtained in real time.

[0119] The liquid drop 500 in the present application can be a water phase system (pure water, a surfactant solution, an enzyme preparation aqueous solution, an enzyme preparation aqueous solution containing an organic solvent), an oil-water system (a liquid drop on a silicon oil), and the like, and contains a surfactant, a biochemical enzyme reagent and the like.

[0120] Further, the fourth aspect of the present application provides a sequencing device comprising the microfluidic chip, which can prevent volatilization and accurately control the contact between the upper electrode (the end of the sensing electrode 202) and droplets of different sizes, and is fully automated, greatly reducing the manual operation time and effectively improving the accuracy of test data.

[0121] Further, the fifth aspect of the present application provides a method for manufacturing a droplet control chip for a sequencer, which comprises determining the process parameters of the droplet control chip by using the detection device, the process parameters at least including position information and voltage control parameters; the sensing component 200 comprises a top plate 201 movably arranged with the substrate 101 and at least one sensing electrode 202 arranged on the top plate 201, and a channel is formed between the top plate 201 and the substrate 101; the process parameters of the droplet control chip are determined by:

[0122] selecting droplets 500 of a specified size to be tested and applying the droplets 500 to be tested to the channel;

[0123] adjusting the relative distance between the top plate 201 and the substrate 101, and further adjusting the position between the sensing electrode 202 and the droplets 500 to be tested, to obtain the position information corresponding to the top plate 201, the substrate 101, the sensing electrode 202 and the driving electrode 400 when the end of the sensing electrode 202 is in contact with the droplets 500 to be tested;

[0124] adjusting the output module 700 to output different voltage driving signals to the electrical connection path comprising the sensing electrode 202, the droplets 500 to be tested and the driving electrode 400, to obtain the voltage control information corresponding to the droplets 500 to be tested;

[0125] based on the topography and contact angle size of the droplets 500 to be tested under different voltage driving signals detected by the image processing module 800, and the signal detected by the sensing electrode 202 to determine the optimal voltage control parameters.

[0126] It should be noted that the substrate used in the microfluidic chip in this embodiment is at least one of PDMS, glass, PC and PMMA, the thickness of the first dielectric layer is 0-2000 nm, the type of the first dielectric layer is SiN, aluminum oxide, PTFE, perlaplastin and PDMS, etc., the distance between the sensing electrode 202 and the driving electrode 400 can be coarsely adjusted to within 2000 μm by adjusting the distance between the top plate 201 and the substrate 101, and the distance between the sensing electrode 202 and the droplets 500 to be tested can be further adjusted by combining the position of the sensing electrode 202, so that the distance between the sensing electrode 202 and the driving electrode 400 can be finely adjusted to within 500 μm, and the optimal process conditions and parameters can be determined by one process, wherein each parameter variable can be continuous or random.

[0127] In the preparation process of the microfluidic chip, the voltage measurement module and the topographic image measurement module are integrated, the sensing electrode 202 can detect the threshold voltage, saturation voltage, breakdown voltage, etc. under the single or double electrode plate, the image processing module 800 can detect the change amount and change rate of the droplet contact angle, and the photoelectric probe can be used to detect the droplet moving rate, etc. Through one process, the optimal power supply voltage condition and parameters can be determined without the need of customizing various specifications of chips for small batch verification. The chip design has small volume, small loss and pollution of biochemical reagents in the later recovery processing, saves process time and production cost, and is worth popularizing.

[0128] The following will be specifically described in combination with related embodiments to detect the water droplet angle and topographic change diagram of the droplet under different conditions.

[0129] In an embodiment, as shown in Figure 1 , a sample spotter or sample injection needle is used to drop 2 microliters of droplets on the driving electrode 400, and the top plate 201 is immediately covered. The position of the top plate 201 is adjusted so that the electrode wire end of the lower surface of the top plate 201 reaches the instrument cursor indication interval. The positioning device is a CMOS sensor installed on the side wall of the chip, and the CMOS sensor senses the electrode wire position. The output module 700 is an oscilloscope and a power supply generating device. The output module 700 applies positive and negative 10V, 20V, 50V, 100V, 150V, 200V, 300V, 400V to the electrical connection path where the driving electrode 400 is located. The pulse waveform is one of square wave, triangular wave and sine wave, the pulse time is 0.5 seconds, 1 second, 1.5 seconds, 2 seconds, and the duty cycle is 1:1 voltage.

[0130] The water droplet angle and topographic change diagram under different conditions are tested. The voltage range of the power supply generating device used is positive and negative 800V, the contact angle range is 0-130 degrees, and the movement rate is calculated by using multiple photoelectric detection probes through software, which will not be described here.

[0131] In another embodiment, as shown in Figure 1 , a sample spotter or sample injection needle is used to drop 5 microliters of droplets on the driving electrode 400, and the top plate 201 is immediately covered. The position of the top plate 201 is adjusted so that the electrode wire end of the lower surface of the top plate 201 reaches the instrument cursor indication interval. The temperature control device is adjusted so that the temperature in the sealed cavity changes within 95 degrees, 60 degrees and 72 degrees, and the switching time is 15 seconds.

[0132] An oscilloscope and a power supply generating device are used to apply positive and negative 10V, 20V, 50V, 100V, 150V, 200V, 300V, 400V, the pulse waveform is one of square wave, triangular wave and sine wave, the pulse time is 0.5 seconds, 1 second, 1.5 seconds, 2 seconds, and the duty cycle is 1:1 voltage.

[0133] The water drop angle and morphology change diagrams under different test conditions, the voltage range of the power generator used is plus or minus 800V, the contact angle range is 0 to 130 degrees, and the movement rate is converted by software using multiple photoelectric detection probes.

[0134] In another embodiment, Figure 1 As shown, use a spotter or syringe to apply five 2-μl droplets of liquid onto the driving electrode 400. Immediately cover it with the top plate 201. Adjust the top plate 201 so that the end of the electrode wire on the lower surface of the top plate 201 reaches the instrument cursor indication area. Using an oscilloscope and a power generator, apply voltages of positive and negative 10V, 20V, 50V, 100V, 150V, 200V, 300V, or 400V. The pulse waveforms are square, triangular, or sinusoidal, with pulse durations of 0.5 seconds, 1 second, 1.5 seconds, or 2 seconds, and a duty cycle of 1:1.

[0135] At the same time, multiple water droplet angle and morphology change diagrams under different conditions were tested. The voltage range of the power supply device used was plus or minus 800V, the contact angle range was 0 to 130 degrees, and the movement rate was converted by software using multiple photoelectric detection probes.

[0136] In another embodiment, Figure 1 As shown, use a spotter or injection needle to add five 5-μl droplets onto the driving electrode 400. Immediately cover the top plate 201 and adjust the top plate 201 so that the end of the electrode wire on the lower surface of the top plate 201 reaches the instrument cursor indication area. Adjust the temperature control device to switch the temperature within the sealed chamber between 95°C, 60°C, and 72°C, with a switching time of 15 seconds.

[0137] Use an oscilloscope and a power generator to apply voltages of positive and negative 10V, 20V, 50V, 100V, 150V, 200V, 300V, and 400V, with pulse waveforms selected from square, triangle, and sine waves, pulse times of 0.5 seconds, 1 second, 1.5 seconds, and 2 seconds, and a duty cycle of 1:1.

[0138] At the same time, multiple water droplet angle and morphology change diagrams under different conditions were tested. The voltage range of the power supply device used was plus or minus 800V, the contact angle range was 0 to 130 degrees, and the movement rate was converted by software using multiple photoelectric detection probes.

[0139] As shown in Table 1 below, the detection device in the prior art and the sequencing device provided by the present application are used to detect the water drop angles under multiple different conventional test conditions and special test conditions, and the test performance under different detection conditions is statistically summarized in Table 1.

[0140] As can be seen from Table 1, the sequencing device provided by the present application is superior to the detection devices in the prior art in terms of at least the accuracy of electrode adjustment, the time consumption of the detection process, and the simultaneous detection of multiple droplets. In addition, the sequencing device of the present application can effectively prevent the volatilization of droplets, can detect the angle of droplets in a heated state, and has the functions of automatic detection, automatic data collation, automatic equipment protection, and backward compatibility with multiple library construction instrument chips and sequencing chips.

[0141] Table 1 Comparison of water drop angle test performance between existing instruments and the sequencing device of this application

[0142]

[0143]

[0144] In addition, if Figure 6 As shown, when the detection device in the prior art is used to detect the droplet angle, the shape and size of the droplet will change due to volatilization during the detection process; Figure 7 As shown, when the sequencing device of the present application is used to detect the droplet angle, the droplet will remain in its original state until the detection is completed, and the shape and size of the droplet will not change during the entire detection process.

[0145] When using existing devices to detect the droplet angle of EB liquid, because EB liquid contains surfactants and additives, as the water evaporates, the droplet size changes rapidly (for example, from 3 to 5 microliters to 2 to 3 microliters), and the concentration of each component changes greatly, which has a great impact on the properties such as the droplet angle and rheological properties. Figure 8 As shown in the figure, the data fluctuates greatly during process testing. Figure 9 As shown, when the existing device is used to detect the water drop angle of ultrapure water (testing four sets of data), the data during the test process will also fluctuate greatly due to the volatilization of the droplets.

[0146] like Figure 10 As shown in FIG, when the sequencing device provided by the present invention is used to detect the angle of ultrapure water droplets and the angle of EB liquid droplets, the angle of droplets and the voltage are almost linearly related, and the data fluctuation is small. Figure 11 The voltage in is the real-time voltage value at the droplet monitored by an oscilloscope when a voltage of ±300 V is applied to the electrical connection path where the driving electrode 400 of the present invention is located.

[0147] The microfluidic chip provided in the first aspect of the present invention can accurately control the distance between the sensing component 200 and the droplets 500 to be tested of different sizes, thereby improving the accuracy of the test data; and when the microfluidic chip of the present invention adopts a sealed structure, it can effectively slow down the evaporation rate of the droplets;

[0148] The detection device provided by the second aspect of the application comprises a microfluidic chip, can automatically adjust the position of the sensing electrode 202 to make it contact with the to-be-detected liquid drop 500, provide different voltage driving signals to the electrical connection channel, finally acquire the morphology of the liquid drop in the channel under different voltage driving signals through the image processing module 800, and detect the contact angle of the to-be-detected liquid drop 500, so that the whole process is automatically configured, the operation time is greatly reduced, and the test data accuracy is improved;

[0149] The third aspect of the application provides a method for detecting the contact angle and morphology change of a liquid drop under a sealed state, which can not only avoid the volatilization of the liquid drop, but also automatically control the end of the sensing electrode 202 to contact with the to-be-detected liquid drop 500 of different sizes through the control device, so that the sensing electrode 202 forms an electrical connection channel with the driving electrode 400 through the to-be-detected liquid drop 500, and the automation control is convenient, fast and accurate;

[0150] The fourth aspect of the application provides a sequencing device comprising a microfluidic chip, which adopts a sealed chip device, can prevent volatilization, and can accurately control the upper electrode (the end of the sensing electrode 202) to contact with liquid drops of different sizes.

[0151] The fifth aspect of the application provides a manufacturing method of a liquid drop control chip for a sequencer, which can automatically integrate various process parameters into the liquid drop control chip, is suitable for rapid detection of a multi-channel and complex system, can quickly locate the optimal process parameters and conditions, and saves process groping time and cost.

[0152] Although the embodiments of the application have been shown and described above, it should be understood that the above embodiments are exemplary and should not be construed as limiting the application, and those skilled in the art can make changes, modifications, replacements and variations to the above embodiments within the scope of the application.

Claims

1. A microfluidic chip, characterized in that: The device comprises at least a substrate (101) and a sensing device arranged opposite to each other, wherein a driving electrode (400) is provided on the substrate (101), and a channel for accommodating a droplet to be detected (500) is formed between the substrate (101) and the sensing device; The sensing device comprises a control component and a sensing component (200) that are interconnected, wherein the sensing component (200) is used to sense the distance between the droplet to be detected (500) and the sensing component (200), and the control component is capable of controlling at least one of the sensing component (200) and the substrate (101) to move relative to each other in a direction of approaching or moving away from each other, so that the sensing component forms an electrical connection path with the driving electrode (400) via the droplet to be detected (500).

2. The microfluidic chip according to claim 1, characterized in that The sensing component (200) comprises a top plate (201) and at least one sensing electrode (202) arranged on the top plate (201); The microfluidic chip further comprises a side wall (300) connected to the top plate (201) and extending toward the substrate (101); the side wall (300), the top plate (201) and the substrate (101) enclose a sealed cavity; when the control component controls the top plate (201) to drive the sensing electrode (202) to move, the top plate (201) changes position relative to the substrate (101) in the height direction of the side wall (300); the driving electrode (400) is at least partially located in the sealed cavity.

3. The microfluidic chip according to claim 2, characterized in that: At least one driving electrode (400) is provided on the upper surface of the substrate (101), and at least one detection area is provided on the upper surface of the driving electrode (400); The sensing electrodes (202) are arranged in a one-to-one correspondence with the detection areas, and the microfluidic chip further comprises a positioning device for positioning the side of the sensing electrode (202) close to the detection area.

4. The microfluidic chip according to claim 3, characterized in that All the sensing electrodes (202) can be movably arranged on the top plate (201) and are connected to the control component; the control component further controls the sensing electrodes (202) to move relative to the top plate (201) toward or away from the droplet (500) to be detected based on the movement of the top plate (201) relative to the substrate (101).

5. The microfluidic chip according to claim 3, characterized in that: A light-transmitting portion for light to pass through is provided on the side wall (300), and the light transmittance of the light-transmitting portion is greater than or equal to 0.8, and an external light source transmits light into the sealed cavity through the light-transmitting portion.

6. The microfluidic chip according to claim 5, characterized in that: The side wall (300) comprises an inner wall (301) made of a transparent material and an outer wall (302) made of an opaque material, and the light-transmitting portion is arranged on the outer wall (302).

7. The microfluidic chip according to any one of claims 3 to 6, characterized in that: The sensing electrode (202) comprises an electrode wire and a shaft sleeve axially sleeved on the outer periphery of the electrode wire, and the shaft sleeve drives the electrode wire to be movably connected relative to the top plate (201).

8. The microfluidic chip according to claim 6, characterized in that: The driving electrode (400) comprises a patterned electrode sheet and a first protective layer provided on a side of the electrode sheet close to the top plate (201); the first protective layer comprises at least a first dielectric layer and a first hydrophobic layer; the driving electrode (400) is used to control the movement of the droplet to be measured (500); and / or; A second protective layer is provided on a side of the top plate (201) close to the substrate (101); the second protective layer comprises at least a conductive layer and a second hydrophobic layer located on a side of the conductive layer close to the substrate (101).

9. The microfluidic chip according to claim 2, characterized in that: It also includes a temperature control component (103) connected to the substrate (101), and the temperature control component (103) is used to adjust the temperature of the substrate (101) to control the temperature in the sealed cavity to 4-97°C.

10. A detection device comprising the microfluidic chip according to any one of claims 1 to 9, characterized in that: Also included is a light source (600); and an output module (700), comprising a first output terminal connected to the driving electrode (400), and a second output terminal connected to the sensing component (200); the output module (700) is capable of outputting different voltage driving signals to the electrical connection path; The image processing module (800) is used to collect the morphology of the droplet to be tested (500) in the channel under different voltage driving signals, and detect the contact angle of the droplet to be tested (500).

11. The detection device according to claim 10, characterized in that: The driving electrodes (400) are patterned and arranged at intervals on the substrate (101), and the control component further controls the output module (700) to output a corresponding voltage signal to the driving electrodes (400) to control the movement of the droplet (500) to be tested.

12. The detection device according to claim 11, characterized in that: The image processing module (800) comprises a camera device (801) for acquiring the morphology of the droplet to be measured (500); and a main control device (802) connected to the camera device (801) and for analyzing and processing image data.

13. A detection method using the detection device according to any one of claims 10 to 12, characterized in that: The sensing component (200) comprises a top plate (201) movably arranged with the substrate (101) and at least one sensing electrode (202) arranged on the top plate (201), wherein the top plate (201) and the substrate (101) are spaced apart to form the channel; the detection method comprises at least the following steps: a. providing a droplet to be tested (500) into the channel; b. After the top plate (201) is driven to move to an initial position relative to the substrate (101) by a control device, the position information of the sensing electrode (202) is detected by a positioning device and fed back to the control component. The control component further adjusts the position of the sensing electrode (202) based on the position information so that the end of the sensing electrode (202) contacts the droplet to be detected (500), so that the sensing electrode (202) forms an electrical connection path with the driving electrode (400) through the droplet to be detected (500); c. Using the output module (700) to apply voltage to the driving electrode (400) and the sensing component (200), and using the image processing module (800) to obtain a water drop angle and morphology change image of the droplet (500) to be tested under corresponding conditions.

14. The detection method of the detection device according to claim 13, characterized in that: In step a, at least two droplets (500) to be detected having different sizes are located in the channel, and step b further comprises: adjusting the distance between the sensing electrodes (202) corresponding to different droplets (500) to be detected and the corresponding droplets (500) to be detected, respectively.

15. A sequencing device, characterized in that: The microfluidic chip comprises the microfluidic chip according to any one of claims 1 to 9.

16. A method for manufacturing a droplet control chip for a sequencer, characterized in that: The method comprises determining the process parameters of the droplet control chip using the detection device according to claim 13, wherein the process parameters at least include position information and voltage control parameters; the sensing component (200) comprises a substrate (101), a movably arranged top plate (201), and at least one sensing electrode (202) arranged on the top plate (201), and the top plate (201) and the substrate (101) are spaced apart to form the channel; Determining the process parameters of the droplet control chip includes: Selecting a droplet (500) to be tested of a specified size, and applying the droplet (500) to be tested into the channel; Adjusting the relative distance between the top plate (201) and the substrate (101), and further adjusting the position between the sensing electrode (202) and the droplet to be measured (500), to obtain the position information corresponding to the top plate, the substrate (101), the sensing electrode (202), and the driving electrode (400) when the end of the sensing electrode (202) contacts the droplet to be measured (500); adjusting the output module (700) to output different voltage drive signals to the electrical connection path, thereby obtaining voltage control information corresponding to the droplet to be tested (500); The optimal voltage control parameter is determined based on the morphology and contact angle of the droplet (500) to be tested under different voltage driving signals detected by the image processing module.

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