Regional digital micro-fluidic chip, driving method and device

Abstract

The invention discloses a regional digital micro-fluidic chip, relates to the field of micro-fluidics, and particularly relates to a regional digital micro-fluidic chip, a driving method and a driving device.According to the regional digital micro-fluidic chip, a micro-fluidic chip is partitioned, different electrode designs are adopted for different partitions, and different driving modes are adopted for different regions for control, so that the regional digital micro-fluidic chip is obtained. And more functions can be integrated on one chip. And the areas and the electrodes are numbered or marked, so that the functional areas and the electrodes can be quickly distinguished.

Description

Technical Field

[0001] The present application relates to the field of microfluidics, and in particular to a regional digital microfluidics chip, a driving method and a device. Background Art

[0002] Digital microfluidics (DMF) is a platform for lab-on-a-chip systems based on droplet manipulation. Droplets are distributed, moved, stored, mixed, reacted, or analyzed on a platform with a set of insulated electrodes. Digital microfluidics can be used with analytical analysis procedures such as mass spectrometry, colorimetry, electrochemistry, and electrochemiluminescence.

[0003] Digital microfluidic chips are generally made of array substrates; array substrates are made by simultaneously making multiple array units on a substrate, and then cutting the array units after production to form independent array substrates. After that, the array substrate is usually pasted with an electronic paper film to form an electronic device.

[0004] At present, the electrode types of digital microfluidic chips can be roughly divided into AM (active array) and PM (passive array). AM and PM each have their own advantages and disadvantages. PM has a simple structure and a multi-channel dynamic drive method. It is constrained by the number of scanning electrodes, has a large duty cycle, and cannot achieve large area and large flux. However, PM has a large driving power and high stability. Each electrode of AM is a low-temperature polysilicon thin-film transistor with switching function. There is no duty cycle problem, the drive is not constrained by the number of scanning electrodes, and the integration is high.

[0005] However, traditional digital microfluidic chips are either all-PM electrodes or all-AM electrodes; and the conventional electrode shapes are square or hexagonal. Although the square electrode can move droplets laterally or vertically, the square has only four sides, so the droplet fullness after movement is relatively poor; the hexagonal electrode has two more sides than the square, so its droplet fullness is better than the square electrode, but it cannot move droplets laterally; and both electrodes require a large number of signal lines. Summary of the invention

[0006] The purpose of the present invention is to avoid the deficiencies in the prior art and provide a regional digital microfluidic chip, a driving method and a device.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] According to one aspect disclosed in the present invention, there is provided a regional digital microfluidic chip, comprising: a plurality of electrode arrays, each electrode array being arranged on the same substrate and forming a corresponding functional area respectively; the functional area comprises a reaction culture area and a plurality of pipetting areas; the reaction culture area is used for actual reaction or cell culture; the pipetting area is used for moving droplets; the electrode array corresponding to the reaction culture area is a passive electrode array; the pipetting area and the corresponding electrode array are an active electrode array.

[0009] Specifically, the electrode array includes a plurality of electrodes, and the electrodes include a gate layer, a gate insulating layer, an active layer, an original drain electrode layer, a first passivation layer, a driving electrode layer, a second passivation layer and a hydrophobic layer.

[0010] In the above, the electrode array includes an array composed of several groups of hexagonal electrodes and waist-shaped electrodes; wherein the hexagonal electrodes in the same group are arranged in sequence; a group of waist-shaped electrodes is provided between two adjacent groups of hexagonal electrodes, and the shape of the waist-shaped electrodes matches the adjacent hexagonal electrodes.

[0011] In the above, the electrode array includes an array composed of a plurality of unidirectional electrodes; the unidirectional electrode includes a first connecting portion and a second connecting portion; the second connecting portion is provided with a connecting port, and the connecting port matches the shape of the first connecting portion.

[0012] Furthermore, the first connecting portion is an equilateral triangle; and the connecting port is also an equilateral triangle.

[0013] In the above, each functional area is respectively provided with a corresponding functional area label.

[0014] Furthermore, each electrode on the electrode array is provided with a corresponding electrode number.

[0015] According to another aspect of the present disclosure, a chip driving method is provided, which is applied to the above-mentioned regional digital microfluidic chip, comprising the following steps:

[0016] S1: determining the original position of the droplet, the original position includes the original functional area and the corresponding original electrode position;

[0017] S2: determining a target position for the droplet to move, where the target position includes a target functional area and a corresponding target electrode position;

[0018] S3: Calculate the moving path of the droplet according to the original position and the target position;

[0019] S4: determining a corresponding electrode driving signal according to the moving path of the droplet;

[0020] S5: driving the corresponding electrodes on the moving path of the droplet in sequence through the electrode driving signal.

[0021] Specifically, the following steps are also included:

[0022] S0: Identify the chip type of the microfluidic chip and match the corresponding style template according to the chip type.

[0023] According to another aspect disclosed in the present invention, there is provided a chip driving device, which adopts the above-mentioned chip driving method, and includes: a storage module, which is used to store corresponding style templates of microfluidic chips of various chip types, and the style templates include attributes and position relationship information of each functional area and each electrode in each functional area; an identification module, which is used to identify the chip type of the microfluidic chip and match the corresponding style template according to the chip type; a setting module, which is used to determine the original position and target position of the droplet; a path generation module, which is used to calculate the movement path of the droplet according to the original position, the target position and the style template; a drive signal generation module, which is used to determine and generate the corresponding electrode drive signal for output according to the movement path of the droplet.

[0024] The beneficial effects of the present invention are as follows: a regional digital microfluidic chip can integrate more functions on a chip by partitioning a microfluidic chip, using different electrode designs for different partitions, and controlling different regions by different driving modes. Different types of electrodes are made on the same substrate, which is not a common splicing of different electrodes. There will be no gaps or voids between different electrodes, which will not affect the generation or movement of droplets. The regions and electrodes are numbered or marked, so that the functional regions and electrodes can be quickly distinguished. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0026] Figure 1 It is a schematic diagram of the structure of a regional digital microfluidic chip according to an embodiment of the present application;

[0027] Figure 2 It is a plan view of a design layout of a regional digital microfluidic chip according to an embodiment of the present application;

[0028] Figure 3 is a schematic structural diagram of another regional digital microfluidic chip according to an embodiment of the present application;

[0029] Figure 4 It is a schematic structural diagram of another regional digital microfluidic chip according to an embodiment of the present application;

[0030] Figure 5 is a schematic structural diagram of an array composed of several groups of hexagonal electrodes and waist-shaped electrodes in an embodiment of the present application;

[0031] Figure 6 is a first structural schematic diagram of an array composed of a plurality of unidirectional electrodes according to an embodiment of the present application;

[0032] Figure 7 is a schematic diagram of a first structure of a plurality of unidirectional electrodes according to an embodiment of the present application;

[0033] Figure 8 is a second structural schematic diagram of an array composed of a plurality of unidirectional electrodes according to an embodiment of the present application;

[0034] Fig. 9 is a second structural schematic diagram of a plurality of unidirectional electrodes according to an embodiment of the present application;

[0035] Fig.10 This is an example diagram of droplet movement in an embodiment of the present application;

[0036] Fig.11 is a schematic diagram of the electrode timing state of an embodiment of the present application;

[0037] in, Figure 7 and Fig. 9 Including:

[0038] 01. First connecting part;

[0039] 02. Second connecting part;

[0040] 03. Connection port. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical solution and advantages of the present application clearer, the technical solution of the present application will be clearly and completely described through the implementation method with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present application.

[0042] In the description of the present invention, "several" means more than one, "many" means more than two, "greater than", "less than", "exceed", etc. are understood to exclude the number itself, and "above", "below", "within", etc. are understood to include the number itself. If there is a description of "first" or "second", it is only used for the purpose of distinguishing the technical features, and cannot be understood as indicating or implying the relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0043] In the description of the present invention, unless otherwise clearly defined, words such as "setting" should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meaning of the above words in the present invention in combination with the specific content of the technical solution.

[0044] In the description of the present invention, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0045] Example 1

[0046] like Figure 1 and Figure 2 As shown, a regional digital microfluidic chip includes: a plurality of electrode arrays, each electrode array is arranged on the same substrate and forms a corresponding functional area respectively; the functional area includes a reaction culture area and a plurality of pipetting areas; the reaction culture area is used for actual reaction or cell culture; the pipetting area is used for moving droplets; the electrode array corresponding to the reaction culture area is a passive electrode array; the pipetting area and the corresponding electrode array are active electrode arrays.

[0047] In this embodiment, the two functional areas are functional area 1 and functional area 2, and functional area 1 and functional area 2 are designed according to the requirements of the chip. The shape, size, driving mode, arrangement mode of the electrodes in functional area 1 and functional area 2 or the structure of the triode may be completely different or partially the same. For example, on a chip that needs to move droplets and culture cells, two areas are designed according to different functional requirements. Functional area 1 is a functional area for moving droplets. This functional area can be designed using the AM design method, and the driving method of the AM design is more efficient and flexible. Cells are cultured in functional area 2. Since the PM design has higher stability, the PM design can be used in functional areas that need to be cultured or preserved for a long time. Due to the different designs of the two functional areas, the two functional areas need to be controlled by different data lines so that the coordinated work of different functional areas can be achieved.

[0048] Specifically, the electrode array includes a plurality of electrodes, and the electrodes include a gate layer, a gate insulating layer, an active layer, an original drain electrode layer, a first passivation layer, a driving electrode layer, a second passivation layer and a hydrophobic layer.

[0049] Among them, the AM and PM regions share the same substrate. The choice of substrate is diverse, such as transparent glass substrate and plastic substrate. The gate, source and drain can be made of metals such as aluminum, molybdenum, copper, nickel, nickel-manganese alloy, nickel-chromium alloy, etc., which have large work function, good shape stability, electrical conductivity and thermal conductivity. It can be a single material conductive layer, or a composite conductive layer of multiple conductive materials. The film thickness ranges from 200 to 400nm.

[0050] The gate insulating layer has a thickness ranging from 200 to 400 nm, and the insulating layer material may be a single material such as silicon oxide, silicon nitride, aluminum oxide, or a composite insulating layer of multiple insulating materials.

[0051] The active layer is generally made of hydrogenated amorphous silicon (a-Si:H), low temperature polycrystalline silicon (LTPS) and oxide (such as IGZO). The film thickness ranges from 50 to 150nm. The electron mobility of hydrogenated amorphous silicon (a-Si:H) is generally less than 1 (cm 2 / v*s), oxide is between 5-50, and low-temperature polysilicon (LTPS) is generally greater than 100. The choice can be made based on actual application requirements.

[0052] The passivation layer plays the role of insulating and protecting the active layer. The film material can be the same as the gate insulating layer material, or an organic dielectric material such as epoxy resin, phenolic varnish, etc. can be selected. The film thickness ranges from 200 to 2000nm.

[0053] For the application of digital microfluidics, a hydrophobic layer material needs to be prepared on top of the passivation layer. Teflon can be used as the hydrophobic layer material. Teflon has high crystallinity, tightly oriented molecules, and small porosity. The process for electrodes of different sizes, shapes, and structures described below is the same.

[0054] In another embodiment, if Figure 3 As shown, the microfluidic chip is divided into three functional areas, namely functional area 1, functional area 2 and functional area 3. The size, structure, shape and arrangement of electrodes in different functional areas are designed according to the requirements of the chip. Figure 3 The functional area 1 given in the figure is exactly the same as the functional area 3, but different from the functional area 2. In the microfluidic chip, the functional area 2 is generally the actual reaction or culture area, and the functional areas 1 and 3 are water or nutrient solution. During the reaction process, the reaction area is prevented from contacting with the air, and during the culture process, the evaporation of water in the culture area is suppressed. Regardless of whether the three functional areas are exactly the same, different data lines are used to control the three areas to achieve the coordinated work of different functional areas.

[0055] In another embodiment, if Figure 4 As shown in FIG. 1 , the microfluidic chip is divided into nine functional areas, among which functional area 5 is the actual reaction / culture area, and the other functional areas are all auxiliary.

[0056] Furthermore, in the process of using the microfluidic chip, in order to distinguish the functional areas and find the target functional areas or electrodes, each functional area in the above-mentioned microfluidic chip can be marked so that each functional area is provided with a corresponding functional area number.

[0057] The mark can be not only Arabic numerals, but also uppercase English letters A, B, C... or lowercase English letters a, b, c..., and uppercase Roman numerals Ⅰ, Ⅱ, Ⅲ... or lowercase Roman numerals ⅰ, ⅱ, ⅲ...

[0058] The numbering or marking method can be applied not only to functional areas to quickly distinguish each functional area, but also to electrodes. Each electrode in a functional area is numbered so that each electrode on the electrode array is provided with a corresponding electrode number. When the electrode needs to be observed under a microscope, a certain electrode can be quickly found according to the mark or serial number. Or when checking the electrode, check it in the order of the serial number to avoid repeated observation.

[0059] Not only are there various methods for marking electrodes and functional areas, but also various locations for marking. Figure 4 The marking positions of the five electrodes or functional areas preferred by the present invention are upper left, upper right, lower left, lower right or middle. The marking symbol can be located in one pixel area or across multiple pixels. In the actual design process, the marking position is varied and can be modified according to the design. The principle of selecting the marking position is not to block the working area of ​​the electrode or the functional area, that is, not to affect the normal use of the microfluidic chip.

[0060] Furthermore, in some embodiments, Figure 5 As shown, the electrode array includes an array composed of several groups of hexagonal electrodes and waist-shaped electrodes; wherein the hexagonal electrodes in the same group are arranged in sequence; a group of waist-shaped electrodes is provided between two adjacent groups of hexagonal electrodes, and the shape of the waist-shaped electrodes matches the adjacent hexagonal electrodes. This electrode array combines the advantages of both the square electrode array and the hexagonal electrode array, and it can move droplets horizontally or vertically, and can also improve the fullness of the moved droplets.

[0061] Furthermore, in some embodiments, Figures 6 to 9 As shown, the electrode array includes an array composed of a plurality of unidirectional electrodes. The size, shape, arrangement and driving method of the unidirectional electrodes are different from other electrodes. The number of signal lines can be reduced and the requirement of unidirectional movement of droplets can be met.

[0062] The unidirectional electrode includes a first connecting portion 01 and a second connecting portion 02 ; the second connecting portion 02 is provided with a connecting port 03 , and the shape of the connecting port 03 matches that of the first connecting portion 01 .

[0063] Furthermore, the first connection portion 01 is an equilateral triangle; the connection port 03 is also an equilateral triangle.

[0064] based on Figure 6 and Figure 7 Due to the unidirectional electrode structure and the electrode array, the droplets can only move in one direction in a straight line.

[0065] When you need to move the droplet in a curved manner, you need to use the following Fig. 9 Another form of unidirectional electrode is shown, and an example of the electrode array formed by it is as follows Figure 8 shown.

[0066] According to another aspect of the present disclosure, a chip driving method is provided, which is applied to the above-mentioned regional digital microfluidic chip, comprising the following steps:

[0067] S0: Identify the chip type of the microfluidic chip and match the corresponding style template according to the chip type;

[0068] S1: determining the original position of the droplet, the original position includes the original functional area and the corresponding original electrode position;

[0069] S2: determining a target position for the droplet to move, where the target position includes a target functional area and a corresponding target electrode position;

[0070] S3: Calculate the moving path of the droplet according to the original position, the target position and the corresponding style template;

[0071] S4: determining a corresponding electrode driving signal according to the moving path of the droplet;

[0072] S5: driving the corresponding electrodes on the moving path of the droplet in sequence through the electrode driving signal.

[0073] like Fig.10 and Fig.11 , an example of driving a microfluidic chip to move a droplet from one functional area to another. Functional area 1 has a specification of 3*2 and includes 6 electrodes, so each electrode has a corresponding independent driving signal line, and 6 electrodes correspond to 6 signal lines. Functional area 2 has a specification of 6*4 and has more electrodes, so row and column signal driving is selected, including 6 row signal lines and 4 column signal lines.

[0074] Fig.10-a, the electrodes 2 and 6 in the functional area 1 marked by the grid are where the droplets are located. In order to make the droplets move stably from the functional area 1 to the functional area 2, it is necessary to write the driving signal according to the arrangement of the electrodes. The initial driving signal at this time is as follows Fig.11 -a, electrodes 2 and 6 in functional area 1 are in working state, and functional area 2 is not working. In order to move the droplet on electrode 2 in functional area 1 to electrodes 1, 2, 5, and 6 in functional area 2, it is necessary to make electrode 2 in functional area 1 not working, and electrodes 1, 2, 5, and 6 in functional area 2 working. The signal timing diagram is shown in Fig.11 -b, at this time, columns 1 and 2 are scanned simultaneously with rows 1 and 2. At this time, the droplet on the electrode 6 in the functional area 1 does not move. When the driving signal changes, the state of the droplet is as follows Fig.10 -b as shown.

[0075] In order to make the droplets on electrodes 1, 2, 5, 6 of functional area 2 continue to move to the right, at the same time, the droplets on electrode 6 of functional area 1 move to electrodes 17, 18, 21, 22 in functional area 2, the corresponding driving signal is as follows: Fig.11 -c. At this time, functional area 1 is not working, columns 1 and 2 are scanned simultaneously with rows 5 and 6, and columns 3 and 4 are scanned simultaneously with rows 1 and 2. When the driving signal changes, the state of the droplet is as follows Fig.10 -c. At this time, the droplet has successfully completed the stable movement from functional area 1 to functional area 2.

[0076] According to another aspect of the present invention, a chip driving device is provided. In this embodiment, a chip driving device may include or be divided into one or more program modules, one or more program modules are stored in a storage medium and executed by one or more processors to complete the present invention and implement the above-mentioned chip driving method. The program module referred to in the present invention refers to a series of computer program instruction segments that can complete specific functions, which is more suitable for describing the execution process of a chip driving device in a storage medium than the program itself. The following description will specifically introduce the functions of each program module in this embodiment:

[0077] A storage module, used to store corresponding style templates of microfluidic chips of various chip types, wherein the style templates include the properties and position relationship information of each functional area and each electrode in each functional area;

[0078] An identification module, used to identify the chip type of the microfluidic chip and match the corresponding style template according to the chip type;

[0079] A setting module, used to determine the original position and target position of the droplet;

[0080] A path generation module is used to calculate the moving path of the droplet according to the original position, the target position and the style template;

[0081] The driving signal generating module is used to determine and generate a corresponding electrode driving signal for output according to the moving path of the droplet.

[0082] If the integrated unit described in the present application is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present application is essentially or the part that contributes to the prior art or all or part of the technical solution can be embodied in the form of a software product, and the computer software product is stored in a storage medium, including a number of instructions to enable a computer device (which can be a personal computer, a server, or a network device, etc.) to perform all or part of the steps of the method described in each embodiment of the present application. The aforementioned storage medium includes: U disk, mobile hard disk, read-only memory (Read-Only Memory, referred to as ROM), random access memory (Random Access Memory, referred to as RAM), disk or optical disk and other media that can store program codes.

[0083] Note that the above are only preferred embodiments of the present application and the technical principles used. Those skilled in the art will understand that the present application is not limited to the specific embodiments described herein, and that various obvious changes, readjustments and substitutions can be made by those skilled in the art without departing from the scope of protection of the present application. Therefore, although the present application is described in more detail through the above embodiments, the present application is not limited to the above embodiments, and may include more other equivalent embodiments without departing from the concept of the present application, and the scope of the present application is determined by the scope of the appended claims.

Claims

1. A regional digital microfluidic chip, characterized in that: include: A plurality of electrode arrays, each of which is arranged on the same substrate and forms a corresponding functional area; The functional area includes a reaction culture area and a plurality of pipetting areas; The reaction culture area is used for actual reaction or cell culture; The pipetting area is used to move the droplets; The electrode array corresponding to the reaction culture area is a passive electrode array; The pipetting area and the corresponding electrode array are active electrode arrays.

2. A regional digital microfluidic chip according to claim 1, characterized in that: The electrode array includes a plurality of electrodes, and the electrodes include a gate layer, a gate insulating layer, an active layer, an original drain electrode layer, a first passivation layer, a driving electrode layer, a second passivation layer and a hydrophobic layer.

3. A regional digital microfluidic chip according to claim 1 or 2, characterized in that: The electrode array comprises an array composed of a plurality of groups of hexagonal electrodes and waist-shaped electrodes; Among them, the hexagonal electrodes in the same group are arranged in sequence; A group of waist-shaped electrodes is arranged between two adjacent groups of hexagonal electrodes, and the shape of the waist-shaped electrodes matches the adjacent hexagonal electrodes.

4. A regional digital microfluidic chip according to claim 1 or 2, characterized in that: The electrode array comprises an array consisting of a plurality of unidirectional electrodes; The unidirectional electrode comprises a first connecting portion and a second connecting portion; The second connecting portion is provided with a connecting port, and the connecting port matches the shape of the first connecting portion.

5. The regional digital microfluidic chip according to claim 4, characterized in that: The first connecting portion is an equilateral triangle; the connecting port is also an equilateral triangle.

6. A regional digital microfluidic chip according to claim 1 or 2, characterized in that: Each of the functional areas is respectively provided with a corresponding functional area label.

7. The regional digital microfluidic chip according to claim 6, characterized in that: Each electrode on the electrode array is provided with a corresponding electrode number.

8. A chip driving method, applied to a regional digital microfluidic chip according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1: determining an original position of the droplet, wherein the original position includes an original functional area and a corresponding original electrode position; S2: determining a target position for the droplet to move, where the target position includes a target functional area and a corresponding target electrode position; S3: Calculating a moving path of the droplet according to the original position and the target position; S4: determining a corresponding electrode driving signal according to the moving path of the droplet; S5: driving the corresponding electrodes on the moving path of the droplet in sequence through the electrode driving signal.

9. A chip driving method according to claim 8, characterized in that: The following steps are also included: S0: Identify the chip type of the microfluidic chip, and match the corresponding pattern template according to the chip type.

10. A chip driving device, using a chip driving method according to claim 8 or 9, characterized in that: include: A storage module, used to store corresponding style templates of microfluidic chips of various chip types, wherein the style templates include attributes and position relationship information of each functional area and each electrode in each functional area; An identification module, used to identify the chip type of the microfluidic chip and match the corresponding pattern template according to the chip type; A setting module, used to determine the original position and target position of the droplet; A path generation module, used to calculate the moving path of the droplet according to the original position, the target position and the style template; The driving signal generating module is used to determine and generate a corresponding electrode driving signal for output according to the moving path of the droplet.

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