Digital micro-fluidic chip liquid drop operation layout method based on flexible partitioning
Through flexible blocking and layout adjustment, the problem of unbalanced wear of digital microfluidic biochip electrodes is solved, and the balanced wear of chip electrodes is improved and the service life is extended.
Patent Information
- Application Number
- CN202510126826.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-27
- Publication Date
- 2025-05-16
AI Technical Summary
Existing digital microfluidic biochips have problems of uneven electrode wear during droplet operation, resulting in a shortened chip service life and reduced reliability.
The flexible blocking method is adopted to classify the chip area required for different droplet operations, establish corresponding blocking models, and lay out the droplet operations in the center or edge area of the block with the lightest wear and suitable area according to the wear degree and fluid constraints.
Through flexible blocking and layout adjustment, the balance of chip electrode wear is significantly improved, extending the service life of the chip and improving reliability.
Smart Images
Figure CN120012428A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a droplet operation layout of a digital microfluidic chip, and in particular to a droplet operation layout method of a digital microfluidic chip based on flexible block division. Background Art
[0002] Digital microfluidic biochip is an example of a laboratory on a chip, which uses discrete droplets as carriers to realize various fluid operations, biochemical reactions and biological detection at the microscopic scale, and can automatically perform biochemical experiments. Its main features are: (1) Low cost, low power consumption and high integration; (2) Multiple droplets can be controlled to operate in parallel on a large-scale chip; (3) The on-chip addressable electrodes can be reconfigured into a variety of microfluidic modules.
[0003] Digital microfluidic biochips use the dielectric electrowetting principle to operate droplets. Droplets of experimental samples and experimental reagents can be transferred along electrodes, and droplet operations such as distribution, transfer, mixing, dilution and splitting can be performed on the chip.
[0004] In the application process of digital microfluidic biochips, there is a problem of uneven electrode wear, which will shorten the service life of the chip and reduce its reliability. Therefore, it is very necessary to consider the wear balance of chip electrodes when generating high-level comprehensive results for bioassays.
[0005] The existing high-level synthesis method takes into account the problem of poor electrode wear balance during the experiment, and proposes to place the droplet operation at the location where the electrode wear is less during the synthesis. This method first establishes a block model for the digital microfluidic biochip, then finds the block with less wear during the experiment, and then places the droplet operation in the center of the block, so as to achieve the purpose of improving the electrode wear balance, thereby improving the service life and reliability of the digital microfluidic biochip. Existing method source: Z. Zhong, T.-C. Liang, K. Chakrabarty. Enhancing theReliability of MEDA Biochips Using IJTAG and Wear Leveling [J]. IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, 2021, 40(10): 2063-2076. Defects and shortcomings of the existing technology: In the experiment, different droplet operations use different chip areas. The existing method uses the chip area used by the droplet operation with the largest chip area as the standard to establish a chip block model. This will result in that when the droplet operation with a smaller area is laid out, it must also be laid out in the center of the larger block, making the wear degree of the center of the block more serious than the wear degree of the edge of the block. Existing methods place droplet operations in the center of a block, which means that the fluid constraint area reserved at the edge of the block will not be used for droplet operations. This will also cause the wear in the center of the block to be more severe than that at the edge of the block. Summary of the invention
[0006] The first object of the present invention is to provide a method for flexibly partitioning a digital microfluidic biochip, which can establish partition models according to the different chip areas required for different types of droplet operations. Compared with the fixed partition model of the existing method, this method is more flexible and can find a partition with a suitable area for each droplet operation.
[0007] The technical solution for achieving the first object of the present invention is: A method for flexibly dividing a digital microfluidic biochip into blocks comprises the following steps: S1, all droplet operations in the experiment are classified according to the required chip area; S2, building a block model for each type of droplet operation; S3, for each block in each block model, calculate the number of block wear times; S4, when a certain type of droplet operation is arranged, a block with the lightest wear and satisfying the fluid constraint in the block model corresponding to the droplet operation is found, and the droplet operation is arranged in the center of the block, and the number of times the electrode in the region is used by the droplet operation is added to the number of times the electrode is worn; S5, if all droplet operations in the experiment have completed layout, the experiment ends; if there are droplet operations that have not been laid out, the experiment returns to S3.
[0008] The classification method in S1 is to classify droplet operations using the same chip area into one category.
[0009] The S2 includes: (1) Assuming that there are n types of droplet operations in the experiment, a total of n block models are established; (2) For the i-th block model, let the side length of its block be x i , and the area of the digital microfluidic biochip for the experiment is X electrodes × Y electrodes, then there are a total of (X / x i )×(Y / x i ) blocks, each block has an area of xi Electrodes × x i Electrodes; (3) For the i-th block model, let the side length of the chip area required for the i-th type of droplet operation be d i , and the area of the digital microfluidic biochip for the experiment is X electrodes × Y electrodes, and the side length of the block is x i The following requirements must be met: (3-1) d i ≤ x i , that is, the side length x of the block i The side length d of the chip area required for droplet operation must be greater than or equal to i ; (3-2) X % x i = 0, Y % x i = 0, that is, the side length x of the block i It can be divided evenly by the length and width of the digital microfluidic biochip.
[0010] The number of block wear times of the block in S3 is defined as the sum of the number of wear times of all electrodes in the block.
[0011] In S4, assuming that the droplet operation is the i-th type of droplet operation, the conditions that the blocks to be found must satisfy are: 1) The number of block wear of this block is the least in the i-th block model; 2) The blocks satisfy the fluid constraints, i.e. there is at least one row of electrodes between the blocks and the nearest droplets.
[0012] The second purpose of the present invention is to provide a method for adjusting the droplet operation layout position, which can arrange the droplet operation at a position with less wear in a block or between blocks according to the degree of chip wear. Compared with the limitation that the existing method can only arrange the droplet operation in the center of a block, this method can arrange the droplet operation around the block or even between several blocks, and can further utilize the edge area of the block to improve the balance of chip wear.
[0013] The technical solution for achieving the second object of the present invention is: A method for adjusting the droplet operation layout position of a digital microfluidic biochip comprises the following steps: Step A, determine the adjustment range; Step B, removing all layout positions that do not meet the fluid constraints within the adjustment range; Step C, calculating the layout costs of the remaining layout positions within the adjustment range; Step D: Find the layout position with the minimum layout cost within the adjustment range and place the droplet operation there.
[0014] In step A, the adjustment range is all the droplet operation layout positions in the block where the droplet operation layout position is located and the eight adjacent blocks around it.
[0015] In the step B, the condition that the layout position does not meet the fluid constraint is that there is less than one row of electrodes between the position and the nearest droplet.
[0016] In the step C, the layout cost of the layout position is defined as the sum of the wear times of all electrodes in the area occupied by the droplet operation layout at the layout position.
[0017] After software simulation experiments, the method provided by the second purpose of the present invention is combined with S4 of the method provided by the first purpose, and the wear leveling index in CEP, main mixing and continuous dilution experiments is improved by an average of about 113% compared with the existing method.
[0018] Advantages of the present invention: (1) When establishing a block model for a digital microfluidic biochip, the present invention fully considers the different requirements of different droplet operations for chip area, and performs targeted block division for each type of droplet operation with the same chip area requirement, so that each droplet operation has a block corresponding to its usage area, thereby improving the utilization rate of the edge area of the block, thereby improving the wear balance of the entire chip; (2) After finding a block with less wear and appropriate area based on the chip area required for droplet operation, the present invention will evaluate all positions within the block and positions within a certain area around the block, and arrange the droplet operation within a block or at the junction of several blocks while taking into account the fluid constraints. This will increase the utilization rate of the edge area of the block and thereby improve the overall wear balance of the chip. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Figure 1 A schematic diagram of the chip area used for the type A droplet operation and the type B droplet operation in Example 1; Figure 2 Schematic diagram of the number of times the electrode on the chip is worn in Example 1; Figure 3 Schematic diagram of the block model corresponding to the type A droplet operation and the type B droplet operation in Example 1; Figure 4 Schematic diagram of block wear times of the type A droplet operation block model and the type B droplet operation block model in Example 1; Figure 5 Schematic diagram of the layout of type A droplet operation and type B droplet operation in Example 1; Figure 6 This is a flow chart of the method for flexibly partitioning a digital microfluidic biochip in Example 1; Figure 7 A schematic diagram of the adjustment range for determining the layout of type A droplet operation and type B droplet operation in Example 2; Figure 8 Schematic diagram of fluid confinement for type A droplet operation and type B droplet operation in Example 2; Fig. 9 Schematic diagram of the layout of type A droplet operation and type B droplet operation in Example 2; Fig.10 This is a flow chart of the method for adjusting the droplet operation layout position in Example 2. DETAILED DESCRIPTION
[0020] The content of the present invention is further described below in conjunction with the embodiments and drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0021] Embodiment 1: Using the first method proposed by the present invention, Figure 1 A type A droplet operation and a type B droplet operation are placed in Figure 2 The digital microfluidic biochip shown.
[0022] like Figure 6 As shown, a method for flexibly dividing a digital microfluidic biochip into blocks comprises the following steps: Step 1: Classify all droplet operations in the experiment according to the required chip area. Suppose there are two types of droplet operations, A and B, which use chip areas of 2 electrodes × 2 electrodes and 3 electrodes × 3 electrodes respectively. Figure 1 ; Step 2: For each type of droplet operation, a block model is established. For a digital microfluidic biochip with 12 electrodes × 12 electrodes, a block model is established for two types of droplet operations, A and B, according to this method; (1) It is found that there are two types of droplet operations in the experiment, so two block models are established, such as Figure 3 As shown; (2) For the first block model, i.e., the block model for type A droplet operation, the block side length is set to 2 electrodes, so there are 36 blocks in the block model; for the second block model, i.e., the block model for type B droplet operation, the block side length is set to 3 electrodes, so there are 16 blocks in the block model; Step 3: Calculate the block wear times of each block in the two block models, and calculate the block wear times of the first block model as Figure 4 As shown on the left, the block wear times of the second block model are calculated as Figure 4 As shown on the right; Step 4: Layout the droplet operation. Figure 4 The left analysis shows Figure 5 Left, right Figure 4 Right analysis shows Figure 5 Right: Assume that the blue area is the area where other droplets exist, and the green area is the droplet operation layout position that meets the conditions. The droplet operation is placed in the green area. (1) Figure 5 The yellow and green blocks are the blocks with the least block wear in the two block models; (2) Figure 5 The middle green block is the block that satisfies the fluid constraint in the two-block model, that is, it is separated from other droplets by at least one row of electrodes; Step 5: If all droplet operations in the experiment have completed layout, the experiment ends; if there are droplet operations that have not been laid out, the experiment returns to step 3.
[0023] Embodiment 2: For step 4 in Example 1, the second method proposed by the present invention is used to adjust the droplet operation layout position.
[0024] like Fig.10 As shown, a method for adjusting the droplet operation layout position of a digital microfluidic biochip comprises the following steps: Step a, determine the adjustment range Figure 7 All green areas in the image are adjusted to the dark green block where the droplet operation layout is located and the eight adjacent light green blocks around it; Step b: remove all layout positions that do not meet the fluid constraint within the adjustment range. A layout position that does not meet the fluid constraint means that there is no gap between the position and the nearest droplet. After removal, the adjustment range is Figure 8 All green areas in Step c, calculating the layout costs of the remaining layout positions within the adjustment range, where the layout cost of the layout position refers to the sum of the number of wear times of all electrodes in the layout area; Step d, find the layout position with the minimum layout cost within the adjustment range and place the droplet operation there. Analyze the results obtained in steps b and c, the droplet operation layout position is Fig. 9 Medium to dark green area.
[0025] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of protection of the present invention is defined by the appended claims and their equivalents.
Claims
1. A method for flexibly partitioning a digital microfluidic biochip, characterized in that: The following steps are involved: S1, all droplet operations in the experiment are classified according to the required chip area; S2, building a block model for each type of droplet operation; S3, for each block in each block model, calculate the number of block wear times; S4, when a certain type of droplet operation is arranged, a block with the lightest wear and satisfying the fluid constraint in the block model corresponding to the droplet operation is found, and the droplet operation is arranged in the center of the block, and the number of times the electrode in the region is used by the droplet operation is added to the number of times the electrode is worn; S5, if all droplet operations in the experiment have completed layout, the experiment ends; if there are droplet operations that have not been laid out, the experiment returns to S3.
2. A method for flexibly dividing a digital microfluidic biochip according to claim 1, characterized in that: The classification method in S1 is to classify droplet operations using the same chip area into one category.
3. The method for flexibly dividing a digital microfluidic biochip according to claim 1, characterized in that: The S2 includes: (1) Assuming that there are n types of droplet operations in the experiment, a total of n block models are established; (2) For the i-th block model, let the side length of its block be x i , and the area of the digital microfluidic biochip for the experiment is X electrodes × Y electrodes, then there are a total of (X / x i )×(Y / x i ) blocks, each block has an area of x i Electrodes × x i Electrodes; (3) For the i-th block model, let the side length of the chip area required for the i-th type of droplet operation be d i , and the area of the digital microfluidic biochip for the experiment is X electrodes × Y electrodes, and the side length of the block is x i The following requirements must be met: (3-1) d i ≤ x i , that is, the side length x of the block i The side length d of the chip area required for droplet operation must be greater than or equal to i ; (3-2) X % x i = 0, Y % x i = 0, that is, the side length x of the block i It can be divided evenly by the length and width of the digital microfluidic biochip.
4. The method for flexibly dividing a digital microfluidic biochip according to claim 1, characterized in that: The number of block wear times of the block in S3 is defined as the sum of the number of wear times of all electrodes in the block.
5. The method for flexibly dividing a digital microfluidic biochip according to claim 1, characterized in that: In S4, assuming that the droplet operation is the i-th type of droplet operation, the conditions that the blocks to be found must satisfy are: 1) The number of block wear of this block is the least in the i-th block model; 2) The blocks satisfy the fluid constraints, i.e. there is at least one row of electrodes between the blocks and the nearest droplets.
6. A method for adjusting the droplet operation layout position of a digital microfluidic biochip, characterized in that: The following steps are involved: Step A, determine the adjustment range; Step B, removing all layout positions that do not meet the fluid constraints within the adjustment range; Step C, calculating the layout costs of the remaining layout positions within the adjustment range; Step D: Find the layout position with the minimum layout cost within the adjustment range and place the droplet operation there.
7. A method for adjusting the droplet operation layout position of a digital microfluidic biochip according to claim 6, characterized in that: In step A, the adjustment range is all the droplet operation layout positions in the block where the droplet operation layout position is located and the eight adjacent blocks around it.
8. The method for adjusting the droplet operation layout position of a digital microfluidic biochip according to claim 6, characterized in that: In the step B, the condition that the layout position does not meet the fluid constraint is that there is less than one row of electrodes between the position and the nearest droplet.
9. The method for adjusting the droplet operation layout position of a digital microfluidic biochip according to claim 6, characterized in that: In the step C, the layout cost of the layout position is defined as the sum of the wear times of all electrodes in the area occupied by the droplet operation layout at the layout position.