Droplet group wiring method of active pixel array digital microfluidic biochip

Through droplet spacing adjustment, preset path search and line algorithms, the problem of insufficient droplet wiring efficiency and real-time performance in large-scale droplet systems is solved, and efficient droplet group wiring effect is achieved.

CN119558266APending Publication Date: 2025-03-04NORTHWESTERN POLYTECHNICAL UNIV
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Patent Information

Application Number
CN202411701081.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-26
Publication Date
2025-03-04

AI Technical Summary

Technical Problem

The prior art is difficult to effectively solve the droplet wiring problem in high-density array control and large-scale droplet systems, especially in terms of real-time and operating efficiency.

Method used

The initial position of the droplet is obtained through the droplet spacing adjustment algorithm, and the preset path of all droplets is obtained by using the droplet preset path search method. Finally, the line algorithm is used and published to obtain the droplet cluster wiring results to achieve efficient wiring of large-scale droplet clusters.

Benefits of technology

Under the condition that the CPU run time is controlled within 1s, the maximum number of moving droplets at the same time is almost the same as the number of droplets, which achieves efficient wiring of large-scale droplet clusters, and the latest arrival time and average arrival time show superiority.

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Abstract

The invention belongs to the technical field of digital micro-fluidic chip design. The invention provides a droplet group wiring method of an active pixel array digital micro-fluidic biochip. According to the embodiment of the invention, the initial position of a liquid drop is obtained by using a liquid drop spacing adjustment algorithm; secondly, obtaining preset paths of all liquid drops by utilizing a liquid drop preset path searching method; and finally, a droplet group wiring result is obtained by using a concurrent wiring algorithm. On the other hand, according to the method, the maximum number of the liquid drops moved at the same time is almost the same as the number of the liquid drops, efficient wiring of large-scale liquid drop clusters on the active pixel array digital micro-fluidic biochip can be completed under the condition that the CPU operation time is controlled to be 1 s, and the wiring efficiency is greatly improved at the latest arrival time. The average arrival time can show the superiority of the method. According to the method, the resource of the available area of the chip can be utilized to the maximum extent, and the wiring failure condition caused by the conflict of the liquid drops can be efficiently treated.
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Description

Technical Field

[0001] The disclosed embodiments relate to the technical field of digital microfluidic chip design, and in particular to a droplet group wiring method of an active pixel array digital microfluidic biochip. Background Art

[0002] Active-matrix digital microfluidics biochips (AM-DMB) are an emerging microfluidic system control scheme and have become one of the most important technology platforms in the field of microfluidics. As an important milestone in the development of microfluidic technology, AM-DMB provides a highly flexible droplet control method that can control the generation, segmentation, fusion and transportation of droplets with high precision on a two-dimensional plane. This technology has been proven to have significant advantages in improving the efficiency and precision of droplet manipulation. For example, in the field of biomedical applications, AM-DMB has been used in many complex experimental processes such as cell culture and DNA analysis, showing great potential and effectively overcoming the operational limitations brought by traditional microchannel structures. Especially in large-scale array chips, droplet manipulation technology based on electrowetting drive is widely used.

[0003] AM-DMB manipulates droplets by applying voltage to array electrodes. Its core is to establish the movement path of droplets on the chip surface based on the electrowetting phenomenon. Figure 1 The working principle diagram of AM-DMB is shown. In the center of the chip is a 256×256 pixel array, the control electrode is formed on the thin film transistor (TFT) circuit, and around the chip is the interface used to drive the chip. Through this circuit structure, each pixel unit can respond to the control signal independently and accurately perform the droplet movement operation. In particular, when multiple droplets are manipulated simultaneously on the same chip, the chip's independent pixel addressing mechanism can ensure that the movement of each droplet does not interfere with each other, greatly improving the operating efficiency of the chip laboratory.

[0004] Unlike traditional microfluidic chips, the AM-DMB system has higher droplet control accuracy and can control more droplets. Therefore, solving the complex droplet routing problem of AM-DMB is an important challenge. Especially when high-density array control is required, the droplet movement path design involves the series operation of multiple pixel units and how to quickly switch the position of droplets between different areas. These factors make the droplet routing problem on AM-DMB very complicated.

[0005] So far, a variety of methods have been proposed to solve the droplet routing problem for traditional microfluidic chips. Among them, a high-performance droplet routing algorithm is proposed, which gives priority to droplets with stronger detour ability to reduce blockage and solves the deadlock problem through a yield strategy. Although this method improves the fault tolerance and efficiency of routing in complex situations, the real-time performance and operating efficiency of the algorithm may be difficult to meet the requirements for larger-scale droplet systems and complex chip designs. An algorithm is also proposed to optimize the droplet flow path by synchronizing the routing of wash droplets and functional droplets, aiming to reduce routing time and avoid cross-contamination between different droplets. However, this method is mainly aimed at droplet cross-contamination, and does not fully consider the situation of larger droplet scale and wider layout range, and the effect may be limited under higher real-time requirements. A fast algorithm is also proposed for the droplet routing problem of microarray biochips. The algorithm significantly shortens the calculation time, but its advantages are mainly reflected in the processing of small-scale chips and rely on the relationship between droplet velocity and shape. The performance and adaptability of the algorithm may be limited when facing larger-scale droplets and chips. A Q-learning technique based on reinforcement learning is also proposed. By optimizing droplet routing through a deep Q network, obstacles can be avoided effectively and unnecessary path estimation can be reduced. However, this method cannot generate the best solution in a timely manner when real-time requirements are high, especially in scenarios with large-scale droplets and complex environments. Moreover, the training time and convergence speed of reinforcement learning may become a bottleneck for system performance. Therefore, although the existing methods have made progress in droplet routing, in the context of the AM-DMB system, there are still problems such as insufficient algorithm operation efficiency and limited path planning optimization, and they cannot be directly applied to the system.

[0006] Therefore, it is necessary to improve one or more problems existing in the above-mentioned related technical solutions.

[0007] It should be noted that this section is intended to provide background or context for the technical solutions of the present disclosure stated in the claims. The description herein is not admitted to be prior art by virtue of being included in this section. Summary of the invention

[0008] The purpose of the embodiments of the present disclosure is to provide a droplet group wiring method for an active pixel array digital microfluidic biochip, thereby overcoming one or more problems caused by the limitations and defects of the relevant technology at least to a certain extent.

[0009] According to an embodiment of the present disclosure, a droplet group wiring method for an active pixel array digital microfluidic biochip is provided, the method comprising: Obtaining a starting position of a droplet set, an ending position of the droplet set, an obstacle set, a minimum spacing constraint, and a routing area size; Based on the starting position of the droplet set, the ending position of the droplet set, the obstacle set and the minimum spacing constraint, using a droplet spacing adjustment algorithm to obtain the droplet initial position; Based on the initial position of the droplet and the size of the wiring area, a droplet preset path search method is used to obtain the preset paths of all the droplets; Based on the preset paths of all the droplets, a parallel routing algorithm is used to obtain the droplet group routing result.

[0010] Further, the step of obtaining the starting position of the droplet set, the ending position of the droplet set, the obstacle set, the minimum spacing constraint and the size of the wiring area includes: The droplet set is set to ; Obtain the starting position and ending position of each droplet to obtain the droplet set The starting position , the droplet collection The end position of ; Get the position of each obstacle and get the obstacle set ; Get the minimum spacing constraint and the wiring area size .

[0011] Furthermore, the constraints of this method include: Movement constraint: Each droplet moves at most one unit per unit time; Static spacing constraint: If the positions of any two droplets at any time t are , then it satisfies: ; Dynamic spacing constraint: If the positions of any two droplets at any time t are , then it satisfies: ; Obstacle constraint: The droplet cannot pass through the location of the obstacle at any time; Real-time constraint: CPU running time is within 1s.

[0012] Furthermore, based on the starting position of the droplet set, the ending position of the droplet set, the obstacle set and the minimum spacing constraint, the step of obtaining the initial position of the droplet using the droplet spacing adjustment algorithm includes: constructing a coordinate system based on the wiring area; The priority of each droplet is set according to the Manhattan distance from the end position of each droplet in the droplet set to the central grid of the wiring area; wherein the central grid of the wiring area is the central grid; According to the obstacle set , adjusting the gap between each of the droplets in the y-axis direction so that each of the droplets can pass through the gap in the y-direction, so as to obtain the ordinate of each of the droplets after the gap is adjusted ; where the gap is at least ; According to the ordinate of each droplet after adjusting the gap , get the initial position of the droplet after adjusting the position .

[0013] Further, after adjusting the gap, the ordinate of each droplet The expression is:

[0014] in, is the reference position, is the sequence number sorted from small to large according to the y coordinate, , is the gap between droplets, For offset.

[0015] Furthermore, based on the initial position of the droplet and the size of the wiring area, the step of obtaining the preset paths of all the droplets using the droplet preset path search method includes: set up for The initial path of each grid The conflict zone is , interference value To search for the droplet The initial path is the grid By all The number of times the conflict area is covered; among them, For the i The first droplet on its initial path j The position of a unit of time, For the i The first droplet on its initial path k The position of a unit of time; For one of the droplets, based on the initial position of the droplet, the BFS search method is used to obtain the minimum interference value. The minimum initial path is the preset path of the droplet; All the droplets are traversed to obtain the preset paths of all the droplets.

[0016] Furthermore, based on the preset paths of all the droplets, the step of obtaining the droplet group routing result by using the parallel routing algorithm includes: According to the priority of each droplet, check whether there is an obstacle in the next step along the preset path from the current position to obtain the droplet exist Position at the moment wherein the droplet All the grids on the preset path Leave a trail mark on ; If there is an obstacle, stop. ; wherein the droplet exist Position at the moment ; If there is no obstacle, move a unit distance along the preset path, and if the current position of the droplet conflicts with the droplet with a lower priority, return the conflicting droplet to its checkpoint; All of the droplets at the current time After the movement is completed, the droplet is obtained At the moment The checkpoint is ; If the droplet There is no path mark left by the droplet with a higher priority than the current position , then update the position to the new checkpoint, that is, , while removing arrive Path markers for paths between ; where For the droplet exist Checkpoints at all times; All the droplets are traversed to move the droplets to the end position to obtain the droplet group wiring result.

[0017] The technical solution provided by the embodiments of the present disclosure may have the following beneficial effects: In the embodiments of the present disclosure, the droplet cluster wiring method of the above-mentioned active pixel array digital microfluidic biochip is used. On the one hand, the method first uses the droplet spacing adjustment algorithm to obtain the initial position of the droplet; secondly, the preset path of all droplets is obtained by using the droplet preset path search method; finally, the droplet cluster wiring result is obtained by using the parallel wiring algorithm. On the other hand, the maximum number of droplets moving simultaneously in this method is almost the same as the number of droplets, and the efficient wiring of large-scale droplet clusters on the active pixel array digital microfluidic biochip can be completed under the condition that the CPU running time is controlled within 1s, and the latest arrival time and the average arrival time can reflect the superiority of the present application. This method can maximize the utilization of resources in the available area of ​​the chip, and can efficiently handle the wiring failure caused by droplet conflicts. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings herein are incorporated into the specification and constitute a part of the specification, illustrate embodiments consistent with the present disclosure, and together with the specification are used to explain the principles of the present disclosure. Obviously, the accompanying drawings described below are only some embodiments of the present disclosure, and for ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without creative work.

[0019] Figure 1 A schematic diagram showing the logical structure of an active pixel array digital microfluidic biochip in the prior art; Figure 2 A diagram showing the steps of a droplet group wiring method of an active pixel array digital microfluidic biochip in an exemplary embodiment of the present disclosure; Figure 3 A schematic diagram showing the obstruction effect of the end point position of a droplet in an exemplary embodiment of the present disclosure; Figure 4 A schematic diagram showing the obstruction effect of the initial droplet position in an exemplary embodiment of the present disclosure; Figure 5 A schematic diagram showing the spacing adjustment of a droplet collection in an exemplary embodiment of the present disclosure is shown; Figure 6 A schematic diagram showing the wiring of droplets after adjustment in an exemplary embodiment of the present disclosure; Figure 7 A schematic diagram showing a droplet path search in an exemplary embodiment of the present disclosure; Figure 8 A schematic diagram showing a parallel line in an exemplary embodiment of the present disclosure; Fig. 9 A schematic diagram showing a droplet 7 in an exemplary embodiment of the present disclosure. DETAILED DESCRIPTION

[0020] Example embodiments will now be described more fully with reference to the accompanying drawings. However, example embodiments can be implemented in a variety of forms and should not be construed as limited to the examples set forth herein; rather, these embodiments are provided so that the disclosure will be more comprehensive and complete and to fully convey the concepts of the example embodiments to those skilled in the art. The described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0021] In addition, the accompanying drawings are only schematic illustrations of the embodiments of the present disclosure and are not necessarily drawn to scale. The same reference numerals in the figures represent the same or similar parts, and their repeated descriptions will be omitted. Some of the block diagrams shown in the accompanying drawings are functional entities and do not necessarily correspond to physically or logically independent entities.

[0022] In this exemplary embodiment, a droplet group wiring method for an active pixel array digital microfluidic biochip is provided. Figure 2 As shown in , the droplet group wiring method of the active pixel array digital microfluidic biochip may include: step S101 to step S104.

[0023] Step S101: obtaining a starting position of a droplet set, an ending position of the droplet set, an obstacle set, a minimum spacing constraint, and a wiring area size; Step S102: based on the starting position of the droplet set, the ending position of the droplet set, the obstacle set and the minimum spacing constraint, the droplet initial position is obtained by using a droplet spacing adjustment algorithm; Step S103: based on the initial position of the droplet and the size of the wiring area, using a droplet preset path search method to obtain preset paths of all the droplets; Step S104: Based on the preset paths of all the droplets, a droplet group routing result is obtained using a parallel routing algorithm.

[0024] Through the above-mentioned active pixel array digital microfluidic biochip droplet group wiring method, on the one hand, the method first uses the droplet spacing adjustment algorithm to obtain the initial position of the droplet; secondly, the droplet preset path search method is used to obtain the preset path of all droplets; finally, the parallel wiring algorithm is used to obtain the droplet group wiring result. On the other hand, the maximum number of droplets moving simultaneously in this method is almost the same as the number of droplets, and the efficient wiring of large-scale droplet clusters on the active pixel array digital microfluidic biochip can be completed under the condition that the CPU running time is controlled within 1s, and the latest arrival time and the average arrival time can reflect the superiority of this application. This method can maximize the use of resources in the available area of ​​the chip, and can efficiently handle the wiring failure caused by droplet conflicts.

[0025] Next, we will refer to Figures 2 to 9The various steps of the droplet group wiring method of the active pixel array digital microfluidic biochip in this example embodiment are described in more detail.

[0026] In step S101, the droplet group routing problem can be defined as: given a droplet set , and the corresponding starting position , the corresponding end position , obstacle set , the minimum spacing constraint , and the size of the wiring area It is necessary to output the movement path of the droplet per unit time while satisfying the following constraints: Each droplet moves at most one unit per unit time.

[0027] Static spacing constraint: Assume that any time t The positions of any two droplets are , then it is necessary to meet: .

[0028] Dynamic spacing constraint: Assume that at any time t, the positions of any two droplets are , then it is necessary to meet: .

[0029] Obstacle constraint: The droplet cannot pass through the location of the obstacle at any time.

[0030] Real-time constraint: The CPU running time of the method is within 1s.

[0031] In step S102, the droplet routing problem is a three-dimensional problem when considering the time axis, namely the x-axis, the y-axis and the time axis. The three-dimensional problem is difficult to handle, so the two-dimensional problem is handled first, that is, routing the droplet groups one by one in series, rather than moving them in parallel, and then considering parallelizing all the paths. The overall algorithm flow is divided into three steps: 1) preprocessing; 2) path search; 3) parallel path planning.

[0032] In the pre-processing, a priority is set for each droplet to determine the order of their serialized routing and reduce the obstruction of the droplet end point on the routing. Then the gap of the droplet starting point is adjusted to reduce the obstruction of the droplet starting point on other droplets.

[0033] Therefore, it is necessary to plan the order of droplet routing reasonably. In the following description, the definition of the order of droplet routing is that after one droplet moves, other droplets move, and then define the order. Without loss of generality, assume exist Path planning is performed before. Note exist The end point has been reached during routing. Due to the minimum spacing constraint, The end position will be An unreasonable wiring sequence will cause The wiring is blocked by the already routed droplets, causing wiring failure, such as Figure 3 As shown, droplet 1 is Arrive first Afterwards, droplet 2 arrives The only way will be Completely blocked, leading to planning failure. The most central grid in the routing area is called the central grid. The priority of each droplet is set according to the Manhattan distance from the end point of each droplet to the central grid. That is, the farther the droplet end point is from the central grid, the greater the priority, and vice versa. Droplets with higher priorities are routed first.

[0034] After setting the priority, the obstruction of the end point of the droplet is eliminated, but the starting point of the droplet will also have an obstruction effect on the droplet, such as Figure 4 As shown, , , as well as The obstacles Therefore, the gap between the droplets needs to be adjusted so that the droplets for wiring Can bypass The starting position of the droplet is adjusted in the y direction so that the droplet can pass through the gap in the y direction. Then the gap between the droplets in the y direction is at least The adjustment method is to move the droplets with the same initial y coordinate to a new y coordinate as follows: Figure 5 , , and will move in the direction of the red arrow. This will make the distance between adjacent different vertical coordinates at least .set up is the set of initial droplet positions, is the set of ordinates of the droplet position after adjusting the gap. In order to minimize the overall movement distance of the droplet, is the reference position, ,make:

[0035] in, The offset is set to avoid obstacles in the initial routing area. It is the smallest integer that allows all droplets to not overlap with obstacles after moving to the target ordinate. After adjusting the gap, the initial droplet position can reduce the obstruction to droplet routing.

[0036] like Figure 6 As shown, after adjusting the gap, and The gap between Smooth wiring.

[0037] Algorithm 1 shows the pseudo code for droplet gap adjustment, where the initial droplet position refers to the position after the gap is adjusted.

[0038]

[0039] In step S103, in the preprocessing, a priority is set for each droplet to determine their routing order. In this step, a preset path is searched for each droplet to plan the movement direction of the droplet. In order to distinguish it from the final path, the path searched in this step is called the preset path. When searching for its preset path, there are three types of obstacles in the plane: 1) the initial obstacles, 2) The initial position of the droplet, and 3) The end point of the droplet is because the droplet has reached the end point. Without considering the time axis, the other droplets are stationary, only Use breadth-first search (BFS) to search for a preset path with the shortest distance. At the same time, in order to reduce the conflict with other droplet preset paths, the preset path searched is made as close as possible to the preset path of the droplet while ensuring the shortest distance. The influence of the preset path that has already been searched is reduced.

[0040] definition for The preset path is called a grid The conflict zone is , interference value For Search The default path is the grid By all The number of times the conflict area is covered. So we can search for a path that guarantees the shortest path length and the smallest path interference value. The smallest preset path. Repeat the above steps to search for the preset paths of all droplets.

[0041] Figure 7 An example is shown, in which we consider Path search, in , , , If the red preset paths have been searched, consider the path of droplet 5. Path1, Path2, and Path3 are all from arrive The shortest path of Received The area affected by the preset path. According to the above calculation, the path interference value of Path1 is 16, the path interference value of Path2 is 12, and the path interference value of Path3 is 6, so Path3 is better than Path2 and Path1.

[0042] Algorithm 2 shows the pseudocode details of the preset path search. The complexity of this step is O(|N|*H*W) .

[0043]

[0044] In step S104, finally, the paths of all the droplets are considered to be aligned. All grids on the preset path Leave a trail mark on ,express Will pass in the future .

[0045] definition For Grid exist The set of interference markers that exist at time . The maximum priority of all droplets with interference marks in is no greater than priority, then for It is a safe position, that is, there is no priority Larger droplets will pass in the future. All droplets are moved at the same time. If a droplet violates the minimum spacing constraint, the droplet with a lower priority (later in the routing order) will retreat from the conflicting position to a safe position that has been traveled on a preset path and will never conflict with the preset paths of other droplets. The path from the safe position to the conflicting position is canceled, and the behavior of the droplet during this period is changed to waiting at the safe position.

[0046] Figure 7 shows two droplets releasing in parallel. The priority ratio High, when conflict occurs, It is necessary to roll back to the checkpoint and wait for no conflict to continue moving. Therefore, the path that a droplet has traveled can be divided into two parts. One part is the path that is determined not to roll back, called the real path, and the other part is the state that may roll back, called the virtual path. The dividing point between the virtual path and the real path is called the checkpoint, that is, the position where the conflict will roll back, and the checkpoint is also in the real path. Droplets with a lower priority than the current droplet cannot reach the conflict area of ​​the checkpoint, because the current droplet may roll back to the checkpoint at any time, that is, the checkpoint of the droplet with a higher priority will hinder the droplet with a lower priority. At this time, the droplet with a lower priority needs to wait for the checkpoint to be updated before it can continue to move. The checkpoint of each droplet will be updated as the parallel release process progresses, that is, if the current droplet position does not have any interference marks from droplets with a higher priority, then the checkpoint can be updated to the current position. Note that the initial checkpoint is the position of the starting point. This checkpoint must be a feasible checkpoint, that is, no droplets with a higher priority will pass through in the future. This is guaranteed when searching for the preset path.

[0047] Now for the parallel lines, we simulate in chronological order whether each droplet will move along the preset path or stay where it is. Assume that the current time is ,definition exist The position at the moment is , At the moment The checkpoint is Consider all droplets in descending order of priority. Will make a move: check whether there are obstacles in the next step along the preset path from the current position, and calculate There are three types of obstacles: 1) initial obstacles, 2) and and 3) If there is an obstacle, stop. Otherwise, move a unit distance along the preset path. If the current position of the droplet conflicts with the droplets with a lower priority after this step, then let these conflicting droplets fall back to their checkpoints. After the movement is completed, calculate .

[0048] if There is no path mark left by a droplet with a higher priority than it at the current position, so this position is is a safe location and is used as the new checkpoint, i.e. , while removing arrive The interference mark of the path between the two drops is used because this path will not go back. Repeat the above steps until all the droplets have moved to the end position.

[0049] Algorithm 3 shows the algorithm details.

[0050]

[0051] In a specific embodiment, the present application uses 7 benchmark data sets for testing to verify the proposed algorithm.

[0052] Table 1 shows the basic information of the benchmark dataset, parameter test examples, It is the test data number, the number of droplets, the number of obstacles, the obstacle coverage, the minimum constraint spacing, and the area of ​​the wiring area.

[0053] Table 1 Details of the benchmark test cases used

[0054] Table 2 shows the test data of this application on the above 7 test sets, where , , and They represent the latest arrival time of droplets, the average arrival time of droplets, the average moving distance of droplets, and the maximum number of droplets moving simultaneously. It can be found that under the droplet wiring method proposed in the present application, the maximum number of droplets moving simultaneously is almost the same as the number of droplets, and the efficient wiring of large-scale droplet clusters on the active pixel array digital microfluidic biochip can be completed under the condition that the CPU running time is controlled within 1s, and the latest arrival time and the average arrival time can both reflect the superiority of the present application.

[0055] Table 2 Results of this application in terms of the latest droplet arrival time, average droplet arrival time, average droplet movement distance, maximum number of simultaneously moving droplets and CPU time

[0056] In a specific embodiment, Figure 8 This is a schematic diagram of parallel wiring. Figure 8 (a) and The preset path has conflicting locations; Figure 8 (b) When t = 7, and A conflict occurs. Rollback to checkpoint ; Figure 8 (c) When t = 11, No longer Block, start from move; Figure 8 (d) is t = 14, and All reached the end.

[0057] In a specific embodiment, an example of wiring using the method described in this application is as follows: Fig. 9 As shown, this example is implemented based on the benchmark sample of droplet7. The red grid represents the set of starting positions of the droplets, the pink grid represents the set of ending positions of the droplets, and the green grid represents obstacles. It can be found that in this example, the droplets are arranged very closely and the positions of the ending points are highly correlated. The reason why this application can achieve the above results can be attributed to the following: (1) When determining the wiring sequence, congestion problems caused by incorrect droplet sequence can be avoided.

[0058] (2) A BFS search based on the degree of interference can minimize the interference between droplet paths.

[0059] (3) The droplet parallel routing method can maximize the utilization of the resources in the available chip area and can efficiently handle routing failures caused by droplet conflicts.

[0060] Through the above-mentioned active pixel array digital microfluidic biochip droplet group wiring method, on the one hand, the method first uses the droplet spacing adjustment algorithm to obtain the initial position of the droplet; secondly, the droplet preset path search method is used to obtain the preset path of all droplets; finally, the parallel wiring algorithm is used to obtain the droplet group wiring result. On the other hand, the maximum number of droplets moving simultaneously in this method is almost the same as the number of droplets, and the efficient wiring of large-scale droplet clusters on the active pixel array digital microfluidic biochip can be completed under the condition that the CPU running time is controlled within 1s, and the latest arrival time and the average arrival time can reflect the superiority of this application. This method can maximize the use of resources in the available area of ​​the chip, and can efficiently handle the wiring failure caused by droplet conflicts.

[0061] It should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", etc. in the above description indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the embodiments of the present disclosure and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the embodiments of the present disclosure.

[0062] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the embodiments of the present disclosure, the meaning of "multiple" is two or more, unless otherwise clearly and specifically defined.

[0063] In the embodiments of the present disclosure, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present disclosure can be understood according to specific circumstances.

[0064] In the embodiments of the present disclosure, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include the first and second features being in direct contact, or may include the first and second features not being in direct contact but being in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes the first feature being directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes the first feature being directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0065] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example" or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present disclosure. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification.

[0066] Those skilled in the art will readily appreciate other embodiments of the present disclosure after considering the specification and practicing the invention disclosed herein. This application is intended to cover any modification, use or adaptation of the present disclosure, which follows the general principles of the present disclosure and includes common knowledge or customary techniques in the art that are not disclosed in the present disclosure. The specification and examples are intended to be exemplary only, and the true scope and spirit of the present disclosure are indicated by the appended claims.

Claims

1. A droplet group wiring method for an active pixel array digital microfluidic biochip, characterized in that: The method includes: Obtaining a starting position of a droplet set, an ending position of the droplet set, an obstacle set, a minimum spacing constraint, and a routing area size; Based on the starting position of the droplet set, the ending position of the droplet set, the obstacle set and the minimum spacing constraint, using a droplet spacing adjustment algorithm to obtain the droplet initial position; Based on the initial position of the droplet and the size of the wiring area, a droplet preset path search method is used to obtain the preset paths of all the droplets; Based on the preset paths of all the droplets, a parallel routing algorithm is used to obtain the droplet group routing result.

2. The droplet group wiring method of the active pixel array digital microfluidic biochip according to claim 1, characterized in that: The step of obtaining the starting position of the droplet set, the ending position of the droplet set, the obstacle set, the minimum spacing constraint and the size of the wiring area includes: The droplet set is set to ; Obtain the starting position and ending position of each droplet to obtain the droplet set The starting position , the droplet collection The end position of ; Get the position of each obstacle and get the obstacle set ; Get the minimum spacing constraint and the wiring area size .

3. The droplet group wiring method of the active pixel array digital microfluidic biochip according to claim 2, characterized in that: Constraints of this approach include: Movement constraint: Each droplet moves at most one unit per unit time; Static spacing constraint: If the positions of any two droplets at any time t are , then it satisfies: ; Dynamic spacing constraint: If the positions of any two droplets at any time t are , then it satisfies: ; Obstacle constraint: The droplet cannot pass through the location of the obstacle at any time; Real-time constraint: CPU running time is within 1s.

4. The droplet group wiring method of the active pixel array digital microfluidic biochip according to claim 3, characterized in that: The step of obtaining the initial position of the droplets by using a droplet spacing adjustment algorithm based on the starting position of the droplet set, the ending position of the droplet set, the obstacle set and the minimum spacing constraint includes: constructing a coordinate system based on the wiring area; The priority of each droplet is set according to the Manhattan distance from the end position of each droplet in the droplet set to the central grid of the wiring area; wherein the central grid of the wiring area is the central grid; According to the obstacle set , adjusting the gap between each of the droplets in the y-axis direction so that each of the droplets can pass through the gap in the y-direction, so as to obtain the ordinate of each of the droplets after the gap is adjusted ; where the gap is at least ; According to the ordinate of each droplet after adjusting the gap , get the initial position of the droplet after adjusting the position .

5. The droplet group wiring method of the active pixel array digital microfluidic biochip according to claim 4, characterized in that: The ordinate of each droplet after adjusting the gap The expression is: in, is the reference position, is the sequence number sorted from small to large according to the y coordinate, , is the gap between droplets, For offset.

6. The droplet group wiring method of the active pixel array digital microfluidic biochip according to claim 5, characterized in that: The step of obtaining the preset paths of all the droplets using a droplet preset path search method based on the initial positions of the droplets and the size of the wiring area includes: set up for The initial path of each grid The conflict zone is , interference value To search for the droplet The initial path is the grid By all The number of times the conflict area is covered; among them, For the i The first droplet on its initial path j The position of a unit of time, For the i The first droplet on its initial path k The position of a unit of time; For one of the droplets, based on the initial position of the droplet, the BFS search method is used to obtain the minimum interference value. The minimum initial path is the preset path of the droplet; All the droplets are traversed to obtain the preset paths of all the droplets.

7. The droplet group wiring method of the active pixel array digital microfluidic biochip according to claim 6, characterized in that: The step of obtaining the droplet group routing result by using a parallel routing algorithm based on the preset paths of all the droplets includes: According to the priority of each droplet, check whether there is an obstacle in the next step along the preset path from the current position to obtain the droplet exist Position at the moment wherein the droplet All the grids on the preset path Leave a trail mark on ; If there is an obstacle, stop. ; wherein the droplet exist Position at the moment ; If there is no obstacle, move a unit distance along the preset path, and if the current position of the droplet conflicts with the droplet with a lower priority, return the conflicting droplet to its checkpoint; All of the droplets at the current time After the movement is completed, the droplet is obtained At the moment The checkpoint is ; If the droplet There is no path mark left by the droplet with a higher priority than the current position , then update the position to the new checkpoint, that is, , while removing Checkpoints at all times arrive The path markers for the paths between ; For the droplet exist Checkpoints at all times; All the droplets are traversed to move all the droplets to the end position to obtain the droplet group wiring result.

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