CN117629996B - Separation parameter detection method and device for microfluidic chip and computer equipment - Google Patents
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Abstract
The present disclosure relates to the field of microfluidic technologies, and in particular, to a method and an apparatus for detecting separation parameters of a microfluidic chip, and a computer device. The separation parameter detection method of the microfluidic chip comprises the following steps: flowing at least one solution into the microfluidic chip, the at least one solution comprising suspended particles of a plurality of sizes; obtaining inflow data and outflow data of each suspended particle, wherein the inflow data is used for representing the number of particles flowing into each micro-column channel, and the outflow data is used for representing the number of particles flowing out of each micro-column channel; and determining a first separation parameter of the microfluidic chip according to inflow data and outflow data of various suspended particles, wherein the first separation parameter comprises a numerical interval. The embodiment of the specification can accurately detect the separation parameters of the microfluidic chip.
Description
Technical Field
The present disclosure relates to the field of microfluidic technologies, and in particular, to a method and an apparatus for detecting separation parameters of a microfluidic chip, and a computer device.
Background
Microfluidic is a novel interdisciplinary technology, and basic operation units of sample preparation, reaction, separation, detection and the like in biological, chemical and medical analysis processes can be integrated on a micron-scale chip, so that the whole analysis process can be automatically completed. The microfluidic chip has important application value in the fields of disease diagnosis, environment detection, life science and the like.
Deterministic lateral displacement (DETERMINISTIC LATERAL DISPLACEMENT, DLD) is a particle separation technique for microfluidic chips. He is able to separate particles in a fluid according to size, obtained in the biological, medical, chemical and industrial fields. For example, erythrocytes, leukocytes, circulating tumor cells, etc. in blood can be isolated.
In order to enable efficient separation of particles of a specific size, it is necessary to determine the separation parameters of the microfluidic chip. In the prior art, the separation parameters of the microfluidic chip can be calculated through a formula according to some design parameters of the microfluidic chip.
However, in the actual manufacturing process of the microfluidic chip, due to the influence of factors such as material deformation, manufacturing process precision and the like, the error of the separation parameter calculated by the formula is larger.
Disclosure of Invention
The embodiment of the specification provides a detection method, a detection device and computer equipment of a microfluidic chip, which are used for accurately detecting separation parameters of the microfluidic chip. The technical solutions of the embodiments of the present specification are as follows.
The embodiment of the specification provides a separation parameter detection method of a microfluidic chip, wherein the microfluidic chip comprises a plurality of micro-column channels; the method comprises the following steps:
flowing at least one solution into the microfluidic chip, the at least one solution comprising suspended particles of a plurality of sizes;
obtaining inflow data and outflow data of each suspended particle, wherein the inflow data is used for representing the number of particles flowing into each micro-column channel, and the outflow data is used for representing the number of particles flowing out of each micro-column channel;
and determining a first separation parameter of the microfluidic chip according to inflow data and outflow data of various suspended particles, wherein the first separation parameter comprises a numerical interval.
The embodiment of the specification also provides a separation parameter detection device of the microfluidic chip, wherein the microfluidic chip comprises a plurality of micro-column channels; the device comprises:
An inflow unit for flowing at least one solution into the microfluidic chip, the at least one solution comprising suspended particles of a plurality of sizes;
An acquisition unit configured to acquire inflow data and outflow data of each suspended particle, the inflow data being configured to represent the number of particles flowing into each of the microcolumn channels, the outflow data being configured to represent the number of particles flowing out of each of the microcolumn channels;
and the determining unit is used for determining a first separation parameter of the microfluidic chip according to inflow data and outflow data of various suspended particles, wherein the first separation parameter comprises a numerical interval.
The embodiment of the specification also provides a computer device, which comprises a memory, a processor and a computer program stored on the memory and capable of running on the processor, wherein the processor realizes the separation parameter detection method of the microfluidic chip when executing the computer program.
The embodiments of the present disclosure also provide a computer readable storage medium storing a computer program that when executed by a processor implements the separation parameter detection method of a microfluidic chip described above.
Embodiments of the present disclosure also provide a computer program product comprising a computer program which, when executed by a processor, implements the separation parameter detection method of a microfluidic chip described above.
According to the separation parameter detection method of the microfluidic chip, at least one solution can flow into the microfluidic chip, and the at least one solution contains suspended particles with various sizes; inflow data and outflow data of each suspended particle may be acquired, the inflow data representing the number of particles flowing into each of the micro-column channels, and the outflow data representing the number of particles flowing out of each of the micro-column channels; the first separation parameter of the microfluidic chip may be determined according to inflow data and outflow data of a plurality of suspended particles, the first separation parameter including a numerical interval. According to the embodiment of the specification, at least one solution flows into the microfluidic chip, so that inflow data and outflow data of various suspended particles can be obtained, and the first separation parameter of the microfluidic chip can be determined according to the inflow data and the outflow data. Therefore, errors caused by the influences of factors such as material deformation, manufacturing process precision and the like in the manufacturing process of the microfluidic chip can be reduced, and the separation parameters of the microfluidic chip can be accurately obtained.
Drawings
In order to more clearly illustrate the embodiments of the present description or the solutions in the prior art, the drawings that are required for the embodiments or the description of the prior art will be briefly described, the drawings in the following description are only some embodiments described in the present description, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic diagram of a microfluidic chip according to an embodiment of the present disclosure;
Fig. 2 is a flow chart of a method for detecting separation parameters of a microfluidic chip according to an embodiment of the present disclosure;
FIG. 3 is a schematic diagram of a microcolumn channel of a designated portion in an embodiment of the present specification;
FIG. 4 is a schematic diagram of a first reference micro-column and a second reference micro-column in an embodiment of the present disclosure;
FIG. 5 is a schematic diagram of first distribution data according to an embodiment of the present disclosure;
FIGS. 6-11 are schematic diagrams illustrating second distribution data according to embodiments of the present disclosure;
Fig. 12 is a schematic functional structure diagram of a separation parameter detecting device of a microfluidic chip according to an embodiment of the present disclosure.
Detailed Description
The technical solutions of the embodiments of the present specification will be clearly and completely described below with reference to the drawings in the embodiments of the present specification, and it is apparent that the described embodiments are only some embodiments of the present specification, not all embodiments. The specific embodiments described herein are to be considered in an illustrative rather than a restrictive sense. All other embodiments derived by a person of ordinary skill in the art based on the described embodiments of the present disclosure fall within the scope of the present disclosure. In addition, relational terms such as "first" and "second", and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions.
Microfluidic chips for achieving deterministic lateral displacement are also known as deterministic lateral displacement chips (DLD chips). Such a microfluidic chip is provided with a micro-column array for forming a plurality of micro-column channels. The separation parameters of the microfluidic chip include separation diameter. In the prior art, the separation diameter of the microfluidic chip can be calculated according to the formula D c＝αGεβ. G represents the distance between micropillars, alpha and beta are constants corresponding to the micropillars,N represents the periodicity of the microcolumn.
However, in the manufacturing process of the microfluidic chip, due to the influence of factors such as material deformation, manufacturing process precision and the like, the design parameters are not completely consistent with the actual parameters of the microfluidic chip, and the separation parameters of the microfluidic chip also do not completely follow the formula. Resulting in a larger error in the separation parameter calculated by the above formula. In addition, the separation parameter calculated by the above formula is a fixed value. In practice, however, the interior of the microfluidic chip is not identical everywhere, but varies randomly. For example, there are differences in the micro-pillars at different positions of the microfluidic chip. So that the separation parameter of the microfluidic chip is not a fixed value, but a numerical interval.
Therefore, the embodiment of the specification provides a separation parameter detection method of a microfluidic chip.
Please refer to fig. 1. The microfluidic chip may comprise a deterministic lateral displacement chip. The deterministic lateral displacement chip includes an array of micropillars. The array of micropillars may comprise a plurality of micropillars. The micropillars include, but are not limited to, circular micropillars, elliptical micropillars, triangular micropillars, rectangular micropillars, diamond micropillars, and the like. The array of micropillars is used to form a plurality of micropillar channels. In the array of micropillars shown in FIG. 1, the micropillars are circular micropillars. The flow direction of the fluid in the micro-column channel is from left to right. A microcolumn channel is formed between two adjacent rows of microcolumns. Each column of micropillars is offset to some extent relative to the previous column of micropillars.
The deterministic lateral displacement chip is based on the micro-fluid mechanics principle, and particle separation is realized by designing a specific micro-column array, so that particles with different sizes or types are laterally displaced and separated according to the sizes of the particles. The deterministic lateral displacement chip can be used for separation of biological particles (such as cells, proteins), drug screening, particle classification, and the like. The method is an efficient and controllable particle control method and has important significance in fields of microbiology, biomedicine, biochemical research and the like.
The separation parameters include separation diameter, separation radius, etc. The separation parameter may refer to the width or size of the channel in which particles or particulates of a particular size are laterally displaced and separated. The separation parameters are related to the geometry of the micropillars and the design of the micropillar array. By designing the geometry of the micropillars and the array of micropillars, efficient separation of particles of a particular size can be achieved.
During flow through the plurality of micropillar channels, different sized particles can separate into different travel paths. Smaller sized particles do not undergo significant lateral displacement through the microchannels, whereas larger particles undergo significant lateral displacement. The separation parameters can be adjusted as required to adapt to the separation requirements of particles with different sizes. Designing appropriate separation parameters is critical to achieving efficient particle separation in a microfluidic chip.
Please refer to fig. 2. The separation parameter detection method of the microfluidic chip may include the following steps.
Step 11: flowing at least one solution into the microfluidic chip, the at least one solution comprising suspended particles of a plurality of sizes.
In some embodiments, the at least one solution may include one or more solutions. In particular, the at least one solution may include a solution containing a plurality of sizes of suspended particles, and the number of each size of suspended particles may be a plurality. Or the at least one solution may also comprise a plurality of solutions, each solution comprising a plurality of suspended particles of the same size. That is, the size of each suspended particle in each solution is the same. The size of the suspended particles in the plurality of solutions varies.
In some embodiments, the plurality of suspended particles of the same size belong to the same suspended particle. Such that the number of each suspended particle is plural and the plural suspended particles have the same size. The dimensions include the diameter of the suspended particles, the radius of the suspended particles, etc. The suspended particles may include polystyrene fluorescent microspheres and the like. The at least one solution is used for a simulation fluid and the suspended particles are used for particles in the simulation fluid. For example, the fluid comprises blood and the particles comprise cells.
In some embodiments, the second separation parameter of the microfluidic chip may be estimated based on parameters of the micro-column array; various sizes of suspended particles may be determined based on the second separation parameter. The plurality of dimensions may be used to configure the at least one solution.
Parameters of the micro-column array include the shape of the micro-columns, the distance between the micro-columns, etc. The second separation parameter includes a separation diameter, a separation radius, and the like. In some scenario examples, the separation diameter of the microfluidic chip may be calculated as a second separation parameter according to formula D c＝αGεβ. In other examples of scenarios, parameters of the micro-pillar array may also be entered into the simulation software. And outputting the second separation parameter of the microfluidic chip through simulation software. Of course, other means of estimating the second separation parameter may be used.
In the manufacturing process of the micro-fluidic chip, the influence of factors such as material deformation, manufacturing process precision and the like is caused. Therefore, a certain error exists between the second separation parameter estimated according to the micro-column array parameter and the real separation parameter of the micro-fluidic chip. Thus, a plurality of sizes of suspended particles can be determined according to the second separation parameter; the at least one solution may be configured according to a variety of sizes of suspended particles. The true separation parameters of the microfluidic chip can be accurately detected by the at least one solution.
The second separation parameter may be a numerical value. The size interval of suspended particles can be determined according to the numerical value and a preset error value; various sizes of suspended particles may be determined within the size interval. Wherein the error value is used to represent the magnitude of the error between the second separation parameter and the actual separation parameter. For example, the error value may be subtracted from the value to obtain a first boundary value for the size interval; the value may be added to the error value to obtain a second boundary value of the size interval; the size interval may be determined from the first boundary value and the second boundary value. For example, the various sizes of suspended particles may be determined within a predetermined size interval according to the size interval. The size interval is used for representing the detection precision of the separation parameters of the microfluidic chip. The smaller the size interval is, the higher the detection precision of the separation parameters of the microfluidic chip is. The various sizes of suspended particles may be equally spaced. Of course, the spacing of the various sizes of suspended particles may also be different.
For example, the second separation parameter may be a separation diameter and the size may include a diameter of the suspended particles. The separation diameter may be 10um. The error value may be 1um. The size interval may be 9um to 11um. The size separation may be 0.5um. The various sizes of the suspended particles may include 9um, 9.5um, 10um, 10.5um, 11um. Thus, a solution having a suspended particle size of 9um, a solution having a suspended particle size of 9.5um, a solution having a suspended particle size of 10um, a solution having a suspended particle size of 10.5um, and a solution having a suspended particle size of 11um can be prepared. Of course, a solution containing suspended particles of sizes 9um, 9.5um, 10um, 10.5um and 11um may also be provided.
In some embodiments, the at least one solution may be injected into the microfluidic chip by a syringe pump. In particular, the at least one solution may comprise a solution, which may then be injected into the microfluidic chip by means of a syringe pump. Or the at least one solution may also include a plurality of solutions, each solution may be injected into the microfluidic chip separately by a syringe pump.
The at least one solution may be flowed into a particular portion of the plurality of microcolumn channels. The designated portion of the microcolumn channels may include a continuous plurality of microcolumn channels. For example, the specified portion of the micro-column channels may include a set ratio of the plurality of micro-column channels, which may be 1/2, 1/3, 2/3, or the like.
The different sized particles flow differently in the plurality of micropillar channels. When particles with the size larger than the separation parameter flow in the micro-column channels, lateral displacement can be generated after collision with the micro-columns, and the moving track is changed. And, the larger the dimension, the greater the degree of lateral displacement. When particles with the size smaller than the separation parameter flow in the micro-column channels, the particles do not generate lateral displacement after collision with the micro-columns and still follow the original movement track. Particles in the solution may flow in through the inlets of the plurality of microcolumn channels and may flow out through the outlets of the plurality of microcolumn channels. In order to be able to resolve the extent of lateral displacement of particles flowing in the plurality of micro-column channels at the outlet, or to be able to resolve the extent of lateral displacement of particles flowing in the plurality of micro-column channels at the outlet, the solution may be caused to flow into a micro-column channel of a specified portion of the plurality of micro-column channels, instead of into all micro-column channels. Wherein the specified portion of the microcolumn channels may be located at one side of the plurality of microcolumn channels and in the opposite direction to the lateral displacement direction among the plurality of microcolumn channels. For example, the direction of lateral displacement is upward, and the designated portion of the microcolumn channels includes a microcolumn channel below the plurality of microcolumn channels. For another example, the direction of lateral displacement is to the right, and the designated portion of the microcolumn channels may include a microcolumn channel on the left side of the plurality of microcolumn channels.
Please refer to fig. 3. The microfluidic chip shown in fig. 3 includes a plurality of micro-column channels. The flow direction of the solution in the microfluidic chip is from left to right. The lateral displacement direction is upward. The designated portion of the microcolumn channels may include a lower 1/2 number of the plurality of microcolumn channels. That is, at least one solution may be flowed into the lower 1/2 number of micropillar channels.
Step 12: inflow data and outflow data of each suspended particle are acquired, the inflow data being indicative of the number of particles flowing into each of the microcolumn channels, and the outflow data being indicative of the number of particles flowing out of each of the microcolumn channels.
In some embodiments, inflow data and outflow data for each suspended particle may be acquired separately by image processing techniques. Specifically, first video data of the at least one solution flowing into the microfluidic chip may be collected; determining inflow data of each suspended particle from the first video data; second video data of the at least one solution flowing out of the microfluidic chip may be collected; outflow data for each suspended particle may be determined from the second video data. In practice, the at least one solution may comprise a solution. The solution may be injected into the microfluidic chip by a syringe pump; the first video data of the solution flowing into the microfluidic chip can be collected at the inlets of the micro-column channels through a microscope or a camera and the like; the second video data of the solution flowing out of the microfluidic chip can be collected at the outlets of the micro-column channels through a microscope or a camera and the like. Thereby obtaining first video data and second video data of the solution. Or the at least one solution may also comprise a plurality of solutions. Then for each of the plurality of solutions, such solution may be injected into the microfluidic chip separately by means of an injection pump; the first video data of the solution flowing into the microfluidic chip can be collected at the inlets of the micro-column channels through a microscope or a camera and the like; the second video data of the solution flowing out of the microfluidic chip can be collected at the outlets of the micro-column channels through a microscope or a camera and the like. Thereby obtaining first video data and second video data for each solution, respectively.
The first video data may comprise a plurality of frames of images. The position of suspended particles in each frame of image in the first video data can be detected; the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image; the number of particles flowing into each microcolumn channel can be counted according to the moving track of the suspended particles. The second video data may comprise a plurality of frames of images. The position of suspended particles in each frame of image in the second video data can be detected; the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image; the particle number flowing out of each micro-column channel can be counted according to the moving track of the suspended particles.
The positions of the suspended particles in each frame of image in the first video data can be detected through a target tracking algorithm, so that the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image. The target tracking algorithm can automatically identify and track the movement of the particles in continuous image frames, so that the movement track of the suspended particles is obtained. The target tracking algorithm can specifically comprise a Kalman filter, a particle filter, background subtraction, an optical flow method, a convolutional neural network and other methods. The kalman filter is a recursive estimation algorithm that can be used to track the position and velocity of a target. The particle filter is a probability filtering method based on Monte Carlo sampling and is used for tracking targets. It can be used for nonlinear and non-gaussian target tracking problems. The background subtraction method can detect and track objects by separating the objects from the background. The optical flow method may estimate the motion of an object by analyzing the pixel motion between successive image frames. The convolutional neural network may include YOLO (You Only Look Once) and Faster R-CNN, etc., and can be used for detection and tracking of targets.
Please refer to fig. 4. A column of micropillars from the array of micropillars may be selected as a first reference column of micropillars at an inlet of the microfluidic chip; a column of micropillars may be selected from the array of micropillars as a second reference column of micropillars at the outlet of the microfluidic chip. The direction of the first reference micro-column is parallel to the direction of the second reference micro-column. The direction of the first reference micro-column and the direction of the micro-column channel may form a certain included angle, and the included angle may be 85 degrees, 90 degrees, 95 degrees, etc.
The first reference column of micropillars may be used to count the number of inflow particles for each micropillar channel. Specifically, for each particle in the solution, the microcolumn channel where the particle is located at the first reference microcolumn column can be judged according to the movement track of the particle, so that it can be determined that the particle flows into the microcolumn channel, and the number of inflow particles corresponding to the microcolumn channel can be increased by 1. The second reference column may be used to count the number of outflow particles from each of the column channels. Specifically, for each particle in the solution, the microcolumn channel where the particle is located at the second reference microcolumn column can be judged according to the movement track of the particle, so that it can be determined that the particle flows out of the microcolumn channel, and the number of flowing-out particles corresponding to the microcolumn channel can be increased by 1.
It should be noted that, as mentioned above, the at least one solution may include one solution. The first video data and the second video data of the solution may be acquired by a microscope or a camera or the like. The first video data includes a plurality of frames of images. The position of suspended particles in each frame of image in the first video data can be detected; the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image; the number of the suspended particles flowing into each micro-column channel can be counted according to the moving track of the suspended particles and the sizes of the suspended particles. Thus obtaining inflow data for suspended particles of various sizes. The second video data includes a plurality of frame images. The position of suspended particles in each frame of image in the second video data can be detected; the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image; the particle number of each size of suspended particles flowing out of each microcolumn channel can be counted according to the moving track of the suspended particles and the size of the suspended particles. Thus obtaining outflow data for suspended particles of various sizes.
Specifically, for each particle in the solution, the microcolumn channel where the particle is located at the first reference microcolumn column can be judged according to the movement track of the particle, so that it can be determined that the particle flows into the microcolumn channel, and the number of inflow particles corresponding to the particle in the microcolumn channel can be increased by 1. In addition, for each particle in the solution, the microcolumn channel where the particle is located at the second reference microcolumn column can be judged according to the movement track of the particle, so that it can be determined that the particle flows out of the microcolumn channel, and the number of the flowing-out particles corresponding to the particle in the microcolumn channel can be increased by 1.
Thus, inflow data and outflow data of suspended particles of various sizes can be obtained at one time by one solution.
It should also be noted that, as mentioned above, the at least one solution may include a plurality of solutions. The first video data and the second video data of each solution may be acquired separately by a microscope or a camera or the like. Since each solution contains suspended particles of the same size. Each first video data may correspond to one size of suspended particles and each second video data may correspond to one size of suspended particles. Thus, for each first video data, the positions of suspended particles in each frame of image in the first video data can be detected; the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image; the number of the suspended particles with the size flowing into each micro-column channel can be counted according to the moving track of the suspended particles. In addition, for each second video data, the position of suspended particles in each frame of image in the first video data may be detected; the moving track of the suspended particles can be determined according to the positions of the suspended particles in each frame of image; the particle number of the suspended particles with the size flowing out of each microcolumn channel can be counted according to the moving track of the suspended particles.
Specifically, for each particle in the solution, the microcolumn channel where the particle is located at the first reference microcolumn column can be judged according to the movement track of the particle, so that it can be determined that the particle flows into the microcolumn channel, and the number of inflow particles corresponding to the particle in the microcolumn channel can be increased by 1. In addition, for each particle in the solution, the microcolumn channel where the particle is located at the second reference microcolumn column can be judged according to the movement track of the particle, so that it can be determined that the particle flows out of the microcolumn channel, and the number of the flowing-out particles corresponding to the particle in the microcolumn channel can be increased by 1.
Thus, inflow data and outflow data of suspended particles of various sizes can be obtained by various solutions. Inflow data and outflow data for suspended particles of one size can be obtained for each solution.
Step 13: and determining a first separation parameter of the microfluidic chip according to inflow data and outflow data of the plurality of suspended particles.
In some embodiments, for each suspended particle in the plurality of suspended particles, a degree of lateral displacement of the suspended particle may be determined from inflow data and outflow data of the suspended particle. The degree of lateral displacement is related to the size of the particles and the separation parameters of the microfluidic chip. The first separation parameter of the microfluidic chip may be determined according to the degree of lateral displacement of the plurality of suspended particles and the sizes of the plurality of suspended particles. The first separation parameter comprises a numerical interval.
In some embodiments, for each suspended particle in the plurality of suspended particles, first distribution data of such suspended particle in the plurality of microcolumn channels may be determined from inflow data of such suspended particle; determining second distribution data of the suspended particles in the plurality of microcolumn channels according to outflow data of the suspended particles; the degree of lateral displacement of such suspended particles may be determined from the first distribution data and the second distribution data. The first distribution data and the second distribution data are used for representing the distribution condition of suspended particles in the micro-column channels. The first distribution data and the second distribution data may include distribution probability data and distribution number data. The distribution probability data is used for representing the distribution probability of suspended particles in the plurality of micro-column channels. The distribution quantity data is used for representing the distribution quantity of suspended particles in the plurality of micro-column channels. It should be noted that the suspended particles are not laterally displaced at the inlet of the microfluidic chip. The first distribution data of the plurality of suspended particles may be the same or similar. The suspended particles may or may not be laterally displaced at the outlet of the microfluidic chip. The second distribution data of the plurality of suspended particles may be different.
The degree of lateral displacement of each suspended particle may be determined based on the degree of similarity of the first distribution data and the second distribution data for that suspended particle. Specifically, first feature data may be extracted from the first distribution data; second feature data may be extracted from the second distribution data; the degree of lateral displacement of the suspended particles may be determined based on the degree of similarity of the first characteristic data and the second characteristic data. The degree of similarity and the degree of lateral displacement may be inversely related.
In some examples of scenarios, the first distribution data and the second distribution data are distribution probability data. According to the first distribution data, selecting N first micro-column channels with the highest corresponding probability from the plurality of micro-column channels; according to the second distribution data, selecting N second micro-column channels with the highest corresponding probability from the plurality of micro-column channels; the degree of lateral displacement of the suspended particles may be determined based on the degree of similarity of the N first and N second micro-column channels. And N is a natural number greater than or equal to 1. For example, the number of identical micro-column channels in the N first micro-column channels and the N second micro-column channels may be counted; the difference between the N and the same number of microcolumn channels can be calculated as the degree of lateral displacement of the suspended particles. Specifically, for example, the N first micro-column channels may include A, B, C, D, E or the like 5 micro-column channels. The N second micro-column channels may include A, B, C, F, G micro-column channels, etc. The number of identical micro-column channels in the N first micro-column channels and the N second micro-column channels is 3. The extent of lateral displacement of the suspended particles may be 5-3=2. Of course, the degree of lateral displacement of the suspended particles may be determined in other ways based on the degree of similarity of the N first and second micro-column channels. For example, the reciprocal of the number of identical ones of the N first and N second micro-column channels may be calculated as the degree of lateral displacement of the suspended particles.
In other examples of scenarios, the first distribution data and the second distribution data are distribution quantity data. According to the first distribution data, selecting N first microcolumn channels with the largest corresponding number from the plurality of microcolumn channels; selecting N second micro-column channels with the largest corresponding number from the plurality of micro-column channels according to the second distribution data; the degree of lateral displacement of the suspended particles may be determined based on the degree of similarity of the N first and N second micro-column channels. For example, the number of identical micro-column channels in the N first micro-column channels and the N second micro-column channels may be counted; the difference between the N and the same number of microcolumn channels can be calculated as the degree of lateral displacement of the suspended particles.
In some embodiments, the first and second lateral displacement degree thresholds may be preset. The second lateral displacement degree threshold is greater than the first lateral displacement degree threshold. One or more suspended particles can be selected from the plurality of suspended particles according to a preset first lateral displacement threshold and a preset second lateral displacement threshold; the first separation parameter may be determined based on the size of the selected suspended particles.
For each suspended particle in the plurality of suspended particles, the degree of lateral displacement of the suspended particle may be compared with a first lateral displacement threshold and a second lateral displacement degree, respectively; if the lateral displacement degree of the suspended particles is smaller than the first lateral displacement degree threshold value, the particles in the suspended particles are not laterally displaced, so that the size of the suspended particles is smaller than the real separation parameter of the microfluidic chip; if the lateral displacement degree of the suspended particles is larger than the second lateral displacement degree threshold, the lateral displacement degree of the suspended particles is excessively large, so that the size of the suspended particles is larger than the real separation parameter of the microfluidic chip; if the lateral displacement degree of the suspended particles is smaller than or equal to the first lateral displacement degree threshold and larger than or equal to the second lateral displacement degree threshold, the suspended particles are indicated to be laterally displaced, but the lateral displacement degree of the suspended particles is not too large, so that the size of the suspended particles is relatively close to the real separation parameter of the microfluidic chip, and the suspended particles can be selected.
For example, a numerical interval formed by the size of the selected suspended particles may be used as the first separation parameter. Of course, other means of determining the first separation parameter may be used, depending on the size of the suspended particles selected. Specifically, for example, the size of the particles may include the diameter of the particles. The first separation parameter may comprise a separation diameter interval.
In practice, the interior of the microfluidic chip is not identical everywhere, but varies randomly throughout. For example, there may be differences in micropillars at different locations in a microfluidic chip. So that the separation parameter of the microfluidic chip is not a fixed value, but a numerical interval. The first separation parameter determined in this embodiment may be a numerical range, so as to be more compatible with the actual microfluidic chip.
In some examples of the scene, the at least one solution may include a plurality of solutions. The plurality of solutions may include a solution having a suspended particle size of 9um, a solution having a suspended particle size of 10um, a solution having a suspended particle size of 11um, a solution having a suspended particle size of 12um, a solution having a suspended particle size of 13um, a solution having a suspended particle size of 14 um. The first distribution data of the suspended particles having a size of 9um, the first distribution data of the suspended particles having a size of 10um, the first distribution data of the suspended particles having a size of 11um, the first distribution data of the suspended particles having a size of 12um, the first distribution data of the suspended particles having a size of 13um, and the first distribution data of the suspended particles having a size of 14um may be as shown in fig. 5. The second distribution data of the suspended particles having a size of 9um, the second distribution data of the suspended particles having a size of 10um, the second distribution data of the suspended particles having a size of 11um, the second distribution data of the suspended particles having a size of 12um, the second distribution data of the suspended particles having a size of 13um, and the second distribution data of the suspended particles having a size of 14um may be as shown in fig. 6,7, 8, 9, 10, and 11, respectively. Comparing fig. 6-11 with fig. 5, respectively, it can be seen that the suspended particles with the size smaller than 9um do not laterally shift; suspended particles with a size greater than 14um are laterally displaced to an excessive extent. Thus, it is possible to select the suspended particles having a size of 9um, the suspended particles having a size of 10um, the suspended particles having a size of 11um, the suspended particles having a size of 12um, the suspended particles having a size of 13um, the suspended particles having a size of 14 um. The size of the selected suspended particles forms a numerical interval of [9um,14um ]. The first separation parameter is the interval of values 9um,14 um.
It should be noted that the plurality of microcolumn channels may have channel numbers. In fig. 5 to 11, the abscissa indicates the channel number of the microcolumn channel, and the ordinate indicates the number of particles.
According to the separation parameter detection method of the microfluidic chip, at least one solution can flow into the microfluidic chip, and the at least one solution contains suspended particles with various sizes; inflow data and outflow data of each suspended particle may be acquired, the inflow data representing the number of particles flowing into each of the micro-column channels, and the outflow data representing the number of particles flowing out of each of the micro-column channels; the first separation parameter of the microfluidic chip may be determined according to inflow data and outflow data of a plurality of suspended particles, the first separation parameter including a numerical interval. According to the embodiment of the specification, at least one solution flows into the microfluidic chip, so that inflow data and outflow data of various suspended particles can be obtained, and the first separation parameter of the microfluidic chip can be determined according to the inflow data and the outflow data. Therefore, errors caused by the influences of factors such as material deformation, manufacturing process precision and the like in the manufacturing process of the microfluidic chip can be reduced, and the separation parameters of the microfluidic chip can be accurately obtained.
Please refer to fig. 12. The embodiment of the specification also provides a separation parameter detection device of the microfluidic chip, wherein the microfluidic chip comprises a plurality of micro-column channels; the device comprises the following units.
An inflow unit 21 for flowing at least one solution containing suspended particles of various sizes into the microfluidic chip;
An acquisition unit 22 for acquiring inflow data and outflow data of each suspended particle, the inflow data representing the number of particles flowing into each of the micro-column channels, and the outflow data representing the number of particles flowing out of each of the micro-column channels;
and a determining unit 23, configured to determine a first separation parameter of the microfluidic chip according to inflow data and outflow data of the plurality of suspended particles.
The embodiment of the specification also provides a computer device, which comprises a memory, a processor and a computer program stored on the memory and capable of running on the processor, wherein the processor realizes the separation parameter detection method of the microfluidic chip when executing the computer program.
The embodiments of the present disclosure also provide a computer readable storage medium storing a computer program that when executed by a processor implements the separation parameter detection method of a microfluidic chip described above.
Embodiments of the present disclosure also provide a computer program product comprising a computer program which, when executed by a processor, implements the separation parameter detection method of a microfluidic chip described above.
Those skilled in the art will appreciate that the present description may be provided as a method, system, or computer program product. The description may thus take the form of an entirely hardware embodiment, an entirely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, the present description can take the form of a computer program product on one or more computer-usable storage media (including, but not limited to, disk storage, CD-ROM, optical storage, etc.) having computer-usable program code embodied therein.
The present description is described with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the specification. It will be understood that each flow and/or block of the flowchart illustrations and/or block diagrams, and combinations of flows and/or blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. The computer may be a personal computer, a laptop computer, a cellular telephone, a camera phone, a smart phone, a personal digital assistant, a media player, a navigation device, an email device, a game console, a tablet computer, a wearable device, or a combination of any of these devices.
Each functional unit in the embodiments of the present disclosure may be integrated in one processing unit, or each functional unit may exist alone physically, or two or more functional units may be integrated in one processing unit.
Those skilled in the art will appreciate that the descriptions of various embodiments are provided herein with respect to each of the embodiments, and that reference may be made to the relevant descriptions of other embodiments for parts of one embodiment that are not described in detail. In addition, it will be appreciated that those skilled in the art, upon reading the present specification, may conceive of any combination of some or all of the embodiments set forth herein without any inventive effort, and that such combination is within the scope of the disclosure and protection of the present specification.
Although the present specification is depicted by way of example, it will be appreciated by those skilled in the art that the above examples are merely intended to aid in understanding the core ideas of the present specification. Those skilled in the art will appreciate numerous modifications and variations therefrom. It is intended that the appended claims cover such modifications and variations as fall within the true spirit of this present description.
Claims (5)
1. The method for detecting the separation parameters of the microfluidic chip is characterized in that the microfluidic chip comprises a deterministic lateral displacement micro-column array, and the micro-column array is used for forming a plurality of micro-column channels; the method comprises the following steps:
flowing at least one solution into the microfluidic chip, the at least one solution comprising suspended particles of a plurality of sizes;
obtaining inflow data and outflow data of each suspended particle, wherein the inflow data is used for representing the number of particles flowing into each micro-column channel, and the outflow data is used for representing the number of particles flowing out of each micro-column channel;
Determining a first separation parameter of the microfluidic chip according to inflow data and outflow data of various suspended particles, wherein the first separation parameter comprises a numerical interval;
The acquiring inflow data and outflow data of each suspended particle comprises: collecting first video data of at least one solution flowing into a microfluidic chip; detecting the positions of suspended particles in each frame of image in the first video data, determining the moving track of the suspended particles according to the positions of the suspended particles in each frame of image, and counting the number of particles flowing into each micro-column channel according to the moving track of the suspended particles; collecting second video data of at least one solution flowing out of the microfluidic chip; detecting the positions of suspended particles in each frame of image in the second video data, determining the moving track of the suspended particles according to the positions of the suspended particles in each frame of image, and counting the number of particles flowing out of each micro-column channel according to the moving track of the suspended particles;
The determining the first separation parameter of the microfluidic chip includes: determining first distribution data of each suspended particle in the plurality of microcolumn channels according to inflow data of the suspended particle; determining second distribution data of each suspended particle in the plurality of microcolumn channels according to outflow data of the suspended particle; determining a similarity between the first distribution data and the second distribution data of each suspended particle; determining the lateral displacement degree of each suspended particle according to the similarity; determining a first separation parameter of the microfluidic chip according to the lateral displacement degree of the suspended particles and the size of the suspended particles; wherein the determining the first separation parameter of the microfluidic chip includes: selecting one or more suspended particles from a plurality of suspended particles according to a preset first lateral displacement threshold and a preset second lateral displacement threshold; determining the first separation parameter according to the size of the selected suspended particles, wherein the second lateral displacement degree threshold is larger than the first lateral displacement degree threshold;
the first distribution data and the second distribution data include distribution probability data and distribution quantity data, the distribution probability data is used for representing the distribution probability of suspended particles in the plurality of micro-column channels, and the distribution quantity data is used for representing the distribution quantity of suspended particles in the plurality of micro-column channels.
2. The method according to claim 1, wherein the method further comprises:
Estimating a second separation parameter of the micro-fluidic chip according to the parameters of the micro-column array;
Determining a plurality of sizes of suspended particles according to the second separation parameter;
The plurality of dimensions is used to configure the at least one solution.
3. The method of claim 1, wherein flowing at least one solution into a microfluidic chip comprises:
flowing at least one solution into a microcolumn channel of a designated portion of the plurality of microcolumn channels;
The designated portion of the microcolumn channels is located in a direction opposite to the lateral displacement direction among the plurality of microcolumn channels.
4. The device for detecting the separation parameters of the microfluidic chip is characterized in that the microfluidic chip comprises a deterministic lateral displacement micro-column array, and the micro-column array is used for forming a plurality of micro-column channels; the device comprises:
An inflow unit for flowing at least one solution into the microfluidic chip, the at least one solution comprising suspended particles of a plurality of sizes;
An acquisition unit configured to acquire inflow data and outflow data of each suspended particle, the inflow data being configured to represent the number of particles flowing into each of the microcolumn channels, the outflow data being configured to represent the number of particles flowing out of each of the microcolumn channels;
The determining unit is used for determining a first separation parameter of the microfluidic chip according to inflow data and outflow data of various suspended particles, wherein the first separation parameter comprises a numerical value interval;
The acquiring inflow data and outflow data of each suspended particle comprises: collecting first video data of at least one solution flowing into a microfluidic chip; detecting the positions of suspended particles in each frame of image in the first video data, determining the moving track of the suspended particles according to the positions of the suspended particles in each frame of image, and counting the number of particles flowing into each micro-column channel according to the moving track of the suspended particles; collecting second video data of at least one solution flowing out of the microfluidic chip; detecting the positions of suspended particles in each frame of image in the second video data, determining the moving track of the suspended particles according to the positions of the suspended particles in each frame of image, and counting the number of particles flowing out of each micro-column channel according to the moving track of the suspended particles;
The determining the first separation parameter of the microfluidic chip includes: determining first distribution data of each suspended particle in the plurality of microcolumn channels according to inflow data of the suspended particle; determining second distribution data of each suspended particle in the plurality of microcolumn channels according to outflow data of the suspended particle; determining a similarity between the first distribution data and the second distribution data of each suspended particle; determining the lateral displacement degree of each suspended particle according to the similarity; determining a first separation parameter of the microfluidic chip according to the lateral displacement degree of the suspended particles and the size of the suspended particles; wherein the determining the first separation parameter of the microfluidic chip includes: selecting one or more suspended particles from a plurality of suspended particles according to a preset first lateral displacement threshold and a preset second lateral displacement threshold; determining the first separation parameter according to the size of the selected suspended particles, wherein the second lateral displacement degree threshold is larger than the first lateral displacement degree threshold;
the first distribution data and the second distribution data include distribution probability data and distribution quantity data, the distribution probability data is used for representing the distribution probability of suspended particles in the plurality of micro-column channels, and the distribution quantity data is used for representing the distribution quantity of suspended particles in the plurality of micro-column channels.
5. A computer device, comprising:
a processor; a memory for storing processor-executable instructions;
The processor implements the method of any of claims 1-3 by executing the instructions.
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