A bidirectional use method of a deterministic lateral displacement chip and a particle solution processing system

Abstract

The present invention provides a bidirectional use method of a deterministic lateral displacement chip and a particle solution processing system, wherein one method includes performing multiple rounds of processing, wherein two adjacent rounds of processing include: injecting a solution to be processed into the deterministic lateral displacement chip from a first opening, and simultaneously blocking the second opening, and the particles in the solution to be processed flow out from a third opening and a fourth opening after passing through an obstacle zone channel and are collected at the third opening and the fourth opening; injecting the solution flowing out of the third opening into the deterministic lateral displacement chip from the third opening, and simultaneously blocking the fourth opening, and the particles in the solution flow through the obstacle zone channel and are collected at the first opening and the second opening; and using the solution flowing out of the first opening as the solution to be processed to continue the next round of processing. This scheme proposes that the utilization rate of the deterministic lateral displacement chip can be improved, the cost of solution processing can be saved, the practicality is strong, the control process is relatively simple and convenient, and the solution processing can be realized automatically.

Description

Technical Field

[0001] The present application relates to the field of microfluidics technology, and in particular to a bidirectional use method of a deterministic lateral displacement chip and a particle solution processing system. Background Art

[0002] The deterministic lateral displacement (DLD) chip is a microfluidic chip based on the deterministic lateral displacement principle, which includes an obstacle channel and openings on both sides thereof. The obstacle channel is provided with a column array so that particles of different sizes travel in different directions. The openings on both sides are specifically input side openings and output side openings. The input side openings are usually one or two, and the output side openings are usually two. The particles in the solution outputted by one output side opening are mainly large particles, and the particles in the solution outputted by one output side opening are mainly small particles. When in use, the solution to be processed is input into the deterministic lateral displacement chip from the input side opening, and the target liquid is collected from the output side opening.

[0003] When the solution to be processed needs to pass through the obstacle zone channel multiple times, the solution output from the output side opening can only be injected into the deterministic lateral displacement chip from the same deterministic lateral displacement chip or the input side opening of another deterministic lateral displacement chip.

[0004] This processing method requires manual processing of the solution output from the output side opening or increasing the number of deterministic lateral displacement chips, which has high processing costs and low efficiency. Summary of the invention

[0005] The purpose of this specification is to provide a bidirectional use method of a deterministic lateral displacement chip and a particle solution processing system to solve the problem of high solution processing cost and low efficiency.

[0006] To solve the above technical problems, the first aspect of the present specification provides a bidirectional use method of a deterministic lateral displacement chip, wherein the deterministic lateral displacement chip includes an obstacle zone channel, wherein a column array is arranged in the obstacle zone channel so that particles of different sizes travel in different directions; a first opening and a second opening are arranged on a first side of the obstacle zone channel, and a third opening and a fourth opening are arranged on a second side of the obstacle zone channel; the method includes performing multiple rounds of treatment on a solution to be treated to obtain a target solution; wherein two adjacent rounds of treatment include: injecting the solution to be treated into the deterministic lateral displacement chip from the first opening, while blocking the second opening, particles in the solution to be treated flow out from the third opening and the fourth opening after passing through the obstacle zone channel, and collecting the solution at the third opening and the fourth opening respectively; using the solution flowing out of the third opening as the solution to be treated to continue the next round of treatment; injecting the solution to be treated into the deterministic lateral displacement chip from the third opening, while blocking the fourth opening, particles in the solution flow out from the first opening and the second opening after passing through the obstacle zone channel, and collecting the solution at the first opening and the second opening respectively; using the solution flowing out of the first opening as the solution to be treated to continue the next round of treatment.

[0007] In some embodiments, the different moving directions of particles of different sizes include: large particles with a radius greater than or equal to a predetermined separation radius move in a direction parallel to the column array arrangement direction, and small particles with a radius less than the predetermined separation radius move in a Z-shaped direction; the predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array.

[0008] In some embodiments, the method is used in a particle solution concentration scenario, and accordingly, the solution to be treated contains one of the large particles; or, the method is used in a particle solution purification scenario, and accordingly, the solution to be treated contains one of the large particles and at least one of the small particles.

[0009] In some embodiments, when the method is used in a particle solution concentration scenario, before performing multiple rounds of treatment on the solution to be treated, it also includes: obtaining a target concentration ratio; and determining the number of rounds of treatment that need to be performed based on the target concentration ratio.

[0010] The second aspect of the present specification provides a bidirectional use method of a deterministic lateral displacement chip, wherein the deterministic lateral displacement chip comprises an obstacle zone channel, wherein a column array is arranged in the obstacle zone channel so that particles of different sizes travel in different directions; a first opening and a second opening are arranged on a first side of the obstacle zone channel, and a third opening and a fourth opening are arranged on a second side of the obstacle zone channel; the method comprises performing multiple rounds of treatment on a solution to be treated to obtain a target solution; wherein two adjacent rounds of treatment comprise: injecting the solution to be treated from the first opening into the deterministic lateral displacement chip, and injecting a supplementary solution from the second opening at the same time, wherein The replenishing liquid flows out from the third opening and the fourth opening, the particles in the solution to be processed flow out from the third opening after passing through the obstacle zone channel, and the solution is collected at the third opening; the solution flowing out of the third opening is used as the solution to be processed to continue the next round of processing; the solution to be processed is injected into the deterministic lateral displacement chip from the third opening, and the replenishing liquid is injected from the fourth opening at the same time, the replenishing liquid flows out from the first opening and the second opening, the particles in the solution to be processed flow out from the first opening after passing through the obstacle zone channel, and the solution is collected at the first opening; the solution flowing out of the first opening is used as the solution to be processed to continue the next round of processing.

[0011] In some embodiments, the method is used in a particle solution purification scenario, and accordingly, the solution to be treated includes large particles with a radius greater than or equal to a predetermined separation radius and small particles with a radius less than a predetermined separation radius, and the predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array; and the replenishing liquid is the same as the solvent of the solution to be treated.

[0012] In some embodiments, before performing multiple rounds of treatment on the solution to be treated, the method further includes: obtaining a target purification ratio; and determining the number of rounds of treatment to be performed according to the target purification ratio.

[0013] In some embodiments, the method is used in a particle solution replacement scenario, and accordingly, the solution to be treated includes large particles with a radius greater than or equal to a predetermined separation radius, and the predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array; and the replenishing solution is different from the solvent of the solution to be treated.

[0014] In some embodiments, before performing multiple rounds of treatment on the solution to be treated, the method further includes: obtaining a target solvent concentration after replacement; and determining the number of rounds of treatment to be performed according to the target solvent concentration after replacement.

[0015] The third aspect of the present specification provides a particle solution processing system, including: a deterministic lateral displacement chip, the deterministic lateral displacement chip including an obstacle zone channel, the obstacle zone channel being provided with a column array so that particles of different sizes travel in different directions; a first opening and a second opening being provided on a first side of the obstacle zone channel, and a third opening and a fourth opening being provided on a second side of the obstacle zone channel; a first processing device connected to the first opening of the deterministic lateral displacement chip; the first processing device being used to inject a to-be-treated solution as an initial to-be-treated solution, inject the to-be-treated solution from the first opening into the deterministic lateral displacement chip, and collect the solution flowing out of the first opening; a second processing device connected to the second opening of the deterministic lateral displacement chip The first processing device is connected to the third opening of the deterministic lateral displacement chip; the second processing device is used to apply pressure to the second opening to prevent the solution from flowing out of the second opening and to collect the solution flowing out of the second opening; the third processing device is connected to the third opening of the deterministic lateral displacement chip; the third processing device is used to collect the solution flowing out of the third opening and to inject the solution collected at the third opening into the deterministic lateral displacement chip from the third opening; the fourth processing device is connected to the fourth opening of the deterministic lateral displacement chip; the fourth processing device is used to apply pressure to the fourth opening to prevent the solution from flowing out of the fourth opening and to collect the solution flowing out of the fourth opening; the controller is used to control the first processing device, the second processing device, the third processing device and the fourth processing device to implement the method described in any one of claims 1 to 9.

[0016] The bidirectional use method of the deterministic lateral displacement chip and the particle solution processing system provided in this specification propose that the deterministic lateral displacement chip can be used in both directions, and the same obstacle area channel can be reused to improve the utilization rate of the deterministic lateral displacement chip and save the cost of particle solution processing.

[0017] When using existing deterministic lateral displacement chips, solutions are usually not allowed to repeatedly enter a deterministic lateral displacement chip. This is because the design idea of ​​repeatedly entering a deterministic lateral displacement chip is to manually or through a pipeline to introduce the liquid flowing out of the outlet of the deterministic lateral displacement chip to the inlet of the deterministic lateral displacement chip. However, the manual method is cumbersome and inefficient, and cannot be used in scenarios where the solution needs to repeatedly enter the deterministic lateral displacement chip. Due to the particularity of the particles in the solution, a circulating pump cannot usually be used, so it is usually difficult to make the solution flow in the pipeline by pipeline diversion, that is, it is difficult to achieve the liquid flowing out of the outlet of the deterministic lateral displacement chip into the inlet.

[0018] The bidirectional use method and particle solution processing system of the deterministic lateral displacement chip provided in this specification, when the deterministic lateral displacement chip is used forward and reversely, the solution collected at the outlet of the deterministic lateral displacement chip is directly re-injected from the outlet into the deterministic lateral displacement chip to reuse the obstacle zone channel. This implementation method only requires a solution collection device to be set at the opening of the deterministic lateral displacement chip and a controllable pump body using the air pressure principle that can re-inject the solution collected in the solution collection device into the deterministic lateral displacement chip. Therefore, the practicality of this solution is relatively strong.

[0019] The bidirectional use method of the deterministic lateral displacement chip and the particle solution processing system provided in this manual only need to control the pump body using the air pressure principle, and the pump body can be automatically controlled without the need for additional operations or manual operations. The control process is relatively simple and convenient, and the solution processing can be automatically realized. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some implementation methods recorded in this application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0021] Figure 1 It is a cross-sectional schematic diagram of the deterministic lateral displacement chip;

[0022] Figure 2 A schematic diagram of a bidirectional use method of a deterministic lateral displacement chip provided in this specification;

[0023] Figure 3 A schematic cross-sectional view of the obstacle channel in the deterministic lateral displacement chip;

[0024] Figure 4 Another schematic diagram of a bidirectional use method of the deterministic lateral displacement chip provided in this specification;

[0025] Figure 5 A schematic diagram of a particle solution processing system provided for this specification;

[0026] Figure 6 is a schematic diagram of a first processing device in a particle solution processing system;

[0027] Figure 7 is a schematic diagram of a second processing device in a particle solution processing system;

[0028] Figure 8 is a schematic diagram of a third processing device in the particle solution processing system;

[0029] Fig. 9 is a schematic diagram of a fourth processing device in the particle solution processing system;

[0030] Fig.10 Schematic diagrams of two cross sections of the cylinder in the obstacle channel;

[0031] Fig.11 Two other cross-sectional schematic diagrams of the cylinder in the obstacle channel. DETAILED DESCRIPTION

[0032] In order to enable those skilled in the art to better understand the technical solutions in this application, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the drawings in the embodiments of this application. Obviously, the described embodiments are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of this application.

[0033] Through the study of deterministic lateral displacement chips, it was found that the existing technology does not fully exploit the full performance of this chip, which limits the use of deterministic lateral displacement chips.

[0034] Based on this, this specification proposes that the deterministic lateral displacement chip can be used in both positive and negative directions, that is, the solution is first passed through the obstacle channel in the positive direction, and then the treated solution is passed through the obstacle channel in the reverse direction, and this cycle is repeated until the final target solution meets the requirements.

[0035] Before introducing the bidirectional use method of the deterministic lateral displacement chip provided in this specification, the structure of the deterministic lateral displacement chip used in this specification is first introduced. Figure 1 As shown, the deterministic lateral displacement chip includes an obstacle zone channel, in which a column array is arranged to enable particles of different sizes to move in different directions; a first opening O1 and a second opening O2 are arranged on a first side of the obstacle zone channel, and a third opening O3 and a fourth opening O4 are arranged on a second side of the obstacle zone channel.

[0036] The bidirectional use method of the deterministic lateral displacement chip provided in this specification can be used to process cell solutions, particle solutions, blood and other solutions.

[0037] like Figure 2As shown, the bidirectional use method of a deterministic lateral displacement chip provided in this specification includes performing multiple rounds of treatment on the solution to be treated to obtain a target solution. Among them, two adjacent rounds of treatment include the following S110 and S120, that is, the bidirectional use method of a deterministic lateral displacement chip provided in this specification repeatedly performs "S110, S120, S110, S120, ... S110, S120..." until the final target solution meets the requirements. Among them, S110 is one round of treatment, and S120 is another round of treatment.

[0038] S110: Inject the solution to be processed from the first opening into the deterministic lateral displacement chip, and block the second opening at the same time. The particles in the solution to be processed flow out from the third opening and the fourth opening after passing through the obstacle zone channel, and the solution is collected at the third opening and the fourth opening respectively; the solution flowing out of the third opening is used as the solution to be processed to continue the next round of processing.

[0039] In some embodiments, the solution mainly containing "large" particles flowing out of the third opening is set as the target solution, and the solution mainly containing small particles flowing out of the fourth opening is set as the waste solution. Figure 1 As shown, the third opening is arranged diagonally to the first opening.

[0040] In other embodiments, the solution mainly containing "small" particles flowing out of the third opening can be set as the target solution, and the solution mainly containing small particles flowing out of the fourth opening can be set as the waste solution. In this case, the third opening is diagonally opposite to the first opening, but is located on the same side of the deterministic lateral displacement chip, that is, at Figure 1 The positions of the third opening and the fourth opening are interchanged.

[0041] This specification uses the solution containing mainly "large" particles flowing out of the third opening as an example to illustrate this solution. Figure 3 As shown in FIG. 1 , the columns of the obstacle channel in the deterministic lateral displacement chip are arranged in an array, each row in the array is defined as the x direction, and each column is defined as the y direction. By setting the structure of the columns and the arrangement of the column array, the following can be achieved: Figure 3 Two specific fluid streamlines are shown, with the solid red line representing the flow path of large particles and the green line representing the flow path of small particles.

[0042] The critical value of the radius between the large particles and the small particles is the predetermined separation radius. According to the principle of deterministic lateral displacement chip, the predetermined separation radius is related to the shape of the column, the gap between adjacent columns in the same row, the gap between columns in adjacent rows, the arrangement inclination angle of the column array, the arrangement inclination angle of the column array, etc., that is, the predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array.

[0043] S120: Inject the solution to be processed from the third opening into the deterministic lateral displacement chip, and block the fourth opening at the same time. The particles in the solution flow out from the first opening and the second opening after passing through the obstacle zone channel, and the solution is collected at the first opening and the second opening respectively; the solution flowing out of the first opening is used as the solution to be processed to continue the next round of processing.

[0044] The obstacle channel of the deterministic lateral displacement chip can be set to be centrally symmetrical, that is, the obstacle channel is overlapped with the channel before and after rotating 180° around its symmetry center. Then, the large particles in the solution input from the third opening will flow out from the first opening, and the small particles will flow out from the second opening. The principle is the same as the case of inputting the solution from the first opening.

[0045] In an actual deterministic lateral displacement chip, some small particles may also flow out from the first opening or the third opening due to minor problems in the column structure or column array arrangement, or the solution injection speed.

[0046] The above S110 and S120 first input the solution to be processed from the first opening into the deterministic lateral displacement chip, collect the solution containing large particles at the third opening, and then input the solution collected at the third opening into the deterministic lateral displacement chip from the third opening, collect the solution containing large particles at the first opening, and then input the liquid collected at the first opening into the deterministic lateral displacement chip from the first opening... After multiple rounds of processing are performed in this way, the final target solution can meet the predetermined requirements.

[0047] The predetermined requirement may be that the number of macroparticles in the target solution meets the requirement, or the purity of the macroparticles in the target solution meets the requirement, or the concentration of the macroparticles in the target solution meets the requirement, or the volume of the target solution meets the requirement.

[0048] In some embodiments, the bidirectional use method of the deterministic lateral displacement chip can be used in a particle solution concentration scenario, that is, the solution to be processed contains a large particle. After each round of treatment, the amount of solvent in the particle solution is greatly reduced, that is, the particle solution is concentrated to a certain extent, so that after multiple rounds of treatment, the particle solution can be concentrated to the target concentration.

[0049] Before performing multiple rounds of treatment on the solution to be treated, a target concentration ratio may be obtained, and the number of rounds of treatment to be performed may be determined according to the target concentration ratio.

[0050] Specifically, the number of rounds N that need to be processed can be determined according to the following formula: ct, where N is the number of rounds, c is the solvent concentration ratio achieved in each round of processing (i.e., each round of processing can make the solvent become 50% of the input solution volume of that round of processing), and t is the target concentration ratio. For example, if the target concentration ratio is t = 12.5%, and each execution can concentrate c = 50%, then the number of rounds required to be executed is N = log 0.5 0.125=3. The calculated rounds are only reference data for performing multiple rounds of processing, not actual data. The actual rounds may be plus or minus a certain number of rounds based on the calculated rounds. The final number of rounds is determined based on the test results of the target solution.

[0051] In other embodiments, the bidirectional use method of the deterministic lateral displacement chip can also be used for purification of particle solutions, that is, the solution to be processed includes a mixture of a large particle and at least one small particle. After each round of treatment, the number of small particles in the particle solution will be greatly reduced, that is, the solution is purified to a certain extent, and the target solution obtained is a purified solution of large particles.

[0052] In the scenario of particle solution purification, before injecting the solution to be processed into the deterministic lateral displacement chip in S110 and S120, the solvent may be added to the solution to be processed.

[0053] Figure 2 In the bidirectional use method of the deterministic lateral displacement chip shown in the figure, the first opening and the fourth opening of the deterministic lateral displacement chip are arranged on the same side of the chip (ie, both are located on Figure 1 The second opening and the third opening are arranged on the same side of the chip (i.e., both are located on the lower side of the chip). Figure 1 The first opening and the third opening are arranged at the diagonal corners of the chip, and the second opening and the fourth opening are arranged at the diagonal corners of the chip. The width of the second opening may be greater than or equal to the width of the third opening, and the width of the fourth opening may be greater than or equal to the width of the first opening.

[0054] like Figure 4 As shown, another bidirectional use method of a deterministic lateral displacement chip provided in this specification includes performing multiple rounds of treatment on a solution to be treated to obtain a target solution. Figure 4 In the bidirectional use method of the deterministic lateral displacement chip shown in the figure, the first opening and the fourth opening of the deterministic lateral displacement chip are arranged on the same side of the chip (ie, both are located on Figure 1 The second opening and the third opening are arranged on the same side of the chip (i.e., both are located on the lower side of the chip). Figure 1 The first opening and the third opening are arranged at opposite corners of the chip, and the second opening and the fourth opening are arranged at opposite corners of the chip.

[0055] Two adjacent rounds of processing include the following S210 and S220, that is, the bidirectional use method of a deterministic lateral displacement chip provided in this specification repeatedly executes "S210, S220, S210, S220, ... S210, S220..." until the final target solution meets the requirements. Among them, S210 is one round of processing, and S220 is another round of processing.

[0056] S210: Inject the solution to be processed into the deterministic lateral displacement chip from the first opening, and inject the replenishing liquid from the second opening at the same time. The replenishing liquid flows out from the third opening and the fourth opening. The particles in the solution to be processed flow out from the third opening after passing through the obstacle zone channel. The solution is collected at the third opening and the fourth opening respectively; the solution flowing out of the third opening is used as the solution to be processed to continue the next round of processing.

[0057] The working principle of the deterministic lateral displacement chip can be understood by referring to the description of section S110 and will not be described in detail.

[0058] The difference between step S210 and step S110 is that when the solution to be treated is injected into the deterministic lateral displacement chip from the first opening, S110 blocks the second opening, while S210 injects the supplementary solution from the second opening.

[0059] In some embodiments, a width of the second opening is greater than a width of the third opening, and a width of the fourth opening is greater than a width of the first opening.

[0060] In some embodiments, the bidirectional use method of the deterministic lateral displacement chip can be used in a particle solution purification scenario. Accordingly, the solution to be processed includes the above-mentioned large particles and small particles, and the solvent of the replenishing solution is the same as that of the solution to be processed.

[0061] When the third opening is arranged diagonally to the first opening, the target solution collected by the third opening is a purified solution of large particles, that is, compared with the solution to be processed, small particles are removed from the target solution.

[0062] In other embodiments, the bidirectional use method of the deterministic lateral displacement chip can be used in a particle solution replacement scenario, and accordingly, the solution to be processed includes the above-mentioned large particles, and the solvents of the replenishing solution and the solution to be processed are different.

[0063] When the third opening is arranged diagonally to the first opening, the target solution collected by the third opening is a replacement solution for large particles, that is, the solution to be processed includes large particles and solvent A, and the solvent in the target solution is changed to solvent B relative to the solution to be processed.

[0064] In the particle solution replacement scenario, when the solution to be treated is injected into the deterministic lateral displacement chip from the first opening and starts to flow, after the replenishing liquid is injected from the second opening, the replenishing liquid will be stratified from the solution. Since the replenishing liquid does not contain large particles, the replenishing liquid will flow from the second opening along the side wall of the obstacle channel to the third opening. When the width of the second opening is larger than the width of the third opening, part of the replenishing liquid will also flow to the fourth opening. According to the working principle of the deterministic lateral displacement chip, the large particles that flow into the deterministic lateral displacement chip from the first opening will also flow out from the third opening, so that the solution flowing out of the third opening is a solution composed of large particles and replenishing liquid, thereby realizing the replacement of the solvent in the particle solution.

[0065] Normally, due to minor problems in the column structure or column array arrangement, or the injection speed of the solution or supplementary solution, an actual deterministic lateral displacement chip may result in the target solution obtained after one round of treatment being mixed with some small particles in the initial solution to be treated (for the particle solution purification scenario), or the target solution obtained after one round of treatment being mixed with some solvent in the initial solution to be treated (for the particle solution replacement scenario). Therefore, multiple rounds of treatment are required.

[0066] S220: Inject the solution to be processed into the deterministic lateral displacement chip from the third opening, and inject the replenishing liquid from the fourth opening at the same time. The replenishing liquid flows out from the first opening and the second opening. The particles in the solution to be processed flow out from the first opening after passing through the obstacle zone channel. The solution is collected at the first opening and the second opening respectively; the solution flowing out of the first opening is used as the solution to be processed to continue the next round of processing.

[0067] The working principle of the deterministic lateral displacement chip can be understood by referring to the description of part S120, which will not be repeated here.

[0068] The difference between S220 and S120 is that when the solution flowing out of the third opening is injected into the deterministic lateral displacement chip from the third opening, S110 blocks the fourth opening, while S220 injects the supplementary solution from the fourth opening.

[0069] When the solution flowing out of the third opening is injected into the deterministic lateral displacement chip from the third opening and starts to flow, after the supplementary liquid is injected from the fourth opening, the supplementary liquid and the solution will be separated. Since the supplementary liquid does not contain large particles, the supplementary liquid will flow from the fourth opening along the side wall of the obstacle channel to the first opening. Since the width of the fourth opening is larger than that of the first opening, part of the supplementary liquid will also flow to the second opening.

[0070] According to the working principle of the deterministic lateral displacement chip, the large particles flowing into the deterministic lateral displacement chip from the third opening will also flow out from the first opening, so that the solution flowing out of the first opening is a solution composed of large particles and supplementary solution, thereby realizing the replacement of the solvent in the particle solution.

[0071] The above S210 and S220 first input the solution to be processed from the first opening into the deterministic lateral displacement chip, collect the solution containing large particles and replenishing liquid at the third opening, and then input the solution collected from the third opening into the deterministic lateral displacement chip from the third opening, collect the solution containing large particles and replenishing liquid at the first opening, and then input the liquid collected at the first opening into the deterministic lateral displacement chip from the first opening... After multiple rounds of processing are performed in this way, the final target solution can meet the predetermined requirements.

[0072] The predetermined requirement may be that the concentration of the supplementary solution in the target solution meets the requirement, or that the purity of the macroparticles in the target solution meets the requirement, or that the concentration of the macroparticles in the target solution meets the requirement.

[0073] Before performing multiple rounds of treatment on the solution to be treated, the supplementary solution to be injected into the deterministic lateral displacement chip in each round can be predetermined according to the experimental requirements. For example, if the experiment requires fluorescent staining of cells, the cell solution can be injected into the deterministic lateral displacement chip from the first opening, and the fluorescent agent can be injected into the deterministic lateral displacement chip from the second opening, and the solution can be collected at the third opening. The solution collected at the third opening contains the fluorescent agent and cells. After the solution collected at the third opening is allowed to stand for a period of time to stain the cells, the solution collected at the third opening is injected into the deterministic lateral displacement chip from the third opening, and clean water is injected into the deterministic lateral displacement chip from the fourth opening, and the solution is collected at the first opening. The solution collected at the first opening contains fluorescently stained cells and clean water, that is, the fluorescently stained cells are washed.

[0074] In the next round of treatment, when the deterministic lateral displacement chip is injected from the first opening, the antibody protein and the like can be injected from the second opening at the same time. The type of supplement injected into the deterministic lateral displacement chip in the subsequent rounds of treatment is determined according to actual needs.

[0075] In the particle solution purification scenario, before performing multiple rounds of treatment on the solution to be treated, a target purification ratio can be obtained, and the number of rounds of treatment to be performed can be determined according to the target purification ratio.

[0076] Specifically, the number of rounds to be processed can be determined according to the following formula: Where N is the number of rounds, m is the proportion of small particles, t is the proportion of small particles in the target purified solution, and c is the proportion of small particles reduced in each round of treatment. That is, assuming that the number of small particles before a round of treatment is M, the number of small particles after treatment is cM. The calculated rounds are only reference data for performing multiple rounds of treatment, not actual data. The actual number of rounds may be based on the calculated rounds plus or minus a certain number of rounds. The final number of rounds is determined based on the test results of the target solution.

[0077] In the particle solution replacement scenario, before performing multiple rounds of treatment on the solution to be treated, the target solvent concentration can be obtained, and the number of rounds of treatment to be performed can be determined based on the target solvent concentration after replacement.

[0078] Specifically, the number of rounds N that need to be processed can be determined according to the following formula: c t, where N is the number of rounds, c is the solvent replacement ratio achieved in each round of treatment, and t is the target solvent concentration). For example, if the target solvent concentration is t = 87.5%, and each execution can replace c = 50%, then the number of rounds required to be executed is N = log 0.5 (1-0.875)=3. The calculated rounds are only reference data for executing multiple rounds of processing, not actual data. The actual rounds may be plus or minus a certain number of rounds based on the calculated rounds. The final number of rounds is determined based on the test results of the target solution.

[0079] The bidirectional use method of the deterministic lateral displacement chip provided in this specification proposes that the deterministic lateral displacement chip can be used in forward and reverse directions, and the same obstacle area channel can be reused to improve the utilization rate of the deterministic lateral displacement chip and save the cost of solution processing.

[0080] When using existing deterministic lateral displacement chips, solutions are usually not allowed to repeatedly enter a deterministic lateral displacement chip. This is because the design idea for solutions to repeatedly enter a deterministic lateral displacement chip is usually to manually or through a pipeline to introduce the liquid flowing out of the outlet of the deterministic lateral displacement chip to the inlet of the deterministic lateral displacement chip. However, the manual method is cumbersome and inefficient, and cannot be used in scenarios where the solution needs to repeatedly enter the deterministic lateral displacement chip; and the use of a circulating pump will make the system very complex and difficult to control, so it is usually difficult to make the solution flow in the pipeline through pipeline diversion, that is, it is difficult to achieve the liquid flowing out of the outlet of the deterministic lateral displacement chip into the inlet.

[0081] The bidirectional use method of the deterministic lateral displacement chip provided in this specification is that when the deterministic lateral displacement chip is used forwardly and reversely, the solution collected at the outlet of the deterministic lateral displacement chip is directly re-injected from the outlet into the deterministic lateral displacement chip to reuse the obstacle zone channel. This implementation method only requires a solution collection device to be provided at the opening of the deterministic lateral displacement chip and a controllable pump body using the air pressure principle that can re-inject the solution collected in the solution collection device into the deterministic lateral displacement chip. Therefore, the practicality of this solution is relatively strong.

[0082] The bidirectional use method of the deterministic lateral displacement chip provided in this manual only requires controlling a pump body that adopts the air pressure principle, and the pump body can be automatically controlled without the need for additional operations or manual operations. The control process is relatively simple and convenient, and the solution processing can be automatically realized.

[0083] This specification provides a particle solution processing system that can be used to achieve the above Figure 2 and Figure 4 A bidirectional use method of the deterministic lateral displacement chip.

[0084] like Figure 5 As shown, the particle solution processing system includes a deterministic lateral displacement chip, a first processing device, a second processing device, a third processing device, a fourth processing device and a controller.

[0085] The specific description of the deterministic lateral displacement chip can be understood by referring to other parts of this specification and will not be repeated here.

[0086] The first processing device is connected to the first opening of the deterministic lateral displacement chip. The first processing device is used to inject the solution to be processed as the initial solution to be processed, inject the solution to be processed from the first opening into the deterministic lateral displacement chip, and collect the solution flowing out of the first opening.

[0087] Specifically, Figure 6 As shown, the first processing device may include a first collection chamber and a first pump body, the first collection chamber has a fifth opening O5 and a sixth opening O6, the fifth opening is used to input the initial solution to be processed, output the final target solution, or is in an open state so that the solution in the deterministic lateral displacement chip can flow into the first collection chamber, and the sixth opening is used to connect the first opening of the deterministic lateral displacement chip. The solution to be processed can be placed in the first collection chamber, and then the first collection chamber is closed, and then the first pump body is controlled to use air pressure to push the liquid in the first collection chamber into the deterministic lateral displacement chip.

[0088] The fifth opening has multiple functions. In specific implementation, one opening may realize multiple functions, or multiple openings may be provided to realize multiple functions.

[0089] The second processing device is connected to the second opening of the deterministic lateral displacement chip; the second processing device is used to apply pressure to the second opening to prevent the solution from flowing out of the second opening and collect the solution flowing out of the second opening.

[0090] Specifically, Figure 7 As shown, the second processing device may include a second collecting chamber, the second collecting chamber having a seventh opening O7 and an eighth opening O8, the seventh opening being used to output waste liquid collected by the second collecting chamber, being in a closed state to prevent the solution in the deterministic lateral displacement chip from flowing out of the second opening, being in an open state to allow the solution in the deterministic lateral displacement chip to flow into the second collecting chamber, or to inject supplementary liquid, and the eighth opening being used to connect to the second opening of the deterministic lateral displacement chip.

[0091] The seventh opening has multiple functions. In specific implementation, one opening may realize multiple functions, or multiple openings may be provided to realize multiple functions.

[0092] The second processing device "applies pressure to the second opening to prevent the solution from flowing out of the second opening" may be blocking the second opening, or injecting the supplementary liquid into the second opening.

[0093] The third processing device is connected to the third opening of the deterministic lateral displacement chip; the third processing device is used to collect the solution flowing out of the third opening and inject the solution collected at the third opening into the deterministic lateral displacement chip from the third opening.

[0094] Specifically, Figure 8 As shown, the third processing device may include a third collection chamber and a second pump body, the third collection chamber has a ninth opening O9 and a tenth opening O10, the ninth opening is used to output the final target solution, or is in an open state to allow the solution in the deterministic lateral displacement chip to flow into the third collection chamber, and the tenth opening is used to connect to the third opening of the deterministic lateral displacement chip. The second pump body may be controlled to use air pressure to push the liquid in the third collection chamber to be injected into the deterministic lateral displacement chip.

[0095] The ninth opening has multiple functions. In specific implementation, one opening may realize multiple functions, or multiple openings may be provided to realize multiple functions.

[0096] The fourth processing device is connected to the fourth opening of the deterministic lateral displacement chip; the fourth processing device is used to apply pressure to the fourth opening to prevent the solution from flowing out of the fourth opening and to collect the solution flowing out of the fourth opening.

[0097] Specifically, Fig. 9As shown, the fourth processing device may include a fourth collecting chamber, the fourth collecting chamber having an eleventh opening O11 and a twelfth opening O12, the eleventh opening being used to output waste liquid collected by the fourth collecting chamber, being in a closed state to prevent the solution in the deterministic lateral displacement chip from flowing out from the second opening, or being in an open state to allow the solution in the deterministic lateral displacement chip to flow into the fourth collecting chamber, or to inject supplementary liquid, and the twelfth opening being used to connect to the fourth opening of the deterministic lateral displacement chip.

[0098] The eleventh opening has multiple functions. In specific implementation, one opening may realize multiple functions, or multiple openings may be provided to realize multiple functions.

[0099] The fourth processing device "applies pressure to the fourth opening to prevent the solution from flowing out of the fourth opening" may be blocking the fourth opening, or may be injecting a supplementary solution into the fourth opening.

[0100] The controller is used to control the first processing device, the second processing device, the third processing device, and the fourth processing device to achieve Figure 2 or Figure 4 The corresponding bidirectional use method of the deterministic lateral displacement chip.

[0101] In order to use the deterministic lateral displacement chip in both forward and reverse directions, the predetermined separation radius of the obstacle channel needs to be smaller than the radius of the target cell when the solution flows in both forward and reverse directions. That is, if cells with a radius of 8um are expected to be separated, the predetermined separation radius of the obstacle channel is required to be smaller than 8um when the deterministic lateral displacement chip is used in both directions. The predetermined separation radius of the obstacle channel when the deterministic lateral displacement chip is used in both directions can be the same or different.

[0102] To this end, the obstacle zone channel can be set to a central symmetrical structure, that is, the obstacle zone channel is overlapped with the channel before rotation after rotating 180° around its symmetry center. Fig.10 The cylinder with a special cross section shown above or Fig.10 The circular cross-section of the cylinder shown below allows for a centrosymmetric design of the obstacle channel. In this centrosymmetric structure, the separation radius is the same when using the deterministic lateral displacement chip in both the forward and reverse directions.

[0103] The obstacle channel may not be required to be a centrally symmetrical structure, but requires that the predetermined separation radius when using the deterministic lateral displacement chip in both the forward and reverse directions is smaller than the target radius. Fig.11 The cylinder with a special cross section shown above or Fig.11 The "ginkgo leaf-shaped" column with a special cross-section shown below can be used in both directions. The predetermined separation radius of the deterministic lateral displacement chip is different, but all are smaller than the target radius.

[0104] It should be noted that designing the column in the obstacle zone channel according to the predetermined separation radius is a prior art, which is not the focus of this specification and will not be described in detail.

[0105] Although the present application has been described through embodiments, those skilled in the art will appreciate that there are many modifications and variations to the present application without departing from the spirit of the present application, and it is intended that the appended claims include these modifications and variations without departing from the spirit of the present application.

Claims

1. A method for bidirectional use of a deterministic lateral displacement chip, characterized in that: The deterministic lateral displacement chip comprises an obstacle channel, wherein a column array is arranged in the obstacle channel so that particles of different sizes travel in different directions; a first opening and a second opening are arranged on a first side of the obstacle channel, and a third opening and a fourth opening are arranged on a second side of the obstacle channel, wherein the first opening is arranged diagonally to the third opening; a predetermined separation radius of the obstacle channel is smaller than a radius of a target cell when the solution flows in both forward and reverse directions; the method comprises performing multiple rounds of treatment on a solution to be treated to obtain a target solution; The two consecutive rounds of processing include: The solution to be processed is injected into the deterministic lateral displacement chip from the first opening, and the second opening is blocked at the same time, and the particles in the solution to be processed flow out from the third opening and the fourth opening after passing through the obstacle zone channel, and the solution is collected at the third opening and the fourth opening respectively; the solution flowing out of the third opening is used as the solution to be processed to continue the next round of processing; The solution to be processed is injected into the deterministic lateral displacement chip from the third opening, and the fourth opening is blocked at the same time. The particles in the solution flow out from the first opening and the second opening after passing through the obstacle zone channel, and the solution is collected at the first opening and the second opening respectively; the solution flowing out of the first opening is used as the solution to be processed to continue the next round of processing.

2. The method according to claim 1, characterized in that The different moving directions of particles of different sizes include: large particles with a radius greater than or equal to a predetermined separation radius move in a direction parallel to the column array arrangement, and small particles with a radius less than the predetermined separation radius move in a Z-shaped direction; the predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array.

3. The method according to claim 2, characterized in that The method is used in a particle solution concentration scenario, and accordingly, the solution to be treated contains one of the large particles; or, the method is used in a particle solution purification scenario, and accordingly, the solution to be treated contains one of the large particles and at least one of the small particles.

4. The method according to claim 3, characterized in that When the method is used for a particle solution concentration scenario, before performing multiple rounds of treatment on the solution to be treated, the method further includes: Obtaining a target enrichment ratio; The number of processing rounds to be performed is determined according to the target concentration ratio.

5. A bidirectional use method of a deterministic lateral displacement chip, characterized in that: The deterministic lateral displacement chip comprises an obstacle channel, wherein a column array is arranged in the obstacle channel so that particles of different sizes travel in different directions; a first opening and a second opening are arranged on a first side of the obstacle channel, and a third opening and a fourth opening are arranged on a second side of the obstacle channel, wherein the first opening is arranged diagonally to the third opening; a predetermined separation radius of the obstacle channel is smaller than a radius of a target cell when the solution flows in both forward and reverse directions; the method comprises performing multiple rounds of treatment on the solution to be treated to obtain a target solution; The two consecutive rounds of processing include: The solution to be processed is injected into the deterministic lateral displacement chip from the first opening, and the supplementary solution is injected from the second opening at the same time, the supplementary solution flows out from the third opening and the fourth opening, the particles in the solution to be processed flow out from the third opening after passing through the obstacle zone channel, and the solution is collected at the third opening; the solution flowing out of the third opening is used as the solution to be processed to continue the next round of processing; The solution to be processed is injected into the deterministic lateral displacement chip from the third opening, and the replenishing liquid is injected from the fourth opening at the same time. The replenishing liquid flows out from the first opening and the second opening. The particles in the solution to be processed flow out from the first opening after passing through the obstacle zone channel, and the solution is collected at the first opening; the solution flowing out of the first opening is used as the solution to be processed to continue the next round of processing.

6. The method according to claim 5, characterized in that The method is used in the particle solution purification scenario. Accordingly, the solution to be processed includes large particles with a radius greater than or equal to a predetermined separation radius and small particles with a radius less than the predetermined separation radius. The predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array. Furthermore, the replenishing solution has the same solvent as the solution to be treated.

7. The method according to claim 6, characterized in that Before performing multiple rounds of treatment on the solution to be treated, it also includes: Obtaining the target purification ratio; The number of processing rounds to be performed is determined according to the target purification ratio.

8. The method according to claim 5, characterized in that The method is used in a particle solution replacement scenario. Accordingly, the solution to be treated includes large particles with a radius greater than or equal to a predetermined separation radius, and the predetermined separation radius is determined by the structure of each column in the column array and the arrangement of the column array; Furthermore, the replenishing solution and the solution to be treated have different solvents.

9. The method according to claim 8, characterized in that Before performing multiple rounds of treatment on the solution to be treated, it also includes: Obtaining the target solvent concentration after substitution; The number of treatment rounds to be performed is determined according to the target solvent concentration after the replacement.

10. A particle solution processing system, characterized in that: include: A deterministic lateral displacement chip, the deterministic lateral displacement chip comprising an obstacle zone channel, wherein a column array is arranged in the obstacle zone channel so that particles of different sizes travel in different directions; a first opening and a second opening are arranged on a first side of the obstacle zone channel, a third opening and a fourth opening are arranged on a second side of the obstacle zone channel, and the first opening is arranged diagonally to the third opening; a predetermined separation radius of the obstacle zone channel is smaller than a radius of a target cell when the solution flows in both forward and reverse directions; a first processing device connected to the first opening of the deterministic lateral displacement chip; The first processing device is used to inject a solution to be processed as an initial solution to be processed, inject the solution to be processed from the first opening into the deterministic lateral displacement chip, and collect the solution flowing out of the first opening; a second processing device connected to the second opening of the deterministic lateral displacement chip; The second processing device is used to apply pressure to the second opening to prevent the solution from flowing out of the second opening and to collect the solution flowing out of the second opening; a third processing device connected to the third opening of the deterministic lateral displacement chip; The third processing device is used to collect the solution flowing out of the third opening, and inject the solution collected at the third opening into the deterministic lateral displacement chip from the third opening; a fourth processing device connected to the fourth opening of the deterministic lateral displacement chip; The fourth processing device is used to apply pressure to the fourth opening to prevent the solution from flowing out of the fourth opening and to collect the solution flowing out of the fourth opening; A controller, used to control the first processing device, the second processing device, the third processing device, and the fourth processing device to implement the method according to any one of claims 1 to 9.

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