Construction method and system of multi-component solution, electronic equipment and storage medium

By generating random arrays and making micropore masks, combined with spray sample loading technology, the complex operation and high cost problems in the existing multi-component solution construction method are solved, and high-throughput and flexible solution combinations are achieved, which improves experimental efficiency and accuracy.

CN119614669APending Publication Date: 2025-03-14WUHAN DESCARTES BIOTECHNOLOGY CO LTD
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
CN202411665239.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-20
Publication Date
2025-03-14

AI Technical Summary

Technical Problem

The existing multi-component solution construction methods have problems such as complex operation, insufficient applicability and flexibility, large workload, long time and high cost.

Method used

By generating a random array composed of 0 and 1, a solid mask is made and micropores are set at its location, spraying samples are performed, aerosol settles through the mask and into the receiving orifice plate, controlling and recording the type of mask and solution, and outputting multiple random combinations.

Benefits of technology

The construction of high-throughput multi-component solution is achieved, which reduces the intensity of manpower, improves experimental efficiency and accuracy, reduces material and manpower investment, and reduces experimental costs.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN119614669A_ABST
    Figure CN119614669A_ABST
Patent Text Reader

Abstract

The invention provides a multi-component solution construction method and system, electronic equipment and a storage medium. The method comprises the following steps: generating a random array consisting of 0 and 1; a solid mask plate is manufactured according to the random array, and a micropore is formed in the position of 1; spraying and sample adding are carried out, and aerosol penetrates through the mask plate to settle into a bearing pore plate; and controlling and recording the types of the mask plate and the solution, and outputting a plurality of random combinations. According to the algorithm, a large number of random schemes are automatically generated according to the program, so that the labor intensity is reduced. And the high-throughput programmable rapid construction of the random composite reagent or cell combination is realized. A large number of clear and random reagent combination results can be obtained, analysis of reaction or interaction under different combinations is facilitated, and the efficiency and accuracy of experiments can be improved. According to the method, not only can complete random combination be carried out, but also screening and design of specific combinations can be carried out according to experimental requirements, and the flexibility and diversity of experimental design are provided.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present invention relates to the fields of biology, chemistry and microbiology, and in particular to a construction method, system, electronic equipment and storage medium of a multi-component solution. Background Art

[0002] Complex influencing factors, reaction conditions or microbial communities are often extremely critical in the fields of physics, chemistry, materials science, environmental science, life science and microbiology. However, it is very difficult to construct these reaction conditions or combinations in a high-throughput manner. When the number of solution types is less than 10, it is still possible to screen a variety of combination conditions through manual operation. When the number of combinations exceeds a certain number, such as more than 20, it is time-consuming and laborious to construct these random combinations manually, and it is often prone to errors, making it difficult to combine and experiment on a large scale with high throughput. In particular, in the field of microbiology, compared with single strains, microbial communities can better adapt to environmental changes, cooperate in metabolism, and catalyze more complex reactions. Synthetic microbial communities are an important means to analyze microbial functions and strengthen communities.

[0003] However, the number of microbial communities is huge and widely distributed. As the number of species increases, the possibility of random combinations of microorganisms increases exponentially, completely beyond the possibility of human-controlled assembly and increase and decrease. It is currently difficult to find potential stable and valuable synthetic communities in a large number of combinations. Some automated sample addition devices can meet the high-throughput liquid addition to a certain extent, but the current addition method requires manual setting of the specific addition process, which significantly increases the complexity of the operation and is not very applicable. Each time, it must be set up one by one, which is not flexible enough and the workload is huge. Moreover, the machine addition process is executed one by one. When the number is large, the interval between the first sample and the last sample is as long as several hours, which can no longer meet the effect of diverse randomness and consistency. Finally, the machine-operated addition itself is very expensive, and it is difficult for ordinary users to purchase and use it. In summary, the existing methods for constructing multi-component solutions have technical problems such as complex operation, insufficient applicability and flexibility, large workload, long time consumption and high cost. Summary of the invention

[0004] In view of this, it is necessary to provide a method, system, electronic device and storage medium for constructing a multi-component solution to solve the technical problems existing in the prior art, such as complex operation, insufficient applicability and flexibility, large workload, long time consumption and high cost.

[0005] In order to solve the above technical problems, in a first aspect, the present application provides a method for constructing a multi-component solution, comprising the following steps: Generate a random array of 0s and 1s; A physical mask is made according to the random array, and a microhole is set at the position 1; Perform spraying and sampling, and the aerosol passes through the mask plate and settles into the receiving hole plate; The types of the mask and the solution are controlled and recorded, and a plurality of random combinations are output.

[0006] In some embodiments of the present application, generating a random array consisting of 0s and 1s includes: Generates a preset number of random arrays of 0s and 1s within a preset range; By controlling the preset ratio of 1, multiple different random number templates are constructed; The plurality of random digital templates are encoded respectively.

[0007] In some embodiments of the present application, the step of making a physical mask according to the random array and setting microholes at position 1 includes: The random number template is made into a physical mask template by mechanical processing; The mask plate is coaxially connected with the receiving hole plate.

[0008] In some embodiments of the present application, the spraying and sampling, wherein the aerosol passes through the mask plate and settles into the receiving orifice plate, comprises: Performing suction processing to remove the aerosol residue; The sprayer converts the solution or bacterial suspension into the aerosol; The aerosol is confined within a settling space.

[0009] In some embodiments of the present application, the controlling and recording the types of the mask and the solution, and outputting a plurality of random combinations, comprises: replacing the mask; Recording the number of the mask; Counting the results in the receiving orifice plate; By comparing the sample addition situations, the interaction relationship between various components under different combination results was obtained.

[0010] In some embodiments of the present application, the controlling and recording the types of the mask and the solution, and outputting a plurality of random combinations, comprises: Rotating the angle of the mask; Recording the angle of the mask; Counting the results in the receiving orifice plate; By comparing the sample addition situations, the interaction relationship between various components under different combination results was obtained.

[0011] In a second aspect, the present application also provides a system for constructing a multi-component solution, comprising: Random algorithm module, used to generate random arrays composed of 0 and 1; A mask processing module, used for manufacturing a physical mask according to the random array; A spray dosing module, used for spray dosing; A variable adding module, used for changing the type of the mask and the solution; The result building module is used for recording the types of the mask and the solution and outputting a plurality of random combinations.

[0012] In some embodiments of the present application, the preset proportion of 1 in the random algorithm module is 1% to 95%, the spray adding module includes a sprayer and a receiving orifice plate, the sprayer includes an ultrasonic sprayer, the receiving orifice plate includes a 96-hole orifice plate, a 384-hole orifice plate or an array orifice plate, and the variable adding module includes a rotating shaft, which is rotatably connected to the receiving orifice plate and fixedly connected to the mask plate.

[0013] In a third aspect, the present application further provides an electronic device, including a memory and a processor, wherein: The memory is used to store programs; The processor is coupled to the memory, and is used to execute the program stored in the memory to implement the steps in the method for constructing a multi-component solution as described in any one of the embodiments of the first aspect above.

[0014] In a fourth aspect, the present application also provides a computer-readable storage medium for storing computer-readable programs or instructions, which, when executed by a processor, can implement the steps in the method for constructing a multi-component solution described in any one of the first aspects above.

[0015] The beneficial effects of the present invention are as follows: the embodiment of the present application generates a digital template through a random algorithm, and then makes a plurality of physical mask templates, the mask templates correspond to the digital templates one by one, and the algorithm generates a large number of random schemes according to the program, thereby reducing the intensity of manpower work. By spraying, the addition of high-throughput micro-liter or nano-liter solutions of hundreds or even tens of thousands of micropores can be achieved in one spray. By controlling and recording the random distribution, random rotation and mask types with different numbers of holes of the mask, a high-throughput digital random combination can be constructed, and a high-throughput programmable rapid construction of random composite reagents or cell combinations is achieved. The software statistics and outputs the experimental results, and a large number of clear and random reagent combination results can be obtained, which is conducive to analyzing the reactions or interactions under different combinations, and can improve the efficiency and accuracy of the experiment. This method can not only perform completely random combinations, but also screen and design specific combinations according to experimental requirements, providing flexibility and diversity in experimental design. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0017] Figure 1 A schematic diagram of a process for constructing a multi-component solution provided by the present invention; Figure 2 For the present invention Figure 1 A schematic flow chart of an embodiment of S1; Figure 3 For the present invention Figure 1 A schematic flow chart of an embodiment of S2; Figure 4 For the present invention Figure 1 A schematic flow chart of an embodiment of S3; Figure 5 For the present invention Figure 1 A schematic flow chart of an embodiment of S4; Figure 6 For the present invention Figure 1 Another embodiment flow chart of S4; Figure 7 A schematic structural diagram of a mask provided by the present invention; Figure 8 A schematic diagram of the structure of a system for constructing a multi-component solution provided by the present invention; Fig. 9 The present invention provides a schematic structural diagram of an electronic device. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0019] In view of this, it is necessary to provide a method, system, electronic device and storage medium for constructing a multi-component solution to solve the technical problems existing in the prior art, such as complex operation, insufficient applicability and flexibility, large workload, long time consumption and high cost.

[0020] In order to solve the above technical problems, in the first aspect, the present application provides a method for constructing a multi-component solution, such as Figure 1 As shown, Figure 1A schematic flow chart of a method for constructing a multi-component solution provided by the present invention.

[0021] A method for constructing a multi-component solution comprises the following steps: S1. Generate a random array of 0s and 1s; S2. A physical mask 52 is prepared according to the random array, and microholes are set at position 1; S3. Spraying and sampling are performed, and the aerosol passes through the mask plate 52 and settles into the receiving hole plate 53; S4. Control and record the types of the mask 52 and the solution, and output a plurality of random combinations.

[0022] Specifically, the method includes: random array design and mask production, spray addition, receiving porous plate and result output. First, a randomly distributed array of 0 and 1 is formed by a random algorithm. The 1 in these random arrays is set as micropores, and a physical mask plate 52 is made by a mechanical processing process. The solution or bacterial suspension is made into an aerosol by a sprayer 51, and the aerosol fills the sedimentation channel and settles through the mask plate 52 with randomly distributed micropores, and settles in the receiving orifice plate 53 at the bottom, so as to achieve a high-throughput microliter to nanoliter solution addition of hundreds or tens of thousands of micropores in one spray. During the addition of different solutions, pollution prevention and control is carried out at intervals or through a suction system. By using different orifice plates and spraying different targets, a large number of random and determined combinations can be efficiently constructed, and the combination results are statistically counted and the results are output. By controlling and recording the mask type, the combination results are statistically counted and the results are output by software, and a high-throughput digital random combination can be constructed, realizing high-throughput rapid construction of random composite reagents or cell combinations.

[0023] The random array of 0 and 1 is generated by the algorithm, ensuring the randomness and diversity of the solution combination. The 1 position in the random array is made into a microwell to achieve the customization of the physical mask 52. The mask 52 and the solution type are recorded by the software to ensure the traceability and repeatability of the experiment. The whole process has a high degree of automation, which reduces manual operation and reduces the complexity of operation. Different random arrays can be generated according to needs, which is suitable for a variety of experimental scenarios. A large number of solutions can be added to microwells at one time, greatly reducing the workload of experimenters. High-throughput sample addition technology improves the experimental speed and shortens the experimental cycle. Compared with traditional methods, this method has lower investment in materials and manpower, which helps to reduce experimental costs. The accuracy and reliability of experimental data are ensured by recording and outputting results through software.

[0024] like Figure 2 As shown, Figure 2 For the present invention Figure 1 A flow chart of an embodiment of S1 is shown in FIG.

[0025] In some embodiments of the present application, the S1 generates a random array of 0s and 1s, including: S11. Generate a preset number of random arrays of 0 and 1 within a preset range; S12. Constructing multiple different random number templates by controlling the preset ratio of 1; S13. Encode the plurality of random digital templates respectively.

[0026] like Figure 3 As shown, Figure 3 For the present invention Figure 1 A flow chart of an embodiment of S2 is shown in FIG.

[0027] In some embodiments of the present application, the step S2 manufactures a physical mask 52 according to the random array and sets microholes at the position 1, including: S21. The random digital template is made into a physical mask template 52 by mechanical processing; S22. Coaxially connect the mask plate 52 and the receiving hole plate 53.

[0028] Specifically, the preparation of the microwell plate includes a flat plastic plate or a metal plate, and the 1 in the digital array at the predetermined position is set as a microwell through drawing software, wherein the ratio of 0 to 1 ranges from 1% to 95%. In addition, the microwells can be randomly distributed in series or clusters of more than 2 1s to meet the random combination containing multiple fixed combinations.

[0029] The receiving orifice plate 53 is preferably a 96-well plate or a 384-well plate, or a high-density array orifice plate. The micropores on the mask plate are slightly smaller than the receiving orifice plate 53, ranging from 1mm to 10mm, and the micropore plate is made by computer numerical control (CNC) or engraving. The orifice of the mask plate 52 needs to have a protruding extension, or a rubber ring or a protruding funnel ring on the orifice plate, which is used for sealing and docking with the receiving hole to ensure that there is no cross contamination between the holes.

[0030] The mask needs to have three positioning holes, and there is also a hole in the center for matching with the fixed column; by randomly generating a 40×40 binary matrix, "0" represents no hole and "1" represents a hole; a mask with 100 to 1000 holes is designed according to experimental requirements; each mask is set with four fixed inoculation angles: 0°, 90°, 180°, and 270° (only a fixed angle needs to be rotated). The device for placing the receiving well plate 53 can be set with 1 to 4 grooves for fixing the 384 / 96-well plate, four positioning holes are set on the four sides, and a fixed column is set in the center for fixing and rotating the mask plate 52.

[0031] Generate a preset number of random arrays of 0 and 1 within a preset range, ensuring the number and diversity of random arrays to meet different experimental needs. By controlling the preset ratio of 1, multiple different random number templates are constructed. This step allows researchers to adjust the complexity and density of solution combinations according to the purpose of the experiment. Encode multiple random number templates separately, which helps to track and identify the combination corresponding to each template after the experiment, facilitating data management and analysis.

[0032] The random digital template is made into a physical mask plate 52 by mechanical processing. This step converts the digital template into a physical mask plate 52 for the actual sample addition process. The mask plate 52 is coaxially connected with the receiving hole plate 53 to ensure that the aerosol can accurately settle to the corresponding position of the receiving hole plate 53 through the micropores of the mask plate 52.

[0033] By controlling the ratio of 1 and generating multiple random number templates, researchers can customize solution combinations according to experimental requirements, increasing the flexibility and diversity of the experiment. The mechanical processing of the physical mask 52 ensures the precise position and size of the micropores, thereby ensuring the accuracy of sample addition. Through the coaxial connection method, a large number of micropores can be processed at one time, achieving high-throughput solution addition. Encoding the random number template makes it easy to track and record experimental results, improving the manageability of experimental data.

[0034] The use of standardized 96-well plates or 384-well plates facilitates the use with other laboratory equipment and supports high-throughput experiments. The precise size and shape of the microwells ensure the accuracy of solution addition and reduce experimental errors. The protruding extension or rubber ring design effectively prevents cross contamination and ensures the reliability of experimental results. The groove and fixed column design of the base makes the placement and replacement of the receiving well plate 53 and the mask plate 52 simple and quick, improving the experimental efficiency. The design of the base allows the rotation and positioning of the mask plate 52, increasing the flexibility of experimental operations and adapting to different experimental needs.

[0035] like Figure 4 As shown, Figure 4 For the present invention Figure 1 A flowchart of an embodiment of S3 is shown in FIG.

[0036] In some embodiments of the present application, the step S3 performs spraying and sampling, and the aerosol passes through the mask plate 52 and settles into the receiving hole plate 53, including: S31. Perform suction treatment to remove the aerosol residue; S32. The sprayer 51 prepares the aerosol from the solution or bacterial suspension; S33. Confine the aerosol within the sedimentation space.

[0037] Specifically, the sprayer 51 can be an ultrasonic sprayer 51, or other devices capable of making aerosols from a suspension containing reagents and microorganisms. The sprayer 51 can make a suspension containing reagents and microorganisms into millions of aerosols containing single cells, and the aerosol needs to be confined within a certain settling space. The aerosol only settles through random micropores into the receiving orifice plate 53. The amount added can be controlled at the nanoliter to microliter level.

[0038] After each settling, there may be residual solution in the air. By sucking clean air, the solution is removed, and then the next solution addition is completed. The spray reagent can be a chemical reagent, a microbial suspension, etc., or a solid. The solid can be evenly spread and settled by a fan.

[0039] The amount of solution added to the receiving orifice plate 53 can be precisely controlled by the sprayer 51, from nanoliters to microliters, which is particularly important for experiments requiring precise dosage control.

[0040] After each sedimentation, there may be residual solution in the air. By sucking clean air, the solution is removed, and then the next solution addition is completed. The suction treatment step effectively reduces the residue of aerosol in the air, reduces the risk of cross contamination, and improves the reliability of experimental data. The spraying method can achieve high-throughput operation, and a plurality of orifice plates are sampled at one time, which greatly improves the experimental efficiency. This method is not only suitable for liquid reagents, but also for the uniform spreading and sedimentation of solid reagents, which increases the diversity and flexibility of the experiment. The aerosol made is constrained in a specific sedimentation space to ensure that the aerosol only enters the receiving orifice plate 53 through the random micropore sedimentation on the mask plate 52. This constraint can be achieved by physical barriers or airflow control. Ultrasonic sprayer 51 can produce uniform aerosol, ensuring the uniform distribution of solution or solid in the receiving orifice plate 53, which is crucial for the accuracy of the experimental results.

[0041] like Figure 5 As shown, Figure 5 For the present invention Figure 1 A schematic flow chart of an embodiment of S4.

[0042] In some embodiments of the present application, the S4 controls and records the types of the mask 52 and the solution, and outputs a plurality of random combinations, including: S41. Replace the mask 52; S42. Record the number of the mask plate 52; S43. Count the results of the receiving hole plate 53; S44. Compare the sample addition situations to obtain the interaction relationship between various components under different combination results.

[0043] like Figure 6 As shown, Figure 6 For the present invention Figure 1 FIG. 4 is a flow chart of another embodiment of S4.

[0044] In some embodiments of the present application, the S4 controls and records the types of the mask 52 and the solution, and outputs a plurality of random combinations, including: S45. Rotate the angle of the mask plate 52; S46. Record the angle of the mask 52; S47. Count the results of the receiving hole plate 53; S48. Compare the sample addition situations to obtain the interaction relationship between various components under different combination results.

[0045] Specifically, by recording the type of orifice plate and the rotation angle of each spray addition, the results can be counted and output through the program. The results in the receiving orifice plate 53 are counted and compared with the addition conditions to obtain the interaction relationship between various components under different combination results.

[0046] like Figure 7 As shown, Figure 7 This is a schematic diagram of the structure of a mask plate 52 provided by the present invention. The shadow hole corresponds to 0, which is a non-hole, and the blank hole corresponds to 1, which is a micro-hole.

[0047] Each up and down movement of the mask is controlled by a motor, so that the micropores and the receiving orifice plate 53 are properly contacted and sealed to prevent the aerosol from flowing and contaminating above the receiving hole during the sedimentation process after the sprayer 51 sprays. As well as angle rotation, the array mask plate can realize the random combination construction of multiple components by rotating 90, 80 and 270 degrees; the central symmetrical mask plate can realize the effect of multiple addition combinations of one mask plate by designing the rotation angle of 20~350 degrees, and the motor is driven by an automated program to rotate and lift to complete the control of the mask assembly. The microporous mask can also be designed as a centrally supported micropore, and the corresponding bottom receiving plate should also be a corresponding centrally supported orifice plate. The advantage of this design is that a mask plate 52 can obtain a large number of different addition combinations by rotating at more angles.

[0048] The results in the receiving well plate 53 are counted and compared with the addition conditions to obtain the interaction relationship between various components under different combination results. The reaction value of a specific combination under a specific absence is output by software. By controlling and recording the random distribution, random rotation and mask types of different hole numbers of the mask, a high-throughput digital random community can be constructed, and a high-throughput rapid construction of random composite reagents or cell combinations is achieved. The manufacture of the above-mentioned template depends on the generation of a digital array. Therefore, the template manufactured each time corresponds to the digital array one by one and is stored in the program. During use, the digital template is called one by one, and then the superposition and statistics of the added species are performed. According to the statistical results, a diversified result display is performed. According to the experimental requirements, different mask plates 52 can be replaced to achieve different micropore arrangements and combinations. The angle of the mask plate 52 can be controlled by a motor to change the relative position of the micropores and the receiving plate 53, so as to achieve different micropore arrangements and combinations.

[0049] The serial number of the replaced mask plate 52 is recorded for subsequent tracking and statistical experimental results. The rotation angle of the mask plate 52 is recorded for subsequent data analysis.

[0050] The results in the receiving well plate 53 are counted, including which wells have solutions added and the types of solutions added. By comparing the addition of different mask plates 52 (or different angles of the same mask plate 52) and solution combinations, the interaction relationship between various components is analyzed.

[0051] In a second aspect, the present application also provides a multi-component solution construction system 6, such as Figure 8 As shown, Figure 8 A schematic structural diagram of a multi-component solution construction system 6 provided by the present invention.

[0052] A multi-component solution construction system 6, comprising: A random algorithm module 61 is used to generate a random array consisting of 0s and 1s; A mask processing module 62, used for manufacturing a physical mask 52 according to the random array; A spray adding module 63, used for performing spray adding; A variable adding module 64, used to change the type of the mask 52 and the solution; The result building module 65 is used to record the types of the mask 52 and the solution, and output a plurality of random combinations.

[0053] In some embodiments of the present application, the preset proportion of 1 in the random algorithm module is 1% to 95%, the spray adding module 63 includes a sprayer 51 and a receiving hole plate 53, the sprayer 51 includes an ultrasonic sprayer 51, the receiving hole plate 53 includes a 96-hole hole plate, a 384-hole hole plate or an array hole plate, and the variable adding module 64 includes a rotating shaft, which is rotatably connected to the receiving hole plate 53 and fixedly connected to the mask plate 52.

[0054] By generating a specific number of random arrays of 0 and 1, and controlling the proportion of 1, different random digital templates are constructed and encoded. The designed digital mask is supported by a mechanical processing process on the physical plate, in which the number 1 is a micro-hole design. The plate is placed on a tray containing a 96-well plate, positioned by the central hole column, and fixed by manual or automatic control. The holes on the mask plate 52 are closely connected with the holes on the 96-well plate. The support plate assembly is placed in the spray system for spray loading. The aerosol enters the well plate through the hole in the mask plate 52, completes a loading, starts the suction system, and removes the aerosol residue above. Subsequently, different samples are added by exchanging or rotating the mask plate 52. Each spray needs to record the number of the mask plate 52 and the corresponding angle and other information. After the loading is completed, all the combination results are output by the software, and a large number of clear and random reagent combinations can be obtained.

[0055] Diversified digital arrays and microplate manufacturing: A 40X40 01 random matrix is ​​constructed through a computer program. According to the design, the number ratio of 1 can be controlled from 10%, 30%, and 60%. The random array is numbered. Then, in the industrial design software, the digital array is placed in a square graphic of a specific size. In order to match the 96-well commonly used in the laboratory, the side length of the square we designed is 24cm. Four 96-well plates can be placed in it, arranged in a fan blade shape. Then the number 1 in the array is formed into a microcircular hole, the 0 microhole is deleted, and then the 1 is set as a microhole. Its diameter range is 7mm. Aluminum plates are selected for CNC processing and molding. A hole is set in the center for positioning and rotation or fixing. The microholes on the microplate need to be convex, and the outer diameter is 6.5mm. The hole is used for the connection of the 96-well plate. In order to further increase the connection adaptation and sealing between the holes, we add a rubber ring to the microhole for elastic contact with the microhole. Experiments with aerosolizing Escherichia coli in 96-well plates containing culture medium showed that the device can perform aerosol material addition well without causing cross-contamination problems.

[0056] The high-throughput template uses die-casting technology to construct a 100*100 groove structure, and then customizes the mask template 52 to make a convex hollow structure, forming a high-throughput panel when the upper and lower parts are aligned.

[0057] Combined addition of ten microorganisms: The method of using the spray device with random assembly of composite flora relies on the single cell culture omics technology based on spray aerosol to inoculate the target flora, and the method includes the following steps: Before adding the combination, the 96-well plate, mask and spray device are sterilized accordingly (using alcohol, hydrogen peroxide and ultraviolet light, etc.).

[0058] Before inoculation, add an appropriate amount of liquid culture medium to the 96-well plate; name the bacteria to be inoculated one by one: A / B / C / D / E / F / G / H / I / J; inoculate in the order of A / B / C / D / E, etc., place four 96-well plates in the base compartment, and place the mask on the 96-well plate. The mask plate 52 is numbered and recorded. In order to reduce the number of mask plates 52 manufactured, the fixed position of each plate is placed in different orientations to achieve the difference in the well plates. The inoculation angles are named 1 (0°), 2 (90°), 3 (180°), and 4 (270°). 1, 2, 3, and 4 are randomly generated to correspond to the rotation angles of the randomly generated masks. For example, the inoculation of twenty bacteria does not require twenty inoculation plates, but only 5 to 10 mask plates 52 are required. During inoculation, the instrument must be sterile and the strain must be in liquid form. The spray inoculation volume can be set to 200 ml by controlling the spray time. The average amount deposited in each microwell is approximately 200*3.14*6.5*6.5 / 4 / 240*240=0.11 microliters.

[0059] After the experiment, the software records and counts the random combinations to obtain intuitive random statistics. The results can be extremely diverse combinations such as ABDG, ACD, BDFG, CFDGIJ, etc., and combined with the measured OD values, a large number of random combinations and interaction results can be obtained. These results are crucial for analyzing the interaction of multiple factors in complex environments. Programmable combination design and output of combination results: After we obtain the shapes of some strains, we want to further study how other influencing factors affect the specific combination. Instead of completely random combination and result analysis. In this way, it is necessary to conduct combination screening of specific results before the experiment. For example, A / B / C / D / E / F / G / H / I / J; we want more random combinations of differences under the existence of ACD. For example, A, C, D, AC, CD, AD, ACD, ACBD, ACDE, ACDF, ACDGACDH, ACDI. That is, we want to characteristically construct some specific combinations. We use the mask template 52 library, at least 20 pieces, different angle combinations, that is, 80 mask combinations. Through the simulation process and algorithm, by setting up multiple rounds of experiments, you can query whether the combination conditions of the specific mask template 52 meet the combination you selected. Recommend the experimental combination that meets most of the cases. This process avoids the blindness of the experiment and can plan the use of the selected reagents and mask template 52 in advance. Then, by comparing the combination results and the actual measurement results of the 96-well plate, the results of the specific combination are output.

[0060] Microorganisms that construct random and complex chemical environments: The microbial strains in the above examples can be replaced with different single-component solutions, such as glucose, amino acids, inorganic salts, such as NaCl, NH4SO4, or antibiotics. Through random combinations, solution microenvironments with significantly different combinations of components can be obtained. The examples show that we can obtain hundreds of chemical microenvironments within half an hour to cultivate microorganisms. This can be used for culture medium optimization in synthetic biology.

[0061] Optimization of stem cell culture environmental reaction system: In some solution component optimizations, the microbial strains in the above embodiments can be replaced with stem cells, and different single component solutions, such as glucose, amino acids, inorganic salts, such as NaCl, NH4SO4, or antibiotics. Through random combination, significantly different solution microenvironments of combined components can be obtained. The embodiments show that we can obtain hundreds of chemical microenvironments within half an hour to culture mammalian cells such as stem cells, regulate and observe their functional microenvironments.

[0062] Establishment of composite toxicological evaluation: In some ecotoxicology, the toxicity evaluation of some low-dose but multi-component mixed pollutant solutions is involved. The microbial strains in the above embodiments can be replaced with pollutant solutions with different nutrients and different single components, such as glucose, amino acids, inorganic salts, such as NaCl, NH4SO4, or heavy metals Cu, Hg, Cd, Cr salts, etc. Through random combination, solution microenvironments with significantly different combined components can be obtained. As shown in the embodiments, we can obtain hundreds of pollutant chemical microenvironments within half an hour to culture mammalian cells or microorganisms such as stem cells and observe their toxic effect microenvironments. In addition, it is also possible to obtain significantly more concentration gradient microenvironments for large-scale solution culture microenvironments by continuous spraying of a solution. It is also possible to directly spray antibiotics multiple times to obtain their minimum inhibitory concentration MIC curves.

[0063] Programmable material combination synthesis: In some chemical syntheses, specific ion conditions and ligand combinations are often required, especially some organic-inorganic complexes require diversified combination additions. The microbial strains in Example 2 can be replaced with different microorganisms and different single component solutions, such as glucose, amino acids, inorganic salts, such as CaCl2, Na2CO3 salts, etc. Through specific combinations, observe how microorganisms affect the formation environment of calcium carbonate. The device can easily draw a calcium carbonate precipitation phase diagram under a complex environment.

[0064] In a third aspect, the present invention also provides an electronic device. Fig. 9 As shown, Fig. 9 The schematic diagram of the structure of an electronic device 7 provided by the present invention. The electronic device 7 includes a memory 71, a processor 72 and a display 73. In some embodiments, the processor 72 may be a central processing unit (CPU), a microprocessor or other data processing chip, which is used to run the program code stored in the memory 71 or process data, such as the method for constructing a multi-component solution in the present invention.

[0065] Correspondingly, in a fourth aspect, an embodiment of the present application further provides a computer-readable storage medium, which is used to store computer-readable programs or instructions. When the programs or instructions are executed by a processor, the steps or functions in the method for constructing a multi-component solution provided in the above-mentioned method embodiments can be implemented.

[0066] Those skilled in the art will appreciate that all or part of the processes of the above-mentioned embodiments can be implemented by instructing related hardware (such as a processor, a controller, etc.) through a computer program, and the computer program can be stored in a computer-readable storage medium, wherein the computer-readable storage medium is a disk, an optical disk, a read-only storage memory, or a random access memory, etc.

[0067] The beneficial effects of the present invention are as follows: the embodiment of the present application generates a digital template through a random algorithm, and then makes a plurality of physical mask templates 52, the mask templates 52 correspond to the digital template one by one, and the algorithm generates a large number of random schemes according to the program, thereby reducing the intensity of manpower work. By spraying, the addition of high-throughput micro-liter or nano-liter solutions of hundreds or even tens of thousands of micropores can be achieved in one spray. By controlling and recording the random distribution, random rotation and mask types with different numbers of holes of the mask, a high-throughput digital random combination can be constructed, and a high-throughput programmable rapid construction of random composite reagents or cell combinations is achieved. The software statistics and outputs the experimental results, and a large number of clear and random reagent combination results can be obtained, which is conducive to analyzing the reactions or interactions under different combinations, and can improve the efficiency and accuracy of the experiment. This method can not only perform completely random combinations, but also screen and design specific combinations according to experimental requirements, providing flexibility and diversity in experimental design.

[0068] The vehicle body design method and system provided by the present invention are introduced in detail above. Specific examples are used in this article to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core idea. At the same time, for technical personnel in this field, according to the idea of ​​the present invention, there will be changes in the specific implementation method and application scope. In summary, the content of this specification should not be understood as a limitation on the present invention.

Claims

1. A method for constructing a multi-component solution, characterized in that: The following steps are involved: Generate a random array of 0s and 1s; A physical mask is made according to the random array, and a microhole is set at the position 1; Perform spraying and sampling, and the aerosol passes through the mask plate and settles into the receiving hole plate; The types of the mask and the solution are controlled and recorded, and a plurality of random combinations are output.

2. The method for constructing a multi-component solution according to claim 1, characterized in that: The generating of a random array consisting of 0 and 1 includes: Generates a preset number of random arrays of 0s and 1s within a preset range; By controlling the preset ratio of 1, multiple different random number templates are constructed; The plurality of random digital templates are encoded respectively.

3. The method for constructing a multi-component solution according to claim 2, characterized in that: The method of making a physical mask according to the random array and setting microholes at the position 1 includes: The random number template is made into a physical mask template by mechanical processing; The mask plate is coaxially connected with the receiving hole plate.

4. The method for constructing a multi-component solution according to claim 3, characterized in that: The spraying and sampling, wherein the aerosol passes through the mask plate and settles into the receiving hole plate, comprises: Performing suction processing to remove the aerosol residue; The sprayer converts the solution or bacterial suspension into the aerosol; The aerosol is confined within a settling space.

5. The method for constructing a multi-component solution according to claim 2, characterized in that: The controlling and recording of the types of the mask and the solution, and outputting a plurality of random combinations, comprises: replacing the mask; Recording the number of the mask; Counting the results in the receiving orifice plate; By comparing the sample addition situations, the interaction relationship between various components under different combination results was obtained.

6. The method for constructing a multi-component solution according to claim 2, characterized in that: The controlling and recording of the types of the mask and the solution, and outputting a plurality of random combinations, comprises: Rotating the angle of the mask; Recording the angle of the mask; Counting the results in the receiving orifice plate; By comparing the sample addition situations, the interaction relationship between various components under different combination results was obtained.

7. A system for constructing a multi-component solution, characterized in that: include: Random algorithm module, used to generate random arrays composed of 0 and 1; A mask processing module, used for manufacturing a physical mask according to the random array; A spray dosing module, used for spray dosing; A variable adding module, used for changing the type of the mask and the solution; The result building module is used for recording the types of the mask and the solution and outputting a plurality of random combinations.

8. The system for constructing a multi-component solution according to claim 7, characterized in that: The preset ratio of 1 in the random algorithm module is 1% to 95%, the spray adding module includes a sprayer and a receiving hole plate, the sprayer includes an ultrasonic sprayer, the receiving hole plate includes a 96-hole hole plate, a 384-hole hole plate or an array hole plate, and the variable adding module includes a rotating shaft, which is rotatably connected to the receiving hole plate and fixedly connected to the mask plate.

9. An electronic device, characterized in that: comprising a memory and a processor, wherein: The memory is used to store programs; The processor is coupled to the memory and is used to execute the program stored in the memory to implement the steps in the method for constructing a multi-component solution as described in any one of claims 1 to 6.

10. A computer-readable storage medium, characterized in that: Used to store computer-readable programs or instructions, which, when executed by a processor, can implement the steps in the method for constructing a multi-component solution as described in any one of claims 1 to 6.