CN115166154B

CN115166154B - Reagent development experiment method, device, computer equipment and storage medium

Info

Publication number: CN115166154B
Application number: CN202210857317.1A
Authority: CN
Inventors: 王治才; 张毅立; 肖承亮; 骆俊炜; 植立才; 王政
Original assignee: Guangzhou Labsim Biotech Co Ltd
Current assignee: Guangzhou Labsim Biotech Co Ltd
Priority date: 2022-07-20
Filing date: 2022-07-20
Publication date: 2024-10-18
Anticipated expiration: 2042-07-20
Also published as: CN115166154A

Abstract

The application relates to a reagent development experiment method, a reagent development experiment device, computer equipment and a storage medium. According to the raw materials required by the immune reagents to be developed, a plurality of raw material combination results are determined, the raw material combination results are sequenced to be used as an experimental sequence, experiments are carried out on the raw material combination results according to the experimental sequence to obtain a plurality of immune reagents, and then according to the performance test results of the immune reagents, a target immune reagent meeting preset conditions is determined from the immune reagents. According to the method, a plurality of raw material combination results are determined through raw materials required by the immune reagent to be developed, then the raw material combination results are tested according to the test sequence of the raw material combination results, the test is automatically carried out according to the test sequence, and the performance test results of all the immune reagents are obtained, so that the target immune reagent is determined.

Description

Reagent development experiment method, device, computer equipment and storage medium

Technical Field

The application relates to the technical field of reagent development, in particular to a reagent development experiment method, a device, computer equipment and a storage medium.

Background

The reagent is mainly pure chemical used for realizing chemical reaction, analysis and test, research and test, teaching experiment and chemical formula. Taking an immunoreagent as an example, the core of the immunoreagent is that different tracers are crosslinked with specific antigens or antibodies, and the target antigens or antibodies are indirectly measured through the content or the activity of the tracers, so that simple and rapid diagnosis can be realized. Among them, reagent development before the use of an immunoreagent is an important and critical process.

However, in the related art, manual participation is required to complete the reagent development process, which may result in time consuming reagent development.

Disclosure of Invention

In view of the foregoing, it is desirable to provide a reagent development experimental method, apparatus, computer device, and storage medium that can shorten the time in the reagent development process and improve the reagent development efficiency.

In a first aspect, the present application provides a reagent development assay method comprising:

Determining a plurality of raw material combination results according to raw materials required by an immune reagent to be developed;

Sequencing a plurality of raw material combination results to obtain an experimental sequence, and carrying out experiments on the raw material combination results according to the experimental sequence to obtain a plurality of immunoreagents;

and determining the target immunoreagent meeting the preset condition from the plurality of immunoreagents according to the performance test result of each immunoreagent.

In one embodiment, determining a plurality of raw material combination results based on raw materials required for an immunoreagent to be developed, comprises:

Dividing raw materials required by an immunoreagent to be developed according to the types of the raw materials to obtain a plurality of raw material sets, wherein each raw material set corresponds to one raw material type;

And (3) carrying out permutation and combination treatment on the raw materials in each raw material set to obtain a plurality of raw material combination results.

In one embodiment, the results of each raw material combination are tested to obtain a plurality of immunoreagents, including:

acquiring a fixed reagent operation flow combination and a fixed reagent parameter combination;

and aiming at any raw material combination result, carrying out experiments on the raw material combination result based on the fixed reagent operation flow combination and the fixed reagent parameter combination to obtain an immunoreagent corresponding to the raw material combination result.

In one embodiment, obtaining a combination of immobilized reagent operational flows and a combination of immobilized reagent parameters includes:

obtaining a plurality of candidate reagent operation flow combinations according to operation flow needed by an immune reagent to be developed, and determining a fixed reagent operation flow combination according to the plurality of candidate reagent operation flow combinations;

according to the reagent parameters required in the operation flow, a plurality of candidate reagent parameter combinations are obtained, and a fixed reagent parameter combination is determined according to the plurality of candidate reagent parameter combinations.

In one embodiment, obtaining a plurality of candidate reagent operational flow combinations according to operational flow required for an immunoreagent to be developed comprises:

acquiring the execution times of repeatedly executable operation flows in each operation flow;

and according to the execution times of the repeatedly executable operation flows in each operation flow, arranging and combining the execution sequences of the operation flows to obtain a plurality of candidate reagent operation flow combinations.

In one embodiment, obtaining a plurality of candidate reagent parameter combinations based on reagent parameters required in the operational flow includes:

And arranging, combining and setting parameter values of reagent parameters required in each operation flow to obtain a plurality of candidate reagent parameter combinations.

In one embodiment, the performance test comprises at least one of a plateau test, a project experiment, a curve fit, a project assessment, and a stability test.

In a second aspect, an embodiment of the present application provides a reagent development experimental apparatus, the apparatus comprising:

The combination determining module is used for determining a plurality of raw material combination results according to raw materials required by the immune reagent to be developed;

The test module is used for sequencing the combination results of the raw materials as an experimental sequence, and carrying out experiments on the combination results of the raw materials according to the experimental sequence to obtain a plurality of immunoreagents;

The reagent determining module is used for determining a target immune reagent meeting preset conditions from a plurality of immune reagents according to the performance test results of the immune reagents.

In a third aspect, an embodiment of the present application provides a computer device, including a memory and a processor, the memory storing a computer program, the processor implementing the steps of the method provided by any of the embodiments of the first aspect, when the computer program is executed.

In a fourth aspect, embodiments of the present application provide a computer readable storage medium having stored thereon a computer program which, when executed by a processor, implements the steps of the method provided by any of the embodiments of the first aspect described above.

In a fifth aspect, embodiments of the present application also provide a computer program product comprising a computer program which, when executed by a processor, implements the steps of the method provided by any of the embodiments of the first aspect described above.

According to the reagent development experimental method, the device, the computer equipment and the storage medium, a plurality of raw material combination results are determined according to raw materials required by the immune reagent to be developed, the raw material combination results are sequenced to be used as an experimental sequence, experiments are carried out on the raw material combination results according to the experimental sequence to obtain a plurality of immune reagents, and then a target immune reagent meeting preset conditions is determined from the immune reagents according to performance test results of the immune reagents. According to the method, a plurality of raw material combination results are determined through raw materials required by the immune reagent to be developed, then the raw material combination results are tested according to the test sequence of the raw material combination results, the test is automatically carried out according to the test sequence, and the performance test results of all the immune reagents are obtained, so that the target immune reagent is determined.

Drawings

FIG. 1 is a diagram of an application environment for a reagent development experimental method in one embodiment;

FIG. 2 is a schematic flow chart of a reagent development experimental method in one embodiment;

FIG. 3 is a schematic flow chart of another embodiment of a method of testing reagent development;

FIG. 4 is a schematic flow chart of another embodiment of a method of experiment for reagent development;

FIG. 5 is a schematic flow chart of another embodiment of a method of reagent development experiments;

FIG. 6 is a schematic flow chart of another embodiment of a method of reagent development experiments;

FIG. 7 is a schematic flow chart of another embodiment of a reagent development experimental method;

FIG. 8 is a block diagram of a reagent development experimental set-up in one embodiment;

fig. 9 is an internal structural diagram of a computer device in one embodiment.

Detailed Description

The present application will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present application more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the application.

The reagent development experimental method provided by the embodiment of the application can be applied to an application environment shown in figure 1. Wherein. Wherein the terminal 102 communicates with the reagent development experiment platform 104. The terminal 102 may be, but is not limited to, various personal computers, notebook computers, tablet computers, and the like. The reagent development test platform 104 includes a memory and a processor, and may be a device that processes raw material combination results and performs tests and performance tests.

The embodiment of the application provides a reagent development experiment method, a device, computer equipment and a storage medium, which can shorten the time in the reagent development process and improve the reagent development efficiency.

The following describes the technical scheme of the present application and how the technical scheme of the present application solves the above technical problems in detail by examples and with reference to the accompanying drawings. The following embodiments may be combined with each other, and the same or similar concepts or processes may not be described in detail in some embodiments.

For the purpose of making the objects, technical solutions and advantages of the embodiments of the present application more apparent, the technical solutions of the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application, and it is apparent that the described embodiments are some embodiments of the present application, but not all embodiments of the present application.

In one embodiment, with continued reference to fig. 2, a reagent development experimental method is provided, and this embodiment relates to a specific process of determining a plurality of raw material combination results according to raw materials required for an immune reagent to be developed, sequencing the plurality of raw material combination results as an experimental sequence, performing an experiment on each raw material combination result according to the experimental sequence to obtain a plurality of immune reagents, and then determining a target immune reagent meeting a preset condition from the plurality of immune reagents according to performance test results of each immune reagent. This embodiment comprises the steps of:

S201, determining a plurality of raw material combination results according to raw materials required by the immune reagent to be developed.

Immunoreagents are reagents made of specific antigens, antibodies or related biological substances, and can be classified into agglutination reactions, precipitation reactions, complement fixation reactions and labeling immunoreactions according to methodologies.

The immune reagent to be developed is the current immune reagent to be developed, and belongs to the reagent for immune detection. Alternatively, the immunological reagent to be developed may be a fluorescent immunological detection reagent or a chemiluminescent immunological detection reagent.

The fluorescent immunodetection reagent combines antibody molecules with some trace substances, utilizes antigen-antibody reaction to locate antigen substances in tissues or cells, firstly marks known antigens or antibodies with fluorescent groups according to the principle of antigen-antibody reaction, and utilizes the immune reaction and fluorescence principle to calculate the content of detected substances (antigens or antibodies) through the collection of fluorescent signals.

The chemiluminescent immunoassay reagent has a characteristic group which generates luminescence in a chemical structure, can directly or indirectly label an antibody or antigen, and participates in luminescence reaction.

In practical applications, before the development of the immunological reagent to be developed, the raw materials required for developing the immunological reagent to be developed need to be determined. For example, the main raw materials of the ELISA detection reagent can comprise various natural antigens, recombinant antigens, monoclonal antibodies, polyclonal antibodies, polypeptides, hormones and other raw materials; certain immunological reagents include magnetic bead antibodies, blocking agents, marker antibodies, biotin antibodies, and other raw materials. Thus, the raw materials required for the immunoreagent to be developed are determined according to the type of immunoreagent to be developed.

Based on the determined raw materials of the immunological reagent to be developed, a plurality of raw material combination results can be determined; for example, the magnetic bead antibody M, the blocker R1, the tag antibody R2, the biotin antibody R3, and the like based on a certain reagent in the above-described embodiment, that is, the immunological reagent to be developed requires 4 kinds of raw materials, different raw materials may be provided by different suppliers, the same raw material may have a plurality of suppliers, and the same supplier may provide a plurality of raw materials, and thus, a plurality of combination manners, that is, a plurality of raw material combination results, each raw material combination result including four kinds of raw materials required for the immunological reagent to be developed, and each raw material comes from the same supplier, may be obtained by combining one or more raw materials of one or more suppliers.

Alternatively, all raw material combination results may be determined according to an enumeration method, and all raw material combination results may be determined as a plurality of raw material combination results as described above; and a plurality of raw material combination results can be determined according to a self-defining mode, and a plurality of raw material combination results which need to be subjected to experiments are determined according to actual requirements.

S202, sequencing a plurality of raw material combination results to obtain an experimental sequence, and performing experiments on the raw material combination results according to the experimental sequence to obtain a plurality of immunoreagents.

Based on the determined multiple raw material combination results of the to-be-developed immunoreagent, the multiple raw material combination results can be ordered as an experimental sequence, the arrangement is carried out according to the experimental sequence, and then experiments are carried out on the raw material combination results to obtain the multiple immunoreagent.

Alternatively, the sorting of the plurality of raw material combination results may be sorted in a priority manner, for example, a priority of a certain raw material from a specific vendor is higher, and the raw material combination results may be preferentially subjected to experiments, so that the experimental order of the raw material combination results is determined in such a manner that the specific raw material is derived from the specific vendor setting the priority; the experimental order of the raw material combination results may be set in such a manner that the priority of the raw material combination results corresponding to the combination having a large number of raw materials from the same vendor is highest, and the priority is set in accordance with the number of raw materials from the same vendor; if the priorities of the raw material combination results are the same in the priority mode, experimental tasks can be enumerated and custom generated, and the experimental sequence can be automatically generated in the enumeration mode or customized by a reagent developer.

The experiment performed on the results of the combination of the respective raw materials includes. The combined result of the raw materials is configured into corresponding immunoreagent according to a certain rule; the reagent development experiment platform can automatically perform experiments on the raw material combination results according to an experiment sequence to obtain a plurality of immunoreagents, wherein the immunoreagent is determined by the raw material combination results, namely, the immunoreagent corresponding to the raw material combination results can be obtained by configuring the raw material combination results.

S203, determining a target immunoreagent meeting preset conditions from a plurality of immunoreagents according to the performance test results of the immunoreagents.

After obtaining a plurality of immune reagents, performance verification is required to be carried out on each immune reagent, namely, performance test experiments are carried out on each immune reagent according to a preset experiment sequence to obtain performance test results, and then a target immune reagent meeting preset conditions is determined from the immune reagents according to the performance test results of each immune reagent. The criterion meeting the preset condition indicates that the performance verification is qualified, for example, the criterion that the performance verification is qualified may be an international criterion, or a criterion set under other criteria, etc., and may be determined according to the actual situation.

Performance test verification is carried out on each immunoreagent to obtain performance test results of each immunoreagent, and the performance verification can be carried out on the sensibility, the repeatability and the like of each immunoreagent.

Wherein, verifying the repeatability of each immunoreagent indicates the consistency of the results of the same tested object in detection under different conditions, wherein the different conditions comprise: principle or method of detection, result observer, test instrument, location, instrument usage status and time; verification of the sensitivity of an immunoreagent refers to the change in concentration of the substance to be measured in an experimental assay reaction.

According to the reagent development experimental method, a plurality of raw material combination results are determined according to raw materials required by the immune reagent to be developed, the raw material combination results are sequenced to serve as an experimental sequence, experiments are carried out on the raw material combination results according to the experimental sequence to obtain a plurality of immune reagents, and then a target immune reagent meeting preset conditions is determined from the immune reagents according to performance test results of the immune reagents. According to the method, a plurality of raw material combination results are determined through raw materials required by the immune reagent to be developed, then the raw material combination results are tested according to the test sequence of the raw material combination results, the test is automatically carried out according to the test sequence, and the performance test results of all the immune reagents are obtained, so that the target immune reagent is determined.

In one embodiment, as shown in fig. 3, a plurality of raw material combination results are determined according to raw materials required for an immunoreagent to be developed, comprising the steps of:

s301, dividing raw materials required by an immunoreagent to be developed according to the types of the raw materials to obtain a plurality of raw material sets, wherein each raw material set corresponds to one raw material type.

According to the types of raw materials of the immunological reagent to be developed, the raw materials required for the immunity to be developed are divided, and as various raw materials may exist in one or more suppliers, the raw materials of the same type of different suppliers can be divided into one set, and the raw materials of the immunological reagent to be developed are various, so that a plurality of raw material sets are obtained.

For example, if there are 4 raw materials for the immunological agent to be developed, these include: magnetic bead antibody, blocker, label antibody and biotin antibody, and each raw material is available from three suppliers, 4 raw material sets, namely, magnetic bead antibody material set, blocker material set, label antibody material set, biotin antibody material set, are obtained, and each raw material set comprises corresponding same raw materials from three different suppliers.

S302, raw materials in each raw material set are subjected to permutation and combination treatment, and a plurality of raw material combination results are obtained.

The raw materials in each raw material set obtained above are subjected to permutation and combination treatment to obtain a plurality of raw material combination results, and the raw materials of the immunological reagent to be developed, including magnetic bead antibodies, blocking agents, marker antibodies and biotin antibodies, are taken as examples. Each raw material has three suppliers, 4 raw materials of each supplier are cross-combined to obtain a plurality of raw material combination results, namely 4 raw material sets exist, and each raw material set has the same kind of raw materials corresponding to 3 different suppliers, thus obtaining 3 x 3 = 81 raw material combination results, namely

For example, the suppliers include three manufacturers of A, B and C, the raw materials in each raw material collection are arranged and combined, and the obtained multiple raw material combination results comprise a magnetic bead antibody of A manufacturer, a blocking agent of A manufacturer, a labeling antibody of A manufacturer, a biotin antibody of A manufacturer, a magnetic bead antibody of B manufacturer, a blocking agent of A manufacturer, a labeling antibody of A manufacturer, a biotin antibody of A manufacturer, a magnetic bead antibody of A manufacturer, a blocking agent of B manufacturer, a labeling antibody of A manufacturer, a biotin antibody of A manufacturer, a magnetic bead antibody of B manufacturer, a blocking agent of B manufacturer, a labeling antibody of A manufacturer, a biotin antibody of A manufacturer, a magnetic bead antibody of C manufacturer, a blocking agent of B manufacturer, a labeling antibody of A manufacturer, a biotin antibody of B manufacturer, etc.

The raw materials in each raw material set are arranged and combined, if 10 suppliers exist for each raw material, then there are 10000 possible raw material combination results in 10 x 10; it should be noted that, if all possible raw material combination results are tested, the test cost is high, and in order to save the cost, a plurality of raw material combination results may be selected from all the raw material combination results for the test.

The method for selecting a plurality of raw material combination results from all possible raw material combination results is that the plurality of raw material combination results are selected from all possible raw material combination results according to a self-defined mode, wherein the self-defined mode can be to fix which supplier the at least one raw material comes from, and the unconditional raw material combination mode is removed; multiple raw material combination modes can be selected from all possible raw material combination results randomly. The custom mode can be set according to the actual situation.

Alternatively, a plurality of raw material combination results conforming to a preset rule may be selected from all possible raw material combination results according to actual conditions for experiments. Alternatively, the preset rule may be that a certain raw material is fixed from a certain vendor, or that two kinds of raw materials are from the same vendor or the same fixed vendor, and in the embodiment of the application, the preset rule is not limited, and may be set according to practical situations.

According to the reagent development experimental method, the raw materials required by the immune reagent to be developed are divided according to the types of the raw materials, so that a plurality of raw material sets are obtained, each raw material set corresponds to one raw material type, and the raw materials in each raw material set are subjected to permutation and combination treatment, so that a plurality of raw material combination results are obtained. In the method, raw materials are divided into raw material sets according to the types of the raw materials required by the immune reagent to be developed, and the raw materials in the raw material sets are arranged and combined to obtain a plurality of raw material combination results, so that the efficiency of obtaining a plurality of immune reagents is further improved, the time in the reagent development process can be shortened, and the reagent development efficiency is improved.

In one embodiment, as shown in fig. 4, the experiment is performed on each raw material combination result to obtain a plurality of immunoreagents, including the steps of:

s401, acquiring a fixed reagent operation flow combination and a fixed reagent parameter combination.

Optionally, determining a fixed combination of reagent protocols and corresponding combinations of reagent parameters according to the type of immunoreagent to be developed; for example, a reagent operation flow combination and a corresponding parameter combination corresponding to the type of the immune reagent to be developed are obtained from a database, and the reagent operation flow combination and the corresponding parameter combination are determined to be a fixed reagent operation flow combination and a fixed reagent parameter combination; there are a plurality of operation flow combinations and parameter combinations of the immunological reagent to be developed, one reagent operation flow combination and reagent parameter combination is selected from the operation flow combinations according to a preset rule, and the preset rule can be a rule that the priority is higher according to the shorter time, so that the reagent operation flow combination and the reagent parameter combination with the highest priority are determined as a fixed reagent operation flow combination and a fixed reagent parameter combination.

For example, the reagent operation flow of the immunological reagent to be developed includes the flows of adding raw materials of the immunological reagent to be developed, magnetic separation, shaking and the like, and the corresponding reagent parameters include how much amount of raw materials of the immunological reagent to be developed is added, the number of times of magnetic separation, the time and the number of times of shaking and the like, and firstly, the reagent operation flow combination and the reagent parameter combination which are least time-consuming among the reagent operation flow of the immunological reagent to be developed and the corresponding actual parameters are determined as the fixed reagent operation flow combination and the fixed reagent parameter combination.

S402, aiming at any raw material combination result, based on the fixed reagent operation flow combination and the fixed reagent parameter combination, carrying out experiments on the raw material combination result to obtain an immunoreagent corresponding to the raw material combination result.

Based on the obtained multiple raw material combination results of the immunoreagent to be developed, aiming at any one of the raw material combination results and the fixed reagent operation flow combination, carrying out configuration experiments on the immunoreagent to be developed by using the fixed reagent parameter combination, and obtaining the immunoreagent corresponding to the raw material combination results.

For example, if the result of the combination of the raw materials is a magnetic bead antibody of a first manufacturer, a blocker of a first manufacturer, a marker antibody of a first manufacturer, and a biotin antibody of a first manufacturer, the operation flow combination of the fixing reagent is to add the raw materials of the immunological reagent to be developed, then perform shaking operation, then perform magnetic separation operation, the parameter combination of the fixing reagent includes adding 50 microliters of each raw material respectively, then perform shaking operation for 3 seconds once, and then perform magnetic separation operation for 3 times; and carrying out configuration experiments on the raw material combination results based on the conditions to obtain the immunoreagent corresponding to the raw material combination results.

The immune reagent is tested by fixing reagent operation flow combination and fixing reagent parameter combination on raw material combination results, one immune reagent corresponds to one raw material combination, the corresponding reagent operation flow combination and the reagent parameter combination, namely the immune reagent corresponds to one reagent formula and a reaction system, wherein the reagent formula comprises raw material types, content, proportion and preparation process, and the reaction system comprises operation flow and test parameters for preparing the immune reagent.

Optionally, aiming at any raw material combination result, and the fixed reagent operation flow combination and the fixed reagent parameter combination, obtaining a plurality of groups of experimental combinations, namely, the experimental combinations comprise one raw material combination result, and the fixed reagent operation flow combination and the fixed reagent parameter combination; according to a preset certain rule, removing experimental combinations which do not accord with the preset rule, and configuring the experimental combinations which accord with the conditions to obtain immunoreagent corresponding to a plurality of raw material combination results. The final immunoreagent corresponding to the combined result of the raw materials is obtained by removing immunoreagent corresponding to the experimental combination which does not meet the preset rule.

The preset rule may be that the content of a certain raw material corresponding to a certain vendor does not meet the preset liquid amount, for example, if the raw material a required for developing the immunoreagent is a vendor of the first, the liquid amount of the raw material a is 40 ml, and the preset rule is that the raw material a of the vendor of the first cannot be lower than 50 ml when the experiment is performed, the raw material a belonging to the vendor of the first and the raw material combination result corresponding to the liquid amount of 40 ml is removed, that is, the raw material a belonging to the vendor of the first in the experiment combination and the experiment combination corresponding to the liquid amount of lower than 50 ml are removed.

According to the reagent development experimental method, the fixed reagent operation flow combination and the fixed reagent parameter combination are obtained, and the raw material combination result is subjected to experiments based on the fixed reagent operation flow combination and the fixed reagent parameter combination aiming at any raw material combination result, so that the immunoreagent corresponding to the raw material combination result is obtained. According to the method, through the operation flow of the fixed reagent and the parameter combination of the fixed reagent, experiments are respectively carried out on the combination results of the raw materials, so that the immunoreagent corresponding to the combination results of the raw materials is obtained, the efficiency of obtaining a plurality of immunoreagents is further improved, the time in the process of developing the reagent can be shortened, and the reagent development efficiency is improved.

In one embodiment, as shown in FIG. 5, obtaining a set of immobilized reagent operational flow combinations and immobilized reagent parameter combinations includes:

S501, according to the operation flow needed by the immune reagent to be developed, a plurality of candidate reagent operation flow combinations are obtained, and according to the plurality of candidate reagent operation flow combinations, a fixed reagent operation flow combination is determined.

Determining an operation flow needing to perform experiments according to the requirements of an immune reagent to be developed, wherein the operation flow can comprise sample adding, diluent adding, mixing, raw material adding, shaking, magnetic separation, incubation, enzymatic test and direct luminescence test, shaking comprises dilution shaking, sample shaking, enzymatic shaking and the like, magnetic separation comprises single magnetic separation and large magnetic separation, incubation comprises sample incubation and enzymatic incubation, and enzymatic test comprises enzymatic 1 test and enzymatic 2 test; the sequence and the repetition number of the operation flow can be freely configured, and the operation flow is not limited.

For example: the flow of chemiluminescent immunoassay reagent may include adding sample-adding diluent-mixing-adding reagent component M-adding reagent component R1-adding reagent component R2-shaking-incubating-magnetic separation-priming-shaking-incubating-detecting, or adding sample-adding reagent component M-adding reagent component R1-adding reagent component R2-adding reagent component R3-shaking-incubating-magnetic separation-priming-shaking-incubating-detecting, etc.

The different flow sequences are one reagent flow process combination, and thus there are hundreds to thousands of possible flow process combinations, and thus, depending on the flow of operations required for the immunological reagent to be developed, a plurality of reagent flow process combinations can be obtained, which are determined as a plurality of candidate reagent flow process combinations.

Alternatively, the method of obtaining the plurality of candidate reagent operation flows may be to arrange and combine operation flows required by the reagent to be developed, so as to obtain the plurality of candidate reagent operation flows. For example, if there are 10 kinds of operation procedures required for developing the immunological reagent, the operation procedures in 10 kinds of operation procedures may be arranged and combined to obtain a plurality of candidate reagent operation procedure combinations, wherein the operation procedures in the plurality of candidate reagent operation procedure combinations are all different in order, and the arrangement and combination may be that if there are N kinds of operation procedures for developing the immunological reagent, the operation procedures are arranged and combined according to the followingThe number of candidate reagent flow-sheet combinations is counted.

Determining a fixed reagent operation flow combination based on the obtained plurality of reagent operation flow combinations, alternatively, determining a fixed reagent operation flow combination from a plurality of candidate reagent operation flow combinations under preset conditions; for example, selecting a candidate reagent operation flow combination meeting a preset condition from a plurality of candidate reagent operation flow, and then randomly selecting one candidate reagent operation flow combination from the candidate reagent operation flow combinations meeting the preset condition to be determined as a fixed reagent operation flow combination; the preset condition may be a preset evaluation model, that is, a plurality of candidate reagent operation flows are evaluated by using the preset evaluation model, and a candidate reagent operation flow combination satisfying the evaluation model is determined.

The method for determining the fixed reagent operation flow combination may also be that the fixed reagent operation flow combination is determined according to a preset selection mechanism model, specifically, a plurality of candidate reagent operation flow combinations are input into the selection mechanism model, and an analysis of the selection mechanism model is performed to obtain the fixed reagent operation flow combination.

The method of determining the immobilized reagent workflow combination may be to randomly select one candidate reagent workflow combination from a plurality of candidate reagent workflow combinations as the immobilized reagent workflow combination.

S502, acquiring a plurality of candidate reagent parameter combinations according to reagent parameters required in the operation flow, and determining fixed reagent parameter combinations according to the plurality of candidate reagent parameter combinations.

According to the required operation flow of the immune reagent to be developed, the reagent parameters required in the operation flow of the immune reagent to be developed can be determined, including: the method comprises the steps of adding a sample liquid amount into a reaction cup, adding a dilution liquid amount into the reaction cup, adding a reagent name into the reaction cup, corresponding bottle numbers and liquid amounts, carrying out dilution and mixing by using a mixing structure, carrying out sample shaking by using a shaking structure, carrying out sample incubation time by using an incubation plate, carrying out magnetic separation by using a single magnetic separation assembly, carrying out magnetic separation by using a magnetic separation plate, carrying out sample shaking by using an enzymatic shaking structure, carrying out sample incubation time by using an enzymatic incubation plate, carrying out substrate type, substrate liquid amount and test time by using an enzymatic method 1, carrying out substrate type, substrate liquid amount and test time by using an enzymatic method 2, and substrate type, substrate liquid amount and test time by using a direct luminescence method.

Various candidate reagent parameter combinations may be formed according to the ratio parameters of the raw materials of the immunological reagent to be developed, for example, 50 microliters of the raw material M of the immunological reagent to be developed, 100 microliters of the raw material R1 of the immunological reagent to be developed, 50 microliters of the raw material R2 of the immunological reagent to be developed, 50 microliters of the raw material M of the immunological reagent to be developed, 50 microliters of the raw material R1 of the immunological reagent to be developed, 50 microliters of the raw material R2 of the immunological reagent to be developed, and the like.

The multiple candidate reagent parameter combinations are formed according to parameters of the process execution, optionally, the multiple candidate reagent parameter combinations are formed with different interval time between adjacent processes or execution times of the processes, for example, 3 seconds or 4 seconds are evenly distributed, 5 minutes or 10 minutes are incubated, 3 times or 4 times are magnetically separated, and the like.

And generating a plurality of candidate reagent parameter combinations according to the proportion parameters of the raw materials of the reagent to be immunized, the execution time of the operation flow, the execution times of the operation flow and the like.

The manner of determining the immobilized reagent parameter combination according to the plurality of candidate reagent parameter combinations may be the same as the manner of determining the immobilized reagent operation flow combination according to the plurality of candidate reagent operation flow combinations described above, and will not be described herein.

It should be noted that, if the types of the to-be-developed immunoreagent are different, the operation flow and reagent parameters corresponding to the to-be-developed immunoreagent may be different, for example, if the to-be-developed immunoreagent is a fluorescent reagent card, the reagent parameters may include a test sampling position (test tube rack/emergency department), a test number, a sample type, an incubation type, a first test time and test time interval, a sample concentration, and the like.

According to the reagent development experimental method, a plurality of candidate reagent operation flow combinations are obtained according to the operation flow required by the immune reagent to be developed, and the fixed reagent operation flow combinations are determined according to the plurality of candidate reagent operation flow combinations; according to the reagent parameters required in the operation flow, a plurality of candidate reagent parameter combinations are obtained, and a fixed reagent parameter combination is determined according to the plurality of candidate reagent parameter combinations. According to the method, the fixed reagent operation flow combination is determined in the plurality of candidate reagent operation flow combinations, and the fixed reagent parameter combination is determined in the plurality of candidate reagent parameter combinations, so that the execution mode of the immune reagent to be developed can be further generated based on the fixed reagent operation flow combination and the fixed reagent parameter combination, the efficiency of obtaining a plurality of immune reagents is improved, the time in the reagent development process can be shortened, and the reagent development efficiency is improved.

In one embodiment, as shown in FIG. 6, the obtaining of a plurality of candidate reagent operational flow combinations according to the operational flow required for the immunoreagent to be developed, comprises:

s601, the execution times of the repeatedly executable operation flows in the operation flows are obtained.

Analyzing the type of the immune reagent to be developed, and determining the number of times that the operation flow in the development process of the immune reagent to be developed needs to be repeatedly executed; the times of the operation flows which are needed to be repeatedly executed and correspond to the operation flows can also be obtained from the database; in practical application, the number of times that the operation flow needs to be repeatedly executed in the development process of the immune reagent to be developed can be determined according to the practical operation requirement.

For example, the raw materials added with the immunological reagent to be developed in the operation flow are only needed to be executed once, and the times of shaking and magnetic separation can be one or more times, so that the steps can be repeatedly executed.

S602, according to the execution times of the repeatedly executable operation flows in the operation flows, arranging and combining the execution sequences of the operation flows to obtain a plurality of candidate reagent operation flow combinations.

Optionally, if the operation flows have the same operation flow, that is, there is an operation flow that needs to be repeatedly executed, arranging and combining the execution sequences of the operation flows according to the execution times of the operation flows that can be repeatedly executed in each operation flow, so as to obtain a plurality of candidate reagent operation flow combinations; optionally, if there are N operation flows and one operation flow of the N operation flows is repeatedly executed M times, according toThe number of candidate reagent flow-sheet combinations is counted.

If there are two operation flows that need to be repeatedly executed, one operation flow is repeatedly executed M times, and the other operation flow is repeatedly executed T times, according to the execution times of the operation flows that can be repeatedly executed in each operation flow, the execution sequences of each operation flow are arranged and combined to obtain a plurality of candidate reagent operation flow combinations, optionally according to the operation flow combination of the candidate reagentThe number of candidate reagent flow-sheet combinations is counted.

According to the reagent development experimental method, the execution times of the operation flows which can be repeatedly executed in each operation flow are obtained, and the execution sequences of the operation flows are arranged and combined according to the execution times of the operation flows which can be repeatedly executed in each operation flow, so that a plurality of candidate reagent operation flow combinations are obtained. The method considers the execution times of repeatedly executable operation flows in each operation flow, can further accurately obtain a plurality of immunoreagents, has no repeatability, and improves the efficiency of the immunoreagent to be developed in the development process.

In one embodiment, obtaining a plurality of candidate reagent parameter combinations based on reagent parameters required in an operational flow includes: and arranging, combining and setting parameter values of reagent parameters required in each operation flow to obtain a plurality of candidate reagent parameter combinations.

One operation flow may correspond to the parameter values of multiple reagent parameters, so that the parameter values of the reagent parameters required in each operation flow can be arranged and combined to obtain multiple candidate reagent parameter combinations, for example, if 11 operation flows of the immune reagent to be developed exist and two parameter values of the reagent parameters of each operation flow exist, the parameter values of the reagent parameters in each operation flow are arranged and combined; at this time, the number of candidate reagent parameter combinations is 2≡11, i.e. 2048.

In one embodiment, the performance test includes at least one of a plateau test, a project experiment, a curve fit, a project assessment, and a stability test.

The performance test comprises a platform period test, a project experiment, curve fitting, project evaluation and stability test; namely, the platform phase test, the project experiment, the curve fitting, the project evaluation or the stability test can be carried out on each immunoreagent, and in practical application, the type of performance test on each immunoreagent can be determined according to practical requirements.

And the whole process of the development of the reagent to be immune developed comprises a plurality of main processes of platform period test, project experiment, curve fitting, project evaluation, stability test and the like.

The platform phase test is mainly used for testing the platform phase of a reagent luminescence curve, the project test is mainly used for testing the repeatability of test points with different concentrations of related combinations (raw materials, processes and parameters) to confirm the authenticity of test results, the curve fitting is mainly used for fitting the test results of reagents to form the reagent luminescence curve, the project evaluation is mainly used for verifying the reliability of fitting results of non-test points of the luminescence curve obtained by fitting, and the stability test is mainly used for verifying whether the test results of available reagent combinations obtained by a previous experiment after time change conform to the luminescence curve so as to determine the stability time of the test results.

In practical application, based on the obtained raw material combination results, each raw material combination result can be subjected to experiments on a reagent development experiment platform according to a preset experiment sequence to obtain a plurality of immune reagents, and performance tests are carried out on the corresponding obtained immune reagents to obtain performance test results. And the method can be regarded as that a plurality of raw material combination results are subjected to performance test experiments on a reagent development experiment platform according to a preset experiment sequence, and performance test results are obtained.

Firstly, carrying out a platform phase test on the immunoreagent corresponding to each raw material combination result according to a preset experimental sequence, determining the reaction platform phase of each raw material combination result, obtaining a platform phase test result, and if the raw material combination result which has the platform phase and meets other related requirements in the platform phase test result is determined as the raw material combination result passing the platform phase test.

And determining an experimental sequence of the immunoreagent corresponding to the raw material combination result passing the platform period test according to a certain rule, carrying out project experiments to obtain project experiment results, determining the repeatability and reliability of each raw material combination result according to a detection result curve and a sample result statistic value in the project experiment results, and determining the raw material combination result which has better repeatability and reliability and meets other related requirements as the raw material combination result passing the project experiments, wherein the better repeatability and reliability can be the error that the immunoreagent corresponding to the raw material combination result passing the preset experiment times is in a preset reliability range, and no larger deviation exists.

According to the method, an experimental sequence of immunoreagents corresponding to raw material combination results of project experiments is determined according to a certain rule, curve fitting is carried out, verification experiments are carried out on experimental points of other non-project experiments on a fitted curve to evaluate the correctness of the curve fitting results, therefore, verification experiments are carried out on experimental points of the non-project experiments of the raw material combination results corresponding to the fitted curve, project evaluation experiments are carried out on the raw material combination results at the stage, whether the fitted curve corresponding to the raw material combination results accords with the fitted linear relation is judged, and raw material combinations corresponding to immunoreagents in preset deviation are determined to be the raw material combination results passing the project evaluation experiments.

And determining an experimental sequence of the immunoreagent corresponding to the raw material combination result through the project experiment according to a certain rule, and performing a stability test, wherein the stability test is to test the raw material combination again after a preset time length to obtain a test result so as to judge whether the test result accords with the fitting curve, and determining the raw material combination result which accords with the fitting curve as the raw material combination result which passes the stability test, so that the immunoreagent corresponding to the raw material combination result which accords with the reliability test can be determined as the target immunoreagent.

Alternatively, the assay device is an immunofluorescence reaction apparatus.

It should be noted that, the performance test experiment is performed on each immunoreagent, and each immunoreagent may pass through at least one of the platform phase test, the project experiment, the curve fitting, the project evaluation and the stability test, and the test sequence of each performance test is not limited, and in practical application, the type of performance test to be performed on each immunoreagent is determined according to the actual requirement.

In one embodiment, as shown in FIG. 7, the embodiment includes the following steps;

S701, determining raw materials required by the development of the to-be-developed immune reagent according to the reagent type of the to-be-developed immune reagent.

S702, obtaining manufacturers corresponding to the raw materials, and arranging and combining the raw materials according to the raw materials corresponding to different manufacturers of the raw materials to obtain a plurality of raw material combination results in the to-be-developed immunoreagent; each raw material combination result includes different kinds of raw materials, and one of the various kinds of raw materials exists.

S703, determining the operation flow and the corresponding reagent parameters when the immunological reagent to be developed is developed according to the type of the immunological reagent to be developed and the raw materials of the immunological reagent to be developed.

S704, determining a fixed operation flow combination mode of the immune reagent to be developed according to the operation flow of the immune reagent to be developed during development, and determining a fixed reagent parameter combination mode of the immune reagent to be developed according to the reagent parameters of the immune reagent to be developed.

And S705, sequencing a plurality of raw material combination results to obtain an experimental sequence, and according to the experimental sequence, carrying out experiments on any raw material combination result according to a fixed operation flow combination mode and a fixed reagent parameter combination mode of the immune reagent to be developed, so as to obtain the immune reagent corresponding to the raw material combination result.

S706, performing performance test experiments on the immunoreagent according to a preset experiment sequence to obtain a test result;

the performance test includes at least one of a plateau test, a project experiment, a curve fit, a project assessment, and a stability test.

S707, determining the target immunoreagent meeting the preset conditions from the immunoreagents according to the performance test results of the immunoreagents.

The implementation principle and technical effects of each step in the reagent development experimental method provided in this embodiment are similar to those in the previous embodiments of each reagent development experimental method, and are not described here again.

It should be understood that, although the steps in the flowcharts related to the embodiments described above are sequentially shown as indicated by arrows, these steps are not necessarily sequentially performed in the order indicated by the arrows. The steps are not strictly limited to the order of execution unless explicitly recited herein, and the steps may be executed in other orders. Moreover, at least some of the steps in the flowcharts described in the above embodiments may include a plurality of steps or a plurality of stages, which are not necessarily performed at the same time, but may be performed at different times, and the order of the steps or stages is not necessarily performed sequentially, but may be performed alternately or alternately with at least some of the other steps or stages.

Based on the same inventive concept, the embodiment of the application also provides a reagent development experimental device for realizing the reagent development experimental method. The implementation of the solution provided by the device is similar to that described in the above method, so the specific limitations in the embodiments of the one or more reagent development experimental devices provided below can be referred to above for limitations of the reagent development experimental method, and are not repeated here.

In one embodiment, as shown in fig. 8, a reagent development experimental apparatus 800 is provided, comprising: a combination determination module 801, a test module 802, and a reagent determination module 803, wherein:

a combination determining module 801, configured to determine a plurality of raw material combination results according to raw materials required by an immunoreagent to be developed;

The test module 802 is configured to sort the multiple raw material combination results as an experimental sequence, and perform an experiment on each raw material combination result according to the experimental sequence to obtain multiple immunoreagents;

The reagent determining module 803 is configured to determine a target immunoreagent meeting a preset condition from a plurality of immunoreagents according to a performance test result of each immunoreagent.

In one embodiment, the combination determination module 801 includes:

a raw material set determining unit for dividing raw materials required by the immunoreagent to be developed according to the types of the raw materials to obtain a plurality of raw material sets, wherein each raw material set corresponds to one raw material type;

And the combination determining unit is used for carrying out permutation and combination treatment on the raw materials in each raw material set to obtain a plurality of raw material combination results.

In one embodiment, the test module 802 includes:

The combination acquisition unit is used for acquiring a fixed reagent operation flow combination and a fixed reagent parameter combination;

The experimental unit is used for carrying out experiments on the raw material combination results based on the fixed reagent operation flow combination and the fixed reagent parameter combination aiming at any raw material combination result to obtain the immunoreagent corresponding to the raw material combination result.

In one embodiment, the combination obtaining unit includes:

A flow combination obtaining unit, configured to obtain a plurality of candidate reagent operation flow combinations according to an operation flow required by an immune reagent to be developed, and determine a fixed reagent operation flow combination according to the plurality of candidate reagent operation flow combinations;

And the parameter combination acquisition unit is used for acquiring a plurality of candidate reagent parameter combinations according to reagent parameters required in the operation flow and determining fixed reagent parameter combinations according to the plurality of candidate reagent parameter combinations.

In one embodiment, the flow combination acquisition unit includes:

the acquisition subunit is used for acquiring the execution times of the repeatedly executable operation flows in the operation flows;

The flow combination determining subunit is configured to arrange, combine and set the execution sequence of each operation flow according to the execution times of the repeatedly executable operation flow in each operation flow, so as to obtain a plurality of candidate reagent operation flow combinations.

In one embodiment, the parameter combination obtaining unit includes:

And the parameter combination determining subunit is used for arranging, combining and setting the parameter values of the reagent parameters required in each operation flow to obtain a plurality of candidate reagent parameter combinations.

The various modules in the reagent development experimental device described above may be implemented in whole or in part by software, hardware, and combinations thereof. The above modules may be embedded in hardware or may be independent of a processor in the computer device, or may be stored in software in a memory in the computer device, so that the processor may call and execute operations corresponding to the above modules.

In one embodiment, a computer device is provided, which may be a terminal, and the internal structure thereof may be as shown in fig. 9. The computer device includes a processor, a memory, a communication interface, a display screen, and an input device connected by a system bus. Wherein the processor of the computer device is configured to provide computing and control capabilities. The memory of the computer device includes a non-volatile storage medium and an internal memory. The non-volatile storage medium stores an operating system and a computer program. The internal memory provides an environment for the operation of the operating system and computer programs in the non-volatile storage media. The communication interface of the computer device is used for carrying out wired or wireless communication with an external terminal, and the wireless mode can be realized through WIFI, a mobile cellular network, NFC (near field communication) or other technologies. The computer program is executed by the processor to implement a reagent development experimental method. The display screen of the computer equipment can be a liquid crystal display screen or an electronic ink display screen, and the input device of the computer equipment can be a touch layer covered on the display screen, can also be keys, a track ball or a touch pad arranged on the shell of the computer equipment, and can also be an external keyboard, a touch pad or a mouse and the like.

It will be appreciated by persons skilled in the art that the architecture shown in fig. 9 is merely a block diagram of some of the architecture relevant to the present inventive arrangements and is not limiting as to the computer device to which the present inventive arrangements are applicable, and that a particular computer device may include more or fewer components than shown, or may combine some of the components, or have a different arrangement of components.

In one embodiment, there is also provided a computer device comprising a memory and a processor, the memory storing a computer program, the processor implementing the following steps when executing the computer program:

In one embodiment, the processor when executing the computer program further performs the steps of:

The implementation principle and technical effect of each step implemented by the processor in this embodiment are similar to those of the above reagent development experimental method, and are not described herein.

In one embodiment, a computer readable storage medium is provided having stored thereon a computer program which when executed by a processor performs the steps of:

In one embodiment, the computer program when executed by the processor further performs the steps of:

The steps of the computer program implemented when executed by the processor in this embodiment realize the principle and technical effects similar to those of the above-described reagent development experimental method, and will not be described here again.

In one embodiment, a computer program product is provided comprising a computer program which, when executed by a processor, performs the steps of:

The user information (including but not limited to user equipment information, user personal information, etc.) and the data (including but not limited to data for analysis, stored data, presented data, etc.) related to the present application are information and data authorized by the user or sufficiently authorized by each party.

Those skilled in the art will appreciate that implementing all or part of the above described methods may be accomplished by way of a computer program stored on a non-transitory computer readable storage medium, which when executed, may comprise the steps of the embodiments of the methods described above. Any reference to memory, database, or other medium used in embodiments provided herein may include at least one of non-volatile and volatile memory. The nonvolatile Memory may include Read-Only Memory (ROM), magnetic tape, floppy disk, flash Memory, optical Memory, high density embedded nonvolatile Memory, resistive random access Memory (ReRAM), magneto-resistive random access Memory (Magnetoresistive Random Access Memory, MRAM), ferroelectric Memory (Ferroelectric Random Access Memory, FRAM), phase change Memory (PHASE CHANGE Memory, PCM), graphene Memory, and the like. Volatile memory can include random access memory (Random Access Memory, RAM) or external cache memory, and the like. By way of illustration, and not limitation, RAM can be in various forms such as static random access memory (Static Random Access Memory, SRAM) or dynamic random access memory (Dynamic Random Access Memory, DRAM), etc. The databases referred to in the embodiments provided herein may include at least one of a relational database and a non-relational database. The non-relational database may include, but is not limited to, a blockchain-based distributed database, and the like. The processor referred to in the embodiments provided in the present application may be a general-purpose processor, a central processing unit, a graphics processor, a digital signal processor, a programmable logic unit, a data processing logic unit based on quantum computing, or the like, but is not limited thereto.

The technical features of the above embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The foregoing examples illustrate only a few embodiments of the application and are described in detail herein without thereby limiting the scope of the application. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the application, which are all within the scope of the application. Accordingly, the scope of the application should be assessed as that of the appended claims.

Claims

1. A method of reagent development experiments, the method comprising:

the raw materials in each raw material set are subjected to permutation and combination treatment to obtain a plurality of raw material combination results;

sequencing the combined results of the raw materials as an experimental sequence, and acquiring the execution times of the repeatedly executable operation flow in the operation flow required by the immunoreagent to be developed according to the experimental sequence;

according to the execution times of the repeatedly executable operation flows in the operation flows, arranging and combining the execution sequences of the operation flows to obtain a plurality of candidate reagent operation flow combinations;

Determining a fixed reagent operational flow combination from the plurality of candidate reagent operational flow combinations;

arranging and combining parameter values of reagent parameters required in each operation flow to obtain a plurality of candidate reagent parameter combinations, and determining fixed reagent parameter combinations according to the plurality of candidate reagent parameter combinations;

For any raw material combination result, carrying out experiments on the raw material combination result based on the fixed reagent operation flow combination and the fixed reagent parameter combination to obtain an immunoreagent corresponding to the raw material combination result;

and determining the target immunoreagent meeting the preset condition from a plurality of immunoreagents according to the performance test result of each immunoreagent.

2. The method of claim 1, wherein the performance test comprises at least one of a plateau test, a project experiment, a curve fit, a project assessment, and a stability test.

3. A reagent development experimental device, characterized in that the device comprises:

The combination determining module is used for dividing raw materials required by the immunoreagent to be developed according to the types of the raw materials to obtain a plurality of raw material sets, wherein each raw material set corresponds to one raw material type; the raw materials in each raw material set are subjected to permutation and combination treatment to obtain a plurality of raw material combination results;

The test module is used for sequencing the combined results of the raw materials to obtain an experimental sequence, and acquiring the execution times of the repeatedly executable operation flow in the operation flow required by the immune reagent to be developed according to the experimental sequence; according to the execution times of the repeatedly executable operation flows in the operation flows, arranging and combining the execution sequences of the operation flows to obtain a plurality of candidate reagent operation flow combinations; determining a fixed reagent operational flow combination from the plurality of candidate reagent operational flow combinations; arranging and combining parameter values of reagent parameters required in each operation flow to obtain a plurality of candidate reagent parameter combinations, and determining fixed reagent parameter combinations according to the plurality of candidate reagent parameter combinations; for any raw material combination result, carrying out experiments on the raw material combination result based on the fixed reagent operation flow combination and the fixed reagent parameter combination to obtain an immunoreagent corresponding to the raw material combination result;

and the reagent determining module is used for determining a target immunoreagent meeting preset conditions from a plurality of immunoreagents according to the performance test result of each immunoreagent.

4. A computer device comprising a memory and a processor, the memory storing a computer program, characterized in that the processor implements the steps of the method of any one of claims 1 to 2 when the computer program is executed.

5. A computer readable storage medium, on which a computer program is stored, characterized in that the computer program, when being executed by a processor, implements the steps of the method of any of claims 1 to 2.