Method and device for expanding linear range of detection reagent

Abstract

The invention relates to a method and a device for expanding the linear range of a detection reagent. The method comprises the following steps: applying to a finished product sample analyzer and an immunodetection kit, obtaining a first detection mode, detecting a sample according to the first detection mode to obtain first calculation information, constructing a second detection mode according to the first detection mode, and detecting the sample according to the second detection mode to obtain second calculation information, the first calculation information is adopted to calculate and obtain concentration data in the linear range of the detection reagent, the first calculation information and the second calculation information are adopted to jointly calculate and obtain concentration data outside the linear range of the detection reagent, and the ratios of the dosage of the sample to the dosage of the reagent in the first detection mode and the second detection mode are different. According to the scheme provided by the invention, on the premise of not changing reagent components, concentration data outside a linear range can be quickly and accurately obtained through result operation, and the accuracy and efficiency of sample detection are improved.

Description

Technical Field

[0001] This application relates to the technical field of sample detection, and particularly to a method and device for expanding the linear range of detection reagents. Background Art

[0002] Immunoassay technology refers to immunoassay of samples through antigens or antibodies. The reaction curve generated during the immunoassay process is expected to be in a linear reaction shape. When using a corresponding kit to perform immunoassay on a sample, the linear reaction shape in the immunoassay is the linear range of the kit, and this linear range belongs to a fixed interval value.

[0003] Since the kit cannot accurately detect high-concentration samples beyond the above linear range, relevant technicians often change the reagent components of the kit to increase the linear range of the kit to meet the needs of high-concentration sample detection. However, this direct way of changing reagent components is not only limited by the concentration of the detected sample, but also requires repeated changes of reagent components in the case of detecting a large number of samples, resulting in low detection efficiency. Summary of the Invention

[0004] This application provides a method, a device, a finished sample analyzer, and a storage medium for expanding the linear range of detection reagents to solve or partially solve the problems that it is difficult to detect high-concentration samples and the detection efficiency is low in related technologies.

[0005] The first aspect of this application provides a method for expanding the linear range of detection reagents, which is applied to a finished sample analyzer and an immunoassay kit, and includes:

[0006] Obtain a first detection method, and detect a sample according to the first detection method to obtain first calculation information;

[0007] Construct a second detection method according to the first detection method, and detect a sample according to the second detection method to obtain second calculation information;

[0008] Calculate the concentration data within the linear range of the detection reagent by using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together;

[0009] Wherein, the ratio of the sample and reagent dosages in the first detection method and the second detection method is different.

[0010] In an embodiment, the constructing the second detection method according to the first detection method includes:

[0011] The first detection method is preset according to the product instruction manual of the immunoassay kit;

[0012] Increase the second sample volume in the second detection method to N times the first sample volume in the first detection method, and reduce the second reagent volume in the second detection method to 1 / N times the first reagent volume in the first detection method, where 2 ≤ N ≤ 100;

[0013] Construct the second detection method using the second sample volume and the second reagent volume.

[0014] In one embodiment, the step of calculating the concentration data within the linear range of the detection reagent using the first calculation information includes:

[0015] Calculate using the signal values in the first calculation information and the second calculation information to obtain a signal ratio;

[0016] When the signal ratio is less than or equal to the detection cut-off value, determine that the sample to be detected is within the linear range, and calculate the concentration data within the linear range of the detection reagent using the first calculation information;

[0017] Preferably, substitute the signal value in the first calculation information into the calibration curve of the immunoassay kit to obtain the concentration data of the sample to be detected within the linear range.

[0018] In one embodiment, the step of jointly calculating the concentration data outside the linear range of the detection reagent using the first calculation information and the second calculation information includes:

[0019] Calculate using the signal values in the first calculation information and the second calculation information to obtain a signal ratio;

[0020] When the signal ratio is greater than the detection cut-off value, determine that the sample to be detected is outside the linear range, and jointly calculate the concentration data outside the linear range of the detection reagent using the first calculation information and the second calculation information;

[0021] Preferably, substitute the signal ratio into the standard curve of the concentration-signal ratio relationship to obtain the concentration data of the sample to be detected outside the linear range.

[0022] In one embodiment, the method further includes:

[0023] Prepare several groups of simulated samples with gradient concentrations using the pure product of the target molecule to be detected in the immunoassay kit. Some of the simulated samples have concentrations within the linear range of the kit, and some of the simulated samples have concentrations greater than the upper limit of the linear range concentration of the kit;

[0024] The simulation sample is detected by using the first detection method and the second detection method respectively to obtain a first simulation signal value and a second simulation signal value of the simulation sample, and a first detection curve and a second detection curve are generated based on the sample concentration and the simulation signal value;

[0025] The ratio between the first simulation signal value and the second simulation signal value at the same sample concentration is determined as the simulation signal ratio;

[0026] A mapping relationship curve between the sample concentration and the simulation signal ratio is constructed, and the mapping relationship curve is used as the standard curve of the concentration and signal ratio relationship.

[0027] In one embodiment, the method further includes:

[0028] Determine a detection cut-off value according to the mapping relationship curve between the sample concentration and the simulation signal ratio;

[0029] Wherein, the detection cut-off value is the simulation signal ratio obtained by testing the simulation sample with a concentration of (1±5%) at the upper limit of the linear range of the kit by using the first detection method and the second detection method.

[0030] In one embodiment, the method further includes:

[0031] When the detection cut-off value is less than the preset ratio, shift the first detection curve to the right and shift the second detection curve to the left simultaneously to make the simulation signal ratio equal to the preset ratio, and determine the simulation signal ratio as the detection cut-off value;

[0032] Or, when the detection cut-off value is greater than the preset ratio, shift the first detection curve to the left and shift the second detection curve to the right simultaneously to make the simulation signal ratio equal to the preset ratio, and determine the simulation signal ratio as the detection cut-off value.

[0033] The second aspect of the present application provides a device for expanding the linear range of a detection reagent, including:

[0034] A detection method acquisition module, configured to acquire a first detection method and construct a second detection method according to the first detection method;

[0035] A detection information acquisition module, configured to obtain first calculation information by detecting a sample according to the first detection method and obtain second calculation information by detecting a sample according to the second detection method;

[0036] A concentration data calculation module, configured to calculate the concentration data within the linear range of the detection reagent by using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together;

[0037] Among them, the ratios of the sample and reagent dosages in the first detection method and the second detection method are different.

[0038] The third aspect of the present application provides a finished product sample analyzer, including the device described above, and executing the method described above.

[0039] The fourth aspect of the present application provides a computer-readable storage medium, on which executable code is stored. When the executable code is executed by a processor of an electronic device, the processor is caused to execute the method described above.

[0040] The technical solution provided by the present application may include the following beneficial effects:

[0041] In the embodiments of the present application, applied to a finished product sample analyzer and an immunoassay kit, a first detection method is obtained. The sample is detected according to the first detection method to obtain first calculation information. A second detection method is constructed according to the first detection method. The sample is detected according to the second detection method to obtain second calculation information. Concentration data within the linear range of the detection reagent is calculated using the first calculation information, and concentration data outside the linear range of the detection reagent is calculated using the first calculation information and the second calculation information together. Among them, the ratios of the sample and reagent dosages in the first detection method and the second detection method are different. For the sample to be detected within the linear range, the concentration data can be obtained using the first calculation information, and for the sample to be detected outside the linear range, the concentration data can be calculated using the first calculation information and the second calculation information together. Thus, without changing the reagent components, the concentration data outside the linear range can be quickly and accurately obtained through result calculation, improving the accuracy and efficiency of sample detection.

[0042] It should be understood that the above general description and the following detailed description are only exemplary and explanatory, and cannot limit the present application. Description of the Drawings

[0043] By describing the exemplary embodiments of the present application in more detail in conjunction with the drawings, the above and other objects, features, and advantages of the present application will become more obvious. Among them, in the exemplary embodiments of the present application, the same reference numerals generally represent the same components.

[0044] Figure 1 is a flowchart showing a method for expanding the linear range of a detection reagent according to an embodiment of the present application;

[0045] Figure 2 is another flowchart showing a method for expanding the linear range of a detection reagent according to an embodiment of the present application;

[0046] Figure 3It is a schematic diagram of the first sample loading amount list shown in the embodiments of the present application;

[0047] Figure 4 It is a schematic diagram of the first detection result list shown in the embodiments of the present application;

[0048] Figure 5 It is a schematic diagram of the first mapping relationship curve shown in the embodiments of the present application;

[0049] Figure 6 It is a schematic diagram of the first calibration detection result of samples outside the linear range shown in the embodiments of the present application;

[0050] Figure 7 It is a schematic diagram of the detection results of 10 samples outside the linear range shown in the embodiments of the present application;

[0051] Figure 8 It is a schematic diagram of the first sample detection result outside the linear range shown in the embodiments of the present application;

[0052] Figure 9 It is a schematic diagram of the detection results of 10 high and low value samples with unknown AFP concentrations shown in the embodiments of the present application;

[0053] Figure 10 It is a schematic diagram of the consistency detection result shown in the embodiments of the present application;

[0054] Figure 11 It is a schematic diagram of the first day's repeatability detection result shown in the embodiments of the present application;

[0055] Figure 12 It is a schematic diagram of the second day's repeatability detection result shown in the embodiments of the present application;

[0056] Figure 13 It is a schematic diagram of the second sample loading amount list shown in the embodiments of the present application;

[0057] Figure 14 It is a schematic diagram of the second detection result list shown in the embodiments of the present application;

[0058] Figure 15 It is a schematic diagram of the second mapping relationship curve shown in the embodiments of the present application;

[0059] Figure 16 It is a schematic diagram of the second calibration detection result of samples outside the linear range shown in the embodiments of the present application;

[0060] Figure 17 It is a schematic diagram of the detection results of 8 samples outside the linear range shown in the embodiments of the present application;

[0061] Figure 18It is a schematic diagram of the detection result of a second sample outside the linear range shown in the embodiments of the present application;

[0062] Figure 19 It is a schematic structural diagram of a device for expanding the linear range of a detection reagent shown in the embodiments of the present application;

[0063] Figure 20 It is a schematic structural diagram of a finished sample analyzer shown in the embodiments of the present application. Detailed implementation manners

[0064] The embodiments of the present application will be described in more detail below with reference to the accompanying drawings. Although the embodiments of the present application are shown in the drawings, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to make the present application more thorough and complete, and to fully convey the scope of the present application to those skilled in the art.

[0065] The terms used in the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The singular forms "a", "said" and "the" used in the present application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term "and / or" used herein refers to and includes any and all possible combinations of one or more of the associated listed items.

[0066] It should be understood that although the terms "first", "second", "third", etc. may be used in the present application to describe various information, these information should not be limited to these terms. These terms are only used to distinguish the same type of information from each other. For example, without departing from the scope of the present application, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of the present application, "a plurality" means two or more unless otherwise specifically defined.

[0067] In the core of immunoassay technology, the reaction curve between antigen and antibody is expected to be linear. Since the linear range interval of currently sold reagent kits and the linear range of finished reagents are fixed, it is impossible to accurately detect high-concentration samples beyond the linear range.

[0068] The traditional solution is to change the reagent components to expand the linear range of the reagent. However, this direct way of changing the reagent components has great limitations and low detection efficiency.

[0069] In view of the above problems, an embodiment of the present application provides a method for expanding the linear range of a detection reagent, which can obtain concentration data by using first calculation information for the samples to be detected within the linear range, and can jointly calculate the concentration data by using the first calculation information and the second calculation information for the samples to be detected outside the linear range, so as to quickly and accurately obtain the concentration data outside the linear range through result operation without changing the reagent components, and improve the accuracy and efficiency of sample detection.

[0070] The technical solutions of the embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0071] Figure 1 is a schematic flowchart of a method for expanding the linear range of a detection reagent shown in an embodiment of the present application. Refer to Figure 1 , which is applied to a finished product sample analyzer and an immunoassay kit. The method at least includes the following steps:

[0072] Step 101, obtain a first detection method, and detect a sample according to the first detection method to obtain first calculation information;

[0073] In an embodiment of the present application, the finished product sample analyzer can automatically obtain the first detection method corresponding to the immunoassay kit, and detect the sample according to the first detection method to obtain first calculation information.

[0074] Among them, the finished product sample analyzer refers to an instrument for analyzing, measuring, and detecting finished product samples. In the present application, the finished product sample analyzer is mainly used to detect data such as signal values and concentration data of finished product samples.

[0075] An immunoassay kit is a kit for quantitatively or semi-quantitatively determining the concentration of a specific biomarker in a sample to be detected, which contains pure products of target molecules to be detected such as proteins, antibodies, and antigens. The pure products of target molecules to be detected are usually used as controls or standards during the detection process.

[0076] In actual detection, the target molecule in the sample to be detected binds to the specific antibody in the immunoassay kit to form an antigen-antibody complex, and then by adding a specific label, such as an enzyme or a fluorescent label, the signal intensity of the antigen-antibody complex is detected, so as to determine the concentration data of the target molecule in the sample to be detected.

[0077] The first detection method is the original detection mode of the immunoassay kit, which is set in advance according to the product manual of the immunoassay kit.

[0078] The first calculation information refers to the relevant information generated when the finished product sample analyzer detects the sample by using the first detection method.

[0079] Step 102: Construct a second detection method based on the first detection method, and detect the sample according to the second detection method to obtain second calculation information;

[0080] In the embodiments of the present application, the finished product sample analyzer can construct a second detection method according to the first detection method, and then detect the sample according to the second detection method to obtain second calculation information.

[0081] Among them, the second detection method can be a detection method in which the sample volume and reagent dosage are changed on the basis of the first detection method.

[0082] The second calculation information refers to the relevant information generated when the finished product sample analyzer detects the sample using the second detection method.

[0083] Step 103: Calculate the concentration data within the linear range of the detection reagent using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent using the first calculation information and the second calculation information together; wherein, the ratio of the sample and reagent dosages in the first detection method and the second detection method is different.

[0084] In the embodiments of the present application, the finished product sample analyzer can calculate the concentration data within the linear range of the detection reagent using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent using the first calculation information and the second calculation information together.

[0085] The embodiments provided above in the present application are applied to a finished product sample analyzer and an immunoassay kit, obtain the first detection method, detect the sample according to the first detection method to obtain the first calculation information, construct the second detection method according to the first detection method, detect the sample according to the second detection method to obtain the second calculation information, calculate the concentration data within the linear range of the detection reagent using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent using the first calculation information and the second calculation information together, wherein, the ratio of the sample and reagent dosages in the first detection method and the second detection method is different. The technical solution provided by the present application can obtain the concentration data using the first calculation information for the samples to be detected within the linear range, and can calculate the concentration data using the first calculation information and the second calculation information together for the samples to be detected outside the linear range, so as to quickly and accurately obtain the concentration data outside the linear range through result calculation without changing the reagent components, and improve the accuracy and efficiency of sample detection.

[0086] Figure 2 It is another process schematic diagram of a method for expanding the linear range of a detection reagent shown in the embodiments of the present application. Figure 2 Relative Figure 1 It describes the technical solution of the embodiments of the present application in more detail. The method may include the following steps:

[0087] Step 201: Obtain a first detection method, and detect a sample according to the first detection method to obtain first calculation information;

[0088] In an embodiment of the present application, the finished product sample analyzer may preset the first detection method according to the product instruction manual of the immunoassay kit, and detect the sample according to the first detection method to obtain first calculation information.

[0089] As an example, the first detection method may obtain a first analog signal value by detecting a simulated sample with a known concentration, and the analog signal value belongs to the first calculation information. In addition, the first calculation information further includes a first sample volume, a first reagent volume, and a first detection curve.

[0090] In an embodiment, the generation process of the first detection curve at least includes the following sub-steps:

[0091] 1) Configure several groups of simulated samples with gradient concentrations using the pure product of the target molecule to be detected in the immunoassay kit. The concentrations of some simulated samples are within the linear range of the kit, and the concentrations of some simulated samples are greater than the upper limit of the linear range concentration of the kit.

[0092] 2) Detect the simulated samples using the first detection method to obtain the first analog signal values of the simulated samples;

[0093] 3) Generate a first detection curve based on the sample concentration and the first analog signal value.

[0094] Step 202: Construct a second detection method according to the first detection method, and detect the sample according to the second detection method to obtain second calculation information;

[0095] In an embodiment of the present application, constructing the second detection method according to the first detection method may be: the finished product sample analyzer increases the second sample volume in the second detection method to N times the first sample volume in the first detection method, and reduces the second reagent volume in the second detection method to 1 / N times the first reagent volume in the first detection method, where 2 ≤ N ≤ 100, and then constructs the second detection method using the second sample volume and the second reagent volume.

[0096] As an example, the second detection method may obtain a second analog signal value by detecting a simulated sample with a known concentration, and the analog signal value belongs to the second calculation information. In addition, the second calculation information further includes a second sample volume, a second reagent volume, and a second detection curve.

[0097] In an embodiment, the generation process of the second detection curve at least includes the following sub-steps:

[0098] 1) Prepare several groups of simulated samples with gradient concentrations using the pure target molecule to be measured in the immunoassay kit. The concentrations of some simulated samples are within the linear range of the kit, and the concentrations of some simulated samples are greater than the upper limit of the linear range concentration of the kit.

[0099] 2) Detect the simulated samples using the second detection method to obtain the second simulated signal values of the simulated samples.

[0100] 3) Construct a second detection curve based on the sample concentration and the second simulated signal value.

[0101] Step 203: Generate a standard curve of the concentration and signal ratio relationship according to the first simulated signal value and the second simulated signal value.

[0102] In the embodiment of the present application, the finished sample analyzer can determine the ratio between the first simulated signal value and the second simulated signal value at the same sample concentration as the simulated signal ratio, and then construct a mapping relationship curve between the sample concentration and the simulated signal ratio, and use this mapping relationship curve as the standard curve of the concentration and signal ratio relationship.

[0103] Among them, the curve fitting of the concentration and signal ratio relationship includes, but is not limited to, fitting algorithms such as linear fitting, polynomial fitting, cubic spline interpolation fitting, and four-parameter fitting.

[0104] Step 204: Determine the detection cut-off value according to the mapping relationship curve between the sample concentration and the simulated signal ratio.

[0105] In the embodiment of the present application, the detection cut-off value can be the simulated signal ratio obtained by testing the simulated sample with the upper limit (1±5%) concentration of the linear range of the immunoassay kit by the first detection method and the second detection method.

[0106] In one embodiment, relevant personnel can also set a preset ratio according to actual needs. The preset ratio can be a signal ratio set in advance. When the detection cut-off value is less than the preset ratio, shift the first detection curve to the right and shift the second detection curve to the left at the same time, so that the simulated signal ratio is equal to the preset ratio, and determine this simulated signal ratio as the detection cut-off value. Or, when the detection cut-off value is greater than the preset ratio, shift the first detection curve to the left and shift the second detection curve to the right at the same time, so that the simulated signal ratio is equal to the preset ratio, and determine this simulated signal ratio as the detection cut-off value.

[0107] Step 205: Calculate using the signal values in the first calculation information and the second calculation information to obtain the signal ratio.

[0108] In the embodiment of the present application, the finished sample analyzer calculates using the signal values in the first calculation information and the second calculation information to obtain the signal ratio of the sample to be detected.

[0109] Step 206, when the signal ratio is less than or equal to the detection cut-off value, it is determined that the sample to be detected is within the linear range, and the concentration data within the linear range of the detection reagent is obtained by using the calibration curve of the immunoassay kit.

[0110] In the embodiment of the present application, if the sample to be detected is within the linear range, the finished sample analyzer can substitute the signal value in the first calculation information into the calibration curve of the immunoassay kit to obtain the concentration data of the sample to be detected within the linear range.

[0111] Step 207, when the signal ratio is greater than the detection cut-off value, it is determined that the sample to be detected is outside the linear range, and the concentration data outside the linear range of the detection reagent is obtained by using the standard curve of the relationship between concentration and signal ratio.

[0112] In the embodiment of the present application, if the sample to be detected is outside the linear range, the finished sample analyzer can substitute the signal ratio into the standard curve of the relationship between concentration and signal ratio to obtain the concentration data of the sample to be detected outside the linear range, so as to realize the detection of the sample to be detected outside the linear range without changing the reagent components and improve the detection efficiency.

[0113] The following will further illustrate the content of expanding the linear range of the detection reagent of the present application with multiple examples:

[0114] Example ①: The finished sample analyzer is a photoactivated chemiluminescence detector (homogeneous non-washing reaction platform). The experimental materials include an Alpha Fetoprotein (AFP) detection kit with a linear range of 0.5 ng / mL to 1000 ng / mL, a dilution gradient sample (20 series gradients) of AFP antigen, 10 high and low value samples with unknown AFP concentration, and 10 samples outside the AFP linear range. The photoactivated chemiluminescence detector first sets the first detection method in advance according to the product manual of the AFP kit. The first sample volume of the first detection method is a, and the first reagent volume is b. Based on the first detection method, a second detection method is constructed. The second sample volume of the second detection method is 5a, and the second reagent volume is 1 / 5b. In this example, it can be set according to the Figure 3 schematic diagram of the first sample addition amount shown.

[0115] Then, the experimental materials are used for detection to obtain the Figure 4 schematic diagram of the first detection result shown. The detection results include the first simulated signal value detected by the first detection method, the second simulated signal value detected by the second detection method, and the simulated signal ratio between the first simulated signal value and the second simulated signal value under the same sample concentration. According to the detection results, draw the Figure 5Schematic diagram of the first mapping relationship curve shown, where curve a is the second detection curve drawn based on the results of the second detection method, curve b is the first detection curve drawn based on the results of the first detection method, and curve c is the standard curve of the concentration and signal ratio relationship fitted based on the mapping relationship between the analog signal ratio and the sample concentration. In curve c, the signal ratio increases as the sample concentration increases.

[0116] The detection cutoff value can be directly determined through curve c. For example, taking the signal ratio "1.04" corresponding to the upper limit of the linear range of 1000 as the detection cutoff value (cutoff value), when the signal ratio result of the sample to be detected is ">1.04", it is determined to be outside the linear range, and when the signal ratio result of the sample to be detected is "≤1.04", it is determined to be within the linear range.

[0117] In Example ①, it can be observed that there is an obvious intersection point between curve a and curve b near the sample concentration of 1000 ng / ml (the upper limit of the linear range). The signal ratio at this intersection point is "1.04", reflecting that in the actual application process, the signal ratio of the concentration of 1000 ng / ml (the upper limit of the linear range) is not "1", but close to "1", and may be ">1" or "<1". For example, the actual signal ratio may be "0.96", and in this application, "0.96" can be directly used as the detection cutoff value. Since the signal ratio shows a monotonically increasing trend as the concentration of the analyte increases, samples exceeding this detection cutoff value can be determined to be above the linear range.

[0118] Moreover, for the case where the signal ratio of the upper limit concentration of the linear range is not "1", this application can adjust the signal ratio of the upper limit concentration of the linear range to "1" through the following two methods:

[0119] (1) For the case where the signal ratio is ">1": In the first detection method, the sample loading volume is reduced, or the reagent loading volume is increased, or both of the above changes occur simultaneously, causing the first detection curve to shift to the right. In the second detection method, the sample loading volume is increased, or the reagent loading volume is reduced, or both of the above changes occur simultaneously, causing the second detection curve to shift to the left. The first detection curve and the second detection curve move simultaneously.

[0120] (2) For the case where the signal ratio is "<1": In the first detection method, the sample loading volume is increased, or the reagent loading volume is reduced, or both of the above changes occur simultaneously, causing the first detection curve to shift to the left. In the second detection method, the sample loading volume is reduced, or the reagent loading volume is increased, or both of the above changes occur simultaneously, causing the second detection curve to shift to the right. The first detection curve and the second detection curve move simultaneously.

[0121] By adjusting the relative positions of the two detection curves, moving one of the curves left or right or moving both curves simultaneously, the signal ratio at the upper limit concentration of the linear range is fixed at "1".

[0122] After determining the detection cut-off value, if the signal ratio of the sample to be detected is less than or equal to the detection cut-off value, it is determined to be within the linear range, and the signal value in the first calculation information is substituted into the calibration curve of the immunoassay kit to obtain the concentration data of the sample to be detected within the linear range. If the signal ratio of the sample to be detected is greater than the detection cut-off value, it is determined to be outside the linear range, and the signal ratio is substituted into the standard curve of the relationship between concentration and signal ratio to obtain the concentration data of the sample to be detected outside the linear range.

[0123] Example ②: For 10 samples outside the linear range, the calibration detection can be carried out using the gradient antigen results in Example ①. After the detection, the first calibration detection result schematic diagram of the samples outside the linear range as shown in Figure 6 is obtained. Then, the signal ratios of the samples outside the linear range in the sample result information are substituted into the curve of the relationship between concentration and signal ratio, and the detection result schematic diagram of 10 samples outside the linear range as shown in Figure 7 is calculated.

[0124] Example ③: The above 10 samples outside the linear range in Example ② are respectively diluted at different dilution multiples, and then the 10 diluted samples outside the linear range are detected. The original results are calculated and the dilution recovery rates are calculated to verify the credibility of the detection results of this application.

[0125] As shown in Figure 8 and Figure 8 the first sample detection result schematic diagram outside the linear range is shown. It can be seen from the detection results that the dilution recovery rates of the above 10 samples outside the linear range are all between 95% and 105%, indicating that the concentration results of the samples outside the linear range detected by this application are highly credible.

[0126] Example ④: For 10 high and low value samples with unknown AFP concentrations, the calibration detection in Example ① is used. The signal ratios are calculated by the above two detection methods respectively. The ratio 1.04 corresponding to the upper limit of the linear range of 1000 is used as the detection cut-off value. If the signal ratio is ">1.04", it is determined to be outside the linear range. If the signal ratio is "≤1.04", it is determined to be within the linear range. As shown in Figure 9 the detection result schematic diagram of 10 high and low value samples with unknown AFP concentrations is shown. It can be seen from Figure 9 whether the sample is within the linear range. To verify the accuracy of the above detection results, we use the reagent detection method for calibration detection, and the results are as shown in Figure 10Schematic diagram of the consistency detection results shown, from Figure 10 it can be seen that it is feasible for this application to determine whether the sample is within the linear range.

[0127] Example ⑤: Two high and low concentration samples outside the linear range can also be selected from the above examples to verify the result repeatability of this application. Use 2 instruments to detect once in the morning and afternoon every day for a total of 5 days. The imprecision of the calibration calculation results in Example 6 is used to evaluate the repeatability of this technical method. Through Figure 11 the schematic diagram of the repeatability detection results shown on the first day, Figure 12 it can be seen from the schematic diagram of the repeatability detection results shown on the second day that the calculated coefficient of variation of the results is less than 5%, and the precision is good.

[0128] Example ⑥: The finished product sample analyzer is a photochemiluminescence detector (homogeneous non-washing reaction platform). The experimental raw materials include a tumor-associated antigen 125 (CA125) detection kit, whose linear range is 0.6 U / mL to 1000 U / mL, diluted gradient samples (15 series gradients) configured with CA125 antigen, and 8 samples outside the CA125 linear range. The photochemiluminescence detector first sets the first detection method in advance according to the product manual of the CA125 kit. The first sample volume of the first detection method is a, and the first reagent volume is b. Based on the first detection method, a second detection method is constructed. The second sample volume of the second detection method is 5a, and the second reagent volume is 1 / 5b. In this example, it can be set according to the Figure 13 schematic diagram of the second sample addition amount list shown.

[0129] Then use the experimental raw materials for detection to obtain the Figure 14 schematic diagram of the second detection result list shown. The detection results include the first analog signal value detected by the first detection method, the second analog signal value detected by the second detection method, and the analog signal ratio between the first analog signal value and the second analog signal value under the same sample concentration. According to the detection results, draw the Figure 15 schematic diagram of the second mapping relationship curve shown. Among them, curve d is the second detection curve drawn based on the results detected by the second detection method, curve e is the standard curve of the concentration and signal ratio relationship fitted according to the mapping relationship between the analog signal ratio and the sample concentration, and curve f is the first detection curve drawn based on the results detected by the first detection method.

[0130] The detection cut-off value can be directly determined through curve f. For example, use the signal ratio "1.59" corresponding to the upper limit of the linear range of 1000 as the detection cut-off value (cutoff value). When the signal ratio result of the sample to be detected is ">1.59", it is determined to be outside the linear range. When the signal ratio result of the sample to be detected is "≤1.59", it is determined to be within the linear range.

[0131] Example ⑦: For Example ⑦, the gradient antigen results in Example ⑥ can be used to calibrate and detect 8 samples outside the linear range. After the detection, the second calibration detection result schematic diagram of the samples outside the linear range as shown in Figure 16 is obtained. Then, the signal ratios of the samples outside the linear range in the sample result information are substituted into the concentration-signal ratio relationship curve, and the detection result schematic diagram of 8 samples outside the linear range as shown in Figure 17 is calculated.

[0132] Example ⑧: The above 8 samples outside the linear range in Example ⑦ are respectively diluted with different dilution factors, and then the 8 diluted samples outside the linear range are detected. The original results are calculated and the dilution recovery rates are calculated to verify the credibility of the detection results of this application.

[0133] As Figure 18 shown in the second sample detection result schematic diagram of the samples outside the linear range, it can be seen from the detection results that the dilution recovery rates of the above 8 samples outside the linear range are all between 95% and 105%, indicating that the concentration results of the samples outside the linear range detected by this application are highly credible.

[0134] It should be noted that the embodiments of the present invention include but are not limited to the above examples. It can be understood that under the guidance of the ideas of the embodiments of the present invention, those skilled in the art can set according to the actual situation, and the present invention does not limit this.

[0135] In the embodiments of this application, it is applied to a finished sample analyzer and an immunoassay kit. The first detection method is obtained, the sample is detected according to the first detection method to obtain the first calculation information, the second detection method is constructed according to the first detection method, the sample is detected according to the second detection method to obtain the second calculation information, the concentration data within the linear range of the detection reagent is calculated by using the first calculation information, and the concentration data outside the linear range of the detection reagent is jointly calculated by using the first calculation information and the second calculation information. Among them, the ratios of the sample and reagent dosages in the first detection method and the second detection method are different. The technical solution provided by this application can obtain the concentration data for the samples to be detected within the linear range by using the first calculation information, and for the samples to be detected outside the linear range, the concentration data can be jointly calculated by using the first calculation information and the second calculation information. Thus, without changing the reagent components, the concentration data outside the linear range can be quickly and accurately obtained through result operation, improving the accuracy and efficiency of sample detection.

[0136] Corresponding to the foregoing application function implementation method embodiments, this application also provides a device, an electronic device for expanding the linear range of a detection reagent, and corresponding embodiments.

[0137] Figure 19 This is a schematic structural diagram of a device for expanding the linear range of a detection reagent shown in an embodiment of the present application. Refer to Figure 19 , this device at least includes the following modules:

[0138] A detection method acquisition module 1901, configured to acquire a first detection method and construct a second detection method according to the first detection method;

[0139] A detection information acquisition module 1902, configured to detect a sample according to the first detection method to obtain first calculation information, and detect the sample according to the second detection method to obtain second calculation information;

[0140] A concentration data calculation module 1903, configured to calculate concentration data within the linear range of the detection reagent by using the first calculation information, and calculate concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together;

[0141] Among them, the ratios of the sample and reagent dosages in the first detection method and the second detection method are different.

[0142] In an embodiment, the detection method acquisition module 1901 is configured to:

[0143] The first detection method is preset according to the product specification of the immunoassay kit;

[0144] Increase the second sample amount in the second detection method to N times the first sample amount in the first detection method, and reduce the second reagent amount in the second detection method to 1 / N times the first reagent amount in the first detection method, where 2 ≤ N ≤ 100;

[0145] Construct the second detection method by using the second sample amount and the second reagent amount.

[0146] In an embodiment, the concentration data calculation module 1903 includes:

[0147] A first calculation sub-module, configured to calculate by using the signal values in the first calculation information and the second calculation information to obtain a signal ratio;

[0148] When the signal ratio is less than or equal to the detection cut-off value, it is determined that the sample to be detected is within the linear range, and the concentration data within the linear range of the detection reagent is calculated by using the first calculation information;

[0149] Preferably, substitute the signal value in the first calculation information into the calibration curve of the immunoassay kit to obtain the concentration data of the sample to be detected within the linear range.

[0150] In an embodiment, the concentration data calculation module 1903 includes:

[0151] A second calculation sub-module, configured to perform calculations using the signal values in the first calculation information and the second calculation information to obtain a signal ratio;

[0152] When the signal ratio is greater than the detection cut-off value, it is determined that the sample to be detected is outside the linear range, and the concentration data outside the linear range of the detection reagent is obtained by jointly calculating the first calculation information and the second calculation information;

[0153] Preferably, the signal ratio is substituted into the standard curve of the concentration-signal ratio relationship to obtain the concentration data of the sample to be detected outside the linear range.

[0154] In one embodiment, the device further includes:

[0155] A standard curve generation module, configured to configure a plurality of groups of simulated samples with gradient concentrations using the pure product of the target molecule to be detected in the immunoassay kit, where the concentrations of some of the simulated samples are within the linear range of the kit, and the concentrations of some of the simulated samples are greater than the upper limit of the linear range concentration of the kit;

[0156] The simulated samples are respectively detected by the first detection method and the second detection method to obtain the first simulated signal value and the second simulated signal value of the simulated samples, and a first detection curve and a second detection curve are generated based on the sample concentration and the simulated signal value;

[0157] The ratio between the first simulated signal value and the second simulated signal value at the same sample concentration is determined as the simulated signal ratio;

[0158] A mapping relationship curve between the sample concentration and the simulated signal ratio is constructed, and the mapping relationship curve is used as the standard curve of the concentration-signal ratio relationship.

[0159] In one embodiment, the device further includes:

[0160] A first detection cut-off value determination module, configured to determine the detection cut-off value according to the mapping relationship curve between the sample concentration and the simulated signal ratio;

[0161] Wherein, the detection cut-off value is the simulated signal ratio obtained by testing the simulated samples with the concentration of the upper limit (1±19%) of the linear range of the immunoassay kit by the first detection method and the second detection method.

[0162] In one embodiment, the device further includes:

[0163] A second detection cut-off value determination module, configured to shift the first detection curve to the right and the second detection curve to the left at the same time when the detection cut-off value is less than the preset ratio, so that the simulated signal ratio is equal to the preset ratio, and determine the simulated signal ratio as the detection cut-off value;

[0164] Alternatively, when the detected cut-off value is greater than the preset ratio, shift the first detection curve to the left and the second detection curve to the right simultaneously, so that the analog signal ratio is equal to the preset ratio, and determine that the analog signal ratio is the detected cut-off value.

[0165] Regarding the device in the above embodiments, the specific manners in which each module performs operations have been described in detail in the embodiments related to the method, and will not be elaborated herein.

[0166] Figure 20 It is a schematic structural diagram of a finished product sample analyzer shown in an embodiment of the present application.

[0167] See Figure 20 , the finished product sample analyzer 2000 includes a memory 2010 and a processor 2020.

[0168] The processor 2020 may be a central processing unit (CPU), or may also be other general-purpose processors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor may be a microprocessor or the processor may also be any conventional processor, etc.

[0169] The memory 2010 may include various types of storage units, such as system memory, read-only memory (ROM), and permanent storage devices. Among them, the ROM can store static data or instructions required by the processor 2020 or other modules of the computer. The permanent storage device can be a readable and writable storage device. The permanent storage device can be a non-volatile storage device that does not lose the stored instructions and data even when the computer is powered off. In some embodiments, the permanent storage device uses a mass storage device (such as a magnetic or optical disk, flash memory) as the permanent storage device. In some other embodiments, the permanent storage device can be a removable storage device (such as a floppy disk, optical drive). The system memory can be a readable and writable storage device or a volatile readable and writable storage device, such as dynamic random access memory. The system memory can store some or all of the instructions and data required by the processor during operation. In addition, the memory 2010 can include any combination of computer-readable storage media, including various types of semiconductor storage chips (such as DRAM, SRAM, SDRAM, flash memory, programmable read-only memory), and magnetic disks and / or optical disks can also be used. In some embodiments, the memory 2010 can include removable storage devices that are readable and / or writable, such as compact discs (CDs), read-only digital versatile discs (such as DVD-ROM, dual-layer DVD-ROM), read-only Blu-ray discs, high-density discs, flash memory cards (such as SD cards, min SD cards, Micro-SD cards, etc.), magnetic floppy disks, etc. Computer-readable storage media do not include carrier waves and instantaneous electronic signals transmitted wirelessly or by wire.

[0170] Executable code is stored on the memory 2010, and when the executable code is processed by the processor 2020, it can cause the processor 2020 to execute some or all of the methods described above.

[0171] In addition, the method according to the present application can also be implemented as a computer program or a computer program product, which includes computer program code instructions for executing some or all of the steps in the above method of the present application.

[0172] Alternatively, the present application can also be implemented as a computer-readable storage medium (or non-transitory machine-readable storage medium or machine-readable storage medium), on which executable code (or computer program or computer instruction code) is stored. When the executable code (or computer program or computer instruction code) is executed by a processor of an electronic device (or a server, etc.), it causes the processor to execute some or all of the steps of the above method according to the present application.

[0173] The embodiments of the present application have been described above. The above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations are obvious to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The choice of terms used herein is intended to best explain the principles of the embodiments, the practical application, or the improvement of the technology in the market, or to enable other ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A method for expanding the linear range of a detection reagent, characterized in that, Applied to a finished product sample analyzer and an immunoassay kit, including: Obtain a first detection method, and detect a sample according to the first detection method to obtain first calculation information; Construct a second detection method according to the first detection method, and detect a sample according to the second detection method to obtain second calculation information; Calculate the concentration data within the linear range of the detection reagent by using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together; Wherein, the ratio of the sample amount to the reagent amount in the first detection method and the second detection method is different.

2. The method according to claim 1, characterized in that, The constructing the second detection method according to the first detection method includes: The first detection method is preset according to the product instruction manual of the immunoassay kit; Increase the second sample amount in the second detection method to N times the first sample amount in the first detection method, and reduce the second reagent amount in the second detection method to 1 / N times the first reagent amount in the first detection method, where 2 ≤ N ≤ 100; Construct the second detection method by using the second sample amount and the second reagent amount.

3. The method according to claim 1 or 2, characterized in that, The calculating the concentration data within the linear range of the detection reagent by using the first calculation information includes: Calculate by using the signal values in the first calculation information and the second calculation information to obtain a signal ratio; When the signal ratio is less than or equal to the detection cut-off value, determine that the sample to be detected is within the linear range, and calculate the concentration data within the linear range of the detection reagent by using the first calculation information; Preferably, substitute the signal value in the first calculation information into the calibration curve of the immunoassay kit to obtain the concentration data of the sample to be detected within the linear range.

4. The method according to claim 1 or 2, characterized in that, The calculating the concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together includes: Calculate by using the signal values in the first calculation information and the second calculation information to obtain a signal ratio; When the signal ratio is greater than the detection cut-off value, determine that the sample to be detected is outside the linear range, and calculate the concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together; Preferably, substitute the signal ratio into the standard curve of the relationship between concentration and signal ratio to obtain the concentration data of the sample to be detected outside the linear range.

5. The method according to claim 1 or 2, characterized in that, The method further includes: Configure several groups of gradient concentration simulated samples by using the pure product of the target molecule to be detected in the immunoassay kit, and the concentrations of some of the simulated samples are within the linear range of the kit, and the concentrations of some of the simulated samples are greater than the upper limit of the linear range concentration of the kit; Detect the simulated samples by using the first detection method and the second detection method respectively to obtain the first simulated signal value and the second simulated signal value of the simulated samples, and generate a first detection curve and a second detection curve through the sample concentration and the simulated signal value; Determine the ratio between the first simulated signal value and the second simulated signal value at the same sample concentration as the simulated signal ratio; Construct a mapping relationship curve between the sample concentration and the ratio of the analog signals, and use the mapping relationship curve as the standard curve for the concentration and signal ratio relationship.

6. The method according to claim 5, wherein The method further includes: Determine a detection cut-off value according to the mapping relationship curve between the sample concentration and the ratio of the analog signals; Wherein, the detection cut-off value is the ratio of the analog signals obtained by testing the analog sample at the upper limit (1±5%) of the linear range of the kit by the first detection method and the second detection method.

7. The method according to claim 6, characterized in that, The method further includes: When the detection cut-off value is less than the preset ratio, shift the first detection curve to the right and shift the second detection curve to the left at the same time, so that the ratio of the analog signals is equal to the preset ratio, and determine the ratio of the analog signals as the detection cut-off value; Or, when the detection cut-off value is greater than the preset ratio, shift the first detection curve to the left and shift the second detection curve to the right at the same time, so that the ratio of the analog signals is equal to the preset ratio, and determine the ratio of the analog signals as the detection cut-off value.

8. An apparatus for expanding the linear range of a detection reagent, characterized in that, It includes: A detection method acquisition module, configured to acquire a first detection method and construct a second detection method according to the first detection method; A detection information acquisition module, configured to obtain first calculation information by detecting a sample according to the first detection method, and obtain second calculation information by detecting the sample according to the second detection method; A concentration data calculation module, configured to calculate the concentration data within the linear range of the detection reagent by using the first calculation information, and calculate the concentration data outside the linear range of the detection reagent by using the first calculation information and the second calculation information together; Wherein, the ratio of the sample and reagent dosages in the first detection method and the second detection method is different.

9. A finished product sample analyzer, characterized in that, The finished sample analyzer includes the device described in claim 8 and executes the method described in any one of claims 1-7.

10. A computer-readable storage medium, on which executable code is stored, and when the executable code is executed by a processor of an electronic device, the processor is caused to execute the method described in any one of claims 1-7.

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