A method for correcting the test value of HbA1c by latex turbidimetry and a device for correcting the test value of HbA1c by latex turbidimetry

Abstract

The application discloses a method for correcting latex turbidimetry test HbA1c value and a device for correcting latex turbidimetry test HbA1c value, and relates to the technical field of detection methods. The method for correcting latex turbidimetry test HbA1c value comprises the following steps: obtaining Hb information of a sample to be detected, HbA1c value of the sample to be detected and scattering light intensity value M of the sample to be detected; comparing preset Hb information with the Hb information of the sample to be detected; when the Hb information of the sample to be detected is greater than the preset Hb information, displaying the HbA1c value of the sample to be detected; when the Hb information of the sample to be detected is less than or equal to the preset Hb information, correcting the HbA1c value of the sample to be detected to obtain the corrected HbA1c value of the sample to be detected; wherein the Hb information comprises Hb value and HCT value. The corrected HbA1c value is closer to the real value, the accuracy of the HbA1c value result is improved, the detection range and the use range of the latex turbidimetry are expanded, the Hb range tolerated by the corrected latex turbidimetry is 30-200 g / L, the detection result of the HbA1c value of the sample to be detected is directly corrected, and the detection time and the detection cost are saved.

Description

Technical Field

[0001] This invention relates to the field of detection method technology, and in particular to a method and apparatus for testing HbA1c values ​​using a modified latex turbidimetric method. Background Technology

[0002] Diabetes is an endocrine and metabolic disease. In recent years, its incidence has been rising, making it the third leading cause of non-communicable disease after cardiovascular disease and cancer, and a major cause of disability and death. Traditional methods for diagnosing and monitoring diabetes include fasting blood glucose, postprandial blood glucose, and oral glucose tolerance tests. However, these blood glucose parameters only represent the instantaneous blood glucose level at the time of blood draw, resulting in inaccurate measurements.

[0003] In the human body, the combination of blood glucose and hemoglobin (Hb) to form glycated hemoglobin (HbA1c) is an irreversible reaction. HbA1c is directly proportional to blood glucose concentration and can be maintained for about 120 days. Therefore, HbA1c is the most important and stable form of glycated hemoglobin. Thus, observing the HbA1c concentration over 120 days can more accurately reflect the blood glucose concentration in the human body.

[0004] Currently, the main methods used to detect HbA1c concentration include high performance liquid chromatography (HPLC) and latex immunoturbidimetry. HPLC is more expensive, so latex immunoturbidimetry is more suitable for testing at the grassroots level.

[0005] The prerequisite for detecting HbA1c concentration using latex immunoturbidimetric assay is that the latex microspheres must reach a saturated adsorption state. However, due to individual differences, the hemoglobin Hb concentration varies among most people clinically. Normal hemoglobin Hb concentration ranges from 110-160 g / L, while in anemic patients, it can be as low as 30 g / L. In such cases, the hemoglobin Hb concentration is too low to allow the latex microspheres to reach saturation, resulting in a lower-than-expected HbA1c test value. This could lead to misdiagnosis by doctors and delay in diagnosis. Summary of the Invention

[0006] The main objective of this invention is to provide a method and apparatus for testing HbA1c values ​​using a modified latex turbidimetric method, aiming to solve the problem in the prior art where low Hb samples lead to inaccurate test results when testing HbA1c content using latex immunoturbidimetric methods.

[0007] To achieve the above objectives, this invention proposes a method for testing HbA1c values ​​using a modified latex turbidimetric method, comprising the following steps:

[0008] S10. Obtain the Hb information of the sample to be tested, the HbA1c value of the sample to be tested, and the scattered light intensity value M of the sample to be tested;

[0009] S20. Compare the preset Hb information with the Hb information of the sample to be tested;

[0010] S30. When the Hb information of the sample to be tested is greater than the preset Hb information, the HbA1c value of the sample to be tested is displayed.

[0011] S40. When the Hb information of the sample to be tested is less than or equal to the preset Hb information, the HbA1c value of the sample to be tested is corrected to obtain the corrected HbA1c value of the sample to be tested.

[0012] The Hb information includes Hb value and HCT value.

[0013] In one embodiment, step S40, the correction method includes:

[0014] S410. Calculate the corrected scattered light intensity value of the sample under test according to the correction formula E=k*D+b, where E is the corrected scattered light intensity value of the sample under test, k is the correction slope, D is the converted scattered light intensity value of the scattered light intensity M of the sample under test, and b is the correction intercept.

[0015] S420. Calculate the corrected HbA1c value of the test sample based on the corrected scattered light intensity value E of the test sample and the standard curve between the scattered light intensity value and HbA1c value of the hemoglobin standard.

[0016] In one embodiment, before step S410, the method further includes obtaining a modified formula, the step of obtaining the modified formula including:

[0017] S401. Obtain the hemoglobin set of HbA1c determined by latex turbidimetric assay, wherein the hemoglobin set contains an HbA1c value under a first Hb information and an HbA1c value under a second Hb information, the first Hb information > preset Hb information > second Hb information, and obtain the scattered light intensity value B1 corresponding to the first Hb information and the scattered light intensity value B2 corresponding to the second Hb information determined by latex turbidimetric assay.

[0018] S402. Obtain the HbA1c value corresponding to the first Hb information and the HbA1c value corresponding to the second Hb information in the hemoglobin group by HPLC determination.

[0019] S403. The scattered light intensity value B2 corresponding to the second Hb information determined by the latex turbidimetric method and the second Hb information are used to calculate the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group, where C = B2 / second Hb information;

[0020] S404. Calculate the converted scattered light intensity value D of the second Hb information using the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group and the first Hb information, where D = C * first Hb information;

[0021] S405. The first linear regression equation is obtained by taking the HbA1c value corresponding to the first Hb information in the hemoglobin group determined by HPLC and the scattered light intensity value B1 corresponding to the first Hb information determined by latex turbidimetric assay: y1 = a1*x1 + b1; where y1 is the HbA1c value corresponding to the first Hb information in the hemoglobin group determined by HPLC, x1 is the scattered light intensity value B1 corresponding to the first Hb information determined by latex turbidimetric assay, a1 is the slope of the first linear regression equation, and b1 is the intercept of the first linear regression equation.

[0022] S406. By using the converted scattered light intensity value D of the second Hb information and the HbA1c value corresponding to the second Hb information in the hemoglobin group determined by HPLC, the second linear regression equation y2=a2*x2+b2 is obtained; where y2 is the HbA1c value corresponding to the second Hb information in the hemoglobin group determined by HPLC, x2 is the converted scattered light intensity value D of the second Hb information, a1 is the slope of the second linear regression equation, and b2 is the intercept of the second linear regression equation.

[0023] S407. Calculate the corrected formula using the first and second linear regression equations;

[0024] Wherein, the first Hb information includes a first Hb value, and the second Hb information includes a second Hb value; or,

[0025] The first Hb information includes a first HCT value, and the second Hb information includes a second HCT value.

[0026] In one embodiment, the number of hemoglobin groups is multiple.

[0027] In one embodiment, step S407 includes:

[0028] S4071. Using the slope a1 of the first linear regression equation and the slope a2 of the second linear regression equation, we obtain the corrected slope k = a2 / a1.

[0029] S4072. Using the intercept b1 of the first linear regression equation and the intercept b2 of the second linear regression equation, we obtain the corrected intercept b = (b2 - b1) / a1.

[0030] S4073. The converted scattered light intensity value D, the corrected slope k, and the corrected intercept b of the scattered light intensity value M of the sample to be tested determined by the latex turbidimetric method are used to obtain the correction formula E = k * D + b, where E is the corrected scattered light intensity value.

[0031] In one embodiment, the first Hb information includes a first Hb value, wherein the first Hb value ranges from 120 to 160 g / L; or,

[0032] The first Hb information includes a first HCT value, which ranges from 37% to 50%.

[0033] In one embodiment, before step S20, a preset Hb information is calculated. The step of calculating the preset Hb information includes:

[0034] S21. Calculate the corrected scattered light intensity value E corresponding to the second Hb information in multiple hemoglobin groups using the corrected formula E=k*D+b.

[0035] S22. Calculate the corrected Hb information Z of the second Hb information in multiple hemoglobin groups by using multiple corrected scattered light intensity values ​​E and the scattered light intensity coefficient C corresponding to the second Hb information in multiple hemoglobin groups, where Z = E / C;

[0036] S23. Calculate the average value X of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups using the corrected Hb information Z of the second Hb information in multiple hemoglobin groups;

[0037] S24. Calculate the standard deviation SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups using the corrected Hb information Z of the second Hb information in multiple hemoglobin groups.

[0038] S25. Calculate the preset Hb information using the average value X of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups and the standard deviation SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups.

[0039] In one embodiment, in step S25, the relationship between the average value X of the preset Hb information and the corrected Hb information Z of the second Hb information in multiple hemoglobin groups and the standard deviation value SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups is: preset Hb information = X + 2 * SD.

[0040] The present invention also provides an apparatus for modifying the latex turbidimetric method for testing HbA1c values, comprising the steps of the method for modifying the latex turbidimetric method for testing HbA1c values, including:

[0041] The acquisition module is used to acquire the Hb information of the sample to be tested, the HbA1c value of the sample to be tested, and the scattered light intensity value M of the sample to be tested.

[0042] The comparison module is used to compare the preset Hb information with the Hb information of the sample to be tested;

[0043] The correction module is used to correct the HbA1c value of the sample under test when the Hb information is less than or equal to a preset Hb information, thereby obtaining the corrected HbA1c value of the sample under test; and,

[0044] The display module is used to display the Hb information of the sample under test and the corrected HbA1c value of the sample under test.

[0045] In one embodiment, the apparatus for correcting the HbA1c value by latex turbidimetric assay further includes a calculation module for calculating the corrected HbA1c value of the sample to be tested.

[0046] This invention proposes a method for correcting HbA1c values ​​obtained by latex turbidimetric testing. First, a comparison is made between preset Hb information and the Hb information of the sample to be tested, allowing for a quick determination of whether the HbA1c value of the sample needs correction. When the Hb information of the sample to be tested is greater than the preset Hb information, the HbA1c value obtained by latex turbidimetric testing is close to the true value, and no correction is needed, saving correction time. When the Hb information of the sample to be tested is less than or equal to the preset Hb information, the HbA1c value obtained by latex turbidimetric testing is less than the true value. The true HbA1c value is low, requiring correction of the HbA1c value of the sample to be tested. The corrected HbA1c value is closer to the true value, improving the accuracy of the latex turbidimetric method for testing HbA1c, and expanding the detection range and application scope of the latex turbidimetric method. After correction, the Hb value range of the Hb sample used in the latex turbidimetric method is 30-200 g / L, meeting the clinical requirements for the range of Hb content. Moreover, the test results of the HbA1c value of the sample to be tested are directly corrected, eliminating the need for retesting, thus saving testing time and costs. Attached Figure Description

[0047] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0048] Figure 1 A simplified flowchart of the modified latex turbidimetric method for testing HbA1c values ​​provided by the present invention;

[0049] Figure 2 The correlation analysis diagram of HbA1c value before correction by latex turbidimetric method and HbA1c value tested by HPLC method in Example 1 of the present invention;

[0050] Figure 3The correlation analysis diagram of HbA1c value corrected by latex turbidimetric method and HbA1c value tested by HPLC in Example 1 of the present invention;

[0051] Figure 4 The correlation diagram of HbA1c value before correction by latex turbidimetric method and HbA1c value tested by HPLC method in Example 2 of the present invention is provided.

[0052] Figure 5 The correlation diagram of HbA1c value corrected by latex turbidimetric method and HbA1c value tested by HPLC method in Example 2 of the present invention is shown.

[0053] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0054] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially. Furthermore, the meaning of "and / or" throughout the text includes three parallel solutions; for example, "A and / or B" includes solution A, or solution B, or a solution where both A and B are satisfied simultaneously. In addition, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0055] Diabetes is an endocrine and metabolic disease. In recent years, its incidence has been rising, making it the third leading cause of non-communicable disease after cardiovascular disease and cancer, and a major cause of disability and death. Traditional methods for diagnosing and monitoring diabetes include fasting blood glucose, postprandial blood glucose, and oral glucose tolerance tests. However, these blood glucose parameters only represent the instantaneous blood glucose level at the time of blood draw, resulting in inaccurate measurements.

[0056] Total hemoglobin (Hb) can be divided into three components: hemoglobin A (HbA), hemoglobin A2 (HbA2), and hemoglobin F (HbF). HbF is mainly found in fetal blood and is composed of two α-chains and two γ-chains. In adult blood, HbA accounts for 97% of Hb and is composed of two α-chains and two β-chains. HbA2 has a lower proportion in hemoglobin and is composed of two α-chains and two δ-chains. HbA is further divided into two types: HbA0 and HbA1. HbA0 is the unglycosylated portion, while HbA1 is the glycosylated portion, with HbA1 accounting for approximately 6% of HbA. HbA1 is divided into HbA1a, HbA1a2, HbA1b, and HbA1c. HbA1c is the most abundant and stable form of glycosylated hemoglobin. The average HbA1c level in normal individuals is about 5% of total HbA1, while the combined proportion of HbA1a and HbA1b is less than 1%. The binding of blood glucose and hemoglobin to form glycosylated hemoglobin (HbA1c) is an irreversible reaction. HbA1c is directly proportional to blood glucose concentration and can be maintained for approximately 120 days. Therefore, by monitoring HbA1c concentration over 120 days, blood glucose concentration can be reflected, thus indicating the patient's blood glucose control over the past 8–12 weeks. The World Health Organization also recommends using HbA1c as a diagnostic indicator for diabetes.

[0057] Methods for determining HbA1c can be categorized into three main types based on their detection principles: the first type is based on differences in charge, including electrophoresis and high-performance liquid chromatography (HPLC); the second type is based on differences in chemical structure, including affinity chromatography and immunoassays; and the third type distinguishes based on the characteristics of HbA1c participation in specific biochemical reactions, including enzymatic methods. Among these, HPLC and latex immunoturbidimetry are the most common. While HPLC is the most reliable method for HbA1c detection, it is relatively expensive. In comparison, latex immunoturbidimetry is more suitable for widespread use at the grassroots level.

[0058] The basic principle of latex immunoturbidimetric assay for HbA1c content is as follows: Latex microspheres can simultaneously adsorb unglycated hemoglobin (HbA0) and glycated hemoglobin (HbA1). The loading of latex microspheres in the reaction system is less than the total content of these two substances, thus the latex microspheres are in a saturated adsorption state. At this point, the amount of HbA1c adsorbed on the surface of the latex microspheres is positively correlated with the percentage concentration of HbA1c in the sample. Because the complex formed after the latex microspheres and HbA1c bind increases in size, light scattering is significantly enhanced. Therefore, the change in the intensity of this scattered light can be measured using a photodetector. By establishing a correlation curve between the percentage concentration of HbA1c and the intensity of scattered light, the percentage content of HbA1c in the total hemoglobin (Hb) in the sample can be obtained. However, due to individual differences, the hemoglobin (Hb) content varies among most people in clinical practice. The normal hemoglobin (Hb) concentration is in the range of 110-160 g / L, while the hemoglobin (Hb) concentration in anemic patients can be as low as 30 g / L. At this point, the hemoglobin (Hb) concentration is too low to allow the latex microspheres to be saturated with adsorption, making the directly read HbA1c percentage inaccurate and lower than the true value. This may lead to misdiagnosis by doctors and delay in diagnosis.

[0059] To address the issue of low HbA1c levels in samples with low hemoglobin concentrations, there are two main existing methods: 1) increasing the binding capacity of latex microspheres for Hb and HbA1c, and 2) increasing the sample concentration. However, the former is suitable for eliminating the influence of low Hb concentration on HbA1c measurement results in the Hb concentration range of 50-160 g / L, but it cannot fully meet the needs of testing samples with severe anemia; the latter requires analysis of the results, processing of low Hb samples, and repeated testing, which is relatively cumbersome.

[0060] In view of this, the present invention provides a method for modifying the latex turbidimetric method for testing HbA1c values, comprising the following steps:

[0061] S10. Obtain the Hb information of the sample to be tested, the HbA1c value of the sample to be tested, and the scattered light intensity value M of the sample to be tested;

[0062] S20. Compare the preset Hb information with the Hb information of the sample to be tested;

[0063] S30. When the Hb information of the sample to be tested is greater than the preset Hb information, the HbA1c value of the sample to be tested is displayed.

[0064] S40. When the Hb information of the sample to be tested is less than or equal to the preset Hb information, the HbA1c value of the sample to be tested is corrected to obtain the corrected HbA1c value of the sample to be tested.

[0065] The Hb information includes Hb value and HCT value.

[0066] A simplified flowchart of the above correction method is shown below. Figure 1 As shown.

[0067] In step S10, the preset Hb information can be HGB value and HCT value. The HGB value represents hemoglobin Hb, i.e., Hb value. The HCT is hematocrit, which is the percentage of red blood cells in the total blood volume. It is used to measure the proportion of red blood cells in the blood relative to the total blood volume. There is a correlation between hematocrit (HCT) and hemoglobin concentration (Hb). Therefore, both the HGB value and the HCT value can be used to confirm whether the HbA1c of the sample to be tested is within the range that needs correction.

[0068] The modified HbA1c value of this invention is the HbA1c concentration in the sample, that is, the percentage content of glycated hemoglobin HbA1c in the sample relative to total hemoglobin Hb, as detected by latex turbidimetry. When testing HbA1c concentration using latex turbidimetry, with a fixed amount of latex microspheres and saturated adsorption, the absolute content of HbA1c on the latex microspheres is only related to the HbA1c concentration of the sample itself, which is the percentage content of glycated hemoglobin HbA1c in the blood sample relative to total hemoglobin Hb. Monoclonal antibodies that specifically bind to HbA1c are immobilized on the surface of latex microspheres. When a sample containing HbA1c is added, the HbA1c in the sample binds to the antibody on the latex microspheres, forming a latex-antibody-HbA1c complex. The aggregation of multiple latex-antibody-HbA1c complexes significantly increases the turbidity of the reaction system. The higher the HbA1c concentration in the sample, the greater the turbidity. Therefore, turbidity and the percentage concentration of HbA1c in the sample are positively correlated. By establishing a turbidity-HbA1c percentage concentration curve, the percentage concentration of HbA1c in the sample can be obtained. Turbidity is a measure of liquid transparency, mainly characterizing the scattering and absorption effects of suspended particles in a solution on light. Solutions with high turbidity contain more and larger suspended particles, leading to increased scattered light intensity. Therefore, changes in turbidity correspond to changes in scattered light intensity.

[0069] Taking Hb information as an example, for high-Hb concentration samples with the same HbA1c concentration (i.e., Hb values ​​greater than the preset Hb value), even if the Hb concentration is higher, the absolute content of HbA1c on the latex microspheres will not change when the latex microspheres are already saturated with adsorption. Therefore, the measured HbA1c concentration will remain unchanged, and no correction is needed for the HbA1c concentration of high-Hb concentration samples. When the Hb concentration in the sample is too low, i.e., below the preset Hb value, the latex microspheres are not saturated with adsorption, and the absolute content of HbA1c on the latex microspheres is below the saturation state. When using the standard curve of scattered light intensity and HbA1c percentage concentration when latex microspheres are saturated, the measured HbA1c percentage will be lower than the true value and needs to be corrected. In low-Hb samples, the Hb concentration is less than the preset Hb value. When the Hb value of the low-Hb sample increases within the range below the preset Hb value, the latex microspheres will continue to adsorb hemoglobin Hb and glycated hemoglobin HbA1c in the sample. The absolute content of HbA1c on the latex microspheres increases, and the measured HbA1c concentration will also increase accordingly. At this time, the HbA1c concentration and the Hb concentration are positively correlated.

[0070] In the technical solution of this invention, the preset Hb information and the Hb information of the sample to be tested are first compared, which can quickly determine whether the HbA1c value of the sample to be tested needs to be corrected. When the Hb information of the sample to be tested is greater than the preset Hb information, the HbA1c value obtained by the latex turbidimetric method is close to the true value, and there is no need to correct its HbA1c value, saving correction time. When the Hb information of the sample to be tested is less than or equal to the preset Hb information, the HbA1c value obtained by the latex turbidimetric method is less than the true HbA1c value. The method is small and requires calibration of the HbA1c value of the sample to be tested. The calibrated HbA1c value is closer to the true value, which improves the accuracy of HbA1c testing by latex turbidimetric assay and expands the detection range and application scope of latex turbidimetric assay. The Hb value range of the Hb sample used by latex turbidimetric assay after calibration is 30-200 g / L, which meets the clinical requirements for Hb content range. Moreover, the test results of HbA1c value of the sample to be tested are directly corrected without retesting, saving test time and test costs.

[0071] In any embodiment of the present invention, step S40, the correction method includes:

[0072] S410. Calculate the corrected scattered light intensity value of the sample under test according to the correction formula E=k*D+b, where E is the corrected scattered light intensity value of the sample under test, k is the correction slope, D is the converted scattered light intensity value of the scattered light intensity M of the sample under test, and b is the correction intercept.

[0073] S420. Calculate the corrected HbA1c value of the test sample based on the corrected scattered light intensity value E of the test sample and the standard curve between the scattered light intensity value and HbA1c value of the hemoglobin standard.

[0074] In step S410, the formula for calculating the converted scattered light intensity value D of the scattered light intensity M of the sample to be tested is: D = M / Hb information of the sample to be tested * first Hb information, where M is the scattered light intensity value of the sample to be tested, and the first Hb information is the same as the first Hb information in step S404.

[0075] Before step S420, the method further includes: obtaining a standard curve between the scattered light intensity value and the HbA1c value of the hemoglobin standard, which includes:

[0076] A. Prepare multiple hemoglobin standards with different HbA1c concentrations, wherein the hemoglobin standards contain different concentrations of glycated hemoglobin (HbA1c);

[0077] B. Add latex microspheres to the multiple hemoglobin standards with different HbA1c concentrations to obtain multiple mixtures; the latex microspheres have antibodies that can specifically bind to glycated hemoglobin HbA1c;

[0078] C. The scattered light intensity values ​​of the multiple mixtures are obtained by detecting the multiple mixtures using a spectrophotometer.

[0079] D. Establish a standard curve of scattered light intensity versus HbA1c concentration by using the scattered light intensity values ​​of multiple mixtures and the HbA1c concentration in the corresponding hemoglobin standards of multiple mixtures.

[0080] In the above steps, the HbA1c concentration refers to the percentage of HbA1c content in the hemoglobin standard relative to the total Hb content.

[0081] Taking Hb information as an example, when using Hb values, the scattered light intensity in the sample during latex turbidimetric analysis reflects the absolute content of HbA1c adsorbed on the latex microspheres. The absolute content of HbA1c on the latex microspheres when they are saturated with adsorption differs from the absolute content when they are unsaturated. Therefore, the scattered light intensity under saturated and unsaturated adsorption conditions differs. Correction parameters are used to adjust the scattered light intensity of the sample, i.e., to adjust the absolute content of HbA1c in the sample, to the theoretically expected scattered light intensity and absolute HbA1c content under saturated adsorption conditions. Since the scattered light intensity in the sample is positively correlated with the percentage of HbA1c in total hemoglobin, the corrected percentage of HbA1c in total hemoglobin corresponding to the adjusted scattered light intensity can be calculated using the standard curve of the scattered light intensity and HbA1c concentration. Therefore, when the Hb value of the sample to be tested is less than the preset Hb value, the intensity of scattered light detected by latex turbidimetry is corrected by specific correction parameters or algorithms to obtain a scattered light intensity close to the true value. Then, by using the standard curve of scattered light intensity and HbA1c concentration, a result close to the true value of HbA1c concentration is obtained. This allows latex turbidimetry to better reflect the true percentage of HbA1c in total hemoglobin in the sample to be tested, and to obtain a more accurate percentage of HbA1c in total hemoglobin in the sample to be tested.

[0082] In any embodiment of the present invention, before step S410, a step of obtaining a modified formula is included, the step of obtaining the modified formula including:

[0083] S401. Obtain the hemoglobin set of HbA1c determined by latex turbidimetric assay, wherein the hemoglobin set contains an HbA1c value under a first Hb information and an HbA1c value under a second Hb information, the first Hb information > preset Hb information > second Hb information, and obtain the scattered light intensity value B1 corresponding to the first Hb information and the scattered light intensity value B2 corresponding to the second Hb information determined by latex turbidimetric assay.

[0084] S402. Obtain the HbA1c value corresponding to the first Hb information and the HbA1c value corresponding to the second Hb information in the hemoglobin group by HPLC determination.

[0085] S403. The scattered light intensity value B2 corresponding to the second Hb information determined by the latex turbidimetric method and the second Hb information are used to calculate the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group, where C = B2 / second Hb information;

[0086] S404. Calculate the converted scattered light intensity value D of the second Hb information using the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group and the first Hb information, where D = C * first Hb information;

[0087] S405. The first linear regression equation is obtained by taking the HbA1c value corresponding to the first Hb information in the hemoglobin group determined by HPLC and the scattered light intensity value B1 corresponding to the first Hb information determined by latex turbidimetric assay: y1 = a1*x1 + b1; where y1 is the HbA1c value corresponding to the first Hb information in the hemoglobin group determined by HPLC, x1 is the scattered light intensity value B1 corresponding to the first Hb information determined by latex turbidimetric assay, a1 is the slope of the first linear regression equation, and b1 is the intercept of the first linear regression equation.

[0088] S406. By using the converted scattered light intensity value D of the second Hb information and the HbA1c value corresponding to the second Hb information in the hemoglobin group determined by HPLC, the second linear regression equation y2=a2*x2+b2 is obtained; where y2 is the HbA1c value corresponding to the second Hb information in the hemoglobin group determined by HPLC, x2 is the converted scattered light intensity value D of the second Hb information, a1 is the slope of the second linear regression equation, and b2 is the intercept of the second linear regression equation.

[0089] S407. Calculate the corrected formula using the first and second linear regression equations;

[0090] Wherein, the first Hb information includes a first Hb value, and the second Hb information includes a second Hb value; or, the first Hb information includes a first HCT value, and the second Hb information includes a second HCT value.

[0091] Preferably, step S401 includes: obtaining the hemoglobin set of HbA1c determined by latex turbidimetric assay, wherein the hemoglobin set contains an HbA1c value under a first Hb information and an HbA1c value under a second Hb information, wherein the HbA1c value under the first Hb information and the HbA1c value under the second Hb information are the same, the first Hb information > preset Hb information > the second Hb information, and obtaining the scattered light intensity value B1 corresponding to the first Hb information and the scattered light intensity value B2 corresponding to the second Hb information determined by latex turbidimetric assay.

[0092] It should be noted that the HbA1c values ​​under the first Hb information and the second Hb information of the hemoglobin group can be different, which facilitates sample selection and the establishment of a linear equation. Preferably, the HbA1c values ​​under the first Hb information and the second Hb information of the hemoglobin group can be the same, which places stricter requirements on sample selection and can obtain a more accurate linear equation.

[0093] Taking Hb information as an example, the HbA1c value measured by latex turbidimetry in the hemoglobin group at the first Hb value is the same as the HbA1c value at the second Hb value. The first Hb value is greater than the second Hb value, the second Hb value is less than the preset Hb value, and the first Hb value is greater than the preset Hb value. Since the HbA1c value is a relative content, its value is affected by the mass concentration of Hb and the absolute content of HbA1c in the sample. When both the mass concentration of Hb and the absolute content of HbA1c in the sample change, there may be cases where the mass concentration of Hb and the absolute content of HbA1c in two hemoglobin standards are different, but the HbA1c value is the same. For samples with Hb values ​​higher than the preset Hb, the HbA1c values ​​measured by latex turbidimetry are close to the true values ​​and do not require correction. Therefore, the first linear regression equation between the scattered light intensity value measured by latex turbidimetry and the HbA1c value measured by HPLC for the first hemoglobin standard can be used as the correction standard to obtain correction parameters for the scattered light intensity value measured by latex turbidimetry for the second hemoglobin standard. Before correction, the scattered light intensity value of the second hemoglobin group needs to be processed: first, obtain the scattered light intensity value per unit Hb value in the second hemoglobin group, i.e., the scattered light intensity coefficient C; then calculate the result of multiplying the first Hb value in the first hemoglobin group by the scattered light coefficient C of the second hemoglobin group to obtain the converted scattered light intensity value D of the second Hb value. The reason for obtaining the scattered light intensity D corresponding to the second Hb value is to predict the Δ scattered light intensity of a low Hb sample when Hb and HbA1c are increased proportionally to the normal Hb concentration. The scattered light intensity C per unit Hb is to eliminate the influence of Hb concentration on the scattered light intensity B2. After eliminating the influence of Hb, multiplying by the normal Hb value can predict the Δ scattered light intensity D that latex can saturately adsorb at the HbA1c concentration. The second linear regression equation is established by using the scattered light intensity D of the second Hb value and the HbA1c value corresponding to the second Hb value in the hemoglobin group determined by HPLC. The purpose of obtaining this linear regression equation is to determine whether the predicted scattered light intensity D of the low Hb value is correct. If it is correct, no correction is needed, and the "D" value is the Δ scattered light intensity corresponding to the correct low Hb value. If it is incorrect, "D" needs to be corrected.

[0094] In step S407, the method for calculating the correction parameter in the correction formula through the first linear regression equation and the second linear regression equation includes making y1 = y2.

[0095] In any embodiment of the present invention, the number of hemoglobin groups is multiple. When the number of hemoglobin groups is greater than 5, a more accurate first linear regression equation and second linear regression equation can be obtained. The more hemoglobin groups there are, the more data is available for fitting the first and second linear regression equations, resulting in more accurate and reliable equations. This leads to more accurate correction parameters obtained from the first and second linear regression equations, and thus, a more accurate determination of the true HbA1c concentration can be obtained through these correction parameters.

[0096] When the HbA1c value under the first Hb information of the hemoglobin group is different from the HbA1c value under the second Hb information, a batch of samples with the same Hb value but different HbA1c and scattered light intensity can be selected from multiple hemoglobin groups as the first hemoglobin sample.

[0097] In any embodiment of the present invention, step S407 includes:

[0098] S4071. Using the slope a1 of the first linear regression equation and the slope a2 of the second linear regression equation, we obtain the corrected slope k = a2 / a1.

[0099] S4072. Using the intercept b1 of the first linear regression equation and the intercept b2 of the second linear regression equation, we obtain the corrected intercept b = (b2 - b1) / a1.

[0100] S4073. The converted scattered light intensity value D, the corrected slope k, and the corrected intercept b of the scattered light intensity value M of the sample to be tested determined by the latex turbidimetric method are used to obtain the correction formula E = k * D + b, where E is the corrected scattered light intensity value.

[0101] The correction parameters include the correction slope and the correction intercept. Using the above calculation method, the correction slope k and correction intercept b are calculated when y1 = y2. The reason for obtaining the correction slope k and correction intercept b through y1 = y2 is to correct the predicted low Hb value Δscattered light intensity "D". Tests have errors; the HbA1c results of two samples tested by HPLC may be the same, possibly due to the number of decimal places retained or other errors, and their true HbA1c values ​​may not be the same. Similarly, the same situation exists when testing HbA1c concentration by latex turbidimetric methods. Therefore, the regression equation of "D" with HPLC will inevitably differ from the regression equation of Δscattered light intensity of a normal Hb concentration sample with HPLC. The correction parameters directly act on "D" and can correct this difference. By correcting the converted scattered light intensity value D of the scattered light intensity value M of the test sample determined by the latex turbidimetric method using the correction slope k and correction intercept b, the accuracy of the corrected Δscattered light intensity D can be guaranteed. The “D” value is the predicted Δ scattered light intensity of HbA1c concentration under normal Hb concentration, but this value is bound to have errors and needs to be corrected.

[0102] In some embodiments of the present invention, the first Hb information includes a first Hb value, which ranges from 120 to 160 g / L. The first Hb value can be 120 g / L, 140 g / L, or 160 g / L. The range of 120 to 160 g / L is chosen to ensure that the HbA1c value corresponding to the first Hb value detected by the latex turbidimetric method is close to the true value and does not require correction. Using this as a benchmark to correct the HbA1c value corresponding to the second Hb value ensures the accuracy of the corrected HbA1c value. It should be noted that the range of the first Hb value is not limited to this; any Hb range that allows for normal HbA1c test values ​​without requiring correction is acceptable.

[0103] In some embodiments of the present invention, the first Hb information includes a first HCT value, which ranges from 37% to 50%. The first HCT value can be 37%, 45%, or 50%, and the range of 37% to 50% is to ensure that the HbA1c value corresponding to the first HCT value detected by the latex turbidimetric method is close to the true value. It should be noted that the range of the first HCT value is not limited to this; any HCT range that allows the HbA1c test value to be normal and does not require correction is acceptable. Low HCT samples can be samples with an HCT value <15%.

[0104] In latex turbidimetry, the following factors affect the Hb criticality information used to determine whether correction is needed: 1) the size, surface modification, and concentration of latex microspheres used vary among different detection reagents; 2) the types of antibodies used differ (including primary and secondary antibodies); 3) the antibody concentrations differ; 4) the types and concentrations of buffers, salt ions, protective agents, preservatives, and blocking agents in the reagent system differ; and 5) the hemolysis methods, hemolysin types, dilution factors, hemolyzed sample volumes, concentrations of physically adsorbed latex, concentrations of monoclonal antibody-antibody complexes, reaction times, and reaction temperatures differ among reaction systems. These factors lead to variations in the Hb criticality information used to determine whether correction is needed for different detection systems. The corrected Hb criticality information is the preset Hb information. Methods for confirming the critical Hb / HCT value requiring correction for each detection system include comparing it with the HbA1c value detected by the gold standard HPLC. If the correlation coefficient R... 2 If the Hb value is >0.95 and the relative deviation from the HPLC result is <7% (accuracy requirements of the domestic industry standard for glycated hemoglobin), then the Hb information is confirmed as the preset Hb information. In any embodiment of the present invention, before step S20, the preset Hb information is calculated. The step of calculating the preset Hb information includes:

[0105] S21. Calculate the corrected scattered light intensity value E corresponding to the second Hb information in multiple hemoglobin groups using the corrected formula E=k*D+b.

[0106] S22. Calculate the corrected Hb information Z of the second Hb information in multiple hemoglobin groups by using multiple corrected scattered light intensity values ​​E and the scattered light intensity coefficient C corresponding to the second Hb information in multiple hemoglobin groups, where Z = E / C;

[0107] S23. Calculate the average value X of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups using the corrected Hb information Z of the second Hb information in multiple hemoglobin groups;

[0108] S24. Calculate the standard deviation SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups using the corrected Hb information Z of the second Hb information in multiple hemoglobin groups.

[0109] S25. Calculate the preset Hb information using the average value X of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups and the standard deviation SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups.

[0110] In step S22, the corrected Hb value Z for the second Hb value in the hemoglobin group is calculated by comparing the corrected scattered light intensity value E with the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group. This is because both C and E change with HbA1c concentration; comparing the two eliminates the influence of HbA1c concentration, and their ratio is only affected by Hb concentration. E represents the corrected Δscattered light intensity. For the same sample, the Δscattered light intensity is the same when Hb / HCT is equal to or higher than the critical value, i.e., "E". Therefore, E / C can be used to obtain the critical Hb concentration or HCT value to be corrected. The corrected Hb information Z for the second Hb information calculated by Z = E / C is the critical Hb information for a hemoglobin group. Statistical processing is performed on the multiple critical Hb information values ​​calculated from multiple hemoglobin groups, i.e., the average value X and standard deviation SD of the multiple critical Hb information values ​​are taken. Based on X and SD, the preset Hb information is calculated. Preset Hb information calculated from multiple hemoglobin groups can eliminate errors introduced by testing, ensuring that the preset Hb information is applicable to samples with a wider range of HbA1c and Hb concentrations.

[0111] In any embodiment of the present invention, in step S25, the relationship between the average value X of the preset Hb information and the corrected Hb information Z of the second Hb information in multiple hemoglobin groups and the standard deviation value SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups is: preset Hb information = X + 2*SD.

[0112] The formula for calculating the preset Hb information is: Preset Hb information = X + 2 * SD. Calculating the preset Hb information using this formula ensures that samples with critical Hb information higher than the mean of critical Hb information can also be corrected.

[0113] The present invention also provides an apparatus for modifying the latex turbidimetric method for testing HbA1c values, used to implement the steps of the method for modifying the latex turbidimetric method for testing HbA1c values, the apparatus comprising:

[0114] The acquisition module is used to acquire the Hb information of the sample to be tested, the HbA1c value of the sample to be tested, and the scattered light intensity value M of the sample to be tested.

[0115] The comparison module is used to compare the preset Hb information with the Hb information of the sample to be tested;

[0116] The correction module is used to correct the HbA1c value of the sample under test when the Hb information is less than or equal to a preset Hb information, thereby obtaining the corrected HbA1c value of the sample under test; and,

[0117] The display module is used to display the Hb information of the sample under test and the corrected HbA1c value of the sample under test.

[0118] In any embodiment of the present invention, the apparatus for correcting the HbA1c value by latex turbidimetric method further includes a calculation module for calculating the corrected HbA1c value of the sample to be tested.

[0119] The device for testing HbA1c values ​​using the modified latex turbidimetric method includes a module for acquiring Hb information of the sample and a module for acquiring the HbA1c value and scattered light intensity value M of the sample. The detection method used by the module for acquiring the HbA1c value and scattered light intensity value M is the latex turbidimetric method. Therefore, the device for testing HbA1c values ​​using the modified latex turbidimetric method can simultaneously detect the Hb information, HbA1c value, and scattered light intensity value of the sample. Based on the Hb information of the sample, the system automatically corrects and adjusts the HbA1c value result, and the correction is performed simultaneously with the HbA1c test. The corrected result is directly displayed without the need for retesting.

[0120] The apparatus for testing HbA1c using the modified latex turbidimetric method possesses all the technical solutions of the method for testing HbA1c using the modified latex turbidimetric method, and therefore also has all the beneficial effects brought about by the aforementioned technical solutions, which will not be elaborated upon here. The apparatus for testing HbA1c using the modified latex turbidimetric method can be applied to special application scenarios, including but not limited to laboratories.

[0121] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that the following embodiments are only used to explain the present invention and are not intended to limit the present invention.

[0122] Example 1

[0123] A method for correcting the latex turbidimetric assay for HbA1c values, wherein the latex turbidimetric assay is performed using a glycated hemoglobin assay kit (immunoturbidimetric assay) (Zhongyuan Huiji, Lot: H231104). The reagents include R0, R1, and R2, where R0 is a hemolysin, R1 is physically adsorbed latex, and R2 is a monoclonal antibody-antibody complex. The detection steps are as follows: The sample is aspirated into the fully automated glycated hemoglobin analyzer, and hemolyzed using R0 for 30 seconds. The hemolyzed sample is then reacted with R1 at 37°C for 3 minutes, followed by the addition of R2 and a reaction for 1 minute. The absorbance value (i.e., the intensity of scattered light) at 600 nm is then measured. The correction method includes the following steps:

[0124] S10. Obtain the Hb value, HbA1c value, and scattered light intensity M of the sample to be tested; the sample information is shown in Table 1, and there are 145 samples to be tested.

[0125] Table 1 Information on the samples to be tested

[0126]

[0127]

[0128]

[0129]

[0130] S20. Obtain a preset Hb value, wherein the preset Hb value is 51.48908059; compare the preset Hb value with the Hb value of the sample to be tested;

[0131] S30. When the Hb value of the sample to be tested is greater than the preset Hb value, the HbA1c value of the sample to be tested is displayed; the sample to be tested with an Hb value greater than the preset Hb value is sample number 55 to 145, and its HbA1c is shown in Table 1.

[0132] S40. When the Hb value of the sample to be tested is less than the preset Hb value, the HbA1c value of the sample to be tested is corrected to obtain the corrected HbA1c value of the sample to be tested; the samples to be tested whose Hb value is less than the preset Hb value are sample numbers 1 to 54, and their corrected HbA1c values ​​are shown in Table 1.

[0133] S401-S404. Obtain the hemoglobin information of HbA1c determined by latex turbidimetric assay, as shown in Table 2.

[0134] Table 2 Hemoglobin group information

[0135]

[0136]

[0137] S405-S406. Using the HbA1c value of the first hemoglobin standard determined by HPLC in Table 2 and the scattered light intensity value of the first hemoglobin standard determined by latex turbidimetric method, the first linear regression equation y1 = 0.0024x1 + 2.2939 is obtained; using the scattered light intensity value D of the second hemoglobin standard in Table 2 and the HbA1c value of the second hemoglobin standard determined by HPLC, the second linear regression equation y2 = 0.0011x2 + 1.9711 is obtained.

[0138] S4071, Corrected slope k = a2 / a1 = 0.455398813;

[0139] S4072, Corrected intercept b = (b2 - b1) / a1 = -135.6166042;

[0140] S4073, The corrected formula is E=k*D+b;

[0141] S410. Calculate the corrected scattered light intensity value of the sample under test according to the correction formula E=k*D+b, where E is the correction parameter of the scattered light intensity value, k is the correction slope, D is the converted scattered light intensity value of the sample under test, and b is the correction intercept.

[0142] S420. Based on the corrected scattered light intensity value E of the sample to be tested and the standard curve between the scattered light intensity value and the HbA1c value of the hemoglobin standard, calculate the corrected HbA1c value of the sample to be tested; the standard curve between the scattered light intensity value and the HbA1c value of the hemoglobin standard is: y=(AD) / [1+(x / C)^B]+D, where A=7110.56964, B=-2.09311, C=10.87478, D=-50.39333, y is the scattered light intensity value of the hemoglobin standard, and x is the HbA1c value of the hemoglobin standard;

[0143] The hemoglobin group information used to calculate the preset Hb value is shown in Table 3.

[0144] Table 3 shows the hemoglobin group information used to calculate the preset Hb value.

[0145]

[0146]

[0147] The average value of the corrected Hb value Z is X = 49.88708485; the standard deviation of the corrected Hb value Z is SD = 0.80099787; the preset Hb value is X + 2 * SD = 51.48908059.

[0148] Example 2

[0149] A method for correcting the HbA1c value test using the latex turbidimetric assay, wherein the latex turbidimetric assay is performed using the method of Example 1, and the correction method includes the following steps:

[0150] S10. Obtain the HCT value, HbA1c value, and scattered light intensity value M of the sample to be tested; the sample information is shown in Table 4, and there are 145 samples to be tested.

[0151] Table 4 Information on the samples to be tested

[0152]

[0153]

[0154]

[0155]

[0156] S20. Obtain a preset HCT value, wherein the preset HCT value is 20.6347301; compare the preset HCT value with the HCT value of the sample to be tested;

[0157] S30. When the HCT value of the sample to be tested is greater than the preset HCT value, the HbA1c value of the sample to be tested is displayed; the sample to be tested with an HCT value greater than the preset HCT value is sample number 56 to 130, and its HbA1c is shown in Table 4.

[0158] S40. When the HCT value of the sample to be tested is less than the preset HCT value, the HbA1c value of the sample to be tested is corrected to obtain the corrected HbA1c value of the sample to be tested; the sample to be tested whose HCT value is less than the preset HCT value is sample number 1 to 55, and its corrected HbA1c value is shown in Table 4.

[0159] S401-S404. Obtain the hemoglobin information of HbA1c determined by latex turbidimetric assay, as shown in Table 5.

[0160] Table 5 Hemoglobin group information

[0161]

[0162]

[0163] S405-S406. Using the HbA1c value of the first hemoglobin standard determined by HPLC in Table 5 and the scattered light intensity value of the first hemoglobin standard determined by latex turbidimetric method, the first linear regression equation y1 = 0.0021x1 + 2.7973 is obtained; using the scattered light intensity value D of the second hemoglobin standard in Table 5 and the HbA1c value of the second hemoglobin standard determined by HPLC, the second linear regression equation y2 = 0.0012x2 + 2.3382 is obtained.

[0164] S4071, Corrected slope k = a2 / a1 = 0.565560722;

[0165] S4072, Corrected intercept b = (b2 - b1) / a1 = -220.8464131;

[0166] S4073. The formula for calculating the corrected scattered light intensity value E is E=k*D+b;

[0167] S410. Calculate the corrected scattered light intensity value of the sample under test according to the correction formula E=k*D+b, where E is the correction parameter of the scattered light intensity value, k is the correction slope, D is the converted scattered light intensity value of the sample under test, and b is the correction intercept.

[0168] S420. Based on the corrected scattered light intensity value E of the sample to be tested and the standard curve between the scattered light intensity value and the HbA1c value of the hemoglobin standard, calculate the corrected HbA1c value of the sample to be tested; the standard curve between the scattered light intensity value and the HbA1c value of the hemoglobin standard is: y=(AD) / [1+(x / C)^B]+D, where A=7110.56964, B=-2.09311, C=10.87478, D=-50.39333, y is the scattered light intensity value of the hemoglobin standard, and x is the HbA1c value of the hemoglobin standard;

[0169] The hemoglobin group information used to calculate the preset HCT value is shown in Table 6.

[0170] Table 6 shows the hemoglobin group information used to calculate the preset HCT value.

[0171] serial number Corrected scattered light intensity value E Scattered light intensity coefficient C Corrected HCT value Z (%) 1 1946 95.79 20.31688941 2 1505 76.31 19.72838556 3 1076 57.31 18.76921199 4 1277 66.19 19.28611276 5 1535 77.61 19.7770082 6 956 52.03 18.37803689 7 1576 79.41 19.84139998 8 1328 68.46 19.3962877 9 1817 90.09 20.17094844 10 1528 77.31 19.76582855 11 1082 57.60 18.78850981 12 1053 56.30 18.6999329 13 1298 67.14 19.33322699 14 1475 74.96 19.67623875 15 1727 86.08 20.05693329 16 1366 70.16 19.47445239 17 1672 83.65 19.98232945 18 1768 87.92 20.11052701 19 994 53.72 18.51143505 20 1104 58.55 18.85039649 21 1361 69.92 19.46403586 22 1768 87.91 20.11015488 23 1435 73.19 19.60492344 24 1186 62.17 19.07000627 25 1268 65.83 19.26749431 26 1801 89.37 20.15117667 27 1666 83.41 19.97457441 28 1434 73.17 19.60397742 29 1097 58.26 18.83140175 30 1101 58.41 18.84149823 31 1901 93.79 20.2678164 32 1738 86.60 20.07223936

[0172] The average value of the corrected HCT value Z is X = 19.50541846; the standard deviation of the corrected HCT value Z is SD = 0.56465582; the preset HCT value is X + 2 * SD = 20.6347301.

[0173] Comparative Example 1

[0174] Comparative Example 1 uses a latex microsphere coupled with antibodies that can simultaneously bind to hemoglobin and glycated hemoglobin to test the HbA1c value of anemic patients using a latex turbidimetric method in a manner that solidifies hemoglobin and glycated hemoglobin.

[0175] Since this method also tests the HbA1c value in the sample by quantifying the content of latex microspheres in the reaction system, it also has the problem of low HbA1c test value when the Hb content in the sample is insufficient to saturate the latex microspheres, resulting in relatively low detection accuracy.

[0176] Performance testing

[0177] The accuracy of the modified latex turbidimetric method for testing HbA1c values ​​in Examples 1, 2 and Comparative Example 1 was investigated.

[0178] Hb information was used to correct the test samples in Table 1 of Example 1. Correlation analysis was performed on the HbA1c values ​​before correction detected by latex turbidimetry and the HbA1c values ​​detected by the HPLC gold standard method, respectively. Two correlation coefficients were obtained, and the accuracy of the correction method was determined by the magnitude of the correlation coefficients. The results are shown in Table 7. Figure 2 and Figure 3 As shown.

[0179] Table 7. HbA1c values ​​of the test samples before and after testing using the latex turbidimetric method for Hb value correction.

[0180]

[0181]

[0182] Table 7 shows that for the 54 samples (sample numbers 1-54) with Hb levels within 60 g / L, using Hb information for correction reduced the maximum relative deviation between the corrected HbA1c values ​​and the HPLC HbA1c values ​​from 33% to 4%, significantly improving accuracy. For the 145 samples with Hb levels ranging from 26 to 207 g / L, the accuracy was further improved. Figure 2 and Figure 3 The comparison shows that the correlation coefficient R between the HbA1c values ​​before and after correction by the latex turbidimetric method and the HbA1c values ​​detected by the HPLC method is [missing information]. 2 The correlation was significantly improved, increasing from 0.8694 to 0.9925 (>0.95).

[0183] HCT information was used to correct the HbA1c values ​​in Table 4 of Example 2. Correlation analysis was performed on the uncorrected HbA1c values ​​detected by latex turbidimetry and the HbA1c values ​​detected by the HPLC gold standard method, and two correlation coefficients were obtained. The accuracy of the correction method was determined by the magnitude of the correlation coefficients. The results are shown in Table 8. Figure 4 and Figure 5 As shown.

[0184] Table 8. HbA1c values ​​of the test samples before and after testing using the HCT-corrected latex turbidimetric method.

[0185]

[0186]

[0187] Table 8 shows that for the 55 samples (sample numbers 1-55) with Hb levels within 60 g / L, HCT was used to correct the results. After correction, the maximum relative deviation between the HbA1c values ​​and the HPLC HbA1c values ​​decreased from 33% to 5%, significantly improving accuracy. For the 145 samples with Hb levels ranging from 26 to 207 g / L, the results were further improved. Figure 4 and Figure 5 It can be seen that the correlation coefficient R between the HbA1c values ​​before and after correction by the latex turbidimetric method and the HbA1c values ​​detected by the HPLC method is... 2The correlation was significantly improved, increasing from 0.8694 to 0.991 (>0.95).

[0188] Samples with Hb < 110 g / L or HCT < 40% were tested using the method described in Comparative Example 1, and the results are shown in Table 9.

[0189] Table 9. Samples tested using the modified latex turbidimetric method in Comparative Examples 1, 1, and 2

[0190]

[0191]

[0192]

[0193] As shown in Table 9, when measuring samples with Hb > 80 g / L, the method used in Comparative Example 1 showed a deviation of less than 7% from the HPLC results, indicating relatively accurate results. However, when the sample Hb < 80 g / L, the deviation from the HPLC results was greater than 7%, with the deviation increasing as the Hb level decreased. When Hb was as low as 30 g / L, the deviation from the HPLC results exceeded 10%, failing to completely eliminate the influence of low Hb samples on HbA1c measurements. In contrast, after correcting the results using the method of this invention, even when the sample Hb was as low as 30 g / L, the deviation from the HPLC results was less than 5%, making it closer to the true value than the method used in Comparative Example 1 when measuring low Hb samples.

[0194] In summary, the modified latex turbidimetric method for testing HbA1c values ​​of the present invention has a wide range of applicable Hb samples, ranging from 30 to 200 g / L, meeting the clinical needs for Hb content range. By correcting the test results based on Hb or HCT values, the method can eliminate the influence of individual differences in Hb or HCT levels on HbA1c results, meeting the testing needs of individuals with different degrees of anemia and healthy individuals. Furthermore, the method directly corrects the HbA1c value of the sample to be tested, eliminating the need for retesting and saving testing time and costs.

[0195] The above are merely preferred embodiments of the present invention and do not limit the patent scope of the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the patent protection scope of the present invention.

Claims

1. A method for testing HbA1c values ​​using a modified latex turbidimetric method, characterized in that, Includes the following steps: S10. Obtain the Hb information of the sample to be tested, the HbA1c value of the sample to be tested, and the scattered light intensity value M of the sample to be tested; S20. Compare the preset Hb information with the Hb information of the sample to be tested; S30. When the Hb information of the sample to be tested is greater than the preset Hb information, the HbA1c value of the sample to be tested is displayed. S40. When the Hb information of the sample to be tested is less than or equal to the preset Hb information, the HbA1c value of the sample to be tested is corrected to obtain the corrected HbA1c value of the sample to be tested. The Hb information includes Hb value and HCT value; In step S40, the correction method includes: S401. Obtain the hemoglobin set of HbA1c determined by latex turbidimetric assay, wherein the hemoglobin set contains an HbA1c value under a first Hb information and an HbA1c value under a second Hb information, wherein the first Hb information > preset Hb information > second Hb information; obtain the scattered light intensity value B1 corresponding to the first Hb information and the scattered light intensity value B2 corresponding to the second Hb information determined by latex turbidimetric assay; wherein the first Hb information includes a first Hb value and the second Hb information includes a second Hb value; or, the first Hb information includes a first HCT value and the second Hb information includes a second HCT value. S402. Obtain the HbA1c value corresponding to the first Hb information and the HbA1c value corresponding to the second Hb information in the hemoglobin group by HPLC determination. S403. The scattered light intensity value B2 corresponding to the second Hb information determined by the latex turbidimetric method and the second Hb information are used to calculate the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group, where C=B2 / second Hb information; S404. Calculate the converted scattered light intensity value D of the second Hb information using the scattered light intensity coefficient C corresponding to the second Hb information in the hemoglobin group and the first Hb information, where D = C * first Hb information; S405. The first linear regression equation is obtained by taking the HbA1c value corresponding to the first Hb information in the hemoglobin group determined by HPLC and the scattered light intensity value B1 corresponding to the first Hb information determined by latex turbidimetric method: y1=a1*x1+b1; where y1 is the HbA1c value corresponding to the first Hb information in the hemoglobin group determined by HPLC, x1 is the scattered light intensity value B1 corresponding to the first Hb information determined by latex turbidimetric method, a1 is the slope of the first linear regression equation, and b1 is the intercept of the first linear regression equation. S406. By using the converted scattered light intensity value D of the second Hb information and the HbA1c value corresponding to the second Hb information in the hemoglobin group determined by HPLC, the second linear regression equation y2=a2*x2+b2 is obtained; where y2 is the HbA1c value corresponding to the second Hb information in the hemoglobin group determined by HPLC, x2 is the converted scattered light intensity value D of the second Hb information, a1 is the slope of the second linear regression equation, and b2 is the intercept of the second linear regression equation. S407. Calculate the corrected formula using the first and second linear regression equations; Step S407 includes: S4071. Using the slope a1 of the first linear regression equation and the slope a2 of the second linear regression equation, we obtain the corrected slope k = a2 / a1. S4072. Using the intercept b1 of the first linear regression equation and the intercept b2 of the second linear regression equation, we obtain the corrected intercept b = (b2 - b1) / a1. S4073. The converted scattered light intensity value D, the corrected slope k, and the corrected intercept b of the scattered light intensity value M of the sample to be tested determined by the latex turbidimetric method are used to obtain the correction formula E=k*D+b, where E is the corrected scattered light intensity value. S410. Calculate the corrected scattered light intensity value of the sample under test according to the correction formula E=k*D+b, where E is the corrected scattered light intensity value of the sample under test, k is the correction slope, D is the converted scattered light intensity value of the scattered light intensity M of the sample under test, and b is the correction intercept. S420. Calculate the corrected HbA1c value of the test sample based on the corrected scattered light intensity value E of the test sample and the standard curve between the scattered light intensity value and HbA1c value of the hemoglobin standard.

2. The method for testing HbA1c values ​​using the modified latex turbidimetric method as described in claim 1, characterized in that, The number of hemoglobin groups is multiple.

3. The method for testing HbA1c values ​​using the modified latex turbidimetric method as described in claim 1, characterized in that, The first Hb information includes a first Hb value, which ranges from 120 to 160 g / L; or, The first Hb information includes a first HCT value, which ranges from 37% to 50%.

4. The method for testing HbA1c values ​​using the modified latex turbidimetric method as described in claim 1, characterized in that, Before step S20, the calculation of preset Hb information includes the following steps: S21. Calculate the corrected scattered light intensity value E corresponding to the second Hb information in multiple hemoglobin groups using the corrected formula E=k*D+b. S22. Calculate the corrected Hb information Z of the second Hb information in multiple hemoglobin groups by using multiple corrected scattered light intensity values ​​E and the scattered light intensity coefficient C corresponding to the second Hb information in multiple hemoglobin groups, where Z=E / C; S23. Calculate the average value X of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups using the corrected Hb information Z of the second Hb information in multiple hemoglobin groups; S24. Calculate the standard deviation SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups using the corrected Hb information Z of the second Hb information in multiple hemoglobin groups. S25. Calculate the preset Hb information using the average value X of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups and the standard deviation SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups.

5. The method for testing HbA1c values ​​using the modified latex turbidimetric method as described in claim 4, characterized in that, In step S25, the relationship between the average value X of the preset Hb information and the corrected Hb information Z of the second Hb information in multiple hemoglobin groups and the standard deviation value SD of the corrected Hb information Z of the second Hb information in multiple hemoglobin groups is: preset Hb information = X + 2 * SD.

6. An apparatus for testing HbA1c values ​​using a modified latex turbidimetric method, characterized in that, include: The acquisition module is used to acquire the Hb information of the sample to be tested, the HbA1c value of the sample to be tested, and the scattered light intensity value M of the sample to be tested. The comparison module is used to compare the preset Hb information with the Hb information of the sample to be tested; The correction module is configured to correct the HbA1c value of the test sample by means of the method for correcting the HbA1c value of the latex turbidimetric method as described in any one of claims 1 to 5 when the Hb information of the test sample is less than or equal to a preset Hb information, thereby obtaining the corrected HbA1c value of the test sample; and, The display module is used to display the Hb information of the sample under test and the corrected HbA1c value of the sample under test.

7. The apparatus for testing HbA1c values ​​using the modified latex turbidimetric method as described in claim 6, characterized in that, The apparatus for correcting the latex turbidimetric method for testing HbA1c values ​​also includes a calculation module for calculating the corrected HbA1c value of the sample to be tested.

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