Biochemical analyzer and detection method for detecting glycated hemoglobin

Abstract

The application relates to a biochemical analyzer and a detection method for detecting glycated hemoglobin. The hemoglobin concentration and the glycated hemoglobin concentration of a to-be-detected whole blood sample are obtained, and the content proportion of the glycated hemoglobin is calculated according to the hemoglobin concentration and the glycated hemoglobin concentration. The hemoglobin concentration is obtained by the following steps: obtaining a first absorbance of a to-be-detected sample liquid at a hemoglobin measurement wavelength, wherein the to-be-detected sample liquid is prepared by mixing a to-be-detected whole blood sample, a hemolytic agent and a hemoglobin detection reagent; obtaining at least two second absorbances of the to-be-detected sample liquid at at least two different correction wavelengths, wherein the correction wavelengths are designed so that the absorbance of a lipid interferent at the correction wavelength is greater than the absorbance of hemoglobin at the correction wavelength; correcting the first absorbance according to the second absorbance; and determining the hemoglobin concentration according to the corrected first absorbance. The application can improve the accuracy of hemoglobin detection.

Description

Technical Field

[0001] This application relates to the field of in vitro diagnostics, and in particular to a biochemical analyzer and detection method for detecting glycated hemoglobin. Background Technology

[0002] Glycated hemoglobin (HbA1c), also known as glycosylated hemoglobin, is a product of a non-enzymatic catalytic reaction between glucose and other sugars and the amino groups of hemoglobin (Hb). Its level is positively correlated with the concentration of blood glucose in the human body. Since protein glycation is an irreversible reaction and red blood cells have a lifespan of 120 days in the bloodstream, glycated hemoglobin can reflect the average blood glucose concentration over the past three months, thus serving as a blood glucose control indicator and is widely used in clinical diagnosis and treatment monitoring.

[0003] In existing technologies, immunoturbidimetry or enzymatic methods are known to be used for the detection of glycated hemoglobin (HbA1c). However, when using immunoturbidimetry and enzymatic methods to detect HbA1c in samples with lipid turbidity, they are easily affected by the negative interference of lipid interfering substances; the higher the concentration of lipid interfering substances, the lower the HbA1c detection result. Furthermore, the pathological symptoms of clinical hyperglycemia and the testing scenario exacerbate the influence of lipid interfering substances on HbA1c detection. This is because hyperglycemia and hyperlipidemia are positively correlated, and patients with hyperglycemia often also have hyperlipidemia in clinical examinations. Therefore, the HbA1c measurement results of samples from patients with hyperglycemia are also easily affected by lipid interference. In addition, patients are not required to be in a fasting state for HbA1c testing in clinical practice. Therefore, patients may undergo HbA1c testing immediately after eating, leading to chylous particles entering the bloodstream after a meal interfering with the HbA1c results. Furthermore, since glycated hemoglobin testing uses whole blood samples, blood cells are mixed with plasma. Even though lipids appear milky white in plasma and can be identified by the naked eye, they are difficult for clinical laboratory personnel to detect in a lipid-laden sample after mixing with blood cells. This lipid component mixed in the sample solution affects the detection process of the photometric device, thus affecting the accuracy of hemoglobin testing, and consequently affecting the accuracy of glycated hemoglobin testing. Summary of the Invention

[0004] Therefore, the objective of this application is to provide a biochemical analyzer and corresponding detection method for detecting glycated hemoglobin, which can reduce the influence of lipid interfering substances on hemoglobin detection, thereby obtaining more accurate glycated hemoglobin detection results.

[0005] To achieve the aforementioned objectives of this application, the first aspect of this application proposes a biochemical analyzer for detecting glycated hemoglobin, comprising:

[0006] The sample preparation apparatus is configured to prepare a lysis buffer from a whole blood sample to be tested and a hemolysin, prepare a first test sample solution from the lysis buffer and a first detection reagent for detecting hemoglobin, and prepare a second test sample solution from the first test sample solution and a second detection reagent for glycated hemoglobin.

[0007] An optical detection device is configured to perform optical measurements on the first sample liquid to be tested and the second sample liquid to be tested, respectively.

[0008] The controller is communicatively connected to the optical detection device and is configured to:

[0009] The optical detection device is controlled to detect the first absorbance of the first test sample solution at the hemoglobin measurement wavelength, and to detect at least two second absorbances of the first test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than the absorbance of hemoglobin at the calibration wavelength.

[0010] The first absorbance is corrected based on the at least two second absorbance values, and the hemoglobin concentration is determined based on the corrected first absorbance value;

[0011] The optical detection device is controlled to perform optical measurements on the second sample solution to obtain the glycated hemoglobin concentration of the whole blood sample; and

[0012] The percentage of glycated hemoglobin in the whole blood sample to be tested is calculated based on the hemoglobin concentration and the glycated hemoglobin concentration.

[0013] In the biochemical analyzer for detecting glycated hemoglobin provided in the first aspect of this application, the first absorbance of the first sample solution at the hemoglobin measurement wavelength can be corrected according to multiple second absorbances at multiple different correction wavelengths to obtain a more accurate first absorbance, thereby obtaining a more accurate hemoglobin concentration, and thus obtaining a more accurate detection result of the content ratio of glycated hemoglobin.

[0014] The second aspect of this application provides another biochemical analyzer for detecting glycated hemoglobin, comprising:

[0015] The sample preparation apparatus is configured to prepare a lysis buffer from a whole blood sample to be tested and a hemolysin, prepare a first test sample solution from the lysis buffer and a first detection reagent for hemoglobin, and prepare a second test sample solution from the first test sample solution and a second detection reagent for glycated hemoglobin.

[0016] An optical detection device is configured to perform optical measurements on the first sample liquid to be tested and the second sample liquid to be tested, respectively.

[0017] The controller is communicatively connected to the optical detection device and is configured to:

[0018] The optical detection device is controlled to detect the first absorbance of the first test sample solution at the hemoglobin measurement wavelength, and to detect at least two second absorbances of the first test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than the absorbance of hemoglobin at the calibration wavelength.

[0019] Whether to correct the first absorbance is determined based on the relationship between the at least two second absorbances;

[0020] When the relationship between the at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on at least one second absorbance, and the hemoglobin concentration is determined based on the corrected first absorbance.

[0021] The optical detection device is controlled to perform optical measurements on the second sample solution to obtain the glycated hemoglobin concentration of the whole blood sample; and

[0022] The percentage of glycated hemoglobin in the whole blood sample to be tested is calculated based on the hemoglobin concentration and the glycated hemoglobin concentration.

[0023] In the biochemical analyzer for detecting glycated hemoglobin provided in the second aspect of this application, the relationship between multiple second absorbances is used to determine whether to correct the measured first absorbance, so as to avoid correcting samples with no lipid interference or minimal lipid interference, making the correction more targeted to samples affected by lipid interference.

[0024] A third aspect of this application provides a corresponding method for detecting glycated hemoglobin, the method comprising:

[0025] Obtain the hemoglobin concentration of the whole blood sample to be tested; obtain the glycated hemoglobin concentration of the whole blood sample to be tested; and calculate the percentage of glycated hemoglobin in the whole blood sample to be tested based on the hemoglobin concentration and the glycated hemoglobin concentration.

[0026] The method is characterized in that obtaining the hemoglobin concentration of the whole blood sample to be tested includes the following steps:

[0027] The first absorbance of the test sample solution at the hemoglobin measurement wavelength is obtained, wherein the test sample solution is prepared from the test whole blood sample, hemolysin, and hemoglobin detection reagent;

[0028] Obtain at least two second absorbance values ​​of the test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than that of hemoglobin at the calibration wavelength;

[0029] The first absorbance is corrected based on the at least two second absorbance values;

[0030] The hemoglobin concentration is determined based on the corrected first absorbance.

[0031] The method for detecting glycated hemoglobin according to the third aspect of this application is particularly applicable to a biochemical analyzer for detecting glycated hemoglobin according to the first aspect of this application.

[0032] The features and advantages of the method for detecting glycated hemoglobin according to the second aspect of this application can be found in the above description of the biochemical analyzer for detecting glycated hemoglobin according to the first aspect of this application. Attached Figure Description

[0033] Figure 1 These are schematic block diagrams illustrating some embodiments of a biochemical analyzer for detecting glycated hemoglobin provided in this application;

[0034] Figure 2 The diagram shows a structural schematic of some embodiments of a biochemical analyzer for detecting glycated hemoglobin according to this application.

[0035] Figures 3 to 7 This is a schematic flowchart illustrating different embodiments of the controller of a biochemical analyzer for detecting glycated hemoglobin provided in this application for obtaining detection results of glycated hemoglobin;

[0036] Figure 8 A schematic diagram showing the deviation of hemoglobin concentration results before and after correction according to some embodiments of this application;

[0037] Figure 9 This is a schematic diagram showing the deviation of the percentage of glycated hemoglobin content before and after correction according to some embodiments of this application;

[0038] Figure 10 Flowcharts illustrating further embodiments of the acquisition of glycated hemoglobin detection results by the controller of a biochemical analyzer for detecting glycated hemoglobin according to the present application; and

[0039] Figures 11 to 12 This is a schematic flowchart of different embodiments of the glycated hemoglobin detection method provided in this application. Detailed Implementation

[0040] The embodiments of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0041] It should be noted that the terms "first, second, and third" used in the embodiments of this application are merely to distinguish similar objects and do not represent a specific order of objects. It can be understood that "first, second, and third" can be interchanged in a specific order or sequence where permitted.

[0042] In clinical testing, the percentage of glycated hemoglobin concentration to hemoglobin concentration is generally used as the reporting unit. The unit can be, for example, IFCC (mmol / mol), US NGSP (%), Japanese JDS / JSCC (%), and Swedish MonoS (%).

[0043] Currently, the detection of glycated hemoglobin using immunoturbidimetry or enzymatic methods on a biochemical analyzer typically involves the following steps: First, the concentration of hemoglobin in the whole blood sample is determined by measuring the absorbance of the hemoglobin. Then, the concentration of glycated hemoglobin in the whole blood sample is determined by immunoturbidimetry or enzymatic methods. Finally, the percentage of glycated hemoglobin is calculated based on the concentrations of glycated hemoglobin and hemoglobin.

[0044] However, during this process, the lipid components in the whole blood sample scattered some of the light at the wavelength of hemoglobin measurement, leading to a falsely high hemoglobin concentration result, which in turn resulted in a lower calculated percentage of glycated hemoglobin. The lipid components in the whole blood sample can originate from chylomicrons absorbed into the bloodstream after a meal, fats synthesized in the liver (mainly VLDL), or fat emulsions used for energy supplementation in clinical patients (such as Intralipid and Intralipos).

[0045] To address this, existing technology proposes an improved method in which the detection results of glycated hemoglobin are corrected using the absorbance of lipid interfering substances at a single wavelength and a pre-determined formula relating the absorbance of lipid interfering substances to hemoglobin concentration. However, the determination of this formula can be affected by reagent batches and machine variations.

[0046] In view of this, this application proposes a technical solution that can obtain more accurate glycated hemoglobin detection results.

[0047] Please refer to Figure 1This application first proposes a biochemical analyzer for detecting glycated hemoglobin. The biochemical analyzer 100 includes a sample preparation device 110, an optical detection device 120, and a controller 130. The sample preparation device 110 can be configured to prepare a lysis buffer from a whole blood sample to be tested and a hemolysin, prepare a first test sample solution from the lysis buffer and a first detection reagent for detecting hemoglobin, and prepare a second test sample solution from the first test sample solution and a second detection reagent for glycated hemoglobin. The optical detection device 120 can be configured to perform optical measurements on the first and second test sample solutions, respectively. The controller 130 is communicatively connected to the optical detection device 120 and can be configured to control the optical detection device 120 to perform optical measurements on the first and second test sample solutions, respectively, to obtain the detection result of glycated hemoglobin in the whole blood sample (i.e., the percentage of glycated hemoglobin content).

[0048] In this embodiment, a hemolytic agent is used to lyse red blood cells in a whole blood sample to release hemoglobin.

[0049] In some embodiments, the first and second detection reagents may be immunoturbidimetric detection reagents. For example, the first detection reagent may include a glycated hemoglobin-specific antibody (e.g., an anti-human glycated hemoglobin antibody), while the second detection reagent may include a multi-cluster monoantigen (e.g., a glycated hemoglobin polyploid hapten) carrying several glycated hemoglobin antigenic determinants.

[0050] In other alternative embodiments, the first and second detection reagents may be enzymatic detection reagents. For example, the first detection reagent may include a proteolytic enzyme for reacting with glycated hemoglobin to produce glycosylated peptides or glycosylated amino acids, while the second detection reagent may include a specific oxidase for reacting with glycosylated peptides or glycosylated amino acids to generate detectable products such as hydrogen peroxide.

[0051] In some embodiments, the optical detection device 120 can be configured to detect the absorbance of a first test sample solution at a hemoglobin measurement wavelength to obtain the hemoglobin concentration of the whole blood sample based on the absorbance; and to detect the absorbance of a second test sample solution at a glycated hemoglobin measurement wavelength to obtain the glycated hemoglobin concentration of the whole blood sample based on the absorbance. When the first and second detection reagents are enzymatic detection reagents, the hemoglobin measurement wavelength can be approximately 505 nm, and the glycated hemoglobin measurement wavelength can be approximately 660 nm. When the first and second detection reagents are immunoturbidimetric detection reagents, the hemoglobin measurement wavelength can be approximately 505 nm, and the glycated hemoglobin measurement wavelength can be approximately 340 nm.

[0052] In some embodiments, the optical detection device 120 may be configured as a photometer.

[0053] In some embodiments, the controller 130 may include a processor and a storage medium storing a computer program. The controller 130 may be configured to control the optical detection device 120 to perform optical measurements on the first and second sample solutions to obtain the detection results of glycated hemoglobin in the whole blood sample (i.e., the percentage of glycated hemoglobin content).

[0054] Figure 2 A schematic diagram of one embodiment of the biochemical analyzer 100 is shown. Figure 2 As shown, the sample preparation device 110 of the biochemical analyzer 100 includes a sample carrying component 111, a sample dispensing mechanism 112, a reagent carrying component 113, a reagent dispensing mechanism 114, and a reaction component 115.

[0055] The sample carrier 111 is used to carry whole blood samples. For example, the sample carrier 111 can be configured as a sample tray including multiple sample positions for placing the container 10, and the sample tray can be rotated to move the container containing the whole blood sample to a corresponding position, such as a position for the sample dispensing mechanism 112 to aspirate the whole blood sample. The sample dispensing mechanism 112 is used to aspirate the whole blood sample from the container 10 and dispense it into a reaction cup to be dispensed. For example, the sample dispensing mechanism 112 may include a sample needle that can move in two or three dimensions in space via a two-dimensional or three-dimensional drive mechanism, thereby moving the sample needle to the position for aspirating the blood sample and to the reaction cup to be dispensed, and dispensing the aspirated whole blood sample into the reaction cup.

[0056] The reagent carrier 113 is used to carry reagents, including a hemolysin, a first detection reagent, and a second detection reagent. In some embodiments, the reagent carrier 113 may be configured as a reagent tray with a disc-shaped structure having multiple positions for carrying reagent containers. The reagent carrier 113 is rotatable and drives the reagent containers it carries to rotate, so as to rotate the reagent containers to a specific position, such as the position where the reagent dispensing mechanism 114 draws in the reagent. The number of reagent carriers 113 may be one or more. The reagent dispensing mechanism 114 is used to draw in reagents and discharge them into a reaction cup to which the reagent is to be added. For example, the reagent dispensing mechanism 114 may include a reagent needle, which is capable of two-dimensional or three-dimensional movement in space via a two-dimensional or three-dimensional drive mechanism, so that the reagent needle can move to the position for drawing in the reagent and to the reaction cup to which the reagent is to be added, and discharge the drawn-in reagent into the reaction cup.

[0057] The reaction component 115 has at least one placement position for placing a reaction cup and incubating the test solution, such as a first test sample solution and a second test sample solution, in the reaction cup. For example, the reaction component 115 can be configured as a reaction disk with a disk-shaped structure having one or more placement positions for placing reaction cups. The reaction disk is rotatable and can move the reaction cups in its placement positions to adjust the position of the reaction cups and incubate the test solution within the reaction disk.

[0058] The optical detection device 120 is used to detect the sample solution to be tested after incubation in the reaction component 115 to obtain hemoglobin detection results and / or glycated hemoglobin detection results. The optical detection device 120 is, for example, located outside the reaction component 115. The reaction component 115 rotates to move the container containing the sample solution to be tested to the optical detection device 120 for optical measurement.

[0059] Furthermore, in Figure 2 In the illustrated embodiment, the sample preparation apparatus 110 may further include a sample transfer unit (not shown) for transferring the sample solution into a corresponding reaction vessel. In some embodiments, the sample dispensing mechanism 112 may be used as the sample transfer unit.

[0060] by Figure 2 Using the biochemical analyzer 100 shown as an example, an exemplary process for detecting glycated hemoglobin is described. The controller 130 controls the reagent dispensing mechanism 114 to add the lysing agent from the reagent carrier 113 to the first reaction cup located in the reaction unit 115. Then, the controller 130 controls the sample dispensing mechanism 112 to draw a portion of whole blood sample from the container 10 and add it to the first reaction cup containing the lysing agent, thus obtaining a pretreated solution. Next, the controller 130 controls the reagent dispensing mechanism 114 to add the first detection reagent from the reagent carrier 113 to the second reaction cup located in the reaction unit 115. Then, the controller 130 controls the solution transfer unit to draw a portion of the pretreated solution from the first reaction cup and add it to the second reaction cup containing the first detection reagent, thus obtaining a first test sample solution. The reaction disk rotates, moving the second reaction cup to the optical detection device 120, so that the optical detection device 120 can perform optical measurement on the first test sample solution in the second reaction cup, thereby obtaining the hemoglobin concentration of the whole blood sample. Next, the controller 130 controls the reagent dispensing mechanism 114 to add the second detection reagent from the reagent carrier 113 into the second reaction cup located in the reaction component 115 to obtain the second sample solution to be tested. The optical detection device 120 performs optical measurement on the second sample solution to be tested in the second reaction cup to obtain the glycated hemoglobin concentration of the whole blood sample. Finally, the percentage of glycated hemoglobin content is obtained based on the hemoglobin concentration and the glycated hemoglobin concentration.

[0061] The following will combine Figures 3 to 10 The specific procedure for obtaining glycated hemoglobin detection results using the controller 130 of the biochemical analyzer provided in this application is described.

[0062] In some embodiments, such as Figure 3 As shown, controller 130 can be configured to perform the following steps:

[0063] S1000: Control the optical detection device 120 to detect the first absorbance of the first sample solution to be tested at the hemoglobin measurement wavelength, and to detect the first sample solution to be tested at at least two different calibration wavelengths, wherein the calibration wavelength is designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than the absorbance of hemoglobin at the calibration wavelength.

[0064] S1100: Correct the first absorbance based on at least two second absorbance values;

[0065] S1200: Determine the hemoglobin concentration based on the corrected first absorbance;

[0066] S1300: Control the optical detection device 120 to perform optical measurement on the second sample solution to obtain the glycated hemoglobin concentration of the whole blood sample to be tested;

[0067] S1400: Calculate the percentage of glycated hemoglobin in the whole blood sample to be tested based on the hemoglobin concentration and glycated hemoglobin concentration.

[0068] Steps S1000 and S1300 can be executed simultaneously or sequentially, and this application does not make specific limitations on this.

[0069] It is understood that, in this embodiment of the application, when the controller 130 is configured to execute step 1200, it can convert the hemoglobin concentration in the whole blood sample to be tested using the corrected first absorbance (i.e., the absorbance of hemoglobin) and the hemoglobin standard concentration-absorbance calibration relationship. Here, those skilled in the art will understand that the hemoglobin standard concentration-absorbance calibration relationship can be obtained in advance by detecting whole blood samples with different hemoglobin standard concentrations on a biochemical analyzer.

[0070] On the one hand, compared with the prior art which only uses absorbance at a single calibration wavelength for calibration, in this application, the first absorbance of the first sample solution at the hemoglobin measurement wavelength is calibrated based on multiple second absorbances at multiple different calibration wavelengths. This reduces the impact of systematic errors in absorbance measurement, especially the systematic errors of the optical detection device, on the calibration results, and improves the accuracy of determining hemoglobin concentration based on the calibrated first absorbance, thereby improving the accuracy of the glycated hemoglobin content percentage calculated therefrom.

[0071] On the other hand, the calibration object in this application is the first absorbance of the first sample solution to be tested at the wavelength of hemoglobin measurement, so as to determine the hemoglobin concentration in the whole blood sample to be tested based on the first absorbance after calibration, rather than directly calibrating the hemoglobin concentration. This avoids the influence of different batches of machines and reagents on the calibration results, improves the accuracy of hemoglobin concentration calibration, and thus can more accurately obtain the content ratio of glycated hemoglobin.

[0072] In some embodiments, the calibration wavelength may be in the wavelength range of 660 nm to 900 nm, and the hemoglobin measurement wavelength may be in the wavelength range of 450 nm to 660 nm. For example, the calibration wavelength may include 700 nm, 800 nm, and 850 nm wavelengths, while the hemoglobin measurement wavelength may include 505 nm wavelength.

[0073] In some preferred embodiments, such as Figure 4 As shown, controller 130 can be further configured to perform the following steps during the execution of step 1100:

[0074] S2000: Determine whether to correct the first absorbance based on the relationship between at least two second absorbances;

[0075] S2100: When the relationship between at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on the at least two second absorbances.

[0076] Studies have shown that lipid interfering substances in whole blood samples exhibit increased absorption at shorter wavelengths. Therefore, a predefined relationship could include a higher second absorbance at shorter correction wavelengths. In other words, this is determined by whether the following condition is met for i correction wavelengths: A1>A2>…>A… i And λ1<λ2…<λ i , where A i For lipid interferon in λ i The absorbance at that point is used to determine whether the first absorbance needs to be corrected.

[0077] This avoids correcting samples without lipid interference, making the correction more targeted at samples affected by lipid interference.

[0078] Alternative or additional land, such as Figure 5 As shown, the controller 130 can be further configured to perform the following steps during the execution of step S1100:

[0079] S1110: Determine the third absorbance of the lipid interferon at the correction wavelength based on the second absorbance at different correction wavelengths;

[0080] S1120: Determine the target absorbance increase based on at least two third absorbance values;

[0081] S1130: Correct the first absorbance based on the target absorbance increase.

[0082] Understandably, the second absorbance of the first test sample at the calibration wavelength includes the absorbance of the lipid interfering substance and the absorbance of hemoglobin at the calibration wavelength. Therefore, by determining the third absorbance of the lipid interfering substance at different calibration wavelengths, and then correcting the first absorbance based on the third absorbance, the influence of the hemoglobin absorbance in the second absorbance on the calibration result is avoided, further improving the accuracy of glycated hemoglobin detection.

[0083] In some embodiments, the correction wavelength can be designed such that the absorbance of hemoglobin at the correction wavelength is zero; that is, lipid interfering substances absorb at the correction wavelength, while hemoglobin absorbs almost nothing at the correction wavelength. In this case, such as Figure 6 As shown, the controller 130 can be further configured to perform the following steps when executing step S1110:

[0084] S1111: The second absorbance at the calibration wavelength is determined as the third absorbance of the lipid interfering substance at the calibration wavelength.

[0085] In other words, Figure 6 In the illustrated embodiment, the second absorbance of the first test sample solution at the calibration wavelength contains almost only the absorbance of the lipid interfering substances at that calibration wavelength.

[0086] It should be noted that although the calibration wavelength is preferably designed so that the absorbance of hemoglobin at the calibration wavelength is zero, in actual applications, due to hemolysis reaction conditions and measurement sensitivity issues, the absorbance of hemoglobin at the calibration wavelength may not be zero.

[0087] In this case, to avoid the absorbance of hemoglobin at the correction wavelength affecting the correction of the first absorbance, in the alternative... Figure 6 In other embodiments of the illustrated examples, such as Figure 7 As shown, the controller 130 can be further configured to perform the following steps when executing step S1110:

[0088] S1112: Obtain the fourth absorbance of hemoglobin in the first test sample solution at different calibration wavelengths;

[0089] S1113: Subtract the fourth absorbance at the same correction wavelength from the second absorbance at the same correction wavelength to obtain the third absorbance of the lipid interfering substance at the same correction wavelength.

[0090] As one implementation of step S1112, the controller 130 can calculate the fourth absorbance of hemoglobin at the calibration wavelength using the uncorrected hemoglobin concentration and a preset function, such as a preset linear function, where the preset function characterizes the relationship between the uncorrected hemoglobin concentration and the fourth absorbance of hemoglobin at the calibration wavelength. This preset function can be determined experimentally in advance, for example.

[0091] In one example, the preset function can be A. i =K i *C Hb +B i , where A i C represents the absorbance of hemoglobin at the corrected wavelength i. Hb K represents the uncorrected hemoglobin concentration. i To correct the slope of the linear regression for wavelength i, B i To correct the linear regression intercept of wavelength i, i≥2 and i is an integer.

[0092] Understandably, the controller 130 can determine the uncorrected hemoglobin concentration based on the uncorrected first absorbance of the first test sample solution at the hemoglobin measurement wavelength and the hemoglobin standard concentration-absorbance calibration relationship.

[0093] Understandably, the first absorbance of the first sample solution at the hemoglobin measurement wavelength includes the absorbance of hemoglobin at the hemoglobin measurement wavelength and the absorbance of lipid interfering substances at the hemoglobin measurement wavelength. Therefore, in some embodiments, to further improve the accuracy of hemoglobin detection, the controller 130 may be configured to perform the following steps when executing step S1120:

[0094] The amount of absorbance increase of lipid interfering substances at the hemoglobin measurement wavelength was determined based on at least two third absorbance measurements, and

[0095] The median, average, or weighted average of the increase in absorbance of lipid interfering substances at the hemoglobin measurement wavelength is determined as the target increase in absorbance.

[0096] As one implementation method, the applicant discovered through research that, given a fixed hemoglobin measurement wavelength and a corrected wavelength, the third absorbance of the lipid interfering substance at the corrected wavelength is proportional to the increase in absorbance of the lipid interfering substance at the hemoglobin measurement wavelength, i.e., A 抬升量i =A3 i / m i , where A 抬升量i A3 represents the increase in absorbance of lipid interfering substances at the hemoglobin measurement wavelength at the calibration wavelength i. i m represents the third absorbance of the lipid interfering substance at the corrected wavelength i.i To correct the absorbance conversion coefficient corresponding to wavelength i, i≥2 and i is an integer.

[0097] Studies have shown that the absorption spectra of lipid disruptors conform to the power function model E(λ)=P0*λ b (b < 0), where λ is the wavelength, b is the power exponent coefficient of the lipid interfering substance's absorption spectrum, and P0 is a constant. Based on the above power function model, the absorbance conversion coefficient m between the absorbance of the lipid interfering substance at the correction wavelength and the absorbance of the lipid interfering substance at the hemoglobin measurement wavelength... i It can be determined as follows: A3 i / A Hb =λ i b / λ Hb b =m i Among them, A Hb λ represents the absorbance of lipid interfering substances at the wavelength used for measuring hemoglobin, i.e., the increase in absorbance. i To correct wavelength i, λ Hb The wavelength for measuring hemoglobin.

[0098] Those skilled in the art can obtain b-values ​​by measuring a series of whole blood samples containing lipid interfering substances. It is understood that b-values ​​are related to the biochemical analyzer; that is, different biochemical analyzers typically have different b-values. In some embodiments, the b-value can be between -4 and 0, preferably between -3 and 0.

[0099] In some embodiments, the controller 130 may be further configured to subtract the target absorbance increase from the first absorbance obtained in step S1000 when performing step S1130 to obtain the corrected first absorbance.

[0100] A specific example of this application is described using enzymatic detection of glycated hemoglobin. In step S1000, the hemoglobin concentration is measured at a wavelength of 505 nm, that is, the first absorbance A1 of the first sample solution to be tested is detected at the hemoglobin measurement wavelength of 505 nm, and the second absorbances A21, A22 and A23 of the first sample solution to be tested are detected at the calibration wavelengths of 770 nm, 800 nm and 850 nm. In step S1100, since hemoglobin absorbs at 770nm, 800nm, and 850nm, the second absorbances A21, A22, and A23 of the first test sample solution at the corrected wavelengths of 770nm, 800nm, and 850nm are subtracted from the fourth absorbances A41, A42, and A43 of hemoglobin at the corrected wavelengths of 770nm, 800nm, and 850nm to obtain the third absorbances A31 (=A21-A41), A32 (=A22-A42), and A33 (=A23-A43) of the lipid interfering substances at the corrected wavelengths of 770nm, 800nm, and 850nm. The preset function is determined experimentally to be A41 = 1.1065 * C. Hb A42 = 1.027 * C Hb And A43 = 0.9251 * C Hb , where C Hb This represents the uncorrected hemoglobin concentration. Then, in step S1000, the absorbance conversion coefficients corresponding to the corrected wavelengths of 770 nm, 800 nm, and 850 nm are calculated as follows: m 770 =λ 770 b / λ 505 b =770 -2.5 / 505 -2.5 =0.5097, m 800 =λ 800 b / λ 505 b =800 -2.5 / 505 -2.5 =0.4633, m 850 =λ 850 b / λ 505 b =850 2.5 / 505 -2.5=0.3981; and continue to calculate the absorbance increases A51, A52, and A53 of lipid interfering substances at the hemoglobin measurement wavelength using the following conversion relationships: A51 = A31 / 0.5097, A52 = A32 / 0.4633, and A53 = A33 / 0.3981; then calculate the average of the absorbance increases A51, A52, and A53, and subtract the average of the absorbance increases A51, A52, and A53 from the first absorbance A1 to obtain the corrected first absorbance. Then, in step S1200, the corrected hemoglobin concentration is calculated based on the corrected first absorbance and the hemoglobin standard concentration-absorbance calibration relationship. In step S1300, the glycated hemoglobin concentration is measured using 660nm. Finally, in step S1400, the percentage of glycated hemoglobin content is calculated based on the corrected hemoglobin concentration and the glycated hemoglobin concentration. Figure 8 The diagram shows the hemoglobin concentrations of whole blood samples with different glycated hemoglobin concentrations before and after correction, where the horizontal axis represents the concentration of lipid interferons and the vertical axis represents the hemoglobin concentration. Figure 9 The diagram shows the percentage of glycated hemoglobin (HbA1c) in whole blood samples with different HbA1c concentrations before and after correction. The horizontal axis represents the concentration of lipid interferons, and the vertical axis represents the percentage of HbA1c.

[0101] In the alternative Figure 2 In other embodiments, such as Figure 10 As shown, controller 120 can be configured to perform the following steps:

[0102] S3000: Control the optical detection device 120 to detect the first absorbance of the first sample solution to be tested at the hemoglobin measurement wavelength, and to detect the first sample solution to be tested at at least two different calibration wavelengths, wherein the calibration wavelength is designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than the absorbance of hemoglobin at the calibration wavelength.

[0103] S3100: Determine whether to correct the first absorbance based on the relationship between at least two second absorbances;

[0104] S3200: When the relationship between at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on at least one second absorbance;

[0105] S3300: Determine the hemoglobin concentration based on the corrected first absorbance;

[0106] S3400: Control the optical detection device 120 to perform optical measurement on the second sample solution to obtain the glycated hemoglobin concentration of the whole blood sample to be tested;

[0107] S3500: Calculate the percentage of glycated hemoglobin in the whole blood sample to be tested based on hemoglobin concentration and glycated hemoglobin concentration.

[0108] This avoids correcting samples without lipid interference, making the correction more targeted at samples affected by lipid interference.

[0109] In some embodiments, the preset relationship may include a greater second absorbance at shorter correction wavelengths.

[0110] This application also provides a method for detecting glycated hemoglobin, such as... Figure 11 As shown, the method for detecting glycated hemoglobin includes the following steps:

[0111] S4000: Obtain the hemoglobin concentration of the whole blood sample to be tested;

[0112] S4100: Obtain the glycated hemoglobin concentration of the whole blood sample to be tested;

[0113] S4200: Calculate the percentage of glycated hemoglobin in the whole blood sample to be tested based on hemoglobin concentration and glycated hemoglobin concentration.

[0114] Specifically, step S4000 includes the following steps:

[0115] S4010: Obtain the first absorbance of the test sample solution at the hemoglobin measurement wavelength, wherein the test sample solution is prepared from the test whole blood sample, a hemolysin, and a hemoglobin detection reagent (e.g., an enzyme reagent or an immunoassay reagent);

[0116] S4020: Obtain at least two second absorbances of the test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than that of hemoglobin at the calibration wavelength;

[0117] S4030: Correct the first absorbance based on at least two second absorbance values;

[0118] S4040: Determine the hemoglobin concentration based on the corrected first absorbance.

[0119] In some embodiments, such as Figure 12 As shown, step S4030 may specifically include the following steps:

[0120] S4031: Determine the third absorbance of the lipid interferon at the correction wavelength based on the second absorbance at different correction wavelengths;

[0121] S4032: Determine the target absorbance increase based on at least two third absorbance values;

[0122] S4033: Correct the first absorbance based on the target absorbance increase.

[0123] In some embodiments, the method for detecting glycated hemoglobin may further include:

[0124] Whether to correct the first absorbance is determined based on the relationship between at least two second absorbance values;

[0125] When the relationship between at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on the at least two second absorbances.

[0126] In some embodiments, the preset relationship may include a greater second absorbance at shorter correction wavelengths.

[0127] The method for detecting glycated hemoglobin provided in this application is particularly applicable to the biochemical analyzer described above. The advantages and further embodiments of the method for detecting glycated hemoglobin provided in this application can be found in the above description of the biochemical analyzer, and will not be repeated here.

[0128] All features or combinations thereof mentioned in the specification, drawings, and claims are freely combined or used individually, provided they are meaningful within the scope of this application and do not contradict each other. The advantages and features described for the biochemical analyzer provided in this application are applicable in a corresponding manner to the detection methods provided in this application, and vice versa.

[0129] The above description is merely a preferred embodiment of this application and does not limit the patent scope of this application. All equivalent modifications made based on the inventive concept of this application and the contents of the specification and drawings of this application, or direct / indirect applications in other related technical fields, are included within the patent protection scope of this application.

Claims

1. A biochemical analyzer for detecting glycated hemoglobin, comprising: The sample preparation apparatus is configured to prepare a lysis buffer from a whole blood sample to be tested and a hemolysin, prepare a first test sample solution from the lysis buffer and a first detection reagent for detecting hemoglobin, and prepare a second test sample solution from the first test sample solution and a second detection reagent for glycated hemoglobin. An optical detection device is configured to perform optical measurements on the first sample liquid to be tested and the second sample liquid to be tested, respectively. The controller is communicatively connected to the optical detection device and is configured to: The optical detection device is controlled to detect the first absorbance of the first test sample solution at the hemoglobin measurement wavelength, and to detect at least two second absorbances of the first test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than the absorbance of hemoglobin at the calibration wavelength. The first absorbance is corrected based on the at least two second absorbance values, and the hemoglobin concentration is determined based on the corrected first absorbance value; The optical detection device is controlled to perform optical measurements on the second sample solution to obtain the glycated hemoglobin concentration of the whole blood sample; and The percentage of glycated hemoglobin in the whole blood sample to be tested is calculated based on the hemoglobin concentration and the glycated hemoglobin concentration.

2. The biochemical analyzer according to claim 1, characterized in that, The controller is further configured to perform the following during the correction of the first absorbance based on the at least two second absorbances: The third absorbance of the lipid interferon at the correction wavelength is determined based on the second absorbance at different correction wavelengths. The target absorbance increase is determined based on at least two of the third absorbance values; and The first absorbance is corrected based on the target absorbance increase.

3. The biochemical analyzer according to claim 2, characterized in that, The correction wavelength is designed such that the absorbance of hemoglobin at that correction wavelength is zero; and The controller is further configured to, during the process of determining the third absorbance of the lipid interfering substance at the correction wavelength based on the second absorbance at different correction wavelengths, perform the following: determine the second absorbance at the correction wavelength as the third absorbance of the lipid interfering substance at the correction wavelength.

4. The biochemical analyzer according to claim 2, characterized in that, The controller is further configured to: Obtain the fourth absorbance of hemoglobin in the first test sample solution at different calibration wavelengths; and The third absorbance is obtained by subtracting the fourth absorbance from the second absorbance at the same corrected wavelength.

5. The biochemical analyzer according to any one of claims 2 to 4, characterized in that, The controller is further configured to perform the following during the process of determining the target absorbance increase based on the at least two third absorbance values: The amount of absorbance increase of lipid interfering substances at the hemoglobin measurement wavelength is determined based on the at least two third absorbance values; and The median, average, or weighted average of the increase in absorbance of lipid interfering substances at the hemoglobin measurement wavelength is determined as the target increase in absorbance.

6. The biochemical analyzer according to any one of claims 2 to 4, characterized in that, The controller is further configured to perform the following during the process of correcting the first absorbance according to the target absorbance increase: The first absorbance is subtracted from the target absorbance increase to obtain the corrected first absorbance.

7. The biochemical analyzer according to any one of claims 1 to 4, characterized in that, The controller is further configured to: Whether to perform the correction on the first absorbance is determined based on the relationship between the at least two second absorbances; When the relationship between the at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on the at least two second absorbances.

8. The biochemical analyzer according to claim 7, characterized in that, The preset relationship includes a greater second absorbance at shorter correction wavelengths.

9. The biochemical analyzer according to any one of claims 1 to 4, characterized in that, The calibration wavelength is in the wavelength range of 660nm-900nm, and the hemoglobin measurement wavelength is in the wavelength range of 450nm-660nm.

10. A biochemical analyzer for detecting glycated hemoglobin, comprising: The sample preparation apparatus is configured to prepare a lysis buffer from a whole blood sample to be tested and a hemolysin, prepare a first test sample solution from the lysis buffer and a first detection reagent for hemoglobin, and prepare a second test sample solution from the first test sample solution and a second detection reagent for glycated hemoglobin. An optical detection device is configured to perform optical measurements on the first sample liquid to be tested and the second sample liquid to be tested, respectively. The controller is communicatively connected to the optical detection device and is configured to: The optical detection device is controlled to detect the first absorbance of the first test sample solution at the hemoglobin measurement wavelength, and to detect at least two second absorbances of the first test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than the absorbance of hemoglobin at the calibration wavelength. Whether to correct the first absorbance is determined based on the relationship between the at least two second absorbances; When the relationship between the at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on at least one second absorbance, and the hemoglobin concentration is determined based on the corrected first absorbance. The optical detection device is controlled to perform optical measurements on the second sample solution to obtain the glycated hemoglobin concentration of the whole blood sample; and The percentage of glycated hemoglobin in the whole blood sample to be tested is calculated based on the hemoglobin concentration and the glycated hemoglobin concentration.

11. The biochemical analyzer according to claim 10, characterized in that, The preset relationship includes a greater second absorbance at shorter correction wavelengths.

12. A method for detecting glycated hemoglobin, comprising: Obtain the hemoglobin concentration of the whole blood sample to be tested; Obtain the glycated hemoglobin concentration of the whole blood sample to be tested; And calculate the percentage of glycated hemoglobin in the whole blood sample to be tested based on the hemoglobin concentration and the glycated hemoglobin concentration; The method is characterized in that obtaining the hemoglobin concentration of the whole blood sample to be tested includes the following steps: The first absorbance of the test sample solution at the hemoglobin measurement wavelength is obtained, wherein the test sample solution is prepared from the test whole blood sample, hemolysin, and hemoglobin detection reagent; Obtain at least two second absorbance values ​​of the test sample solution at at least two different calibration wavelengths, wherein the calibration wavelengths are designed such that the absorbance of lipid interfering substances at the calibration wavelength is greater than that of hemoglobin at the calibration wavelength; The first absorbance is corrected based on the at least two second absorbance values; The hemoglobin concentration is determined based on the corrected first absorbance.

13. The method for detecting glycated hemoglobin according to claim 12, characterized in that, The step of correcting the first absorbance based on the at least two second absorbances includes: The third absorbance of the lipid interferon at the correction wavelength is determined based on the second absorbance at different correction wavelengths. The target absorbance increase is determined based on the at least two of the third absorbance values; and The first absorbance is corrected based on the target absorbance increase.

14. The method for detecting glycated hemoglobin according to claim 12 or 13, characterized in that, The process of obtaining the hemoglobin concentration of the whole blood sample to be tested also includes: Whether to perform the correction on the first absorbance is determined based on the relationship between the at least two second absorbances; When the relationship between the at least two second absorbances satisfies a preset relationship, the first absorbance is corrected based on the at least two second absorbances.

15. The method for detecting glycated hemoglobin according to claim 14, characterized in that, The preset relationship includes a greater second absorbance at shorter correction wavelengths.

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