Glycosylated hemoglobin analyzer and method for controlling dilution concentration of sample by using glycosylated hemoglobin analyzer

Abstract

The invention provides a glycosylated hemoglobin analyzer and a sample dilution concentration control method thereof. The glycosylated hemoglobin analyzer comprises a plunger pump, a three-way electromagnetic valve I, a three-way electromagnetic valve II, a sampling assembly, a hemolysis tank, a sample injection valve, a transverse flow infusion pump, a chromatographic separation system, a waste liquid collection assembly, a buffer solution storage assembly and a hemolytic agent H storage assembly, the plunger pump is respectively communicated with the hemolytic agent H storage component and the sample injection valve through a three-way electromagnetic valve I; the sample injection valve is respectively communicated with the sampling assembly and the hemolysis tank through a three-way electromagnetic valve II; the plunger pump is used for quantitatively sucking a hemolytic agent H in the hemolytic agent H storage assembly and a blood sample in the sampling assembly to the hemolysis tank for dilution; and an HGB detection device is also arranged in the hemolysis tank and is used for detecting the hemoglobin concentration of the diluted sample. According to the invention, the concentration of the mixed solution loaded to the chromatographic separation system is ensured to be within a normal preset range through two dilution operations and two HGB concentration detections.

Description

Technical Field

[0001] The present invention relates to the technical field of medical in vitro diagnostic equipment, and in particular to a glycosylated hemoglobin analyzer and a method for controlling sample dilution concentration thereof. Background Art

[0002] Clinical laboratories usually use high performance liquid chromatography (HPLC) to measure glycated hemoglobin (HbA1c) in human blood. The sample is diluted at a certain ratio and loaded into a chromatography separation system for elution and separation. The absorbance spectrum of the separated hemoglobin is collected, and the proportion of glycated hemoglobin is calculated by integration.

[0003] Generally, test tubes containing anticoagulants are used to collect glycated hemoglobin samples. After the blood and anticoagulants are mixed, the samples will be stratified due to different specific gravities. After the sampling and dilution are carried out according to a certain ratio, the sample concentration fluctuates greatly. The analyzer is equipped with a mechanical mixing mechanism to mix the samples to avoid the impact of stratification.

[0004] Mechanical mixing requires at least 3-axis motion mechanisms to complete the actions of grabbing test tubes, lifting test tube racks, and mixing. The complex structure leads to an increase in the size, weight, and cost of the entire machine.

[0005] After the sample is mixed by the mixing mechanism, it is diluted according to a fixed ratio. The concentration of the same sample is basically the same after excluding the sampling error. However, the red blood cell content of different human samples varies greatly, and the concentrations of sample dilutions vary greatly. The chromatographic peak area of ​​anemia samples (low HGB) is low, and the chromatographic area of ​​high red blood cell samples (high HGB) is high, which exceeds the fault tolerance range of the detection system, resulting in a large deviation in HbA1c. Summary of the invention

[0006] In view of the problems existing in the prior art, the present invention provides a method for controlling sample dilution concentration of a glycosylated hemoglobin analyzer.

[0007] The present invention provides a glycosylated hemoglobin analyzer, comprising: a plunger pump, a three-way solenoid valve 1, a three-way solenoid valve 2, a sampling component, a hemolysis tank, an injection valve, a cross-flow infusion pump, a chromatography separation system, a waste liquid collection component, a buffer storage component, and a hemolysis agent H storage component;

[0008] The plunger pump is connected to the hemolytic agent H storage component and the injection valve through the three-way solenoid valve 1; the injection valve is connected to the sampling component and the hemolysis tank through the three-way solenoid valve 2;

[0009] The plunger pump is used to quantitatively draw the hemolytic agent H in the hemolytic agent H storage component and the blood sample in the sampling component to the hemolytic tank for dilution;

[0010] The hemolysis pool is also provided with an HGB detection device for detecting the hemoglobin concentration of the diluted sample; the hemolysis pool is also connected to the waste liquid collection component;

[0011] The cross-flow infusion pump is connected to the buffer storage component and the injection valve respectively; the injection valve is also connected to the chromatography separation system.

[0012] The cross-flow infusion pump is used to deliver the buffer in the buffer storage component into the injection valve to mix with the diluted sample, and then deliver it to the chromatographic separation system to separate and detect the diluted hemoglobin sample.

[0013] Preferably, the sampling assembly includes a sampling needle, a test tube rack, and a test tube placed on the test tube rack; one end of the sampling needle is connected to the second three-way solenoid valve, and the other end is placed directly above the test tube, and is used to puncture the test tube and absorb the blood sample during sampling.

[0014] Furthermore, the HGB detection device includes a mounting seat, a cuvette arranged on the mounting seat, and a light source LED and a photoelectric sensor respectively placed on both sides of the cuvette.

[0015] Preferably, the waste liquid collection component comprises a two-way solenoid valve, a diaphragm liquid pump, and a waste liquid barrel; the two-way solenoid valve is connected to the hemolysis tank and the diaphragm liquid pump respectively; and the diaphragm liquid pump is connected to the waste liquid barrel.

[0016] Preferably, the buffer storage assembly includes a buffer A storage bottle, a buffer B storage bottle, a buffer C storage bottle, a two-way solenoid valve 2, a two-way solenoid valve 3, a two-way solenoid valve 4, and a four-way reflux valve; the corresponding ends of the four-way reflux valve are connected to the corresponding buffer A storage bottle, buffer B storage bottle, and buffer C storage bottle through the two-way solenoid valve 2, the two-way solenoid valve 3, and the two-way solenoid valve 4, respectively; the four-way reflux valve is also connected to the cross-flow infusion pump.

[0017] Preferably, the chromatographic separation system comprises a chromatographic column and a detector, the chromatographic column is connected to the injection valve and the detector respectively, and the detector is also connected to the waste liquid bucket; the chromatographic column is used to separate the diluted hemoglobin sample, the detector detects the concentration of the effluent from the chromatographic column and transports the effluent to the waste liquid bucket; the hemolytic agent H storage component comprises a hemolytic agent H storage bottle; the glycated hemoglobin analyzer also comprises a quantitative ring (23), and the quantitative ring (23) is connected to the injection valve (8).

[0018] The present invention also provides a method for controlling sample dilution concentration using the glycated hemoglobin analyzer, comprising the following steps:

[0019] Step S1: quantitatively collecting blood samples into a hemolysis pool;

[0020] Step S2, first dilution: aspirate the hemolytic agent H into the hemolytic pool according to a fixed dilution ratio and mix it with the blood sample to complete the first dilution;

[0021] Step S3: detecting the HGB concentration of the mixed solution after the first dilution by a HGB detection device;

[0022] Step S4: calculating the ratio of the second dilution according to the HGB concentration of the mixed solution after the first dilution;

[0023] Step S5, second dilution: taking the first dilution mixture and the hemolytic agent H according to the calculated ratio into the hemolytic tank for secondary dilution, and performing hemoglobin (HGB) detection on the HGB concentration of the mixture after the second dilution;

[0024] Step S6: If the HGB concentration is within the preset range, the secondary diluted mixed solution is loaded into the chromatography separation system to separate and detect the diluted hemoglobin sample; otherwise, the dilution is continued.

[0025] Preferably, the specific steps of quantitatively collecting blood samples into the hemolysis pool in step S1 are:

[0026] Step S101: The sampling needle is inserted into the test tube, the three-way solenoid valve 1 is kept in an open state, and the three-way solenoid valve 2 is kept in a closed state;

[0027] Step S102: After the plunger pump sucks the quantitative blood sample, the sampling needle is pulled out of the test tube, the plunger pump plunger is pulled down to attract the sample in the puncture needle to pass through the three-way solenoid valve 2, the three-way solenoid valve 2 is opened, and the plunger pump (3) is pushed back to the original point to push the sample into the hemolysis pool.

[0028] Preferably, the specific steps in the first dilution in step S2 are:

[0029] Step S201: the three-way solenoid valve 1 is closed, the plunger pump draws a quantitative hemolytic agent H from the hemolytic agent H storage assembly, the three-way solenoid valve 1 is opened, the three-way solenoid valve 2 remains open, the plunger pump is pushed back to the origin, and the hemolytic agent H is pushed into the hemolytic tank to complete the first dilution;

[0030] The specific steps of the second dilution in step S5 are:

[0031] Step S501: the three-way solenoid valve 1 is kept in an open state, the three-way solenoid valve 2 is kept in an open state, the plunger pump sucks the volume of the first diluted mixed liquid required by the calculation, the two-way solenoid valve 1 is opened, the diaphragm liquid pump is opened, and the diaphragm liquid pump is closed after the excess mixed liquid is discharged, and the two-way solenoid valve 1 is closed;

[0032] Step S502: close the three-way solenoid valve 1, and the plunger pump draws the calculated volume of the hemolytic agent H. Open the three-way solenoid valve 1, and push the plunger pump back to the origin to inject the hemolytic agent H and the first diluted mixture into the hemolytic pool to complete the second dilution.

[0033] Preferably, the specific step of loading the secondary diluted mixed solution into the chromatographic separation system in S6 comprises:

[0034] Step S601: the injection valve is switched to the sample loading state, the three-way solenoid valve 1 and the three-way solenoid valve 2 are opened, and the plunger pump sucks the secondary diluted mixed solution in the hemolysis tank into the quantitative loop;

[0035] Step S602: Switch the injection valve to the injection state, so that the second diluted mixed solution in the quantitative loop is injected into the injection valve; at the same time, the buffer solution is delivered to the injection valve by the cross-flow infusion pump to mix with the second diluted mixed solution sample;

[0036] Step S603: loading the mixed sample into a chromatography column for separation;

[0037] Step S604: Use a detector to detect the absorbance of the effluent from the chromatography column, and transfer the detected effluent to a waste liquid bucket.

[0038] The technical solution of the present invention has the following beneficial effects:

[0039] The present invention is applied to a fully automatic glycosylated hemoglobin analyzer. The instrument quantitatively collects blood samples in a test tube, and then performs a first dilution in a hemolysis pool according to a fixed dilution ratio. The hemoglobin (HGB) concentration is detected by an HGB detection device on the hemolysis pool. The second dilution ratio is calculated according to the HGB concentration for secondary dilution. After two dilutions to ensure that HGB is within a preset range, the processed sample is loaded into a chromatographic separation system, and the detection deviation problem of existing mechanical mixing when detecting special samples (HGB is too high or too low) can be solved.

[0040] The present invention has accurate sample processing: the absorption and delivery of the blood sample and the hemolytic agent H are accurately controlled by the plunger pump, thereby ensuring the consistency and repeatability of the dilution process, thereby improving the accuracy of the test result.

[0041] The present invention has flexible dilution control: the three-way solenoid valve 1 and the three-way solenoid valve 2 in the design provide flexible fluid path control, allowing precise switching at different dilution stages, thereby enhancing the flexibility and controllability of the dilution process.

[0042] The present invention has efficient sample mixing: through a simplified mechanical mixing mechanism, the complexity of the equipment is reduced, while ensuring that the sample is fully mixed in the hemolysis tank, avoiding test deviations caused by sample stratification.

[0043] The present invention can monitor the concentration in real time: the HGB detection device integrated in the hemolysis pool can monitor the hemoglobin concentration of the diluted sample in real time, providing instant feedback for the subsequent dilution ratio adjustment, thereby ensuring the accuracy of the test.

[0044] The present invention realizes automated waste liquid management: The design of the waste liquid collection component realizes automated collection and treatment of waste liquid, reduces manual operations, reduces the risk of laboratory staff being exposed to hazardous substances, and improves laboratory work efficiency.

[0045] The connection design between the cross-flow infusion pump and the buffer storage assembly of the present invention ensures that the buffer can be quickly and accurately delivered to the injection valve, mixed with the sample and then subjected to chromatographic separation, thereby improving the efficiency of the analysis process.

[0046] The present invention can perform integrated chromatographic separation and detection: the design of the chromatographic separation system integrates the chromatographic column and the detector, realizes rapid separation and concentration detection of samples, simplifies the operation process, and shortens the test time.

[0047] The present invention is easy to maintain and clean: the modular design of the device makes it easy to disassemble and clean the various components (such as the buffer storage component and the hemolytic agent H storage component), which reduces the difficulty of maintenance and prolongs the service life of the device.

[0048] The design of the waste liquid collection component of the present invention meets environmental protection requirements, ensures the safe collection and treatment of laboratory waste liquid, reduces the impact on the environment, and improves the safety of the laboratory. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 It is the liquid circuit diagram of the present invention;

[0050] Figure 2 It is a structural schematic diagram of the HGB detection device of the present invention;

[0051] Figure 3 This is a schematic diagram of the stratification of the blood sample after standing still according to the present invention. DETAILED DESCRIPTION

[0052] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments.

[0053] Reference Figures 1 to 3 The present invention provides a glycosylated hemoglobin analyzer, comprising: a plunger pump 3, a three-way solenoid valve 1 4, a three-way solenoid valve 2 2, a sampling component, a hemolysis pool 5, an injection valve 8, a cross-flow infusion pump 19, a chromatographic separation system, a waste liquid collection component, a buffer storage component, and a hemolytic agent H storage component 11;

[0054] The plunger pump 3 is connected to the hemolytic agent H storage component 11 and the injection valve 8 respectively through the three-way solenoid valve 1 4; the injection valve 8 is connected to the sampling component and the hemolytic pool 5 respectively through the three-way solenoid valve 2 2; wherein the plunger pump 3: is responsible for accurately sucking and transporting blood samples and hemolytic agent H to ensure the accuracy of the dilution process; the three-way solenoid valve 1 4 and the three-way solenoid valve 2 2: control the path of the fluid to ensure the correct flow of the liquid inside the analyzer.

[0055] The plunger pump 3 is used to quantitatively draw the hemolytic agent H in the hemolytic agent H storage component 11 and the blood sample in the sampling component to the hemolytic tank 5 for dilution;

[0056] The hemolysis pool 5 is also provided with an HGB detection device for detecting the hemoglobin concentration of the diluted sample; the hemolysis pool 5 is also connected to a waste liquid collection component; the waste liquid collection component is responsible for collecting and storing waste liquid generated during the experiment to ensure the cleanliness and safety of the experimental environment.

[0057] The cross-flow infusion pump 19 is connected to the buffer storage component and the injection valve 8 respectively; the injection valve 8 is also connected to the chromatography separation system;

[0058] The cross-flow infusion pump 19 is used to deliver the buffer in the buffer storage assembly into the injection valve 8 to mix with the diluted sample, and then deliver it to the chromatography separation system to separate and detect the diluted hemoglobin sample.

[0059] Furthermore, the sampling assembly includes a sampling needle 1, a test tube rack 10, and a test tube 9 placed on the test tube rack 10; one end of the sampling needle 1 is connected to the three-way solenoid valve 22, and the other end is placed directly above the test tube 9, and is used to puncture the test tube and absorb blood samples during sampling; in this embodiment, the design of the sampling needle 1 enables it to accurately puncture the test tube 9 and absorb blood samples, and its fine tip reduces damage to the test tube, while ensuring the accuracy and repeatability of sample absorption; the efficiency and accuracy of sample collection are improved, and the risk of sample loss and cross contamination is reduced, thereby improving the reliability of the entire analysis process and the accuracy of the results; the test tube rack 10 provides a stable and orderly storage platform for the test tube 9; the test tube 9 placed on the test tube rack 10 facilitates the approach and puncture of the sampling needle 1, and is used to store blood samples.

[0060] Furthermore, the HGB detection device includes a mounting seat, a cuvette 200 disposed on the mounting seat, a light source LED 100 and a photoelectric sensor 300 respectively disposed on both sides of the cuvette 200; in this embodiment, the arrangement of the cuvette 200 allows for optical analysis of the diluted sample, and its transparent design ensures that light can pass through the sample evenly, and the light source LED can use a 540nm light source. The photoelectric sensor 300 can sensitively detect the light intensity transmitted through the cuvette, and can accurately measure even when the sample concentration is low. The high sensitivity and accuracy of the photoelectric sensor ensure that an accurate HGB concentration reading can be obtained even at low concentrations, which is particularly important for accurate analysis of glycated hemoglobin. The HGB detection device is used to detect the solubility of diluted blood samples. It adopts the HiCN method to determine hemoglobin (HGB). The HiCN method for determining hemoglobin (HGB) is a reference method recommended by the International Committee for Standardization in Hematology. The determination principle is: HGB is oxidized into methemoglobin by potassium ferrocyanide, and then combines with cyanide ions to form stable cyanomethemoglobin (HiCN). HiCN has a specific absorption peak at a wavelength of 540nm and can be measured by a spectrophotometer.

[0061] Furthermore, the waste liquid collection assembly includes a two-way solenoid valve 6, a diaphragm liquid pump 7, and a waste liquid barrel 22; the two-way solenoid valve 6 is connected to the hemolysis tank 5 and the diaphragm liquid pump 7 respectively; the diaphragm liquid pump 7 is connected to the waste liquid barrel 22. In this embodiment, the two-way solenoid valve 6 is used to control the flow direction of the waste liquid from the hemolysis tank 5 to the diaphragm liquid pump 7. Its precise switch control ensures the accurate transfer of the waste liquid. This design reduces the risk of leakage of the waste liquid during the transfer process and improves the safety of the system and the convenience of operation. The diaphragm liquid pump 7 provides a gentle and effective way to transport waste liquid. Its design can handle liquids of various viscosities. The use of the diaphragm liquid pump improves the efficiency and reliability of waste liquid treatment, while reducing the wear of the pump and extending the service life of the equipment. The waste liquid barrel 22 is the final collection container for the waste liquid. Its design meets the requirements for safe storage and disposal of the waste liquid. The use of the waste liquid barrel ensures that the waste liquid is properly handled, reduces potential pollution to the environment, and also facilitates the recovery and disposal of the waste liquid.

[0062] Furthermore, the buffer storage assembly includes a buffer A storage bottle 12, a buffer B storage bottle 13, a buffer C storage bottle 14, a two-way solenoid valve 15, a two-way solenoid valve 16, a two-way solenoid valve 17, and a four-way reflux valve 18; the corresponding ends of the four-way reflux valve 18 are respectively connected to the corresponding buffer A storage bottle 12, buffer B storage bottle 13, and buffer C storage bottle 14 through the two-way solenoid valve 15, the two-way solenoid valve 16, and the two-way solenoid valve 17; the four-way reflux valve 18 is also connected to the cross-flow infusion pump 19. In this embodiment, the buffer storage assembly includes a buffer A storage bottle 12, a buffer B storage bottle 13 and a buffer C storage bottle 14. This design allows the analyzer to use multiple types of buffers to meet different detection requirements; it improves the applicability and flexibility of the analyzer, so that the same device can handle a variety of different tests, increasing the scope of use of the device; through the coordinated use of two-way solenoid valve 2 15, two-way solenoid valve 3 16 and two-way solenoid valve 4 17, the flow from each buffer storage bottle to the four-way reflux valve 18 can be accurately controlled, and the precise flow control ensures the accurate ratio of the buffer and sample mixing, thereby ensuring the chromatographic separation effect and the accuracy of the detection results. The design of the four-way reflux valve 18 allows for rapid switching and selection of different buffers, and can be directly connected to the cross-flow infusion pump 19 to achieve efficient delivery of the buffer; this design improves the speed and convenience of buffer replacement, reduces the time required to switch between different tests, and improves the efficiency of the entire analysis process.

[0063] Further, the chromatographic separation system includes a chromatographic column 20 and a detector 21, wherein the chromatographic column 20 is connected to the injection valve 8 and the detector 21 respectively, and the detector 21 is also connected to the waste liquid barrel 22; the chromatographic column 20 is used to separate the diluted hemoglobin sample, and the detector 21 detects the concentration of the effluent of the chromatographic column 20 and transports the effluent to the waste liquid barrel 22; the hemolytic agent H storage component 11 includes a hemolytic agent H storage bottle. In this embodiment, the chromatographic column 20 is designed to efficiently separate the diluted hemoglobin sample, ensuring that hemoglobin of different components can be separated quickly and accurately, thereby improving the accuracy and reliability of the test results. The detector 21 is directly connected to the chromatographic column 20, and can monitor the concentration of the effluent in real time. Its high sensitivity and accuracy ensure the accuracy of the test data, and accurate concentration detection helps to more accurately evaluate the level of glycated hemoglobin; the direct connection between the detector 21 and the waste liquid barrel 22 realizes the automated processing of waste liquid and reduces the need for manual operation; automated waste liquid processing not only improves work efficiency, but also reduces the risk of contamination caused by manual operation. The integrated design of the chromatography column 20, the detector 21 and the waste liquid barrel 22 forms a coherent workflow. No additional operations are required from sample separation to waste liquid treatment. The integrated workflow simplifies the operating steps, improves the degree of automation of the entire analysis process, reduces the labor intensity of the operator, and improves the analysis efficiency.

[0064] The present invention also provides a method for performing sample dilution concentration using the glycated hemoglobin analyzer, comprising the following steps:

[0065] Step S1: quantitatively collecting blood samples into the hemolysis pool 5;

[0066] Step S2, first dilution: the hemolytic agent H is drawn into the hemolytic tank 5 according to a fixed dilution ratio to mix with the blood sample to complete the first dilution;

[0067] Step S3: detecting the HGB concentration of the mixed solution after the first dilution by a HGB detection device;

[0068] Step S4: Calculate the ratio of the second dilution (the first diluted mixed solution + the hemolytic agent) according to the HGB concentration of the mixed solution after the first dilution and the preset concentration added to the chromatography system; the calculation formula for the second dilution ratio is:

[0069] The second dilution ratio = (HGB concentration after the first dilution = preset HGB concentration - HGB concentration after the first dilution) / HGB concentration after the first dilution.

[0070] The HGB concentration h1 after the first dilution multiplied by the secondary dilution stock solution sampling volume x, divided by the sum of the secondary dilution hemolytic agent H volume d and the stock solution sampling volume x, equals the preset HGB concentration h2, where d and h2 are preset values, h1 is the calculated value after the first dilution, and the secondary sampling stock solution volume x in the equation can be directly calculated using the equation.

[0071]

[0072] Step S5, second dilution: taking the first dilution mixed solution and the hemolytic agent H according to the calculated ratio to the hemolytic tank 5 for secondary dilution, and performing hemoglobin (HGB) detection on the HGB concentration of the mixed solution after the second dilution;

[0073] Step S6: If the HGB concentration is within the preset range, the secondary diluted mixed solution is loaded into the chromatography separation system to separate and detect the diluted hemoglobin sample; otherwise, the dilution is continued.

[0074] In the above example, two dilution operations and two HGB concentration tests ensure that the concentration of the mixed solution loaded into the chromatographic separation system is within a normal preset range.

[0075] Furthermore, the specific steps of quantitatively collecting blood samples into the hemolysis pool 5 in step S1 are:

[0076] Step S101: the sampling needle 1 punctures the test tube 9, the three-way solenoid valve 1 4 remains in an open state, and the three-way solenoid valve 2 2 remains in a closed state;

[0077] Step S102: After the plunger pump 3 draws a quantitative blood sample, the sampling needle is pulled out of the test tube 9, the plunger of the plunger pump 3 is pulled down to attract the sample in the puncture needle 1 to pass through the three-way solenoid valve 2, the three-way solenoid valve 2 is opened, the plunger pump 3 is pushed back to the original point, and the sample is pushed into the hemolysis pool 5;

[0078] Furthermore, the specific steps of the first dilution in step S2 are:

[0079] Step S201: the three-way solenoid valve 1 4 is closed, the plunger pump 3 draws a quantitative hemolytic agent H from the hemolytic agent H storage assembly 11, the three-way solenoid valve 1 4 is opened, the three-way solenoid valve 2 2 remains open, the plunger pump 3 is pushed back to the origin, and the hemolytic agent H is pushed into the hemolytic tank 5 to complete the first dilution;

[0080] The specific steps of the second dilution in step S5 are:

[0081] Step S501: the three-way solenoid valve 1 4 is kept in an open state, the three-way solenoid valve 2 is kept in an open state, the plunger pump 3 sucks the volume of the first diluted mixed liquid required by the calculation, the two-way solenoid valve 1 6 is opened, the diaphragm liquid pump 7 is opened, and the diaphragm liquid pump 7 is closed after the excess mixed liquid is discharged, and the two-way solenoid valve 1 6 is closed;

[0082] Step S502: close the three-way solenoid valve 4, the plunger pump 3 sucks the calculated volume of the hemolytic agent H, open the three-way solenoid valve 4, push the plunger pump 3 back to the origin, inject the hemolytic agent H and the first diluted mixture into the hemolytic tank 5, and complete the second dilution.

[0083] Furthermore, the specific step of loading the secondary diluted mixed solution into the chromatographic separation system in S6 includes:

[0084] Step S601: the injection valve (8) is switched to the sample loading state, the three-way solenoid valve 1 (4) and the three-way solenoid valve 2 (2) are opened, and the plunger pump (3) sucks the secondary diluted mixed solution in the hemolysis pool into the quantitative loop (23);

[0085] Step S602: Switch the injection valve (8) to the injection state, so that the second diluted mixed solution in the quantitative loop is injected into the injection valve (8), and at the same time, the buffer solution is transported to the injection valve (8) through the cross-flow infusion pump (19) to mix with the second diluted mixed solution sample;

[0086] Step S603: loading the mixed sample into the chromatography column 20 for separation;

[0087] Step S604 : using the detector 21 to detect the absorbance of the effluent from the chromatography column 20 , and transferring the detected effluent to the waste liquid bucket 22 .

[0088] Furthermore, the present invention configures the same sample into different HGB concentrations (4.0-22.0 g / dL basically covers the vast majority of clinical cases) and conducts tests in a conventional manner (fixed sample dilution ratio). The test results are shown in Table 1:

[0089] Table 1

[0090] Serial number HGB(g / dL) S-A1c (%) Total area 1 2.8 5.5 3.7 2 4.4 5.7 6.4 3 5.6 5.8 7.7 4 6.8 6.0 8.9 5 7.9 6.0 10.4 6 10.4 6.1 12.4 7 12.3 (Original HGB concentration of sample) 6.3 14.8 8 14.8 6.4 15.9 9 15.8 6.6 18.1 10 17.9 6.8 20.0 11 20.6 6.3 22.8 12 24.1 7.2 27.2

[0091] From the test results in Table 1, the higher the HGB concentration, the larger the total area, the higher the A1c result, and the change of HGB has a significant impact on the A1c result.

[0092] Furthermore, for the same sample, different HGB concentrations were configured, the machine was equipped with HGB detection and secondary dilution was performed according to the HGB concentration. The test results are shown in Table 2.

[0093] Table 2

[0094] Serial number HGB(g / dL) S-A1c (%) Total area 1 4.0 6.1 10.4 2 5.2 6.0 9.7 3 6.4 6.1 10.5 4 7.9 6.1 11.2 5 8.8 6.1 11.4 6 9.7 6.1 11.8 7 10.8 6.1 12.5 8 12.6 6.0 11.8 9 14.2 6.1 11.9 10 16.7 6.1 12.2 11 18.0 6.1 12.1 12 20.2 6.1 11.7 13 22.8 6.1 12.6

[0095] From the test results in Table 2, it can be seen that after the samples in the range of 4.0-22.8 g / dL were dynamically diluted, the total area of ​​the test results remained within a certain range, and the A1c results were not affected by the initial concentration of the samples.

[0096] Reference Figure 3 , Schematic diagram of the stratification of blood samples after standing, where A represents red blood cells, B represents platelets and white blood cells, and C represents plasma components.

[0097] It can be seen from the above embodiments that the present invention is applied to a fully automatic glycosylated hemoglobin analyzer. The instrument quantitatively collects blood samples in test tubes, and then completes the first dilution in a hemolysis pool according to a fixed dilution ratio. The hemoglobin (HGB) concentration is detected by an HGB detection device on the hemolysis pool. The second dilution ratio is calculated according to the HGB concentration for secondary dilution. After two dilutions to ensure that HGB is within a preset range, the processed samples are loaded into a chromatographic separation system, which can solve the detection deviation problem of existing mechanical mixing when detecting special samples (HGB is too high or too low).

[0098] The present invention has accurate sample processing: the absorption and delivery of the blood sample and the hemolytic agent H are accurately controlled by the plunger pump, thereby ensuring the consistency and repeatability of the dilution process, thereby improving the accuracy of the test result.

[0099] The present invention has flexible dilution control: the three-way solenoid valve 1 and the three-way solenoid valve 2 in the design provide flexible fluid path control, allowing precise switching at different dilution stages, thereby enhancing the flexibility and controllability of the dilution process.

[0100] The present invention has efficient sample mixing: through a simplified mechanical mixing mechanism, the complexity of the equipment is reduced, while ensuring that the sample is fully mixed in the hemolysis tank, avoiding test deviations caused by sample stratification.

[0101] The present invention can monitor the concentration in real time: the HGB detection device integrated in the hemolysis pool can monitor the hemoglobin concentration of the diluted sample in real time, providing instant feedback for the subsequent dilution ratio adjustment, thereby ensuring the accuracy of the test.

[0102] The present invention realizes automated waste liquid management: The design of the waste liquid collection component realizes automated collection and treatment of waste liquid, reduces manual operations, reduces the risk of laboratory staff being exposed to hazardous substances, and improves laboratory work efficiency.

[0103] The connection design between the cross-flow infusion pump and the buffer storage assembly of the present invention ensures that the buffer can be quickly and accurately delivered to the injection valve, mixed with the sample and then subjected to chromatographic separation, thereby improving the efficiency of the analysis process.

[0104] The present invention can perform integrated chromatographic separation and detection: the design of the chromatographic separation system integrates the chromatographic column and the detector, realizes rapid separation and concentration detection of samples, simplifies the operation process, and shortens the test time.

[0105] The present invention is easy to maintain and clean: the modular design of the device makes it easy to disassemble and clean the various components (such as the buffer storage component and the hemolytic agent H storage component), which reduces the difficulty of maintenance and prolongs the service life of the device.

[0106] The design of the waste liquid collection component of the present invention meets environmental protection requirements, ensures the safe collection and treatment of laboratory waste liquid, reduces the impact on the environment, and improves the safety of the laboratory.

[0107] The above description is only a preferred embodiment of the present invention, and does not limit the patent scope of the present invention. All equivalent structural changes made by using the contents of the present invention specification and drawings under the inventive concept of the present invention, or directly / indirectly applied in other related technical fields are included in the patent protection scope of the present invention.

Claims

1. A glycosylated hemoglobin analyzer, characterized in that: include: A plunger pump (3), a three-way solenoid valve 1 (4), a three-way solenoid valve 2 (2), a sampling assembly, a hemolysis tank (5), an injection valve (8), a cross-flow infusion pump (19), a chromatographic separation system, a waste liquid collection assembly, a buffer storage assembly, and a hemolysis agent H storage assembly (11); The plunger pump (3) is connected to the hemolytic agent H storage component (11) and the injection valve (8) respectively through the three-way solenoid valve (4); the injection valve (8) is connected to the sampling component and the hemolytic pool (5) respectively through the three-way solenoid valve (2); The plunger pump (3) is used to quantitatively draw the hemolytic agent H in the hemolytic agent H storage component (11) and the blood sample in the sampling component to the hemolytic tank (5) for dilution; The hemolysis pool (5) is also provided with an HGB detection device for detecting the hemoglobin concentration of the diluted sample; the hemolysis pool (5) is also connected to the waste liquid collection component; The cross-flow infusion pump (19) is connected to the buffer storage assembly and the injection valve (8) respectively; the injection valve (8) is also connected to the chromatographic separation system (20). The cross-flow infusion pump (19) is used to deliver the buffer in the buffer storage assembly into the injection valve (8) to mix with the diluted sample, and then deliver it to the chromatographic separation system to separate and detect the diluted hemoglobin sample.

2. The glycated hemoglobin analyzer according to claim 1, characterized in that: The sampling assembly comprises a sampling needle (1), a test tube rack (10), and a test tube (9) placed on the test tube rack (10); one end of the sampling needle (1) is connected to a second three-way electromagnetic valve (2), and the other end is placed directly above the test tube (9), and is used to puncture the test tube and absorb a blood sample during sampling.

3. The glycated hemoglobin analyzer according to claim 1, characterized in that: The HGB detection device comprises a mounting seat, a cuvette (200) arranged on the mounting seat, and a light source LED (100) and a photoelectric sensor (300) respectively arranged on both sides of the cuvette (200).

4. The glycated hemoglobin analyzer according to claim 1, characterized in that: The waste liquid collection component comprises a two-way solenoid valve (6), a diaphragm liquid pump (7), and a waste liquid bucket (22); the two-way solenoid valve (6) is connected to the hemolysis pool (5) and the diaphragm liquid pump (7) respectively; the diaphragm liquid pump (7) is connected to the waste liquid bucket (22).

5. The glycated hemoglobin analyzer according to claim 1, characterized in that: The buffer storage assembly comprises a buffer A storage bottle (12), a buffer B storage bottle (13), a buffer C storage bottle (14), a two-way solenoid valve (15), a two-way solenoid valve (16), a two-way solenoid valve (17), and a four-way reflux valve (18); the corresponding ends of the four-way reflux valve (18) are respectively connected to the corresponding buffer A storage bottle (12), buffer B storage bottle (13), and buffer C storage bottle (14) through the two-way solenoid valve (15), the two-way solenoid valve (16), and the two-way solenoid valve (17); the four-way reflux valve (18) is also connected to a cross-flow infusion pump (19).

6. The glycated hemoglobin analyzer according to claim 4, characterized in that: The chromatographic separation system comprises a chromatographic column (20) and a detector (21), wherein the chromatographic column (20) is respectively connected to an injection valve (8) and the detector (21), and the detector (21) is also connected to a waste liquid barrel (22); the chromatographic column (20) is used to separate a diluted hemoglobin sample, and the detector (21) detects the concentration of an outflow from the chromatographic column (20) and transports the outflow to the waste liquid barrel (22); the hemolytic agent H storage component (11) comprises a hemolytic agent H storage bottle; the glycated hemoglobin analyzer also comprises a quantitative loop (23), and the quantitative loop (23) is connected to the injection valve (8).

7. A method for controlling sample dilution concentration using the glycated hemoglobin analyzer according to any one of claims 1 to 6, characterized in that: The steps include: Step S1: quantitatively collecting blood samples into a hemolysis pool (5); Step S2, first dilution: aspirate the hemolytic agent H into the hemolytic tank (5) according to a fixed dilution ratio and mix it with the blood sample to complete the first dilution; Step S3: detecting the HGB concentration of the mixed solution after the first dilution by a HGB detection device; Step S4: calculating the ratio of the second dilution according to the HGB concentration of the mixed solution after the first dilution; Step S5, second dilution: taking the first dilution mixed solution and the hemolytic agent H according to the calculated ratio to the hemolytic tank (5) for secondary dilution, and performing hemoglobin (HGB) detection on the HGB concentration of the mixed solution after the second dilution; Step S6: If the HGB concentration is within the preset range, the secondary diluted mixed solution is loaded into the chromatography separation system to separate and detect the diluted hemoglobin sample; otherwise, the dilution is continued.

8. The method for controlling sample dilution concentration by a glycosylated hemoglobin analyzer according to claim 7, characterized in that: The quantitative collection of blood samples in step S1 into the hemolysis pool (5) The specific steps are: Step S101: The sampling needle (1) is inserted into the test tube (9), the three-way solenoid valve 1 (4) is kept in an open state, and the three-way solenoid valve 2 (2) is kept in a closed state; Step S102: After the plunger pump (3) sucks a quantitative blood sample, the sampling needle is pulled out of the test tube (9), the plunger of the plunger pump (3) is pulled down to attract the sample in the puncture needle (1) to pass through the three-way solenoid valve (2), the three-way solenoid valve (2) is opened, and the plunger pump (3) is pushed back to the original point to push the sample into the hemolysis pool (5).

9. The method for controlling sample dilution concentration by a glycosylated hemoglobin analyzer according to claim 8, characterized in that: The specific steps of the first dilution in step S2 are: Step S201: the three-way solenoid valve 1 (4) is closed, the plunger pump (3) draws a quantitative amount of hemolytic agent H from the hemolytic agent H storage assembly (11), the three-way solenoid valve 1 (4) is opened, the three-way solenoid valve 2 (2) remains open, the plunger pump (3) is pushed back to the origin, and the hemolytic agent H is pushed into the hemolytic tank (5), completing the first dilution; The specific steps of the second dilution in step S5 are: Step S501: the three-way solenoid valve 1 (4) remains in an open state, the three-way solenoid valve 2 (2) remains in an open state, the plunger pump (3) draws the volume of the mixed liquid required for the first dilution, the two-way solenoid valve 1 (6) is opened, the diaphragm liquid pump (7) is opened, the diaphragm liquid pump (7) is closed after the excess mixed liquid is discharged, and the two-way solenoid valve 1 (6) is closed; Step S502: close the three-way solenoid valve 1 (4), the plunger pump (3) draws the calculated required volume of the hemolytic agent H, open the three-way solenoid valve 1 (4), push the plunger pump (3) back to the original point, inject the hemolytic agent H and the first diluted mixture into the hemolytic tank (5), and complete the second dilution.

10. The method for controlling sample dilution concentration by a glycosylated hemoglobin analyzer according to claim 7, characterized in that: The specific steps of loading the secondary diluted mixed solution into the chromatographic separation system in S6 include: Step S601: the injection valve (8) is switched to the sample loading state, the three-way solenoid valve 1 (4) and the three-way solenoid valve 2 (2) are opened, and the plunger pump (3) sucks the secondary diluted mixed solution in the hemolysis pool into the quantitative loop (23); Step S602: Switch the injection valve (8) to the injection state, so that the second diluted mixed solution in the quantitative loop is injected into the injection valve (8), and at the same time, the buffer solution is transported to the injection valve (8) through the cross-flow infusion pump (19) to mix with the second diluted mixed solution sample; Step S603: loading the mixed sample into the chromatography column (20) for separation; Step S604: Use the detector (21) to detect the absorbance of the effluent from the chromatography column (20), and transfer the detected effluent to the waste liquid bucket (22).

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