Chemiluminescence analyzer

Abstract

The present invention relates to a chemiluminescence analyzer, which comprises: a sample preparation device, which is used for pre-diluting a to-be-detected blood sample by using a diluent, and mixing the pre-diluted to-be-detected blood sample with a reaction reagent in a reaction container to obtain a to-be-detected sample liquid; the substrate providing device is used for providing a luminous substrate into the reaction container filled with a sample solution to be detected so as to carry out a chemiluminescence reaction; the light measuring device at least comprises a photometer; and the data processing device is used for obtaining a detection result of the human chorionic gonadotropin in the blood sample to be detected according to the light-emitting signal and a preset calibration model. The first linear detection range of the photometer is [A1, A2] photon counting / second, in the first linear detection range, the intensity of a light-emitting signal generated in the chemiluminescence reaction and the photon counting output by the photometer are in a linear relation, A1 is smaller than or equal to 2000, and A2 is larger than or equal to 108. Therefore, the HCG detection efficiency and accuracy can be improved under the condition that the cost is not increased.

Description

Technical Field

[0001] The present disclosure relates to the field of chemiluminescence detection, and more particularly to chemiluminescence analyzers. Background Art

[0002] Chemiluminescence Immunoassay (CLIA) is an immunoassay technique that combines a chemiluminescence system with an immune reaction for detecting antigens, antibodies, hormones, fatty acids, vitamins, drugs, etc. Chemiluminescence refers to the phenomenon that during a chemical reaction, a specific substance absorbs part of the chemical energy to reach an excited state, and the energy released during the return to the ground state is released in the form of photons, thereby generating luminescence. Chemiluminescence immunoassay has both the high sensitivity of chemiluminescence and the characteristics of simple operation and rapid reaction of enzyme-linked immunoassay, and is easy to standardize experimental operations. It has now been widely used in biological, medical research and clinical diagnosis.

[0003] However, for chemiluminescence analyzers based on chemiluminescence immunoassay, it is difficult to balance both detection sensitivity and linear detection range, especially for analytes with a large range span, such as human chorionic gonadotropin (HCG).

[0004] Human chorionic gonadotropin (HCG) is a glycoprotein mainly secreted by placental trophoblast cells. HCG consists of an α subunit and a β subunit, contains 237 amino acids, and has a molecular weight of about 38,000 daltons. Each subunit consists of a single polypeptide. Among them, the α subunit consists of 92 amino acids and has a molecular weight of about 14,900 daltons; the β subunit consists of 145 amino acids and has a molecular weight of about 23,000 daltons. In the HCG structure, the protein content accounts for 70%, and the sugar content accounts for 30%.

[0005] HCG can exist in urine, blood, and placenta, and the existence forms of HCG in each matrix are different. In blood, it mainly exists in the form of intact HCG. Among them, the α subunit has a similar structure to the α subunits of follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone secreted by the pituitary gland; the structures of the β subunits are different, and the differences in the β subunits result in their respective immunological and biological specificities.

[0006] The main function of human chorionic gonadotropin (HCG) is to stimulate the corpus luteum, which is beneficial for the continuous secretion of estrogen and progesterone, so as to promote the formation of the uterine decidua and make the placenta grow and mature. HCG is produced by trophoblast transitional cells and syncytiotrophoblasts and is regulated by multiple factors including autocrine and paracrine. For normal pregnant women, HCG will be produced 2 to 8 days after conception. In the early stage of pregnancy, the content of HCG doubles approximately every 31 - 48 hours until it reaches the peak around 11 weeks of gestation, and then the concentration slowly decreases until the 18th - 20th week, and then remains relatively constant. The detection of HCG is of great significance for the diagnosis of early pregnancy and pregnancy monitoring. In the early stage of pregnancy, a 35 - 50% increase in HCG within two days indicates a possible ectopic pregnancy. An abnormally low or abnormally sharp decline in HCG levels indicates a high risk of ectopic pregnancy. On the other hand, in the second trimester of pregnancy, an increase in HCG levels indicates an adverse reaction during pregnancy, which may be pregnancy-induced hypertension, fetal growth restriction, etc.

[0007] The concentration distribution of HCG is relatively wide among non-pregnant, pregnant, and trophoblastic cell disease populations in normal women: For pregnant populations, their HCG can increase from several hundred mIU / mL in early pregnancy to about 200,000 mIU / mL at most, and then decrease to a level within about 10,000 mIU / mL; For patients with trophoblastic cell diseases (including choriocarcinoma), their HCG concentration can be as high as 1,000,000 mIU / mL or even higher; For non-pregnant women, their HCG concentration is usually below 5 mIU / mL, and even some are as low as 0.5 mIU / mL.

[0008] That is to say, HCG is secreted by placental trophoblast cells and has a very low content in non-pregnant populations, less than 5 mIU / ml. Therefore, high detection sensitivity is the key performance to ensure the use of HCG test results in clinical practice to assist in judging pregnancy or not. At the same time, in the pregnancy monitoring scenario, it is necessary to continuously measure the HCG concentration in the early stage of pregnancy (about 200,000 mIU / ml). Therefore, a wide linear detection range is the key performance to ensure the use of HCG test results in clinical practice for pregnancy status monitoring.

[0009] Therefore, for chemiluminescence analyzers, in the HCG detection scenario, the linear range that needs to be accurately detected spans 6 - 7 orders of magnitude. However, the current linear detection upper limit that chemiluminescence analyzers and their supporting reagents can achieve is at most not greater than 15,000 mIU / mL, far from covering the routine pregnancy test scenario. Summary of the Invention

[0010] Based on this background, the task of the present disclosure is to provide a chemiluminescence analyzer based on chemiluminescence immunoassay with a wide linear detection range, which can balance sensitivity and the upper limit of linear detection. Especially for samples with a high concentration of the analyte (such as HCG or β-HCG), there is no need to dilute and retest, improving efficiency and saving reagent costs.

[0011] In the first aspect of the present disclosure, a chemiluminescence analyzer is provided, including:

[0012] A sample preparation device, at least for: for a blood sample to be tested with a detection item of human chorionic gonadotropin detection item, before performing the human chorionic gonadotropin detection on the blood sample to be tested, pre-diluting the blood sample to be tested with a diluent at a preset dilution ratio, and mixing the pre-diluted blood sample to be tested with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested. The reaction reagent includes a capture reagent coated with a human chorionic gonadotropin antibody and a detection reagent of a human chorionic gonadotropin antibody with a marker;

[0013] A substrate providing device, for providing a luminescent substrate into the reaction container containing the sample solution to be tested, so that the marker in the sample solution to be tested undergoes a chemiluminescence reaction with the luminescent substrate;

[0014] A photometric device, the photometric device at least includes a photometer, and the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction. Among them, the first linear detection range of the photometer is [A1, A2] photon counts per second. The first linear detection range represents the range of photon counts output by the photometer. Within this first linear detection range, the intensity of the luminescence signal generated in the chemiluminescence reaction is linearly related to the photon counts output by the photometer, where A1 is less than or equal to 2000 and A2 is greater than or equal to 10 8 ;

[0015] A data processing device, for obtaining the detection result of human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0016] In the second aspect of the present disclosure, a chemiluminescence analyzer is provided, including:

[0017] A sample preparation device, for preparing a sample solution to be tested from a blood sample to be tested;

[0018] A substrate providing device, for providing a luminescent substrate;

[0019] A photometric device, the photometric device at least includes a photometer, the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction, wherein, the first linear detection range of the photometer is [A1, A2] photon counts per second, the first linear detection range represents the range of photon counts output by the photometer, within this first linear detection range, the intensity of the luminescence signal generated in the chemiluminescence reaction is linearly related to the photon counts output by the photometer, wherein, A1 is less than or equal to 2000 and A2 is greater than or equal to 10 8 ;

[0020] A controller, configured to

[0021] Obtain the test items of the blood sample to be tested,

[0022] When the test item is a human chorionic gonadotropin test item:

[0023] Control the sample preparation device to pre-dilute the blood sample to be tested with a diluent, and mix the pre-diluted blood sample to be tested with the reaction reagent in a reaction vessel, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a test sample solution. The reaction reagent includes a capture reagent coated with a human chorionic gonadotropin antibody and a detection reagent of a human chorionic gonadotropin antibody with a marker. Control the substrate providing device to provide a luminescent substrate to the reaction vessel containing the test sample solution, so that the marker in the test sample solution undergoes a chemiluminescence reaction with the luminescent substrate, and control the photometer to detect the luminescence signal generated in the chemiluminescence reaction,

[0024] Obtain the test result of the human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0025] The third aspect of the present disclosure provides a chemiluminescence analyzer, including:

[0026] A sample preparation device, at least used for: for a blood sample to be tested with a human chorionic gonadotropin test item, before performing the human chorionic gonadotropin test, pre-dilute the blood sample to be tested with a diluent at a preset dilution ratio, and mix the pre-diluted blood sample to be tested with the reaction reagent in a reaction vessel, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a test sample solution. The reaction reagent includes a capture reagent coated with a human chorionic gonadotropin antibody and a detection reagent of a human chorionic gonadotropin antibody with a marker;

[0027] A substrate providing device for providing a luminescent substrate to a reaction vessel containing a sample solution to be tested, so that a marker in the sample solution to be tested reacts with the luminescent substrate in a chemiluminescent reaction. The second linear detection range of the luminescent substrate is [B1, B2] photon counts per second. The second linear detection range represents the range of the intensity of the luminescent signal generated in the chemiluminescent reaction. Within this second linear detection range, the number of markers participating in the chemiluminescent reaction is linearly related to the intensity of the luminescent signal generated in the chemiluminescent reaction, where B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 and / or, the ratio B2 / B1 of B2 to B1 is greater than or equal to 30000;

[0028] A photometric device, the photometry at least includes a photometer for detecting the luminescent signal generated in the chemiluminescent reaction;

[0029] A data processing device for obtaining the detection result of the human chorionic gonadotropin in the blood sample to be tested according to the luminescent signal and a preset calibration model.

[0030] The fourth aspect of the present disclosure provides a chemiluminescent analyzer, including:

[0031] A sample preparation device for preparing a sample solution to be tested from a blood sample to be tested;

[0032] A substrate providing device for providing a luminescent substrate;

[0033] A photometric device, the photometric device at least includes a photometer for detecting the luminescent signal generated in the chemiluminescent reaction;

[0034] A controller configured to

[0035] obtain the test item of the blood sample to be tested,

[0036] When the test item is a human chorionic gonadotropin test item:

[0037] control the sample preparation device to pre-dilute the blood sample to be tested with a diluent, and mix the pre-diluted blood sample to be tested with a reaction reagent in a reaction vessel, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested. The reaction reagent includes a capture reagent coated with an antibody against human chorionic gonadotropin and a detection reagent with a marker-labeled antibody against human chorionic gonadotropin. Control the substrate providing device to provide the luminescent substrate to the reaction vessel containing the sample solution to be tested, so that the marker in the sample solution to be tested reacts with the luminescent substrate in a chemiluminescent reaction, and control the photometer to detect the luminescent signal generated in the chemiluminescent reaction.

[0038] Obtain the detection result of human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0039] Among them, the second linear detection range of the luminescent substrate is [B1, B2] photon counts per second. The second linear detection range represents the range of the intensity of the luminescence signal generated in the chemiluminescence reaction. Within this second linear detection range, the number of markers participating in the chemiluminescence reaction is linearly related to the intensity of the luminescence signal generated in the chemiluminescence reaction, where B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 , and / or, the ratio B2 / B1 of B2 to B1 is greater than or equal to 30000.

[0040] A chemiluminescence analyzer according to the fifth aspect of the present disclosure, characterized by comprising:

[0041] A sample preparation device for pre-diluting all blood samples to be tested containing human chorionic gonadotropin as the substance to be tested with a diluent, and mixing the pre-diluted blood samples to be tested with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood samples to be tested reacts with the reaction reagent to obtain a sample solution to be tested. The reaction reagent includes a capture reagent coated with an antibody against human chorionic gonadotropin and a detection reagent of an antibody against human chorionic gonadotropin with a marker;

[0042] A substrate providing device for providing a luminescent substrate into the reaction container containing the sample solution to be tested, so that the marker in the sample solution to be tested undergoes a chemiluminescence reaction with the luminescent substrate;

[0043] A photometric device. The photometric device at least includes a photometer. The photometer is used to detect the luminescence signal generated in the chemiluminescence reaction. The photometer includes a receiving component and a processing component. The receiving component is configured to receive the optical signal generated in the chemiluminescence reaction and convert the optical signal into a corresponding electrical signal. The processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component. The processing component includes a first photon counting module and a second photon counting module. The first photon counting module is configured to detect the number of pulses of the electrical signal using the pulse recognition method to obtain a first photon counting result. The second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function. Among them, the calibration function represents the mapping relationship between the parameter characterizing the number of photons in the optical signal and the photon counting result. The processing component is further configured to obtain the photon count output by the photometer based on the first photon counting result and the second photon counting result, and output the photon count;

[0044] A data processing device for obtaining a detection result of human chorionic gonadotropin in a blood sample to be tested according to a luminescence signal and a preset calibration model.

[0045] The sixth aspect of the present disclosure provides a chemiluminescence analyzer, including:

[0046] A sample preparation device for preparing a sample solution to be tested from a blood sample to be tested;

[0047] A substrate providing device for providing a luminescent substrate;

[0048] A photometric device, the photometric device at least includes a photometer, the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction, the photometer includes a receiving component and a processing component, the receiving component is configured to receive the optical signal generated in the chemiluminescence reaction and convert the optical signal into a corresponding electrical signal, the processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component, the processing component includes a first photon counting module and a second photon counting module, the first photon counting module is configured to detect the number of pulses of the electrical signal by using a pulse identification method to obtain a first photon counting result, the second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function, wherein, the calibration function represents the mapping relationship between the parameter characterizing the number of photons in the optical signal and the photon counting result, the processing component is further configured to obtain the photon counting output by the photometer based on the first photon counting result and the second photon counting result, and output the photon counting;

[0049] A controller, configured to

[0050] Obtain the detection item of the blood sample to be tested,

[0051] When the detection item is a human chorionic gonadotropin detection item:

[0052] Control the sample preparation device to pre-dilute the blood sample to be tested with a diluent, and mix the pre-diluted blood sample to be tested with a reaction reagent in a reaction vessel, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested, the reaction reagent includes a capture reagent coated with a human chorionic gonadotropin antibody and a detection reagent of a human chorionic gonadotropin antibody with a label, control the substrate providing device to provide the luminescent substrate into the reaction vessel containing the sample solution to be tested, so that the label in the sample solution to be tested undergoes a chemiluminescence reaction with the luminescent substrate, control the photometer to detect the luminescence signal generated in the chemiluminescence reaction,

[0053] Obtain the detection result of human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0054] The seventh aspect of the present disclosure provides a chemiluminescence analyzer, comprising:

[0055] an HCG determination unit configured to obtain a test result of human chorionic gonadotropin in a blood sample to be tested;

[0056] a mode selection unit configured to select a first HCG test mode or a second HCG test mode; and

[0057] a controller configured to,

[0058] receive the mode selection of the mode selection unit,

[0059] when the mode selection unit selects the first HCG test mode, control the HCG determination unit to execute a first determination process, the first determination process comprising: pre-diluting at least a part of the blood sample to be tested with a diluent, and performing chemiluminescence determination on the pre-diluted part of the blood sample to be tested to obtain and output a first HCG test result; and

[0060] when the mode selection unit selects the second HCG test mode, control the HCG determination unit to execute a second determination process, the second determination process comprising: performing chemiluminescence determination on an undiluted part of the blood sample to be tested to obtain a second HCG test result, and when the second HCG test result is abnormal, pre-diluting another part of the blood sample to be tested with a diluent, and performing chemiluminescence determination on the pre-diluted part of the blood sample to be tested to obtain and output a third HCG test result.

[0061] The eighth aspect of the present disclosure provides a chemiluminescence analyzer, comprising:

[0062] a sample preparation device configured to mix a blood sample to be tested with a reaction reagent in a reaction container so that a substance to be tested in the blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested, the reaction reagent comprising a capture reagent and a detection reagent with a label;

[0063] a reagent carrier device configured to place a reagent kit, the reagent kit carrying reaction reagents corresponding to test items, and the reagent kit corresponding to the human chorionic gonadotropin test item further carrying a diluent;

[0064] a substrate providing device configured to provide a luminescent substrate into the reaction container containing the sample solution to be tested so that the label in the sample solution to be tested undergoes a chemiluminescence reaction with the luminescent substrate;

[0065] A photometric device, the photometric device at least including a photometer for detecting a luminescence signal generated in the chemiluminescence reaction;

[0066] A data processing device for obtaining a detection result of the substance to be measured in the blood sample to be measured according to the luminescence signal and a preset calibration model;

[0067] A control device, when the detection item of the blood sample to be measured is a human chorionic gonadotropin detection item, controlling the sample preparation device to pre-dilute the blood sample to be measured with a diluent in a kit corresponding to the human chorionic gonadotropin detection item at a preset dilution ratio, and mixing at least part of the reaction reagent in the kit corresponding to the human chorionic gonadotropin detection item with the pre-diluted blood sample to be measured in the reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be measured reacts with the reaction reagent to obtain a sample solution to be measured,

[0068] Controlling the substrate providing device to provide a luminescent substrate into the reaction container containing the sample solution to be measured, so that the label in the sample solution to be measured undergoes a chemiluminescence reaction with the luminescent substrate,

[0069] Controlling the photometer to detect the luminescence signal generated in the chemiluminescence reaction, and obtaining the detection result of the human chorionic gonadotropin in the blood sample to be measured according to the luminescence signal and a preset calibration model.

[0070] The chemiluminescence analyzer provided in various aspects of the present disclosure can achieve efficient and accurate determination of the HCG concentration without increasing the detection cost through the design of the photometer and pre-diluting the blood sample to be measured in advance. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] The present disclosure will be described more clearly below in conjunction with embodiments and the drawings. Through the detailed description of the embodiments of the present disclosure, the above advantages and other advantages will become clear to those of ordinary skill in the art. The drawings are only used to show the preferred embodiments and should not be considered as a limitation to the present disclosure.

[0072] In the drawings:

[0073] Figure 1 A schematic block diagram of a chemiluminescence analyzer provided by an embodiment of the present disclosure is shown.

[0074] Figure 2 And Figure 3 A calibration curve of a chemiluminescence analyzer provided by an embodiment of the present disclosure is shown.

[0075] Figure 4Shows a schematic structural diagram of a chemiluminescence analyzer provided by an embodiment of the present disclosure.

[0076] Figures 5 to 15 Shows a schematic block diagram of a photometer provided by different embodiments of the present disclosure.

[0077] Figures 16A to 16D Is the linear fitting curve of the luminescence values of chemiluminescent substrate solutions 1-1 to 1-4 of Example 1 in the alkaline phosphatase system.

[0078] Figures 17A to 17D Is the linear fitting curve of the luminescence values of chemiluminescent substrate solutions 2-1 to 2-4 of Example 2 in the alkaline phosphatase system.

[0079] Figures 18A to 18D Is the linear fitting curve of the luminescence values of chemiluminescent substrate solutions 3-1 to 3-4 of Example 3 in the alkaline phosphatase system.

[0080] Figures 19A to 19D Is the linear fitting curve of the luminescence values of chemiluminescent substrate solutions 4-1 to 4-4 of Example 4 in the alkaline phosphatase system.

[0081] Figures 20A to 20D Is the linear fitting curve of the luminescence values of chemiluminescent substrate solutions 5-1 to 5-4 of Example 5 in the alkaline phosphatase system. Detailed implementation manners

[0082] The embodiments of the present disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present disclosure, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present disclosure without creative efforts belong to the scope of protection of the present disclosure.

[0083] It should be noted that the terms "first / second / third" involved in the embodiments of the present disclosure are only used to distinguish similar objects and do not represent a specific order for the objects. It can be understood that "first / second / third" can be interchanged with a specific order or sequence when permitted.

[0084] Those skilled in the art of the present technology can understand that, unless otherwise defined, all terms (including technical terms and scientific terms) used here have the same meaning as the general understanding of those of ordinary skill in the art in the field to which the present disclosure belongs.

[0085] As mentioned in the background art, the HCG detection item has relatively high requirements for the upper limit of linear detection. However, the existing technology cannot simultaneously meet the requirements of high linear detection upper limit and high detection sensitivity, and often needs to be diluted and retested to obtain accurate HCG concentration.

[0086] Based on this, the embodiments of the present disclosure propose a technical solution that can accurately and efficiently obtain the HCG test result without increasing the cost.

[0087] As Figure 1 shown, a chemiluminescence analyzer 100 is proposed in the first aspect of the present disclosure, including a sample preparation device 110, a substrate providing device 120, a photometric device 130, and a data processing device 140.

[0088] The sample preparation device 110 is at least used for a blood sample to be tested with the detection item of human chorionic gonadotropin detection item. Before the human chorionic gonadotropin detection is performed on the blood sample to be tested, the blood sample to be tested is pre-diluted with a diluent at a preset dilution ratio, and the pre-diluted blood sample to be tested is mixed with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested. The reaction reagent includes a capture reagent coated with a human chorionic gonadotropin antibody and a detection reagent of a human chorionic gonadotropin antibody with a label. In some embodiments, the capture reagent can be a magnetic bead reagent for capturing the substance to be tested, and the detection reagent with a label can be a detection reagent with an enzyme label, such as alkaline phosphatase.

[0089] The substrate providing device 120 is used to provide a luminescent substrate into the reaction container filled with the sample solution to be tested, so that the label in the sample solution to be tested undergoes a chemiluminescence reaction with the luminescent substrate;

[0090] The photometric device 130 at least includes a photometer, and the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction. The first linear detection range of the photometer is [A1, A2] photon counts per second. The first linear detection range represents the range of the number of photons output by the photometer. Within this first linear detection range, the intensity of the luminescence signal generated in the chemiluminescence reaction is linearly related to the photon count output by the photometer, where A1 is less than or equal to 2000 and A2 is greater than or equal to 10 8 .

[0091] The data processing device 140 is used to obtain the test result of the human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0092] The photometer is designed in such a way that a chemiluminescence analyzer with a wide linear detection range can be obtained. In addition, by pre-diluting the sample, for example, by a factor of 2, 5, or 10, the HCG test result can be accurately obtained in one test. There is no need to pre-screen the sample in advance and determine whether to apply a dilution test or a non-dilution test, which can largely avoid unnecessary retesting, reduce the retest rate of samples with high HCG concentrations, thereby improving the overall detection efficiency of the chemiluminescence analyzer for HCG detection and reducing the detection cost.

[0093] In particular, the chemiluminescence analyzer according to the present disclosure can accurately and linearly detect HCG as low as 0.5 mIU / ml and as high as 200,000 mIU / ml without the need for dilution and retesting. That is to say, it can accurately obtain HCG with a concentration between 0.5 and 200,000 mIU / ml through one test, meeting the main requirements of clinical use of HCG for assisting in judging pregnancy and monitoring pregnancy status, avoiding re-dilution and retesting when the HCG concentration in the sample exceeds the detection upper limit, greatly improving the work efficiency of the laboratory department and saving costs. As Figure 2 and Figure 3 shown, for the HCG detection item, within the HCG concentration range of 0.5 to 200,000 mIU / ml, the calibration model, or rather the calibration curve, has good linearity in the low HCG concentration range and also has good linearity throughout the entire HCG concentration range.

[0094] In the embodiment of the present disclosure, the linear detection range refers to the linear detection range of a single detection, that is, the linear detection range that can be achieved in one detection of a sample.

[0095] Figure 4 The structure diagram of a chemiluminescence analyzer 100 provided by the embodiment of the present disclosure is shown. As Figure 4 shown, the sample preparation device 110 includes a sample supply unit 111, a reagent supply unit 112, and a reaction incubation unit 113. The sample supply unit 111 is configured to aspirate a blood sample to be tested and supply it to a reaction container. The reagent supply unit 112 is configured to capture a reagent and a detection reagent with a marker and supply them to the reaction container. The reaction incubation unit 113 is configured to provide a place for reaction and incubation for the reaction container containing the blood sample to be tested and the reaction reagent, so that the blood sample to be tested and the reaction reagent in the reaction container form a sample solution to be tested.

[0096] The chemiluminescence analyzer 100 further includes a magnetic separation device 140 and a transfer device 150. The magnetic separation device 140 is configured to perform a magnetic separation operation on a reaction vessel containing a sample liquid to be tested. A substrate supply device 120 (not shown) is configured to supply a luminescent substrate into the reaction vessel that has completed the magnetic separation operation. The transfer device 150 is configured to transfer the reaction vessel that has completed the magnetic separation operation from the magnetic separation device 140 to the reaction incubation section 113. The incubated reaction vessel is transferred to the photometric device 130 for photometry.

[0097] In some embodiments, the chemiluminescence analyzer 100 further includes a sample processing system (not shown) for transporting a test tube containing a blood sample to be tested to a sampling position and transporting the test tube after sampling to a recovery area. Specifically, the sample processing system includes a sample loading area and a transport track. The sample loading area is used to store test tubes containing blood samples to be tested placed by the user, and the transport track is used to transport the test tubes in the sample loading area to the sampling position.

[0098] In addition, the sample processing system further includes a scanning module for scanning the sample barcode to achieve sample identification and management.

[0099] In some embodiments, the sample supply unit 111 may include a sample needle and a driving mechanism. The driving mechanism is used to drive the sample needle to move between the sampling position and the sample adding position. The sample needle samples the sample in the sample tube located at the sampling position and injects the aspirated sample into the reaction vessel located at the sample adding position. Here, the sampling position is, for example, the intersection of the movement trajectory of the sample needle and the sample transport trajectory of the transport track.

[0100] In addition, the sample supply unit 111 further includes a cleaning mechanism for cleaning the sample needle. Further, the sample supply unit 111 further includes a dilution position for placing the reaction vessel that has completed automatic dilution and pretreatment, so that the sample needle can aspirate the diluted sample or the pretreated sample in the reaction vessel located at the dilution position to support the corresponding test mode.

[0101] In some embodiments, the chemiluminescence analyzer further includes a first robotic arm 160 for transferring reaction vessels. The first robotic arm is configured to be capable of three-dimensional movement and can grip the reaction vessel. The first robotic arm is configured to load a new reaction vessel into the sample adding position so that the sample needle can inject the sample. The first robotic arm is also configured to discard the empty reaction cup. The first robotic arm is further configured to transfer the reaction vessel between the sample adding position, the reaction incubation section 113, and the dilution position.

[0102] In some embodiments, the reagent supply unit 112 includes a reagent tray 114 and a reagent needle 115. The reagent tray 114 is used to place reagent bottles containing capture reagents and detection reagents with markers and has the function of refrigerating the reagent bottles. The reagent tray 114 is configured to be rotatable so as to transfer the reagent bottles that need to aspirate reagents to the reagent aspiration position. The reagent needle 115 is used to aspirate reagents from the reagent bottles located at the reagent aspiration position and discharge the aspirated reagents into the reaction vessels located at the sample addition position.

[0103] Further, the reagent tray has a mixing mechanism (not shown) for mixing magnetic bead reagents. This mixing mechanism realizes the mixing of capture reagents, for example, by rotating the reagent bottles containing capture reagents such as magnetic bead reagents.

[0104] Further, the reagent supply unit 112 also includes a cleaning mechanism (not shown) for cleaning the reagent needle.

[0105] In some embodiments, the magnetic separation device 140 has a disk-shaped rotatable magnetic separation disk, a magnetic mechanism, and a temperature control mechanism. The magnetic separation disk is used to drive the reaction vessels therein to sequentially pass through the magnetic mechanism for magnetic separation operations, and the temperature control mechanism is used to maintain the temperature of the magnetic separation disk within a preset range.

[0106] In some embodiments, the substrate providing device has a heating mechanism for preheating the luminescent substrate. The substrate providing device is used to inject the preheated luminescent substrate into the reaction vessels that have completed magnetic separation and are located at the substrate injection position, where the substrate injection position is located on the magnetic separation disk.

[0107] In some embodiments, the reaction incubation unit 113 includes a disk-shaped rotatable reaction disk. The photometric device 130 is arranged on the outer peripheral side of the reaction disk. The reaction vessels after injecting the luminescent substrate are transported into the reaction disk by the transport device 150. The reaction disk drives the reaction vessels that have been incubated for a certain time into the photometric device 130 to complete photometric measurement.

[0108] In some embodiments, the transport device 150 is configured as a second manipulator, which is used to clamp the reaction vessels and transport the reaction vessels between the reaction disk and the magnetic separation disk. This second manipulator is configured to be able to rotate horizontally and perform two-dimensional up-and-down movement.

[0109] In some embodiments, the chemiluminescence analyzer may further include a mixer 170 arranged between the reaction disk and the magnetic separation disk. This mixer is configured to perform a mixing operation on the reaction vessels that have already added reagents and samples. For example, this mixer can be configured as a vortex mixer that realizes non-contact mixing, which can effectively avoid cross-contamination.

[0110] In addition, the chemiluminescence analyzer may further include a hardware control system (not shown) and software systems running on a hardware board and a PC respectively, so as to control the above-mentioned various devices of the chemiluminescence immunoassay analyzer to work in coordination. The chemiluminescence analyzer may further include a mechanical system (not shown) composed of a frame, a front shell, etc., so as to provide support, positioning and protection for the above-mentioned various devices.

[0111] In some embodiments, the data processing device 140 includes, but is not limited to, a Central Processing Unit (CPU), a Micro Controller Unit (MCU), a Field-Programmable Gate Array (FPGA), a Digital Signal Processor (DSP), etc., which are used to interpret computer instructions and process data in computer software. For example, the data processing device is used to execute each computer application program in the computer-readable storage medium, so that the chemiluminescence analyzer 100 executes the corresponding detection process and analyzes in real time the luminescence signal detected by the photometric device 130.

[0112] A specific detection process of the chemiluminescence analyzer is as follows: the sample supply unit 111 aspirates the blood sample to be tested and adds it to the reaction container; the reagent supply unit 112 aspirates the capture reagent and the detection reagent and adds them to the reaction container containing the sample, so as to mix with the sample; then the reaction container is placed in the reaction incubation unit 113 for reaction, incubation and magnetic separation cleaning; then the substrate providing device adds the luminescent substrate to the reaction cup that has completed the reaction, incubation and magnetic separation cleaning, and incubates for a period of time; finally, the photometric device 130 detects the photons emitted by the analyte in the sample to be tested under the action of the luminescent substrate, so as to calculate the concentration level of the analyte through the measured number of photons.

[0113] In some embodiments, the preset dilution ratio includes 2 to 20 times. This can improve the applicability to samples with different concentrations. In other words, for samples with a wide range of HCG concentrations, the HCG detection results can be obtained more accurately, improving the ability of the chemiluminescence analyzer for HCG detection.

[0114] In some embodiments, the calibration model is obtained by the chemiluminescence analyzer using pre-diluted calibration products. Here, calibration is performed using pre-diluted calibration products, that is, the pre-diluted calibration products are directly traced to the reference substance, and a gradient concentration response curve of the pre-diluted calibration products is established, so as to eliminate systematic errors caused by random deviations and matrix effects during the dilution process itself, and improve the accuracy of the measurement results.

[0115] In some embodiments, the pre-dilution multiple of the blood sample to be tested is equal to that of the calibrator. In this way, the matching degree between the calibration model and the actual test result can be improved, and thus the actual content of HCG in the blood sample to be tested can be obtained more accurately.

[0116] In some embodiments, the diluent, the capture reagent, and the detection reagent are placed in a common kit. The kit includes a carrier and a first cavity, a second cavity, and a third cavity opened on the carrier. The first cavity is used to accommodate the diluent, the second cavity is used to accommodate the capture reagent, and the third cavity is used to accommodate the detection reagent.

[0117] Thus, the following many benefits can be achieved:

[0118] a) Automatic in-machine operation for HCG dilution;

[0119] b) The manufacturer provides the diluent, which can ensure the accuracy of the measured value of HCG dilution and avoid poor test results caused by customers preparing the diluent by themselves;

[0120] c) Saving reagent storage space and improving the utilization efficiency of reagent positions;

[0121] d) Saving test costs, and customers do not need to separately inventory and purchase the diluent, which provides great convenience to customers.

[0122] In some embodiments, the calibration model or the calibration curve is obtained by multi-point calibration.

[0123] In the embodiments of the present disclosure, the multi-point calibration method may be: using a series of samples (greater than or equal to 5 samples) pre-assigned by the supplier of the chemiluminescence analyzer, measuring the luminescence signal values of this series of samples on the chemiluminescence analyzer, establishing a curve of sample concentration and luminescence signal, and performing 4PLC fitting regression on the curve to obtain a fitting equation, that is, the calibration model.

[0124] It can be understood that the luminescence signal value measured for the blood sample to be tested on the chemiluminescence analyzer is substituted into the calibration model to calculate the concentration of the substance to be tested in the blood sample to be tested.

[0125] In some embodiments, the calibration model is obtained by the following formula

[0126]

[0127] wherein, RLU is the reactivity, that is, the measured luminescence signal value, C is the concentration of the substance to be measured, P1 to P4 are 4 fitting parameters. Among them, P1 represents the luminescence signal corresponding to zero concentration (asymptote), P4 represents the luminescence signal corresponding to the maximum concentration (asymptote), P2 represents the inflection point where the slope direction of the curve changes, and P3 reflects the slope at P2 (non-real slope).

[0128] It can be understood here that the 4PLC calibration model uses at least 5 (number of fitting parameters + 1) points for 4PLC regression, and obtains the optimal solution through a numerical iteration process to obtain four fitting parameters P1, P2, P3, and P4.

[0129] In some embodiments of the present disclosure, the calibration model is recalibrated when the reagent batch is changed, or the calibration model is recalibrated at fixed intervals of days, or the calibration model is recalibrated when the instrument quality control gets out of control.

[0130] In some embodiments, the ratio A2 / A1 of A2 to A1 is greater than or equal to 30000.

[0131] In some embodiments, the second linear detection range of the chemiluminescent substrate is [B1, B2] photon counts per second. The second linear detection range represents the range of the intensity of the luminescence signal generated in the chemiluminescent reaction. Within this second linear detection range, the number of markers participating in the chemiluminescent reaction is linearly related to the intensity of the luminescence signal generated in the chemiluminescent reaction, where B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 , and / or the ratio B2 / B1 of B2 to B1 is greater than or equal to 30000.

[0132] Here, by designing the photometer and the chemiluminescent substrate in this way, a chemiluminescent analyzer with a wide linear detection range can be obtained. In particular, a chemiluminescent analyzer with a linear detection range of at least [3000, 10 8 photon counts per second can be obtained.

[0133] In some embodiments, the lower limit B1 of the second linear detection range is less than or equal to 2000. Thereby, the sensitivity of the chemiluminescent analyzer can be further improved, and thus the linear detection range of a single detection of the chemiluminescent analyzer can be further broadened.

[0134] In some embodiments, the chemiluminescent analyzer 100 can be designed such that when the concentration of human chorionic gonadotropin in the blood sample to be tested is greater than or equal to 200000 mIU / ml, the intensity of the luminescence signal generated in the chemiluminescent reaction is less than or equal to the smaller value of A2 and B2. Thereby, HCG with a relatively high concentration can be detected more accurately.

[0135] For example, the chemiluminescence analyzer 100 can be designed such that when the concentration of human chorionic gonadotropin in the blood sample to be tested is 200,000 mIU / ml, the intensity of the luminescence signal generated in the chemiluminescence reaction is less than or equal to the smaller value of A2 and B2. Thus, accurate detection of HCG concentrations up to 200,000 mIU / ml can be achieved.

[0136] In some embodiments, the chemiluminescence analyzer 100 can be designed such that when the concentration of human chorionic gonadotropin in the blood sample to be tested is greater than or equal to 0.5 mIU / ml, the intensity C1 of the luminescence signal generated in the chemiluminescence reaction is greater than or equal to the larger value of A1 and B1. Thus, relatively accurate detection of HCG at lower concentrations can be achieved.

[0137] For example, the chemiluminescence analyzer 100 can be designed such that when the concentration of human chorionic gonadotropin in the blood sample to be tested is 0.5 mIU / ml, the intensity C1 of the luminescence signal generated in the chemiluminescence reaction is greater than or equal to the larger value of A1 and B1. Thus, accurate detection of HCG concentrations as low as 0.5 mIU / ml can be achieved.

[0138] Furthermore, the chemiluminescence analyzer 100 can be designed such that when the concentration of human chorionic gonadotropin in the blood sample to be tested is greater than 0.5 mIU / ml and less than or equal to 5 mIU / ml, preferably less than or equal to 2 mIU / ml, the intensity of the luminescence signal generated in the chemiluminescence reaction is C2, where the ratio C2 / C1 of C2 to C1 is greater than 2.

[0139] In some embodiments, the upper limit B2 of the second linear detection range is greater than the upper limit A2 of the first linear detection range.

[0140] Next, some embodiments of the luminescent substrate used in the chemiluminescence analyzer of the present disclosure will be described, but the present disclosure is not limited thereto.

[0141] In some embodiments, the luminescent substrate is designed such that the background of the luminescent substrate is less than 3000, thereby further improving the sensitivity of the chemiluminescence analyzer.

[0142] Alternatively or additionally, the luminescent substrate is designed such that the signal-to-noise ratio of the luminescent substrate is greater than 40,000. Thus, the sensitivity of the chemiluminescence analyzer can be further improved.

[0143] In some embodiments, the luminescent substrate includes a chemiluminescent substrate and a chemiluminescence enhancer. The chemiluminescence enhancer includes a fluorescent agent and a surfactant. The fluorescent agent includes one or more carboxyfluoresceins. Using such a luminescent substrate can achieve high sensitivity of the chemiluminescence analyzer.

[0144] As some implementations, the luminescent substrate is selected from dioxetane compounds, preferably one or more selected from AMPPD, CSPD, CDP-STAR, and more preferably CDP-STAR.

[0145] As some implementations, the luminescent substrate is selected from chlorinated derivatives of AMPPD, fluorescein or its carboxyl-substituted derivatives, and water-soluble polymer quaternary ammonium salt-type cationic surfactants.

[0146] The chlorinated derivative of AMPPD may be, for example, ADP-STAR or CDP-STAR. Alternatively, the fluorescein or its carboxyl substituted derivative may be, for example, fluorescein or 5(6)-carboxyfluorescein. Alternatively, the water-soluble polymer quaternary ammonium salt cationic surfactant may be, for example, polyvinylbenzyltrimethylammonium chloride.

[0147] In some embodiments, the substrate providing device is used to provide a chemiluminescent substrate liquid containing a luminescent substrate or a chemiluminescent substrate, wherein the chemiluminescent substrate liquid includes a chemiluminescent substrate, fluorescein and a water-soluble polymer quaternary ammonium salt, wherein the chemiluminescent substrate is selected from chlorinated dioxetane compounds having a spiro-adamantane substituent.

[0148] Chemiluminescent substrates refer to compounds that participate in energy transfer in chemiluminescent reactions and ultimately release energy in the form of emitted photons. They are also called chemiluminescent agents or luminescent substrates. Dioxetane compounds are enzymatic glow-type chemiluminescent substrates and are a class of ultra-sensitive alkaline phosphatase (AP) substrates. In a suitable buffer, with the catalytic hydrolysis of alkaline phosphatase, the signal emitted by the decomposition of dioxetane compounds can last for more than 20 hours, making them ideal chemiluminescent substances.

[0149] The inventors have found that a chlorinated dioxetane compound having a spiro-adamantane substituent is combined with a specific chemiluminescence enhancer, such as fluorescein or its carboxylic acid derivative, in the presence of a water-soluble polymer quaternary ammonium salt cationic surfactant, to obtain a chemiluminescent substrate solution with a ratio of the number of photons generated per second of the upper detection limit to the lower detection limit of more than 30,000, or even more than 50,000, so that it can be conveniently used in samples such as HCG with a concentration range of up to 10 5 ~10 6 Order of magnitude immunoassay.

[0150] The "dioxetanes having spiro-adamantane substituents" mentioned herein refer to a class of compounds based on the following structure:

[0151]

[0152] For example, it includes the following compounds, but is not limited to:

[0153] AMPPD - (3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)-phenyl-1,2-dioxetane, CAS = 122341-56-4),

[0154] CSPD - (3-(2'-(spiro-5-chloroadamantane))-4-methoxy-4-(3"-phosphoryloxy)-phenyl-1,2-dioxetane, CAS = 142456-88-0),

[0155] ADP-STAR - (3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy-4"-chloro)-phenyl-1,2-dioxetane, CAS = 189942-84-5),

[0156] CDP-STA - (3-(2'-(spiro-5-chloroadamantane))-4-methoxy-4-(3"-phosphoryloxy-4"-chloro)-phenyl-1,2-dioxetane, CAS = 160081-62-9),

[0157] TFE-AMPPD - (3-(2'-spiroadamantane)-4-trifluoroethoxy-4-(3"-phosphoryloxy)-phenyl-1,2-dioxetane).

[0158] The "chlorinated dioxetane compounds with spiro-adamantane substituents" mentioned in this article refer to those containing at least one chlorine atom in the structure of AMPPD.

[0159] In some embodiments, the chlorinated dioxetane compounds with spiro-adamantane substituents are one of ADP-STAR and CDP-STAR.

[0160]

[0161] In a specific embodiment, in the chemiluminescent substrate solution, the chemiluminescent substrate may exist in the form of a salt of the above compounds. According to some embodiments, the salt may be an alkali metal salt, such as sodium salt.

[0162] These dioxetane compounds with chloro groups, especially ADP-STAR and CDP-STAR, when combined with fluorescein or its carboxyl derivatives and water-soluble polymeric quaternary ammonium salts in an alkaline phosphatase catalytic system, unexpectedly can provide a sufficiently low sensitivity while maintaining linearity within a relatively high luminescence value range.

[0163] Fluorescent agents and surfactants can improve the efficiency of chemiluminescence. Among them, surfactants form micelles in solution to protect chemiluminescent substrates, thereby reducing the quenching reaction of chemiluminescent substrates in aqueous solutions. Fluorescent agents, as photon acceptors, receive the photon energy in the system through energy transfer effects and are excited to generate optical signals, thus enhancing the luminescence efficiency.

[0164] The fluorescent agent in the chemiluminescent substrate solution of the present disclosure is at least one of fluorescein and carboxyl-substituted fluorescein.

[0165] The carboxyl-substituted fluorescein includes compounds selected from those shown in General Formula I:

[0166]

[0167] Specifically, the carboxyfluorescein shown in General Formula I can be 5-carboxyfluorescein, 6-carboxyfluorescein, or 5(6)-carboxyfluorescein. Among them,

[0168] The 5-carboxyfluorescein is

[0169]

[0170] The 6-carboxyfluorescein is

[0171]

[0172] The 5(6)-carboxyfluorescein is a mixture of the 5-carboxyfluorescein and the 6-carboxyfluorescein in any ratio.

[0173] In the chemiluminescent substrate solution, the fluorescent agent is fluorescein. In other embodiments, the fluorescent agent can be any carboxyl-substituted fluorescein, especially one of 5-carboxyfluorescein, 6-carboxyfluorescein, and 5(6)-carboxyfluorescein.

[0174] Fluorescein and its carboxyl derivatives can improve the chemiluminescence efficiency of the chemiluminescent system. In addition to effectively improving the chemiluminescence efficiency of the chemiluminescent system, the above-mentioned carboxyl derivatives can also reduce the time required to reach the plateau period and improve the sensitivity.

[0175] In the chemiluminescent substrate solution, the surfactant is a water-soluble polymer quaternary ammonium salt cationic surfactant. According to one embodiment, the water-soluble polymer quaternary ammonium salt is selected from quaternary ammonium salts containing vinyl groups. Such quaternary ammonium salts are, for example, vinylbenzyl-trialkylammonium halides. The three alkyl groups substituted on the N atom can be the same or different, and can be independently selected from, for example, methyl, ethyl, propyl, butyl, pentyl, benzyl, etc. In a specific embodiment, the water-soluble polymer quaternary ammonium salt is selected from at least one of vinylbenzyl-trimethylammonium chloride, vinylbenzyl-benzyldimethylammonium chloride, and vinylbenzyl-tributylammonium chloride.

[0176] The water-soluble polymer quaternary ammonium salt cationic surfactant can also form micelles in an aqueous solution. The chemiluminescent substrate is inside the hydrophobic micelles, and the fluorescent agent is in the hydrophilic part outside the micelles, which is more conducive to the chemiluminescent substrate transferring energy to the fluorescent agent to enhance the light signal. Compared with small molecule quaternary ammonium salts, due to the longer alkane chain of the polymer quaternary ammonium salt, it can more effectively prevent the chemiluminescent substrate from quenching in an aqueous solution. In addition, the polymer quaternary ammonium salt can also suppress the background signal and improve the detection signal. Under the same conditions, the small molecule quaternary ammonium salt has a high background signal value and a low detection signal, and cannot achieve a wide linear detection range.

[0177] In a specific embodiment, the chemiluminescent substrate solution includes ADP-STAR or CDP-STAR as the chemiluminescent substrate, fluorescein, and a water-soluble polymer quaternary ammonium salt.

[0178] In another specific embodiment, the chemiluminescent substrate solution includes ADP-STAR, fluorescein or carboxyl-substituted fluorescein as the fluorescent agent, and a water-soluble polymer quaternary ammonium salt.

[0179] The specific combination of the above chemiluminescent substrate, fluorescent agent, and surfactant provides a chemiluminescent substrate solution with a wide linear luminescence value. The chemiluminescent substrate solution can obtain a linear detection range with a lower limit B1 of less than 3,000 photon counts per second and an upper limit B2 of more than 100,000,000 (100M) photon counts per second in the alkaline phosphatase system. Exemplarily, the chemiluminescent substrate solution can obtain a linear detection range with a lower limit B1 of 1,000 - 3,000 photon counts per second and an upper limit B2 of 100,000,000 (100M) - 200,000,000 (200M) photon counts per second in the alkaline phosphatase system. As shown in the following examples, the chemiluminescent substrate solution can obtain a background luminescence value of 1,000 - 2,000 photon counts per second and a linear detection range with an upper limit B2 of 120,000,000 (120M) - 200,000,000 (200M) photon counts per second in the alkaline phosphatase system. It should be understood that the above lower limit range and upper limit range are only exemplary, and by adjusting the detection device or signal processing method, etc., a lower lower limit of photon counts per second or a higher upper limit of photon counts per second can be obtained.

[0180] In some embodiments, the ratio of the number of photons generated per second of the upper detection limit B2 to the lower detection limit B1 of the chemiluminescent substrate solution is more than 30,000, for example, more than 50,000, and even more than 60,000. In some embodiments, the ratio of the number of photons generated per second of the upper detection limit B2 to the lower detection limit B1 of the chemiluminescent substrate solution is less than 1,000,000, for example, less than 800,000, 600,000, 500,000, and even less than 400,000. Exemplarily, the ratio of the number of photons generated per second of the upper detection limit B2 to the lower detection limit B1 of the chemiluminescent substrate solution is 30,000 - 1,000,000, 30,000 - 800,000, 30,000 - 500,000, 50,000 - 1,000,000, 50,000 - 800,000, 50,000 - 500,000, etc.

[0181] In some embodiments, the chemiluminescent substrate solution includes 50 - 500 mg / L of the chemiluminescent substrate. Preferably, the chemiluminescent substrate solution includes 150 - 250 mg / L of the chemiluminescent substrate, and more preferably, it includes 200 mg / L of the chemiluminescent substrate. Exemplarily, the chemiluminescent substrate solution includes 150 mg / L, 160 mg / L, 170 mg / L, 180 mg / L, 190 mg / L, 200 mg / L, 210 mg / L, 220 mg / L, 230 mg / L, 240 mg / L, 250 mg / L of the chemiluminescent substrate.

[0182] In some embodiments, the chemiluminescent substrate solution comprises 30 to 500 mg / L of a fluorescent agent. Preferably, the chemiluminescent substrate solution comprises 150 to 250 mg / L of a fluorescent agent, and more preferably, 200 mg / L of a fluorescent agent. Exemplarily, the chemiluminescent substrate solution comprises 150 mg / L, 160 mg / L, 170 mg / L, 180 mg / L, 190 mg / L, 200 mg / L, 210 mg / L, 220 mg / L, 230 mg / L, 240 mg / L, 250 mg / L of a fluorescent agent.

[0183] In some embodiments, the chemiluminescent substrate solution comprises 1 to 10 g / L of a water-soluble polymeric quaternary ammonium salt. Preferably, the chemiluminescent substrate solution comprises 3 to 7 g / L of a water-soluble polymeric quaternary ammonium salt, and more preferably, 5 g / L of a water-soluble polymeric quaternary ammonium salt. Exemplarily, the chemiluminescent substrate solution comprises 3 g / L, 4 g / L, 5 g / L, 6 g / L, 7 g / L of a water-soluble polymeric quaternary ammonium salt.

[0184] In a specific embodiment, the chemiluminescent substrate solution comprises 50 - 500 mg / L, preferably 150 - 250 mg / L of ADP-STAR or CDP-STAR, 30 - 500 mg / L, preferably 150 - 250 mg / L of fluorescein, and 1 - 10 g / L, preferably 3 - 7 g / L of a water-soluble polymeric quaternary ammonium salt.

[0185] In another specific embodiment, the chemiluminescent substrate solution comprises 50 - 500 mg / L, preferably 150 - 250 mg / L of ADP-STAR, 30 - 500 mg / L, preferably 150 - 250 mg / L of fluorescein or carboxyl-substituted fluorescein, and 1 - 10 g / L, preferably 3 - 7 g / L of a water-soluble polymeric quaternary ammonium salt.

[0186] The chemiluminescent substrate solution further contains additives such as a buffer and a preservative.

[0187] The present disclosure does not particularly limit the type of buffer, and any buffer conventionally applicable can be used in the chemiluminescent substrate solution of the present disclosure. In some embodiments, the buffer can be selected from Tris buffer, AMP buffer (AMP is 2 - amino - 2 - methylpropanol), AMPD buffer (AMPD is 2 - amino - 2 - methyl - 1,3 - propanediol), DEA buffer (DEA is diethanolamine), CHES buffer (CHES is 2 - (N - cyclohexylamino)ethanesulfonic acid), Mopso buffer, imidazole buffer, phosphate buffer, carbonate buffer, malic acid buffer, glycine buffer, but not limited thereto. Exemplarily, the buffer can be selected from at least one of Tris - HCl, AMP - HCl, AMPD - HCl, DEA - HCl, CHES - HCl, boric acid - NaOH, glycine - NaOH buffer systems. Preferably, the buffer solution is selected from the AMP - HCl buffer system. The AMP - HCl buffer system can play a better buffering role in the range of pH 9.0 - 10.0, and it is found that it is beneficial to the stability of chemiluminescent substrate molecules.

[0188] According to some embodiments, the pH of the buffer is 7.1 - 10.6, preferably about 9.0 - about 10.0, and particularly preferably about 9.5.

[0189] The present disclosure does not particularly limit the dosage of the buffer, which can be determined according to the selected buffer system.

[0190] The present disclosure does not particularly limit the type of preservative, and any preservative conventionally used in detection reagents can be used in the present disclosure. Examples include, but are not limited to, sodium azide, Proclin series, potassium sorbate, sodium benzoate, BND, erythromycin, gentamicin, etc. Preferably, they are sodium azide and Proclin series.

[0191] The present disclosure does not particularly limit the dosage of the buffer, which can be determined according to the selected type of preservative.

[0192] In some embodiments, the chemiluminescent substrate solution may further include magnesium chloride. For example, it may include 0.1 - 2 mM of magnesium chloride.

[0193] According to a specific embodiment, the chemiluminescent substrate solution comprises ADP-STAR or CDP-STAR at 50 - 500 mg / L, preferably 150 - 250 mg / L; fluorescein at 30 - 500 mg / L, preferably 150 - 250 mg / L; a water-soluble polymeric quaternary ammonium salt at 1 - 10 g / L, preferably 3 - 7 g / L; an appropriate amount of (such as 30 - 500 mM) AMP-HCl buffer; an appropriate amount of (such as 0.5 - 2 g / L) sodium azide, with a pH of about 9.0 to about 10.0, such as about 9.5.

[0194] In another specific embodiment, the chemiluminescent substrate solution comprises ADP-STAR at 50 - 500 mg / L, preferably 150 - 250 mg / L; fluorescein or carboxyl-substituted fluorescein at 30 - 500 mg / L, preferably 150 - 250 mg / L; a water-soluble polymeric quaternary ammonium salt at 1 - 10 g / L, preferably 3 - 7 g / L; an appropriate amount of (such as 30 - 500 mM) AMP-HCl buffer; an appropriate amount of (such as 0.5 - 2 g / L) sodium azide, with a pH of about 9.0 to about 10.0, such as about 9.5.

[0195] According to some embodiments, the chemiluminescent substrate solution of the present disclosure has a low background luminescence value, a high luminescence efficiency, a wide linear detection range, is suitable for an alkaline phosphatase-catalyzed chemiluminescence system, and is particularly suitable for chemiluminescent immunoassay.

[0196] According to some specific embodiments, the chemiluminescent substrate solution provided by the present disclosure reacts with alkaline phosphatase in the concentration range of 0.03 - 400 ng / mL, and the luminescence value shows good linearity (R2≥0.99). As shown in the examples, the background value of the chemiluminescent substrate solution can be as low as below 3,000 photon counts / second, and it can detect an ultra-low concentration of alkaline phosphatase as low as 10-19 mol / L, improving the detection sensitivity; at the same time, the detection value of the chemiluminescent substrate solution can be as high as above 100 M photon counts / second, such as 100 M - 200 M photon counts / second, 120 M - 200 M photon counts / second, showing a significantly wider linearity. Without additional dilution of the sample, the above chemiluminescent substrate solution can meet the detection of samples with high analyte concentrations.

[0197] The chemiluminescent substrate solution of the present disclosure is particularly suitable for detecting human chorionic gonadotropin HCG in a test sample.

[0198] HCG is a glycoprotein mainly secreted by placental trophoblast cells. Its content is very low in non-pregnant people, usually less than 3 mIU / ml, while during pregnancy, the HCG concentration can be as high as about 2,000,000 mIU / ml. Clinically, the HCG test results are used to assist in judging pregnancy. At the same time, the detection of HCG during pregnancy is also of great significance. As mentioned above, the chemiluminescent substrate solution of the present disclosure has a wide linear luminescence characteristic and is suitable for samples with a large variation range of analyte concentrations such as HCG.

[0199] According to some embodiments, the concentration range of HCG in the sample is 1 - 200,000 mIU / mL.

[0200] In some embodiments, the detection of HCG is by the double antibody sandwich method. According to specific embodiments, superparamagnetic microparticles coated with HCG antibody are used as the capture reagent in the detection, and an HCG antibody labeled with alkaline phosphatase is used as the label. In some embodiments, the HCG antibody is a monoclonal antibody.

[0201] The chemiluminescent substrate solution of the present disclosure combined with the double antibody sandwich method has high sensitivity and a wide linear detection range for HCG detection.

[0202] In the present disclosure, for the use of the chemiluminescent substrate solution in the immunoassay of HCG, there are no special restrictions on the specific forms and dosages of the corresponding immunoassay reagents such as HCG antibodies, specific capture reagents, alkaline phosphatase labels, etc., and any suitable reagents can be used.

[0203] The "sample" mentioned herein, unless otherwise specified, refers to a biological sample, which can be from a mammal, preferably a blood sample from a human, and more preferably a serum sample.

[0204] In some embodiments, the chemiluminescent detection method is performed using the above chemiluminescent substrate solution in the chemiluminescent analyzer of the embodiments of the present disclosure. The chemiluminescent detection method includes the following steps:

[0205] Mix the sample to be tested with the detection reagent, which includes a capture reagent that can bind to HCG and an alkaline phosphatase label, so as to obtain an alkaline phosphatase-labeled immune complex;

[0206] Mix the alkaline phosphatase-labeled immune complex with the chemiluminescent substrate solution in any of the above embodiments to obtain a mixed solution;

[0207] Measure the optical signal of the mixed solution and obtain the analysis result of the sample to be tested based on the optical signal. Next, some embodiments of the photometer of the chemiluminescent analyzer of the present disclosure are described, but the present disclosure is not limited thereto.

[0208] In some embodiments, such asFigure 5 As shown, the photometer includes a receiving component 10 and a processing component 20 that are electrically connected to each other.

[0209] The receiving component 10 is configured to receive the optical signal generated in the chemiluminescence reaction and convert the optical signal into a corresponding electrical signal. The receiving component 10 can be configured as, for example, a photomultiplier tube that converts a weak optical signal into an electrical signal.

[0210] The processing component 20 is configured to be electrically connected to the receiving component 10 to receive the electrical signal from the receiving component 10, and process the received electrical signal to obtain the number of photons. The processing component 20 includes a first photon counting module 21 and a second photon counting module 22. Among them, the first photon counting module 21 is configured to process the electrical signal using a first photon counting method to obtain a first photon counting result, while the second photon counting module 22 is configured to process the electrical signal using a second photon counting method different from the first photon counting method to obtain a second photon counting result. The processing component 20 is further configured to output the final photon counting result of the sample to be measured based on the first photon counting result and the second photon counting result and use it as the photon counting output by the photometer. This final photon counting result, that is, the photon counting output by the photometer, can subsequently be used to calculate the content of the substance to be measured in the sample to be measured.

[0211] In the embodiment of the present disclosure, two photon counting modules are used to perform photon counting simultaneously. Among them, the first photon counting module uses a first counting method for the weak light segment to obtain a first photon counting result, while the second photon counting module uses a second counting method for the strong light segment to obtain a second photon counting result. Finally, the first photon counting result and the second photon counting result are integrated and the final counting result is output. Thereby, the linear detection range of the photometer can be greatly expanded. In particular, it can be realized that the linear detection range of the photometer is expanded to at least [2000, 100 million (10 8 )] photon counts per second, and even expanded to [2000, 200 million (10 8 )] photon counts per second.

[0212] In the embodiment of the present disclosure, the weak light segment can be understood as an optical signal with the number of photons per second not higher than a predetermined threshold, while the strong light segment can be understood as an optical signal with the number of photons per second higher than the predetermined threshold. For example, the predetermined threshold can be selected from any value between 20 million and 30 million photon counts per second, such as 20 million or 30 million photon counts per second. For example, the first counting method is a photon counting method for optical signals with no more than 30 million photon counts per second, and the second counting method is a photon counting method for optical signals with more than 30 million photon counts per second.

[0213] In some embodiments, the first counting method may be a pulse identification method for calculating photon counts by identifying electrical pulses caused by photons entering the receiving component, while the second counting method does not calculate photon counts by identifying electrical pulses caused by photons entering the receiving component, but estimates the number of photons by processing the electrical signal into a parameter that can characterize the number of photons in the optical signal (i.e., the number of electrical pulses caused by photons entering the receiving component).

[0214] Here, those skilled in the art can understand that in the embodiments of the present disclosure, the pulse identification method can be understood as a method for calculating photon counts by identifying pulses in the electrical signal, that is, when the peak value of the pulse identified from the electrical signal is greater than the threshold, it is considered that a photon is identified.

[0215] In some embodiments, the first photon counting module 21 may be configured to detect the number of pulses of the electrical signal using the pulse identification method to obtain a first photon counting result, while the second photon counting module 22 may be configured to process the electrical signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain, for example, calculate a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function, where the calibration function represents the mapping relationship between the parameter characterizing the number of photons in the optical signal and the photon counting result.

[0216] In some embodiments, after obtaining the first photon counting result and the second photon counting result, the processing component 20 may be further configured:[[]]

[0217] When the first photon counting result is lower than the first threshold, use the first photon counting result as the final photon counting result, that is, the photon counting output by the photometer; and

[0218] When the first photon counting result is not lower than the first threshold, use the second photon counting result as the final photon counting result, that is, the photon counting output by the photometer.

[0219] In some embodiments, as Figure 6 shown, the first photon counting module 21 may include a level discrimination circuit 211, a shaping and frequency division circuit 212, and a first counting circuit 213 that are electrically connected to each other. The level discrimination circuit 211 is configured to convert the electrical signal into a square wave signal, the shaping and frequency division circuit 212 is configured to perform frequency division and shaping on the square wave signal, and the first counting circuit 213 is configured to count the signal output by the shaping and frequency division circuit 212, that is, identify the number of pulses, to obtain a first photon counting result. The first photon counting module 21 according to this example can achieve a linear detection range of 2000 to 30 million photon counts per second.

[0220] In some alternative embodiments, as Figure 7As shown, the first photon counting module 21 may include at least one first AD conversion circuit 214 and a first counting circuit 213 that are electrically connected to each other. The first AD conversion circuit 214 is configured to collect an electrical signal at a sampling frequency greater than 1 GHz / s and convert the collected electrical signal into a digital signal for output to the first counting circuit 213. The first counting circuit 213 is configured to analyze the received digital signal to identify and receive the number of pulses, thereby obtaining a first photon counting result. Thus, through high-speed sampling at a sampling frequency of 1 GHz / s, the first counting circuit 213 can more accurately identify the number of pulses in the electrical signal, and thus obtain a more accurate first photon counting result. Compared with Figure 6 the embodiment shown, the first photon counting module 21 according to this embodiment can achieve a linear detection range of 2000 to 80 million photon counts per second.

[0221] In Figure 7 some variant embodiments of the embodiment shown, the first AD conversion circuit may be configured to collect an electrical signal at a sampling frequency not less than 2 GHz / s. This can further broaden the linear detection range of the first photon counting module 21.

[0222] In Figure 7 some variant embodiments of the embodiment shown, the first photon counting module 21 may include at least two, especially at least four, first AD conversion circuits 214. The sum of the sampling frequencies of each first AD conversion circuit is not less than 1 GHz / s, and each first AD conversion circuit collects the electrical signal by means of asynchronous sampling at a preset interval time. By using multiple first AD conversion circuits to achieve a sampling frequency not less than 1 GHz / s, the performance requirements for a single AD conversion circuit can be reduced, thereby reducing costs.

[0223] Preferably, these first AD conversion circuits 214 have the same sampling frequency, and each first AD conversion circuit collects the electrical signal by means of asynchronous sampling at equal time intervals.

[0224] Correspondingly, the first counting circuit 213 may be configured to rearrange and combine the data collected by the above-mentioned multiple first AD conversion circuits 214, perform filtering processing, and then perform pulse identification on the filtered signal to obtain a first photon counting result.

[0225] Furthermore, the first counting circuit 213 may also be configured to correct the first photon counting result through a Poisson distribution compensation algorithm. This can obtain a more accurate photon counting result.

[0226] In some embodiments, the first counting circuit 213 may include an FPGA chip and its peripheral circuits.

[0227] In some embodiments, the second photon counting module 22 may be configured to process the electrical signal, for example, through integration processing to obtain a DC component signal, and the parameter characterizing the number of photons in the optical signal includes a parameter related to the DC component signal, such as the DC component signal itself per unit time. The second photon counting module 22 is further configured to obtain a second photon counting result according to the parameter related to the DC component signal and a preset calibration function.

[0228] Alternatively or additionally, the second photon counting module 22 is configured to integrate the electrical signal within a predetermined time period to obtain an integration result, such as a DC component signal, and the parameter characterizing the number of photons in the optical signal includes a parameter related to the integration result, such as the integration result per unit time. The second photon counting module 22 is further configured to obtain a second photon counting result according to the parameter related to the integration result and a preset calibration function.

[0229] In a specific example, as Figure 8 and Figure 9 shown, the second photon counting module 22 includes an integration circuit 221 and a second counting circuit 222 that are electrically connected to each other. The integration circuit 221 is configured to integrate the electrical signal within a predetermined time period to obtain a DC component signal, and the parameter characterizing the number of photons in the optical signal includes a parameter related to the DC component signal. The second counting circuit 222 is configured to obtain a second photon counting result according to the parameter related to the DC component signal and a preset calibration function.

[0230] Further, as Figure 10 shown, an AD conversion circuit 224 is further provided between the integration circuit 221 and the second counting circuit 222, and the AD conversion circuit 224 is configured to convert the DC component signal output by the integration circuit 221 into a digital signal. The sampling frequency of the AD conversion circuit 224 may be set to be less than 1 MHz / s, for example, several hundred kHz / s.

[0231] In some embodiments, the second counting circuit 222 may include an FPGA chip and its peripheral circuits.

[0232] Preferably, as Figure 11 and Figure 12 shown, the first counting circuit 213 and the second counting circuit 222 are the same counting circuit, and the same counting circuit includes, for example, an FPGA chip. That is, the counting functions of the first photon counting module 21 and the second photon counting module 22 are integrated in the same FPGA chip. That is, on the one hand, the FPGA chip is configured to count the signal output by the shaping and frequency division circuit 212 to obtain a first photon counting result ( Figure 11) or analyze the digital signal collected by the first AD conversion circuit 214 to obtain a first photon counting result. Figure 12 ) On the other hand, it is configured to obtain a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function.

[0233] In another alternative example, as Figure 13 and Figure 14 shown, the second photon counting module includes a second AD conversion circuit 223 and a second counting circuit 222 that are electrically connected to each other. The second AD conversion circuit is configured to convert the electrical signal output by the receiving component 10 into a digital signal, and the second counting circuit is configured to process the digital signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function.

[0234] Here, a second AD conversion circuit 223 with a sampling frequency less than 10 MHz / s can be adopted. In some embodiments, the sampling frequency of the second AD conversion circuit 223 can be in the range of 1 MHz / s to 10 MHz / s, for example, 1, 2, or 3 MHz / s.

[0235] Preferably, as Figure 15 shown, the first counting circuit 213 and the second counting circuit 222 are the same counting circuit, and this same counting circuit includes, for example, an FPGA chip. That is to say, the counting functions of the first photon counting module 21 and the second photon counting module 22 are integrated in the same chip.

[0236] Equally preferably, as Figure 15 shown, the first AD conversion circuit 214 serves as the second AD conversion circuit 223, that is, the first photon counting module 21 and the second photon counting module 22 use the same AD conversion circuit.

[0237] Furthermore, the second counting circuit 222 can be configured to process the digital signal to obtain a DC component signal, and the parameter characterizing the number of photons in the optical signal includes a parameter related to the DC component signal.

[0238] For example, the second counting circuit 222 can be configured to perform a Fourier transform on the digital signal to obtain a DC component signal.

[0239] Alternatively or additionally, the second counting circuit 222 can be configured to integrate or sum the digital signal within a predetermined time period to obtain a parameter related to the integration result or the summation result and use it as the parameter characterizing the number of photons in the optical signal.

[0240] For more embodiments of the photometer of the present disclosure, reference may be made to the applicant's prior Chinese application CN202211510485.X, the content of which is incorporated herein by reference.

[0241] A chemiluminescence analyzer according to a second aspect of the present disclosure includes a sample preparation device, a substrate providing device, a photometric device, and a controller.

[0242] The sample preparation device is used to prepare a sample solution to be measured from a blood sample to be measured.

[0243] The substrate providing device is used to provide a luminescent substrate.

[0244] The photometric device at least includes a photometer, and the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction. Among them, the first linear detection range of the photometer is [A1, A2] photon counts per second, and the first linear detection range represents the range of the number of photons output by the photometer. Within this first linear detection range, the intensity of the luminescence signal generated in the chemiluminescence reaction has a linear relationship with the photon count output by the photometer, where A1 is less than or equal to 2000 and A2 is greater than or equal to 10 8 .

[0245] The controller is configured to obtain the test item of the blood sample to be measured. When the test item is a human chorionic gonadotropin test item:

[0246] Control the sample preparation device to pre-dilute the blood sample to be measured with a diluent, and mix the pre-diluted blood sample to be measured with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be measured reacts with the reaction reagent to obtain a sample solution to be measured. The reaction reagent includes a capture reagent coated with an antibody against human chorionic gonadotropin and a detection reagent of an antibody against human chorionic gonadotropin with a label;

[0247] Control the substrate providing device to provide the luminescent substrate into the reaction container containing the sample solution to be measured, so that the label in the sample solution to be measured undergoes a chemiluminescence reaction with the luminescent substrate;

[0248] Control the photometer to detect the luminescence signal generated in the chemiluminescence reaction; and

[0249] Obtain the test result of the human chorionic gonadotropin in the blood sample to be measured according to the luminescence signal and a preset calibration model.

[0250] It can be understood that the various embodiments and their advantages described for the chemiluminescence analyzer provided in the first aspect of the present disclosure, especially its sample preparation device 110, substrate providing device 120, photometric device 130, and luminescent substrate, are equally applicable to the chemiluminescence analyzer provided in the second aspect of the present disclosure.

[0251] In some embodiments, the chemiluminescence analyzer provided in the second aspect of the present disclosure further includes a sample identification device, such as a barcode scanner or a camera, for identifying the test items of the blood sample to be tested and providing the identified test items to the controller.

[0252] In other embodiments, the chemiluminescence analyzer provided in the second aspect of the present disclosure further includes an input device, such as a user interface, for receiving user input indicating the test items of the blood sample to be tested, and the controller is configured to receive the user input from the input device to obtain the test items of the blood sample to be tested.

[0253] The third aspect of the present disclosure provides a chemiluminescence analyzer, including a sample preparation device, a substrate providing device, a photometric device, and a data processing device.

[0254] The sample preparation device is at least configured to: for a blood sample to be tested with a test item of human chorionic gonadotropin detection item, before performing the human chorionic gonadotropin detection, pre-dilute the blood sample to be tested with a dilution liquid at a preset dilution ratio, and mix the pre-diluted blood sample to be tested with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested, and the reaction reagent includes a capture reagent coated with a human chorionic gonadotropin antibody and a detection reagent of a human chorionic gonadotropin antibody with a marker;

[0255] The substrate providing device is configured to provide a luminescent substrate into the reaction container containing the sample solution to be tested, so that the marker in the sample solution to be tested undergoes a chemiluminescence reaction with the luminescent substrate. Wherein, the second linear detection range of the luminescent substrate is [B1, B2] photon counts per second, and the second linear detection range represents the range of the intensity of the luminescent signal generated in the chemiluminescence reaction. Within this second linear detection range, the number of markers participating in the chemiluminescence reaction is linearly related to the intensity of the luminescent signal generated in the chemiluminescence reaction, where B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 and / or, the ratio B2 / B1 of B2 to B1 is greater than or equal to 30000;

[0256] The photometric device at least includes a photometer, and the photometer is configured to detect the luminescent signal generated in the chemiluminescence reaction;

[0257] The data processing device is configured to obtain the detection result of human chorionic gonadotropin in the blood sample to be tested according to the luminescent signal and a preset calibration model.

[0258] It is understandable that the various embodiments and their advantages described for the chemiluminescence analyzer provided in the first aspect of the present disclosure, particularly its sample preparation device 110, substrate providing device 120, photometry device 130, and chemiluminescent substrate, are equally applicable to the chemiluminescence analyzer provided in the third aspect of the present disclosure.

[0259] A chemiluminescence analyzer provided in the fourth aspect of the present disclosure includes a sample preparation device, a substrate providing device, a photometry device, and a controller.

[0260] The sample preparation device is used to prepare a sample solution to be measured from a blood sample to be measured.

[0261] The substrate providing device is used to provide a chemiluminescent substrate.

[0262] The photometry device at least includes a photometer, and the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction.

[0263] The controller is configured to obtain the test item of the blood sample to be measured. When the test item is a human chorionic gonadotropin test item:

[0264] Control the sample preparation device to pre-dilute the blood sample to be measured with a diluent, and mix the pre-diluted blood sample to be measured with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be measured reacts with the reaction reagent to obtain a sample solution to be measured. The reaction reagent includes a capture reagent coated with an antibody against human chorionic gonadotropin and a detection reagent of an antibody against human chorionic gonadotropin with a marker;

[0265] Control the substrate providing device to provide the chemiluminescent substrate into the reaction container containing the sample solution to be measured, so that the marker in the sample solution to be measured undergoes a chemiluminescence reaction with the chemiluminescent substrate;

[0266] Control the photometer to detect the luminescence signal generated in the chemiluminescence reaction;

[0267] Obtain the test result of the human chorionic gonadotropin in the blood sample to be measured according to the luminescence signal and a preset calibration model;

[0268] Here, the second linear detection range of the chemiluminescent substrate is [B1, B2] photon counts per second. The second linear detection range represents the range of the intensity of the luminescence signal generated in the chemiluminescence reaction. Within this second linear detection range, the number of markers participating in the chemiluminescence reaction is linearly related to the intensity of the luminescence signal generated in the chemiluminescence reaction, where B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 , and / or, the ratio B2 / B1 of B2 to B1 is greater than or equal to 30000.

[0269] It can be understood that the various embodiments and their advantages described for the chemiluminescence analyzer provided in the first aspect of the present disclosure, especially its sample preparation device 110, substrate providing device 120, photometry device 130, and chemiluminescent substrate, as well as the various embodiments and their advantages described for the chemiluminescence analyzer provided in the second aspect of the present disclosure, are equally applicable to the chemiluminescence analyzer provided in the fourth aspect of the present disclosure.

[0270] The fifth aspect of the present disclosure provides a chemiluminescence analyzer, including a sample preparation device, a substrate providing device, a photometry device, and a data processing device.

[0271] The sample preparation device is used to pre-dilute all the test blood samples containing human chorionic gonadotropin as the substance to be tested with a diluent, and mix the pre-diluted test blood samples with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted test blood samples reacts with the reaction reagent to obtain a test sample solution. The reaction reagent includes a capture reagent coated with an antibody against human chorionic gonadotropin and a detection reagent of an antibody against human chorionic gonadotropin with a label.

[0272] The substrate providing device is used to provide a chemiluminescent substrate into the reaction container containing the test sample solution, so that the label in the test sample solution undergoes a chemiluminescent reaction with the chemiluminescent substrate.

[0273] The photometry device at least includes a photometer, which is used to detect the luminescence signal generated in the chemiluminescent reaction. Here, the photometer includes a receiving component and a processing component. The receiving component is configured to receive the optical signal generated in the chemiluminescent reaction and convert the optical signal into a corresponding electrical signal. The processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component. The processing component includes a first photon counting module and a second photon counting module. The first photon counting module is configured to detect the number of pulses of the electrical signal using the pulse recognition method to obtain a first photon counting result. The second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function. Among them, the calibration function represents the mapping relationship between the parameter characterizing the number of photons in the optical signal and the photon counting result. The processing component is further configured to obtain the photon counting output by the photometer based on the first photon counting result and the second photon counting result, and output the photon counting.

[0274] The data processing device is used to obtain the detection result of human chorionic gonadotropin in the test blood sample according to the luminescence signal and a preset calibration model.

[0275] It can be understood that the various embodiments and their advantages described for the chemiluminescence analyzer provided in the first aspect of the present disclosure, particularly its sample preparation device 110, substrate providing device 120, photometric device 130, and luminescent substrate, are equally applicable to the chemiluminescence analyzer provided in the fifth aspect of the present disclosure.

[0276] A chemiluminescence analyzer provided in the sixth aspect of the present disclosure includes a sample preparation device, a substrate providing device, a photometric device, and a controller.

[0277] The sample preparation device is used to prepare a sample solution to be measured from a blood sample to be measured.

[0278] The substrate providing device is used to provide a luminescent substrate.

[0279] The photometric device at least includes a photometer, and the photometer is used to detect the luminescence signal generated in the chemiluminescence reaction. Here, the photometer includes a receiving component and a processing component. The receiving component is configured to receive the optical signal generated in the chemiluminescence reaction and convert the optical signal into a corresponding electrical signal. The processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component. The processing component includes a first photon counting module and a second photon counting module. The first photon counting module is configured to detect the number of pulses of the electrical signal using the pulse recognition method to obtain a first photon counting result. The second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the optical signal and a preset calibration function, where the calibration function represents the mapping relationship between the parameter characterizing the number of photons in the optical signal and the photon counting result. The processing component is further configured to obtain the photon counting output by the photometer based on the first photon counting result and the second photon counting result, and output the photon counting.

[0280] The controller is configured to obtain the test item of the blood sample to be measured. When the test item is a human chorionic gonadotropin test item:

[0281] Control the sample preparation device to pre-dilute the blood sample to be measured with a diluent, and mix the pre-diluted blood sample to be measured with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be measured reacts with the reaction reagent to obtain a sample solution to be measured. The reaction reagent includes a capture reagent coated with an antibody against human chorionic gonadotropin and a detection reagent of an antibody against human chorionic gonadotropin with a label;

[0282] Control the substrate providing device to provide the luminescent substrate into the reaction container containing the sample solution to be measured, so that the label in the sample solution to be measured undergoes a chemiluminescence reaction with the luminescent substrate;

[0283] Controlling a photometer to detect the luminescence signal generated in a chemiluminescence reaction; and

[0284] Obtaining the detection result of human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0285] It can be understood that the various embodiments and their advantages described for the chemiluminescence analyzer provided in the first aspect of the present disclosure, especially its sample preparation device 110, substrate providing device 120, photometric device 130, and chemiluminescent substrate, and the various embodiments and their advantages described for the chemiluminescence analyzer provided in the second aspect of the present disclosure also apply to the chemiluminescence analyzer provided in the sixth aspect of the present disclosure.

[0286] The seventh aspect of the present disclosure further provides another chemiluminescence analyzer, including:

[0287] An HCG determination unit for obtaining the detection result of human chorionic gonadotropin in the blood sample to be tested;

[0288] A mode selection unit for selecting a first HCG detection mode or a second HCG detection mode; and

[0289] A controller configured to,

[0290] Receive the mode selection of the mode selection unit,

[0291] When the mode selection unit selects the first HCG detection mode, control the HCG determination unit to execute a first determination process, the first determination process including: pre-diluting at least a part of the blood sample to be tested with a diluent, and performing chemiluminescence determination on the pre-diluted part of the blood sample to be tested to obtain and output a first HCG detection result; and

[0292] When the mode selection unit selects the second HCG detection mode, control the HCG determination unit to execute a second determination process, the second determination process including: performing chemiluminescence determination on the undiluted part of the blood sample to be tested to obtain a second HCG detection result, and when the second HCG detection result is abnormal, pre-diluting another part of the blood sample to be tested with a diluent, and performing chemiluminescence determination on the pre-diluted part of the blood sample to be tested to obtain and output a third HCG detection result.

[0293] In some embodiments, the HCG determination unit includes the above-mentioned sample preparation device, the above-mentioned substrate providing device, and the above-mentioned photometric device, and the multi-embodiments and their advantages can be referred to the above description. That is, the above-mentioned features can all be applied to the chemiluminescence analyzer with two HCG determination processes in a corresponding manner.

[0294] In a specific example, the first measurement process includes: the sample preparation device pre-dilutes at least a part of the blood sample to be measured with a diluent, and mixes the pre-diluted part of the blood sample to be measured with a reaction reagent in a reaction container to obtain a first sample solution to be measured; the substrate providing device provides a luminescent substrate into the reaction container containing the first sample solution to be measured, so that the first sample solution to be measured reacts with the luminescent substrate in a chemiluminescence reaction; the photometric device detects the luminescence signal generated in the chemiluminescence reaction to obtain a first HCG measurement result. The second measurement process includes: the sample preparation device mixes a part of the blood sample to be measured with a reaction reagent in a reaction container without dilution to obtain a second sample solution to be measured; the substrate providing device provides a luminescent substrate into the reaction container containing the second sample solution to be measured, so that the second sample solution to be measured reacts with the luminescent substrate in a chemiluminescence reaction; the photometric device detects the luminescence signal generated in the chemiluminescence reaction to obtain a second HCG measurement result. When the second HCG measurement result is abnormal, the sample preparation device pre-dilutes another part of the blood sample to be measured with a diluent, and mixes the pre-diluted part of the blood sample to be measured with a reaction reagent in a reaction container to obtain a third sample solution to be measured; the substrate providing device provides a luminescent substrate into the reaction container containing the third sample solution to be measured, so that the third sample solution to be measured reacts with the luminescent substrate in a chemiluminescence reaction; the photometric device detects the luminescence signal generated in the chemiluminescence reaction to obtain a third HCG measurement result.

[0295] In this embodiment, the chemiluminescence analyzer has two test modes. The first mode is to directly perform dilution and obtain the actual HCG content based on the test result after dilution. The second mode is to directly test. If the test result exceeds the linear detection range, dilution is performed and then re-detection is carried out. Configuring the two modes allows customers to flexibly select according to their needs, providing a better user experience.

[0296] The eighth aspect of the present disclosure provides a chemiluminescence analyzer, including a sample preparation device, a substrate providing device, a photometric device, a data processing device, and a control device.

[0297] The sample preparation device is used to mix the blood sample to be measured with a reaction reagent in a reaction container, so that the substance to be measured in the blood sample to be measured reacts with the reaction reagent to obtain a sample solution to be measured. The reaction reagent includes a capture reagent and a detection reagent with a marker.

[0298] The reagent carrying device is used to place a reagent kit. The reagent kit carries the reaction reagent corresponding to the detection item. The reagent kit corresponding to the human chorionic gonadotropin detection item also carries a diluent.

[0299] A substrate providing device for providing a luminescent substrate into a reaction vessel containing a sample solution to be tested, so that a marker in the sample solution to be tested reacts with the luminescent substrate in a chemiluminescence reaction;

[0300] A photometric device, which at least includes a photometer for detecting the luminescence signal generated in the chemiluminescence reaction;

[0301] A data processing device for obtaining the detection result of the substance to be tested in the blood sample to be tested according to the luminescence signal and a preset calibration model;

[0302] A control device, when the detection item of the blood sample to be tested is a human chorionic gonadotropin detection item, controlling the sample preparation device to pre-dilute the blood sample to be tested with a diluent in a kit corresponding to the human chorionic gonadotropin detection item at a preset dilution ratio, and mixing at least part of the reaction reagent in the kit corresponding to the human chorionic gonadotropin detection item with the pre-diluted blood sample to be tested in a reaction vessel, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample solution to be tested;

[0303] Controlling the substrate providing device to provide the luminescent substrate into the reaction vessel containing the sample solution to be tested, so that the marker in the sample solution to be tested reacts with the luminescent substrate in a chemiluminescence reaction;

[0304] Controlling the photometer to detect the luminescence signal generated in the chemiluminescence reaction, and obtaining the detection result of human chorionic gonadotropin in the blood sample to be tested according to the luminescence signal and a preset calibration model.

[0305] It can be understood that the various embodiments and their advantages described for the chemiluminescence analyzer provided in the first aspect of the present disclosure, especially its sample preparation device 110, substrate providing device 120, photometric device 130 and luminescent substrate, also apply to the chemiluminescence analyzer provided in the eighth aspect of the present disclosure.

[0306] In some embodiments, the kit corresponding to the human chorionic gonadotropin detection item includes a carrier and a first cavity, a second cavity and a third cavity opened on the carrier. The first cavity is used to accommodate the diluent, the second cavity is used to accommodate the capture reagent, and the third cavity is used to accommodate the detection reagent.

[0307] Thus, the following many benefits can be achieved:

[0308] a) Automatic in-machine operation of HCG dilution;

[0309] b) The manufacturer provides the diluent, which can ensure the measurement accuracy of HCG dilution and avoid poor test results caused by customers preparing the diluent by themselves;

[0310] c) Saving reagent storage space and improving the utilization efficiency of reagent positions;

[0311] Saving testing costs, and customers do not need to separately inventory and purchase diluents, which provides great convenience to customers.

[0312] Those skilled in the art should understand that the embodiments of the present disclosure can be provided as a method, a system, or a computer program product. Therefore, the embodiments of the present disclosure can take the form of hardware embodiments, software embodiments, or embodiments combining software and hardware aspects. Moreover, the embodiments of the present disclosure can take the form of a computer program product implemented on one or more computer-usable storage media (including disk memories and optical memories, etc.) containing computer-usable program codes.

[0313] The embodiments of the present disclosure are described with reference to the flowcharts and / or block diagrams of methods, devices (systems), and computer program products according to the embodiments of the present disclosure. It should be understood that each process and / or block in the flowchart and / or block diagram, as well as the combination of processes and / or blocks in the flowchart and / or block diagram, can be implemented by computer program operations. These computer program operations can be provided to the processors of general-purpose computers, special-purpose computers, embedded processors, or other programmable data processing devices to generate a machine, so that the operations executed by the processors of the computer or other programmable data processing devices generate means for implementing the functions specified in Figure 1 one process or multiple processes and / or blocks Figure 1 one block or multiple blocks.

[0314] These computer program operations can also be stored in a computer-readable memory that can direct a computer or other programmable data processing device to work in a specific manner, so that the operations stored in the computer-readable memory generate a manufactured article including operating means, and the operating means implements the functions specified in Figure 1 one process or multiple processes and / or blocks Figure 1 one block or multiple blocks.

[0315] These computer program operations can also be loaded onto a computer or other programmable data processing device, so that a series of operation steps are executed on the computer or other programmable device to generate a computer-implemented process, and thus the operations executed on the computer or other programmable device provide steps for implementing the functions specified in Figure 1 one process or multiple processes and / or blocks Figure 1 one block or multiple blocks.

[0316] The features or combinations of features mentioned in the above description, drawings, and claims, as long as they are meaningful and do not conflict with each other within the scope of the present disclosure, can be arbitrarily combined with each other or used alone.

[0317] The following specific examples are used to illustrate various embodiments and advantages of the chemiluminescent substrate of the present disclosure, but the scope of the present disclosure is not limited by these.

[0318] Example 1: Linear performance of different chemiluminescent substrates

[0319] Chemiluminescent substrate solution formulation:

[0320] Chemiluminescent substrate: 200 mg

[0321] 5(6)-Carboxyfluorescein: 200 mg

[0322] Polyvinylbenzyltrimethylammonium chloride: 5 g

[0323] AMP-HCl: 50 mM

[0324] Magnesium chloride: 200 mg

[0325] Sodium azide: 1 g

[0326] Water: Add to a total volume of 1 L

[0327] According to the above formula, where the chemiluminescent substrate is as shown in Table 1 below, a series of chemiluminescent substrate solutions 1-1 to 1-4 are prepared.

[0328] Table 1

[0329] Chemiluminescent substrate solution Chemiluminescent substrate 1-1 AMPPD 1-2 CSPD 1-3 ADP-STAR 1-4 CDP-STAR

[0330] Using the above chemiluminescent substrate solutions 1-1 to 1-4, tests are carried out on the Mindray CL-6000i fully automatic chemiluminescent immunoassay analyzer. Different concentration gradients of alkaline phosphatase (AP enzyme) solutions are mixed with each chemiluminescent substrate solution respectively. After incubation for a period of time, light signals are collected, and the background signal values (i.e., the alkaline phosphatase concentration is 0) and luminescence signal values under a 2-minute light collection time are obtained respectively. The concentration of alkaline phosphatase in the system and the detection signal values are as shown in Table 2 below.

[0331] Table 2

[0332]

[0333] The light signals (photon counts / second) measured for the chemiluminescent substrate solutions 1-1 to 1-4 are plotted against the concentration of alkaline phosphatase in the system and linearly fitted, as Figures 16A to 16D shown.

[0334] According to the data in Table 2 and Figures 16A to 16DIt can be seen that the chemiluminescent substrate solutions 1-2, 1-3, and 1-4 have low background signals, while the chemiluminescent substrate solutions 1-3 and 1-4 simultaneously have the characteristics of high luminescence efficiency and good linearity (R2≥0.99) within the detected luminescence range, and ADP-STAR performs the best.

[0335] Example 2: Linear performance of ADP-STAR and different fluorescent agents

[0336] Formulation of chemiluminescent substrate solution:

[0337] ADP-STAR: 200 mg

[0338] Fluorescent agent: 200 mg

[0339] Polyvinylbenzyltrimethylammonium chloride: 5 g

[0340] AMP-HCl: 50 mM

[0341] Magnesium chloride: 200 mg

[0342] Sodium azide: 1 g

[0343] Water: Add to a total volume of 1 L

[0344] According to the above formula, with the fluorescent agents shown in Table 3 below, a series of chemiluminescent substrate solutions 2-1 to 2-4 were prepared.

[0345] Table 3

[0346] Chemiluminescent substrate solution Fluorescent agent 2-1 Fluorescein 2-2 5-Carboxyfluorescein 2-3 6-Carboxyfluorescein 2-4 5(6)-Carboxyfluorescein

[0347] Using the above chemiluminescent substrate solutions 2-1 to 2-4, tests were carried out on the Mindray CL-6000i fully automatic chemiluminescent immunoassay analyzer. Alkaline phosphatase solutions with different concentration gradients were mixed with each chemiluminescent substrate solution respectively. After incubation for a period of time, light signals were collected, and the background signal values (i.e., the alkaline phosphatase concentration was 0) and luminescence signal values under a 2-minute light collection time were obtained respectively. The concentration of alkaline phosphatase in the system and the detection signal values are shown in Table 4 below.

[0348] Table 4

[0349]

[0350] Graphs were plotted for the light signals (photon counts / second) measured for the chemiluminescent substrate solutions 2-1 to 2-4 against the concentration of alkaline phosphatase in the system, and linear fitting was performed, as Figures 17A to 17D shown.

[0351] According to the data in Table 4 and Figures 17A to 17DIt can be seen that the chemiluminescent substrate solutions 2-1 to 2-4 all exhibit the characteristics of low background signal and high luminescence efficiency, and have good linearity (R2≥0.99) within the detected luminescence range.

[0352] Example 3: Linear performance of CDP-STAR and different fluorescent agents

[0353] Prepare the chemiluminescent substrate solution according to the following formula:

[0354] CDP-STAR: 200 mg

[0355] Fluorescent agent: 200 mg

[0356] Polyvinylbenzyltrimethylammonium chloride: 5 g

[0357] AMP-HCl: 50 mM

[0358] Magnesium chloride: 200 mg

[0359] Sodium azide: 1 g

[0360] Water: Add to a total volume of 1 L

[0361] According to the above formula, where the fluorescent agent is shown in Table 5 below, a series of chemiluminescent substrate solutions 3-1 to 3-4 are prepared.

[0362] Table 5

[0363] Chemiluminescent substrate solution Fluorescent agent 3-1 Fluorescein 3-2 5-Carboxyfluorescein 3-3 6-Carboxyfluorescein 3-4 5(6)-Carboxyfluorescein

[0364] Using the above chemiluminescent substrate solutions 3-1 to 3-4, test on the Mindray CL-6000i fully automatic chemiluminescent immunoassay analyzer. Mix alkaline phosphatase solutions with different concentration gradients with each chemiluminescent substrate solution respectively. After incubation for a period of time, collect the light signals, and obtain the background signal values (i.e., the alkaline phosphatase concentration is 0) and luminescence signal values under a 2-minute light collection time respectively. The concentration of alkaline phosphatase in the system and the detected signal values are shown in Table 6 below.

[0365] Table 6

[0366]

[0367]

[0368] Plot the light signals (photon counts / second) measured for the chemiluminescent substrate solutions 3-1 to 3-4 against the concentration of alkaline phosphatase in the system, and perform linear fitting, as Figures 18A to 18D shown.

[0369] According to the data in Table 6 and Figures 18A to 18DIt can be seen that the chemiluminescent substrate solutions 3-1 to 3-4 all exhibit the characteristics of low background signal and high luminescence efficiency, and have good linearity (R2≥0.99) within the detected luminescence range.

[0370] Example 4: Linear performance of ADP-STAR and different quaternary ammonium salt cationic surfactants

[0371] Chemiluminescent substrate solution formula:

[0372] ADP-STAR: 200 mg

[0373] Fluorescein: 200 mg

[0374] Quaternary ammonium salt surfactant: 5 g

[0375] AMP-HCl: 50 mM

[0376] Magnesium chloride: 200 mg

[0377] Sodium azide: 1 g

[0378] Water: Add to a total volume of 1 L

[0379] According to the above formula, where the quaternary ammonium salt cationic surfactants are shown in Table 7 below, a series of chemiluminescent substrate solutions 4-1 to 4-4 are prepared.

[0380] Table 7

[0381] Chemiluminescent substrate solution Quaternary ammonium cationic surfactant 4-1 Polyvinylbenzyltrimethylammonium chloride (TMQ) 4-2 Polyvinylbenzyltributylammonium chloride (TBQ) 4-3 Polyvinylbenzyl(benzyldimethyl)ammonium chloride (BDMQ) 4-4 Cetyltrimethylammonium bromide (CTAB)

[0382] Using the above chemiluminescent substrate solutions 4-1 to 4-4, tests are carried out on the Mindray CL-6000i fully automatic chemiluminescent immunoassay analyzer. Alkaline phosphatase solutions with different concentration gradients are respectively mixed with each chemiluminescent substrate solution. After incubation for a period of time, light signals are collected, and the background signal values (i.e., the alkaline phosphatase concentration is 0) and luminescence signal values under a 2-minute light collection time are obtained respectively. The concentration of alkaline phosphatase in the system and the detected signal values are shown in Table 8 below.

[0383] Table 8

[0384]

[0385] The light signals (photon counts / second) measured for the chemiluminescent substrate solutions 4-1 to 4-4 are respectively plotted against the concentration of alkaline phosphatase in the system, and linear fitting is performed, as Figures 19A to 19D shown.

[0386] According to the data in Table 8 and Figures 19A to 19DIt can be seen that the chemiluminescent substrate solutions 4-1 to 4-3 have low background signals and high luminescence efficiencies, and have good linearity (R2≥0.99) within the detected luminescence range. The chemiluminescent substrate solution 4-4 has a high background signal and a low luminescence efficiency, cannot maintain good linearity (R2<0.99) within the detected luminescence range, and the ratio of the optical signal at the upper detection limit to the lower detection limit is also small (less than 3000).

[0387] Example 5: Linear performance of CDP-STAR and different quaternary ammonium salt cationic surfactants

[0388] Chemiluminescent substrate solution formula:

[0389] CDP-STAR: 200 mg

[0390] Fluorescein: 200 mg

[0391] Quaternary ammonium salt surfactant: 5 g

[0392] AMP-HCl: 50 mM

[0393] Magnesium chloride: 200 mg

[0394] Sodium azide: 1 g

[0395] Water: Add to a total volume of 1 L

[0396] According to the above formula, where the quaternary ammonium salt cationic surfactants are as shown in Table 9 below, a series of chemiluminescent substrate solutions 5-1 to 5-4 are prepared.

[0397] Table 9

[0398] Chemiluminescent substrate solution Quaternary ammonium cationic surfactant 5-1 Polyvinylbenzyltrimethylammonium chloride (TMQ) 5-2 Polyvinylbenzyltributylammonium chloride (TBQ) 5-3 Polyvinylbenzyl(benzyldimethyl)ammonium chloride (BDMQ) 5-4 Cetyltrimethylammonium bromide (CTAB)

[0399] Using the above chemiluminescent substrate solutions 5-1 to 5-4, tests are carried out on the Mindray CL-6000i fully automatic chemiluminescent immunoassay analyzer. Alkaline phosphatase solutions with different concentration gradients are mixed with each chemiluminescent substrate solution respectively. After incubation for a period of time, optical signals are collected, and the background signal values (i.e., the alkaline phosphatase concentration is 0) and luminescence signal values at a 2-minute light collection time are obtained respectively. The concentration of alkaline phosphatase in the system and the detection signal values are as shown in Table 10 below.

[0400] Table 10

[0401]

[0402]

[0403] Separate plots are made of the optical signals (photon counts / second) measured for the chemiluminescent substrate solutions 5-1 to 5-4 against the concentration of alkaline phosphatase in the system, and linear fitting is performed, asFigures 20A to 20D as shown

[0404] According to the data in Table 10 and Figures 20A to 20D it can be seen that the chemiluminescent substrate solutions 5-1 to 5-3 have low background signals and high luminescence efficiencies, and have good linearity (R2≥0.99) within the detected luminescence range. The chemiluminescent substrate solution 5-4 has a high background signal and a low luminescence efficiency, cannot maintain good linearity (R2<0.99) within the detected luminescence range, and the optical signal ratio between the detection upper limit and the detection lower limit is also small (less than 3000).

[0405] Example 6: Wide linear detection of HCG

[0406] Prepare the chemiluminescent substrate solution 6-1 according to the following formula:

[0407] ADP-STAR: 200 mg

[0408] Fluorescein: 200 mg

[0409] Polyvinylbenzyltrimethylammonium chloride: 5 g

[0410] AMP-HCl: 50 mM

[0411] Magnesium chloride: 200 mg

[0412] Sodium azide: 1 g

[0413] Water: Add to a total volume of 1 L

[0414] Prepare the chemiluminescent substrate solution 6-2 according to the following formula:

[0415] CDP-STAR: 200 mg

[0416] Fluorescein: 200 mg

[0417] Polyvinylbenzyltrimethylammonium chloride: 5 g

[0418] AMP-HCl: 50 mM

[0419] Magnesium chloride: 200 mg

[0420] Sodium azide: 1 g

[0421] Water: Add to a total volume of 1 L

[0422] Using the above chemiluminescent substrate solutions 6-1 to 6-2, serum samples containing different HCG concentrations were tested on Mindray CL-6000i fully automatic chemiluminescent immunoassay analyzer. The sample concentration range was 1 to 200,000 mIU / mL, and the HCG detection kit was Mindray total β-human chorionic gonadotropin (TotalβHCG) assay kit (chemiluminescent immunoassay method). Record the photon count per second of the optical signal collected when each sample was incubated with chemiluminescent substrate solutions 6-1 and 6-2 for 2 minutes, and calculate the concentration of HCG in the sample based on the optical signal, which is recorded as the back-calculated concentration. Calculate the relative deviation of the back-calculated concentration relative to the nominal concentration of HCG in the sample, and the results are shown in Table 11 - Table 12 below.

[0423] Table 11

[0424]

[0425]

[0426] Table 12

[0427]

[0428] It can be seen from Table 11 and Table 12 that the chemiluminescent substrate solution of the present disclosure can be directly detected and analyzed without dilution in the concentration range of 1 to 200,000 mIU / mL of HCG in the sample during the detection of the HCG item, and the deviation of the detection result relative to the nominal concentration is within ±5%.

[0429] The above are only the preferred embodiments of the present disclosure, and do not limit the patent scope of the present disclosure. Any equivalent transformation made using the content of the specification and drawings of the present disclosure under the inventive concept of the present disclosure, or direct / indirect application in other related technical fields, is included in the patent protection scope of the present disclosure.

Claims

1. A chemiluminescence analyzer, characterized in that: include: A sample preparation device is at least used for: for a blood sample to be tested whose test item is a human chorionic gonadotropin test item, before the blood sample to be tested is tested for human chorionic gonadotropin, using a diluent to pre-dilute the blood sample to be tested at a preset dilution ratio, and mixing the pre-diluted blood sample to be tested with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent coated with human chorionic gonadotropin antibodies and a detection reagent of human chorionic gonadotropin antibodies with a marker; A substrate providing device, used for providing a luminescent substrate into the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to undergo a chemiluminescent reaction; A photometric device, the photometric device at least comprising a photometer, the photometer being used to detect a luminescent signal generated in the chemiluminescent reaction, wherein a first linear detection range of the photometer is [A1, A2] photon counts / second, the first linear detection range representing a range of photon counts output by the photometer, within which the intensity of the luminescent signal generated in the chemiluminescent reaction is linearly related to the photon counts output by the photometer, wherein A1 is less than or equal to 2000 and A2 is greater than or equal to 10 8 ; A data processing device is used to obtain the detection result of the human chorionic gonadotropin in the blood sample to be tested according to the luminescent signal and a preset calibration model.

2. The chemiluminescence analyzer according to claim 1, characterized in that: The calibration model is obtained by using a pre-diluted calibrator on the chemiluminescence analyzer.

3. The chemiluminescence analyzer according to claim 2, characterized in that: The pre-dilution multiple of the blood sample to be tested is equal to the pre-dilution multiple of the calibrator.

4. The chemiluminescence analyzer according to any one of claims 1 to 3, characterized in that: The diluent, the capture reagent and the detection reagent are placed in a common test kit, which includes a carrier and a first cavity, a second cavity and a third cavity opened on the carrier, the first cavity is used to hold the diluent, the second cavity is used to hold the capture reagent, and the third cavity is used to hold the detection reagent.

5. The chemiluminescence analyzer according to any one of claims 1 to 4, characterized in that: A2 / A1, a ratio of A2 to A1, is greater than or equal to 30,000.

6. The chemiluminescence analyzer according to any one of claims 1 to 5, characterized in that: The second linear detection range of the luminescent substrate is [B1, B2] photon counts / second, and the second linear detection range represents the range of the intensity of the luminescent signal generated in the chemiluminescent reaction. Within the second linear detection range, the number of the markers participating in the chemiluminescent reaction is linearly related to the intensity of the luminescent signal generated in the chemiluminescent reaction, wherein B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 , and / or, the ratio of B2 to B1 (B2 / B1) is greater than or equal to 30,000.

7. The chemiluminescence analyzer according to claim 6, characterized in that: in, The lower limit B1 of the second linear detection range is less than or equal to 2000.

8. The chemiluminescence analyzer according to any one of claims 6 to 7, characterized in that: The chemiluminescence analyzer is designed so that when the concentration of human chorionic gonadotropin in the blood sample to be tested is greater than or equal to 200,000 mIU / ml, the intensity of the luminescent signal generated in the chemiluminescent reaction is less than or equal to the smaller value of A2 and B2.

9. The chemiluminescence analyzer according to any one of claims 6 to 8, characterized in that: The chemiluminescence analyzer is designed so that: when the concentration of human chorionic gonadotropin in the blood sample to be tested is greater than or equal to 0.5 mIU / ml, the intensity C1 of the luminescent signal generated in the chemiluminescent reaction is greater than or equal to the larger value of A1 and B1.

10. The chemiluminescence analyzer according to claim 9, characterized in that: The chemiluminescence analyzer is designed so that when the concentration of human chorionic gonadotropin in the blood sample to be tested is greater than 0.5mIU / ml and less than or equal to 5mIU / ml, preferably less than or equal to 2mIU / ml, the intensity of the luminescent signal generated in the chemiluminescence reaction is C2, wherein the ratio of C2 to C1, C2 / C1, is greater than 2.

11. The chemiluminescence analyzer according to any one of claims 6 to 10, characterized in that: An upper limit B2 of the second linear detection range is greater than an upper limit A2 of the first linear detection range.

12. The chemiluminescence analyzer according to any one of claims 1 to 11, characterized in that: The luminescent substrate is designed so that the background of the luminescent substrate is less than 3000; and / or The luminescent substrate is designed such that the signal-to-noise ratio of the luminescent substrate is greater than 40,000.

13. The chemiluminescence analyzer according to any one of claims 1 to 12, characterized in that: The luminescent substrate comprises a chemiluminescent substrate and a chemiluminescent enhancer, the chemiluminescent enhancer comprises a fluorescent agent and a surfactant, and the fluorescent agent comprises one or more carboxyfluoresceins.

14. The chemiluminescence analyzer according to any one of claims 1 to 13, characterized in that: The luminescent substrate is selected from dioxetane compounds, preferably one or more selected from AMPPD, CSPD, CDP-STAR, and more preferably CDP-STAR.

15. The chemiluminescence analyzer according to any one of claims 1 to 14, characterized in that: The luminescent substrate is selected from chlorinated derivatives of AMPPD, fluorescein or its carboxyl substituted derivatives, and water-soluble polymer quaternary ammonium salt cationic surfactants.

16. The chemiluminescence analyzer according to claim 15, characterized in that: The chlorinated derivative of AMPPD is ADP-STAR or CDP-STAR, or The fluorescein or its carboxyl substituted derivative is fluorescein, or 5(6)-carboxyfluorescein, or The water-soluble polymer quaternary ammonium salt cationic surfactant is polyvinylbenzyltrimethylammonium chloride.

17. The chemiluminescence analyzer according to any one of claims 1 to 16, characterized in that: The photometer comprises: a receiving component configured to receive the optical signal generated in the chemiluminescent reaction and convert the optical signal into a corresponding electrical signal; and A processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component, the processing component includes a first photon counting module and a second photon counting module, the first photon counting module is configured to detect the number of pulses of the electrical signal using a pulse recognition method to obtain a first photon counting result, the second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain a second photon counting result based on the parameter characterizing the number of photons in the optical signal and a preset calibration function, wherein the calibration function represents a mapping relationship between the parameter characterizing the number of photons in the optical signal and the photon counting result, and the processing component is further configured to obtain a photon count output by the photometer based on the first photon counting result and the second photon counting result, and output the photon count.

18. The chemiluminescence analyzer according to claim 17, characterized in that: The processing component is further configured to: When the first photon counting result is lower than a first threshold, using the first photon counting result as the photon counting output by the photometer; and When the first photon counting result is not lower than the first threshold, the second photon counting result is used as the photon counting output by the photometer.

19. The chemiluminescence analyzer according to claim 17 or 18, characterized in that: The first photon counting module includes at least one first AD conversion circuit and a first counting circuit electrically connected to each other, the first AD conversion circuit is configured to collect the electrical signal at a sampling frequency greater than 1 GHz / s and convert the collected electrical signal into a digital signal and output it to the first counting circuit, the first counting circuit is configured to analyze the received digital signal to identify and receive the number of pulses, and thereby obtain the first photon counting result.

20. The chemiluminescence analyzer according to any one of claims 17 to 19, characterized in that: The second photon counting module is configured to process the electrical signal to obtain a DC component signal, and the parameters characterizing the number of photons in the optical signal include parameters related to the DC component signal; preferably, the second photon counting module is configured to integrate the electrical signal within a predetermined time period to obtain an integration result, and the parameters characterizing the number of photons in the optical signal include parameters related to the integration result.

21. The chemiluminescence analyzer according to claim 20, characterized in that: The second photon counting module includes a second AD conversion circuit and a second counting circuit electrically connected to each other, the second AD conversion circuit is configured to convert the electrical signal into a digital signal, the second counting circuit is configured to process the digital signal to obtain a parameter characterizing the number of photons in the optical signal, and obtain the second photon counting result based on the parameter characterizing the number of photons in the optical signal and a preset calibration function; preferably, the second counting circuit is configured to integrate or sum the digital signal within a predetermined time period to obtain a parameter related to the integration result or the summation result and use it as the parameter characterizing the number of photons in the optical signal.

22. The chemiluminescence analyzer according to any one of claims 1 to 21, characterized in that: The preset dilution ratio includes 2 to 20 times.

23. A chemiluminescence analyzer, characterized in that: include: A sample preparation device, used for preparing a sample liquid to be tested from a blood sample to be tested; A substrate providing device, used for providing a luminescent substrate; A photometric device, the photometric device at least comprising a photometer, the photometer being used to detect a luminescent signal generated in a chemiluminescent reaction, wherein a first linear detection range of the photometer is [A1, A2] photon counts / second, the first linear detection range representing a range of output photon counts of the photometer, within which the intensity of the luminescent signal generated in the chemiluminescent reaction is linearly related to the photon counts output by the photometer, wherein A1 is less than or equal to 2000 and A2 is greater than or equal to 10 8 ; controller, configured as obtaining the test items of the blood sample to be tested, When the test item is the human chorionic gonadotropin test item: The sample preparation device is controlled to pre-dilute the blood sample to be tested with a diluent, and the pre-diluted blood sample to be tested is mixed with a reaction reagent in a reaction container, so that human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent coated with human chorionic gonadotropin antibodies and a detection reagent of human chorionic gonadotropin antibodies with a marker, Controlling the substrate providing device to provide the luminescent substrate to the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to perform a chemiluminescent reaction, controlling the photometer to detect the luminescent signal generated in the chemiluminescent reaction, The detection result of the human chorionic gonadotropin in the blood sample to be tested is obtained according to the luminescent signal and a preset calibration model.

24. A chemiluminescence analyzer, characterized in that: include: A sample preparation device is at least used for: for a blood sample to be tested whose test item is a human chorionic gonadotropin test item, before performing human chorionic gonadotropin detection, pre-diluting the blood sample to be tested with a diluent at a preset dilution ratio, and mixing the pre-diluted blood sample to be tested with a reaction reagent in a reaction container, so that human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent coated with human chorionic gonadotropin antibodies and a detection reagent of human chorionic gonadotropin antibodies with a marker; A substrate providing device, used for providing a luminescent substrate to the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested and the luminescent substrate undergo a chemiluminescent reaction, wherein the second linear detection range of the luminescent substrate is [B1, B2] photon counts / second, and the second linear detection range represents the range of the intensity of the luminescent signal generated in the chemiluminescent reaction. Within the second linear detection range, the number of the markers participating in the chemiluminescent reaction is linearly related to the intensity of the luminescent signal generated in the chemiluminescent reaction, wherein B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 , and / or, the ratio of B2 to B1 (B2 / B1) is greater than or equal to 30000; A light measuring device, the light measuring device at least comprising a photometer, the photometer being used to detect the luminescent signal generated in the chemiluminescent reaction; A data processing device is used to obtain the detection result of the human chorionic gonadotropin in the blood sample to be tested according to the luminescent signal and a preset calibration model.

25. A chemiluminescence analyzer, characterized in that: include: A sample preparation device, used for preparing a sample liquid to be tested from a blood sample to be tested; A substrate providing device, used for providing a luminescent substrate; A light measuring device, the light measuring device at least comprising a photometer, the photometer being used to detect the luminescent signal generated in the chemiluminescent reaction; controller, configured as obtaining the test items of the blood sample to be tested, When the test item is the human chorionic gonadotropin test item: The sample preparation device is controlled to pre-dilute the blood sample to be tested with a diluent, and the pre-diluted blood sample to be tested is mixed with a reaction reagent in a reaction container, so that human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent coated with human chorionic gonadotropin antibodies and a detection reagent of human chorionic gonadotropin antibodies with a marker, Controlling the substrate providing device to provide the luminescent substrate to the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to perform a chemiluminescent reaction, controlling the photometer to detect the luminescent signal generated in the chemiluminescent reaction, The detection result of the human chorionic gonadotropin in the blood sample to be tested is obtained according to the luminescent signal and a preset calibration model. The second linear detection range of the luminescent substrate is [B1, B2] photon counts / second, and the second linear detection range represents the range of the intensity of the luminescent signal generated in the chemiluminescent reaction. Within the second linear detection range, the number of the markers participating in the chemiluminescent reaction is linearly related to the intensity of the luminescent signal generated in the chemiluminescent reaction, wherein B1 is less than or equal to 3000 and B2 is greater than or equal to 10 8 , and / or, the ratio of B2 to B1 (B2 / B1) is greater than or equal to 30,000.

26. A chemiluminescence analyzer, characterized in that: include: A sample preparation device, used for pre-diluting all blood samples to be tested containing human chorionic gonadotropin as a test substance with a diluent, and mixing the pre-diluted blood samples to be tested with a reaction reagent in a reaction container, so that the human chorionic gonadotropin in the pre-diluted blood samples to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent coated with human chorionic gonadotropin antibodies and a detection reagent of human chorionic gonadotropin antibodies with a marker; A substrate providing device, used for providing a luminescent substrate into the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to undergo a chemiluminescent reaction; A photometric device, the photometric device at least includes a photometer, the photometer is used to detect the luminescent signal generated in the chemiluminescent reaction, the photometer includes a receiving component and a processing component, the receiving component is configured to receive the light signal generated in the chemiluminescent reaction and convert the light signal into a corresponding electrical signal, the processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component, the processing component includes a first photon counting module and a second photon counting module, the first photon counting module is configured to detect the number of pulses of the electrical signal using a pulse recognition method to obtain a first photon counting result, the second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the light signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the light signal and a preset calibration function, wherein the calibration function represents a mapping relationship between the parameter characterizing the number of photons in the light signal and the photon counting result, and the processing component is further configured to obtain the photon count output by the photometer based on the first photon counting result and the second photon counting result, and output the photon count; A data processing device is used to obtain the detection result of the human chorionic gonadotropin in the blood sample to be tested according to the luminescent signal and a preset calibration model.

27. A chemiluminescence analyzer, characterized in that: include: A sample preparation device, used for preparing a sample liquid to be tested from a blood sample to be tested; A substrate providing device, used for providing a luminescent substrate; A photometric device, the photometric device at least includes a photometer, the photometer is used to detect a luminescent signal generated in a chemiluminescent reaction, the photometer includes a receiving component and a processing component, the receiving component is configured to receive the light signal generated in the chemiluminescent reaction and convert the light signal into a corresponding electrical signal, the processing component is configured to be electrically connected to the receiving component and receive the electrical signal from the receiving component, the processing component includes a first photon counting module and a second photon counting module, the first photon counting module is configured to detect the number of pulses of the electrical signal using a pulse recognition method to obtain a first photon counting result, the second photon counting module is configured to process the electrical signal to obtain a parameter characterizing the number of photons in the light signal, and obtain a second photon counting result according to the parameter characterizing the number of photons in the light signal and a preset calibration function, wherein the calibration function represents a mapping relationship between the parameter characterizing the number of photons in the light signal and the photon counting result, and the processing component is further configured to obtain a photon count output by the photometer based on the first photon counting result and the second photon counting result, and output the photon count; A controller is configured to obtain the test items of the blood sample to be tested, When the test item is the human chorionic gonadotropin test item: The sample preparation device is controlled to pre-dilute the blood sample to be tested with a diluent, and the pre-diluted blood sample to be tested is mixed with a reaction reagent in a reaction container, so that human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent coated with human chorionic gonadotropin antibodies and a detection reagent of human chorionic gonadotropin antibodies with a marker, Controlling the substrate providing device to provide the luminescent substrate to the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to perform a chemiluminescent reaction, controlling the photometer to detect the luminescent signal generated in the chemiluminescent reaction, The detection result of the human chorionic gonadotropin in the blood sample to be tested is obtained according to the luminescent signal and a preset calibration model.

28. A chemiluminescence analyzer comprising: HCG measuring section, used to obtain the test result of human chorionic gonadotropin of the blood sample to be tested; A mode selection unit, used to select a first HCG detection mode or a second HCG detection mode; and The controller is configured as, receiving a mode selection of the mode selection unit, When the mode selection unit selects the first HCG detection mode, the HCG determination unit is controlled to execute a first determination process, wherein the first determination process includes: pre-diluting at least a portion of the blood sample to be detected by using a diluent, and performing chemiluminescence determination on the pre-diluted portion of the blood sample to be detected, so as to obtain and output a first HCG detection result; and When the mode selection unit selects the second HCG detection mode, the HCG measurement unit is controlled to execute a second measurement process, which includes: performing chemiluminescence measurement on the undiluted part of the blood sample to be tested to obtain a second HCG detection result; when the second HCG detection result is abnormal, using a diluent to pre-dilute another part of the blood sample to be tested, and performing chemiluminescence measurement on the pre-diluted part of the blood sample to be tested to obtain and output a third HCG detection result.

29. A chemiluminescence analyzer, characterized in that: include: A sample preparation device, used to mix a blood sample to be tested with a reaction reagent in a reaction container so that the substance to be tested in the blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, wherein the reaction reagent includes a capture reagent and a detection reagent with a marker; A reagent carrying device, the reagent carrying device is used to place a test kit, the test kit carries a reaction reagent corresponding to the test item, and the test kit corresponding to the human chorionic gonadotropin test item also carries a diluent; A substrate providing device, used for providing a luminescent substrate into the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to undergo a chemiluminescent reaction; A light measuring device, the light measuring device at least comprising a photometer, the photometer being used to detect the luminescent signal generated in the chemiluminescent reaction; A data processing device, used for obtaining the detection result of the substance to be detected in the blood sample to be detected according to the luminescent signal and a preset calibration model; A control device is used to control the sample preparation device to pre-dilute the blood sample to be tested with a preset dilution ratio using a diluent in a test kit corresponding to the human chorionic gonadotropin test item when the test item of the blood sample to be tested is a human chorionic gonadotropin test item, and to mix the pre-diluted blood sample to be tested with at least part of the reaction reagent in the test kit corresponding to the human chorionic gonadotropin test item in the reaction container, so that the human chorionic gonadotropin in the pre-diluted blood sample to be tested reacts with the reaction reagent to obtain a sample liquid to be tested, Controlling the substrate providing device to provide the luminescent substrate to the reaction container containing the sample liquid to be tested, so that the marker in the sample liquid to be tested reacts with the luminescent substrate to perform a chemiluminescent reaction, The photometer is controlled to detect the luminescent signal generated in the chemiluminescent reaction, and the detection result of the human chorionic gonadotropin in the blood sample to be tested is obtained according to the luminescent signal and a preset calibration model.

30. The chemiluminescence analyzer according to claim 1 or 29, characterized in that: The test kit corresponding to the human chorionic gonadotropin detection item includes a carrier and a first cavity, a second cavity and a third cavity opened on the carrier, the first cavity is used to hold the diluent, the second cavity is used to hold the capture reagent, and the third cavity is used to hold the detection reagent.

Images