A sample analyzer, a sample analysis method, and a reagent

Abstract

This disclosure relates to a sample analyzer, a sample analysis method, and a reagent kit. The controller in the analyzer is configured to perform the following operations: control a reagent dispensing mechanism to draw a first reagent and a sample to be tested into a reaction vessel to obtain a first reaction system and react for a first predetermined time, wherein the first reagent includes a first carrier with a first ligand bound to its surface capable of binding to the analyte; control the reagent dispensing mechanism to further draw a second reagent into a reaction vessel to obtain a second reaction system and react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte; control a photometric component to acquire at least two optical signals and thereby obtain a first reaction analysis value of the first reaction system and a second reaction analysis value of the second reaction system; and obtain an analytical result for the analyte based on the two reaction analysis values.

Description

Sample analyzer, sample analysis method and reagent Technical Field

[0001] The present application relates to the field of in vitro analysis, and in particular to a sample analyzer, a sample analysis method, and corresponding reagents. Background Art

[0002] Immunoturbidimetry is an important method for clinical biochemical testing. It uses the affinity interaction between the analyte (such as a protein) and a ligand (such as an antibody-antigen interaction) to detect the concentration of the analyte in a sample. The use of latex coated with ligands has been proposed to enhance the sensitivity and accuracy of the test.

[0003] The detection limit of latex-enhanced immunoturbidimetry is strongly correlated with the particle size of the latex microspheres used. Generally, latex microspheres with higher light scattering properties (larger particles) have lower lower detection limits, but also lower upper detection limits; while latex microspheres with lower light scattering properties (smaller particles) have higher lower and upper detection limits.

[0004] In clinical testing, many analytes have a wide concentration range, such as C-reactive protein (CRP), microalbuminuria (MALB), rheumatoid factor (RF), β2-microglobulin (β2-MG), etc. Therefore, there has always been a need to expand the linear range of related tests.

[0005] For example, it has been proposed to mix two latex microspheres with different light scattering properties to achieve detection in a wide linear range. The starting point of this method is based on the principle that the detection ranges of different microsphere particle sizes are different. When the concentration of the analyte is low, the microspheres with strong light scattering properties bind to the analyte to achieve a lower detection limit; when the concentration of the analyte is high, the microspheres with weak light scattering properties bind to the analyte to achieve a higher detection limit. However, in actual detection, the two microspheres coexist in the detection system, and it is difficult for them to play a leading role as we wish when the concentration of the analyte is different. For example, when the concentration of the analyte in the sample is low, both microspheres can bind to the analyte, and the opportunity for the microspheres with higher light scattering properties to bind to the analyte is wasted, resulting in the signal failing to meet the detection requirements. Therefore, the latex-enhanced immunoturbidimetric method still needs further improvement.

[0006] Summary of the Invention

[0007] The present disclosure aims to provide a sample analyzer, a sample analysis method, and a reagent. The analyzer and method avoid the problems caused by mixing latex particles with different light scattering properties and further extend the linear range of detection.

[0008] To this end, in a first aspect, in one embodiment, the present disclosure provides a sample analyzer including a sample component, a reagent component, a measurement component, and a controller.

[0009] The sample component includes a sample carrying component for carrying the sample to be tested and a sample dispensing mechanism.

[0010] The reagent component includes a reagent carrying component for carrying reagents and a reagent dispensing mechanism.

[0011] The measuring component includes a reaction component and a light measuring component, wherein the reaction component has at least one placement position for placing a reaction cup.

[0012] The controller is configured to perform the following operations:

[0013] Controlling the reagent dispensing mechanism to draw a first reagent and provide it to the reaction cup, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested, controlling the sample dispensing mechanism to draw the sample to be tested and provide it to the reaction cup to obtain a first reaction system, and controlling the first reaction system to react for a first predetermined time;

[0014] controlling the reagent dispensing mechanism to further draw a second reagent and provide it into the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand capable of binding to the analyte, and controlling the second reaction system to react for a second predetermined time;

[0015] Controlling the optical detection component to obtain at least two optical signals;

[0016] obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and

[0017] A judgment is performed based on the first reaction analysis value and / or the second reaction analysis value, and one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or an optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

[0018] In another embodiment of the first aspect, the present disclosure provides a sample analyzer comprising a sample component, a reagent component, an assay component, and a controller.

[0019] The sample component includes a sample carrying component for carrying the sample to be tested and a sample dispensing mechanism.

[0020] The reagent component includes a reagent carrying component for carrying reagents and a reagent dispensing mechanism.

[0021] The measuring component includes a reaction component and a light measuring component, wherein the reaction component has at least one placement position for placing a reaction cup.

[0022] The controller is configured to perform the following operations:

[0023] Controlling the reagent dispensing mechanism to draw a first reagent and provide it to the reaction cup, wherein the first reagent includes a first microsphere having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested, controlling the sample dispensing mechanism to draw the sample to be tested and provide it to the reaction cup to obtain a first reaction system, and controlling the first reaction system to react for a first predetermined time;

[0024] controlling the reagent dispensing mechanism to further draw a second reagent and provide it into the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand capable of binding to the analyte, and controlling the second reaction system to react for a second predetermined time;

[0025] Controlling the optical detection component to obtain at least two optical signals;

[0026] obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and

[0027] An analysis result of the analyte in the sample to be tested is obtained based on the sum of the first reaction analysis value and the second reaction analysis value.

[0028] In some embodiments, controlling the optical detection component to acquire at least two optical signals includes:

[0029] After controlling the reagent dispensing mechanism to aspirate the first reagent and to provide the reagent into the cuvette, and before controlling the reagent dispensing mechanism to further aspirate the second reagent and to provide the reagent into the cuvette, acquiring the at least one optical signal, and after controlling the reagent dispensing mechanism to further aspirate the second reagent and to provide the reagent into the cuvette, acquiring the at least another optical signal; or

[0030] After controlling the reagent dispensing mechanism to further absorb the second reagent and provide it into the reaction cup, the at least two optical signals are acquired.

[0031] In some embodiments, the performing of judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, includes:

[0032] The first reaction analysis value and the second reaction analysis value are compared, and one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or the light signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0033] Preferably, the first reaction analysis value and the second reaction analysis value are compared, and the larger one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or the light signal corresponding to the larger one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0034] In some embodiments, the performing of judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, includes:

[0035] Determine whether the first reaction analysis value and / or the second reaction analysis value is within a preset range, and select one of the first reaction analysis value and the second reaction analysis value according to the determination result to obtain the analysis result of the analyte in the sample to be tested, or select the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the determination result to obtain the analysis result of the analyte in the sample to be tested.

[0036] In some embodiments, controlling the optical detection component to acquire at least two optical signals includes acquiring the at least one optical signal at a first detection wavelength and acquiring the at least one other optical signal at a second detection wavelength. Preferably, the first detection wavelength and the second detection wavelength are different. Preferably, the first detection wavelength and the second detection wavelength are selected from 320 nm to 860 nm, and more preferably, the first detection wavelength and the second detection wavelength are selected from 340 nm to 850 nm.

[0037] In some embodiments, controlling the optical detection component to acquire at least two optical signals includes:

[0038] A first optical signal is acquired after the reagent dispensing mechanism is controlled to absorb the first reagent and provide it into the reaction cup, or a first optical signal is acquired after the reagent dispensing mechanism is controlled to absorb the first reagent and provide it into the reaction cup and the sample dispensing mechanism is controlled to absorb the sample and provide it into the reaction cup, and before the first predetermined time starts; a second optical signal is acquired after the first predetermined time ends and before the reagent dispensing mechanism is controlled to further absorb the second reagent and provide it into the reaction cup; a third optical signal is acquired after the reagent dispensing mechanism is controlled to further absorb the second reagent and provide it into the reaction cup and before the second predetermined time starts; and a fourth optical signal is acquired after the second predetermined time ends.

[0039] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal; and obtaining the second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal.

[0040] In some embodiments, controlling the optical detection component to obtain at least two optical signals includes: obtaining a second optical signal after the first predetermined time ends and before controlling the reagent dispensing mechanism to further absorb the second reagent and provide it to the reaction cup; and obtaining a fourth optical signal after the second predetermined time ends.

[0041] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the second optical signal.

[0042] In some embodiments, controlling the optical detection component to obtain at least two optical signals includes: obtaining a third optical signal after controlling the reagent dispensing mechanism to further absorb the second reagent and provide it into the reaction cup and before the start of the second predetermined time; and obtaining a fourth optical signal after the end of the second predetermined time.

[0043] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the third optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the third optical signal.

[0044] In some embodiments, controlling the optical detection component to obtain at least two optical signals includes: obtaining a first optical signal after controlling the reagent dispensing mechanism to absorb the first reagent and provide it to the reaction cup, or, obtaining a first optical signal after controlling the reagent dispensing mechanism to absorb the first reagent and provide it to the reaction cup and controlling the sample dispensing mechanism to absorb the sample to be tested and provide it to the reaction cup, and before the start of the first predetermined time; obtaining a second optical signal after the end of the first predetermined time and before controlling the reagent dispensing mechanism to further absorb the second reagent and provide it to the reaction cup; and obtaining a fourth optical signal after the end of the second predetermined time.

[0045] Obtaining a first reaction analysis value of the first reaction system based on the at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the first optical signal and the fourth optical signal or based on the second optical signal and the fourth optical signal.

[0046] In some embodiments, controlling the optical measurement component to obtain at least two optical signals includes: collecting a plurality of the optical signals during at least a period from the first predetermined time to the end of the first predetermined time, thereby obtaining a first reaction curve; and collecting a plurality of the optical signals during at least a period from the second predetermined time to the end of the second predetermined time, thereby obtaining a second reaction curve.

[0047] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first reaction curve, and obtaining the second reaction analysis value of the second reaction system based on the second reaction curve.

[0048] Preferably, a first reaction analysis value of the first reaction system is obtained based on the first reaction curve or based on a characteristic value of the first reaction curve, and the second reaction analysis value of the second reaction system is obtained based on the second reaction curve or based on a characteristic value of the second reaction curve.

[0049] In yet another embodiment of the first aspect, the present disclosure provides a sample analyzer comprising: a sample component, a reagent component, a measurement component, and a controller.

[0050] The sample component includes a sample carrying component for carrying the sample to be tested and a sample dispensing mechanism.

[0051] The reagent component includes a reagent carrying component for carrying reagents and a reagent dispensing mechanism.

[0052] The measuring component includes a reaction component and a light measuring component, wherein the reaction component has at least one placement position for placing a reaction cup.

[0053] The controller is configured to perform the following operations:

[0054] Controlling the reagent dispensing mechanism to draw a first reagent and provide it to the reaction cup, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested, controlling the sample dispensing mechanism to draw the sample to be tested and provide it to the reaction cup to obtain a first reaction system, and controlling the first reaction system to react for a first predetermined time;

[0055] controlling the optical detection component to obtain at least one optical signal;

[0056] acquiring a first reaction analysis value of the first reaction system based on the at least one optical signal;

[0057] The judgment is made based on the first reaction analysis value.

[0058] When the judgment result meets the preset condition, the analysis result of the analyte in the sample to be tested is obtained based on the first reaction analysis value.

[0059] When the judgment result does not meet the preset condition, controlling the reagent dispensing mechanism to further draw a second reagent and provide it into the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand capable of binding to the analyte, and controlling the second reaction system to react for a second predetermined time;

[0060] controlling the optical detection component to obtain at least another optical signal;

[0061] acquiring a second reaction analysis value of the second reaction system based at least on the at least another optical signal; and

[0062] An analysis result of the analyte in the test sample is obtained based at least on the second reaction analysis value.

[0063] In some embodiments, the determining based on the first reaction analysis value includes determining whether the first reaction analysis value is within a preset range:

[0064] If yes, obtaining an analysis result of the analyte in the sample to be tested based on the first reaction analysis value or the optical signal corresponding to the first reaction analysis value;

[0065] If not, the reagent dispensing mechanism is controlled to further absorb a second reagent and provide it to the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand capable of binding to the analyte, and the second reaction system is controlled to react for a second predetermined time.

[0066] controlling the optical detection component to acquire the at least another optical signal,

[0067] obtaining a second reaction analysis value of the second reaction system based at least on the at least another optical signal, and

[0068] An analysis result of the analyte in the test sample is obtained based at least on the second reaction analysis value.

[0069] In some embodiments, obtaining the analysis result of the analyte in the test sample based at least on the second reaction analysis value includes: obtaining the analysis result of the analyte in the test sample based on the first reaction analysis value and the second reaction analysis value.

[0070] In some embodiments, obtaining the analysis result of the analyte in the sample to be tested based at least on the first reaction analysis value and the second reaction analysis value includes: making a judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

[0071] In some embodiments, obtaining the analysis result of the analyte in the test sample based on the first reaction analysis value and the second reaction analysis value includes: obtaining the analysis result of the analyte in the test sample based on the sum of the first reaction analysis value and the second reaction analysis value.

[0072] In some embodiments, the light signal is a scattered light signal and / or a transmitted light signal.

[0073] In a second aspect, in one embodiment, the present disclosure provides a sample analysis method. The method comprises the following steps:

[0074] Controlling the mixing of the test sample and the first reagent to obtain a first reaction system and allowing the first reaction system to react for a first predetermined time, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the test sample;

[0075] controlling a second reagent to mix with the first reaction system to obtain a second reaction system and allowing the second reaction system to react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte;

[0076] acquiring at least two optical signals;

[0077] obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and

[0078] A judgment is performed based on the first reaction analysis value and / or the second reaction analysis value, and one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or an optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

[0079] In another embodiment of the second aspect, the present disclosure provides a sample analysis method, the method comprising the following steps:

[0080] Controlling the mixing of the test sample and the first reagent to obtain a first reaction system and allowing the first reaction system to react for a first predetermined time, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the test sample;

[0081] controlling a second reagent to mix with the first reaction system to obtain a second reaction system and allowing the second reaction system to react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte;

[0082] acquiring at least two optical signals;

[0083] obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and

[0084] An analysis result of the analyte in the sample to be tested is obtained based on the sum of the first reaction analysis value and the second reaction analysis value.

[0085] In some embodiments, obtaining at least two optical signals includes: obtaining at least one optical signal after controlling the mixing of the test sample with the first reagent and before controlling the mixing of the second reagent with the first reaction system, and obtaining at least another optical signal after controlling the mixing of the second reagent with the first reaction system; or, obtaining the at least two optical signals after controlling the mixing of the second reagent with the first reaction system.

[0086] In some embodiments, the performing of judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, includes:

[0087] Comparing the first reaction analysis value and the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested;

[0088] Preferably, the first reaction analysis value and the second reaction analysis value are compared, and the larger one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or the light signal corresponding to the larger one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0089] In some embodiments, the performing of judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the test sample, includes:

[0090] Based on the first reaction analysis value or the second reaction analysis value, it is determined whether it is within a preset range, and according to the determination result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or according to the determination result, the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested.

[0091] In some embodiments, acquiring at least two optical signals includes acquiring the at least one optical signal at a first detection wavelength and acquiring the at least one other optical signal at a second detection wavelength. Preferably, the first detection wavelength and the second detection wavelength are different. Preferably, the first detection wavelength and the second detection wavelength are selected from 320 nm to 860 nm, and more preferably, the first detection wavelength and the second detection wavelength are selected from 340 nm to 850 nm.

[0092] In some embodiments, acquiring at least two optical signals includes: acquiring a first optical signal based on the first reagent or acquiring a first optical signal after controlling the mixing of the test sample and the first reagent and before the start of the first predetermined time; acquiring a second optical signal after the end of the first predetermined time and before controlling the mixing of the second reagent and the first reaction system; acquiring a third optical signal after controlling the mixing of the second reagent and the first reaction system and before the start of the second predetermined time; and acquiring a fourth optical signal after the end of the second predetermined time.

[0093] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal.

[0094] In some embodiments, acquiring at least two optical signals includes: acquiring a second optical signal after the first predetermined time ends and before the second reagent is controlled to mix with the first reaction system; and acquiring a fourth optical signal after the second predetermined time ends.

[0095] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the second optical signal.

[0096] In some embodiments, acquiring at least two optical signals includes: acquiring a third optical signal after controlling the mixing of the second reagent and the first reaction system and before the start of the second predetermined time; and acquiring a fourth optical signal after the end of the second predetermined time.

[0097] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the third optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the third optical signal.

[0098] In some embodiments, acquiring at least two optical signals includes: acquiring a first optical signal based on the first reagent or acquiring a first optical signal after controlling the mixing of the test sample and the first reagent and before the start of the first predetermined time; acquiring a second optical signal after the end of the first predetermined time and before controlling the mixing of the second reagent and the first reaction system; and acquiring a fourth optical signal after the end of the second predetermined time.

[0099] Obtaining a first reaction analysis value of the first reaction system based on the at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the first optical signal and the fourth optical signal or based on the second optical signal and the fourth optical signal.

[0100] In some embodiments, acquiring at least two optical signals includes: continuously collecting the optical signals during at least a period from the first predetermined time to the end of the first predetermined time, and acquiring a first reaction curve; and continuously collecting the optical signals during at least a period from the second predetermined time to the end of the second predetermined time, thereby acquiring a second reaction curve.

[0101] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first reaction curve, and obtaining the first reaction analysis value of the first reaction system based on the second reaction curve. Preferably, the first reaction analysis value of the first reaction system is obtained based on the first reaction curve or based on a characteristic value of the first reaction curve, and the first reaction analysis value of the first reaction system is obtained based on the second reaction curve or based on a characteristic value of the second reaction curve.

[0102] In some embodiments, the binding ability of the first ligand to the analyte is higher than the binding ability of the second ligand to the analyte.

[0103] In some embodiments, the second ligand in the second reagent exists in a free form and / or exists in a form bound to the surface of the second carrier.

[0104] In some embodiments, the first carrier in the first reagent comprises latex microspheres having a first particle size, and the second carrier in the second reagent comprises latex microspheres having a second particle size, wherein the second particle size is smaller than the first particle size.

[0105] In some embodiments, the first ligand and the second ligand are antigens or antibodies that can bind to the analyte.

[0106] In some embodiments, the light signal is a scattered light signal and / or a transmitted light signal.

[0107] A third aspect of the present disclosure provides a reagent kit comprising a first reagent and a second reagent. The first reagent comprises a first carrier having a first ligand bound to its surface. The second reagent comprises a free second ligand. The first and second ligands may be the same or different and may bind to the same analyte in the same sample.

[0108] In some embodiments, the first carrier includes first latex microspheres, and the particle size of the first latex microspheres is 40 nm to 500 nm, preferably 80 nm to 400 nm.

[0109] In some embodiments, the first ligand and the second ligand are antigens or antibodies that can bind to the analyte in the sample to be tested.

[0110] In some embodiments, the binding ability of the first ligand to the analyte is higher than the binding ability of the second ligand to the analyte.

[0111] In some embodiments, the first reagent further comprises a first buffer and an optional anti-interference agent; and the second reagent further comprises a second buffer.

[0112] In some embodiments, the reagents further include a pretreatment reagent, wherein the pretreatment reagent includes a third buffer and an optional anti-interference agent.

[0113] In the analyzer and method, a reagent with a lower detection limit and a reagent with a higher detection limit are used as two reagents, which are added to the sample to be tested in sequence, and the concentration of the analyte in the sample is obtained by using the optical signals generated by the two-stage reaction between the sample and the two reagents. This avoids the problem of the reaction order between the ligands coated on different light scattering particles in the reagent and the analyte being not ideal due to the mixing of the two reagents, and makes full use of the signals of the two-stage reaction to obtain more accurate results and further expand the linear range of detection. In addition, since the two reagents are added to the sample to be tested in sequence, and multiple optical signals in the two stages can be obtained in this process, there are more flexible and diverse detection methods to meet the needs of different detection scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0114] Throughout the drawings, the same reference numerals refer to the same or similar components.

[0115] FIG1 is a schematic flow chart of a sample analysis method according to one embodiment.

[0116] FIG2 is a schematic flow chart of a sample analysis method according to another embodiment.

[0117] FIG3 is a schematic diagram of components of a sample analyzer according to one embodiment.

[0118] FIG. 4 is a schematic diagram of components of a sample analyzer according to another embodiment.

[0119] FIG5 is a schematic structural diagram of some components of a sample analyzer according to one embodiment. DETAILED DESCRIPTION

[0120] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the specific embodiments and drawings of the present invention. Obviously, the embodiments described are only part of the implementation methods of the present invention, not all of the implementation methods. Based on the implementation methods of the present invention, all other implementation methods obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0121] Throughout this specification, unless otherwise specified, the terms used herein should be understood as having the same meaning as commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the event of any conflict, the present specification shall take precedence.

[0122] In this disclosure, the steps of a method are described in a certain order, or different steps are indicated by numbers in the accompanying drawings. It should be understood that the order in which the steps are described, or the size of the numbers indicating the steps, does not limit the order in which the steps of the method are actually performed. That is, the steps may be performed in the order described or in ascending order of the numbers in the accompanying drawings, or they may not be performed in the order described or in ascending order of the numbers in the accompanying drawings. For example, a step described later may be performed before a step described earlier; or two or more steps may be performed simultaneously.

[0123] As mentioned above, to achieve a wider detection range for latex-enhanced immunoturbidimetry, it has been proposed to mix two latex microspheres with different light scattering properties in the detection reagent. Generally speaking, microspheres with larger particle sizes are more favorable for extending the lower limit of detection, while microspheres with smaller particle sizes are more favorable for extending the upper limit of detection. Ideally, the ligand coated on the surface of the larger microspheres reacts first with the analyte. After the reaction is complete, if any free analyte (analyte binding sites not bound by the ligand) remains unreacted, these unreacted analytes will then react further with the ligand coated on the surface of the smaller microspheres. This fully utilizes the advantages of both ligands, allowing detection regardless of whether the analyte concentration in the sample is low or high. However, because both microspheres are present in the same reagent, the ligands coated on different microspheres may react simultaneously with the analyte in the sample. For example, at low concentrations, the ligand on the smaller microspheres may bind to some of the analyte, preventing sufficient amplification of the reaction signal and thus failing to fully utilize the advantages of both ligands.

[0124] Some improved methods have been proposed to address the above problems. For example, ligands with different affinities to the analyte are used to coat microspheres with different particle sizes, and the ligands with higher affinity are coated on the surface of the microspheres with larger particle sizes to promote the analyte to first bind to the ligands on the surface of the microspheres with larger particle sizes. However, this method cannot completely solve the above problems. For another example, a method is proposed to make microspheres of two particle sizes into two reagents respectively, and by adding the reagents in sequence, it is ensured that the ligand in the first reagent reacts completely with the analyte in the sample, and then reacts with the ligand in the second reagent, thereby completely avoiding the problem of two microspheres binding to the analyte at the same time. However, the inventors found that this method causes the reaction system that already contains the first reagent and the sample to be affected by the change in total volume when the second reagent is added, and the change in the optical properties of the reaction solution by the microspheres in the second reagent, which will introduce a background signal, resulting in inaccurate final detection results. Moreover, because the optimal main detection wavelengths of microspheres of different particle sizes are different, in order to obtain better detection results, it is necessary to select a microsphere particle size and concentration combination that is roughly suitable for the same wavelength. This greatly limits the reagent formulation, and the linear expansion is not ideal. The needs of some detection projects are still not met.

[0125] Based on the above problems, the present disclosure proposes an improved sample analysis method, wherein two reagents each containing a ligand capable of binding to an analyte in the sample are used, mixed and reacted with the sample in sequence, and the signal obtained by the reaction of the analyte in the sample with the first reagent and the signal obtained by the reaction with the second reagent are obtained, and the final detection result is determined based on the signals obtained in the two stages of the reaction. On the one hand, unlike the traditional method of obtaining the detection result by only using the signal at the end of the reaction, the above scheme of the present disclosure makes full use of the signal of the reaction of the first reagent with the analyte in the sample, as well as the signal of the further reaction after further addition of the second reagent, and obtains the detection result using the signals of the two stages of the reaction. On the other hand, in the above scheme of the present disclosure, not only are the two reagents added successively, but the signals generated by the reaction in the two stages are obtained respectively, so that the systems of the two stages of the reaction can be considered separately, thereby adopting more accurate and more sensitive detection methods respectively, thereby further expanding the lower limit and / or upper limit of the detection. For example, different wavelengths (or combinations of primary and secondary wavelengths) of detection light can be used in different reaction stages, or even different optical detection systems, such as scattered light detection and transmitted light detection, so that the type of carrier in the two reagents, particle size, affinity of the ligand, etc. can be more selective. For another example, the sample in the first-stage reaction system can be made relatively more concentrated to improve reaction sensitivity at low concentrations, and / or the sample in the second-stage reaction system can be made relatively more diluted to eliminate the hook effect at high concentrations or exceed the detection limit of the equipment, etc., but the present invention is not limited to this. The following description of different embodiments further illustrates the scheme of the present disclosure and its various advantages. Moreover, such a method is not limited to application in immunoturbidimetry and can also be extended to other detection methods such as non-immune turbidimetry or immunocolorimetry.

[0126] To this end, the present disclosure provides a sample analysis method, in particular an immunoturbidimetric analysis method.

[0127] 1 , according to one embodiment, the sample analysis method includes the following steps.

[0128] S110, controlling the sample to be tested to mix with a first reagent to obtain a first reaction system and allowing the first reaction system to react for a first predetermined time, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested.

[0129] S120, controlling a second reagent to mix with the first reaction system to obtain a second reaction system and allowing the second reaction system to react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte.

[0130] S130: Acquire at least two optical signals.

[0131] S140 , obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal.

[0132] S150, performing a judgment based on the first reaction analysis value and / or the second reaction analysis value, selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or selecting an optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

[0133] In the sample analysis method disclosed herein, a sample to be tested and a second reagent are sequentially treated with a first reagent, and at least two optical signals are obtained during the treatment process, and an analysis result of the analyte in the sample to be tested is finally obtained based on the at least two optical signals obtained.

[0134] In S110, the sample to be tested is controlled to be mixed with the first reagent to obtain a first reaction system and the first reaction system is reacted for a first predetermined time. The first reagent contains a first ligand coated on the surface of the first carrier. The first ligand can bind to the analyte in the sample to be tested. The first reaction system is obtained by mixing the first reagent with the sample to be tested, and the first reaction system is further reacted for a first predetermined time, for example, incubated at a certain temperature for a period of time. Generally speaking, for immune reactions (such as antibody-antigen reactions), it can be incubated at approximately 37±3°C for several minutes (such as 1-5 minutes, preferably 3-5 minutes) to allow the first ligand to fully bind to the analyte. In S110, the analyte undergoes a first stage reaction with the first ligand in the first reagent.

[0135] In the first reagent, the first ligand is coated on the surface of the first carrier. When the first ligand binds to the analyte in the first reaction system, the agglutination effect causes a significant change in the optical signal of the first reaction system, thereby reflecting the concentration information of the portion of the analyte bound to the first ligand through the detection of the optical signal. When the concentration of the analyte in the sample to be tested is low, the analyte will react entirely or mostly with the first ligand. Carriers with larger particle sizes (or carriers with significant spectral changes after agglutination, such as colloidal gold) are usually used to increase the degree of change in the optical signal after the ligand reacts with the analyte, thereby improving the sensitivity of the detection and widening the detection limit.

[0136] Compared with the conventional method of adding a mixture of latex microspheres of two particle sizes into the reagent at one time, by first mixing the first reagent with the sample to be tested and allowing the first ligand to react with the analyte, it is avoided that after the microspheres of two particle sizes are mixed with the sample to be tested at the same time, the ligands on the two microspheres may bind to the analyte, resulting in inaccurate results.

[0137] In S120, a second reagent is controlled to mix with the first reaction system to obtain a second reaction system, and the second reaction system is allowed to react for a second predetermined time. The second reagent includes a second ligand that can bind to the analyte.

[0138] The second ligand is present in a free form in the second reagent, or the second ligand is coated on the surface of the second carrier. If there is still residual analyte in the first reaction system that has not bound to the first ligand, after reacting for a second predetermined time, this analyte will continue to bind to the second ligand in the second reagent, causing a further significant change in the optical signal. In S120, the unreacted analyte (if any) reacts with the second ligand in the second reagent in a second stage.

[0139] The second ligand in the second reagent can be present in the second reagent in the form of being bound to the surface of the second carrier. Since the reaction of the sample to be tested with the two reagents is carried out in sequence in the method, and the light signals of the reactions are obtained respectively, the two carriers have a larger range of choices and a more flexible combination. The second carrier can be different from the first carrier or the same. According to one example, a carrier with a smaller particle size is used as the second carrier relative to the particle size of the first carrier. Since the degree of change in the light signal after the ligand combines with the analyte is relatively small when a carrier with a smaller particle size is used, it is suitable for situations where the concentration of the analyte in the sample is high, thereby widening the upper limit of detection. In some detection examples, the second ligand can be present in the second reagent in a free form. However, the present disclosure is not limited to this. For example, the particle size of the first carrier, which will be described in detail below, can be smaller than the particle size of the second carrier.

[0140] In the method, there is no particular limitation on the mixing time of the sample to be tested and the first reagent, or the mixing time of the second reagent and the first reaction system. Those skilled in the art can determine the mixing time according to actual needs. The exemplary mixing time is generally less than 1 minute, such as 10s, 20s, 30s, 40s, 50s, etc. During the mixing stage, it is understood that the reagents are not yet evenly dispersed, and the ligands in the reagents are not yet fully in contact with the analyte, so that substantially no reaction occurs or only a small amount of reaction occurs.

[0141] After mixing, the first and second reaction systems are further reacted for a predetermined time. In the method, there is no particular limitation on the length of the first predetermined time and the second predetermined time. Those skilled in the art can determine the lengths based on actual needs, such as the specific analyte and the first and second ligands used. Exemplarily, the first and second predetermined times are greater than 1 minute, such as 1 to 5 minutes, preferably 3 to 5 minutes, and specifically, 3 minutes, 4 minutes, or 5 minutes.

[0142] The term "incubation" as used herein generally refers to the process of combining the reagents and sample and maintaining them at a predetermined temperature for a period of time to allow the reactants to fully react. In a test device, the incubation time is typically measured from the moment the reactants are added. Therefore, the "incubation" process encompasses both the mixing and the reaction (first or second) predetermined time periods.

[0143] In S130 , at least two optical signals are acquired.

[0144] In S140 , a first reaction analysis value of the first reaction system is obtained based on at least one optical signal, and a second reaction analysis value of the second reaction system is obtained based on at least another optical signal.

[0145] In the method, at least two optical signals can respectively reflect the binding of the analyte to the first ligand and the further binding of the analyte to the second ligand, thereby obtaining a first reaction analysis value of the first reaction system based on at least one of the optical signals and a second reaction analysis value of the second reaction system based on at least another of the optical signals.

[0146] In the present disclosure, in some embodiments, obtaining a reaction analysis value based on a light signal can be obtaining a reaction analysis value through a light signal. In some cases, the light signal itself can be directly used as the reaction analysis value. In other cases, the light signal is used as the reaction analysis value after processing, such as after correction, multiplication by a coefficient (such as a volume correction coefficient, a weighting coefficient, etc.), or subtraction of an instrument background signal.

[0147] In addition, in other embodiments, obtaining a reaction analysis value based on a light signal can also be a reaction analysis value obtained by calculating two or more light signals. For example, the light signal of the reagent or the light signal after the reagent is mixed with the sample is first measured as a blank light signal, and the light signal at the end point of the reaction system is subtracted from the blank light signal as the reaction analysis value. For another example, multiple light signals (such as reaction kinetics curves) can be obtained during the entire process or part of the reaction, and a reaction analysis value is obtained from the multiple light signals or a part thereof. Similarly, one, more or all of the two or more light signals can also be processed first and then used to calculate the reaction analysis value. In some other embodiments, the reaction analysis value can also be a preliminary analysis result (such as concentration) of the analyte further obtained based on a standard curve (or calibration curve). For example, a correspondence between the light signal and the analyte concentration value (i.e., a standard curve) is pre-established, and the collected one or more light signals are corresponded to the standard curve to obtain the corresponding analyte concentration value as the reaction analysis value.

[0148] Unlike conventional methods in which the optical signal of the reaction endpoint is detected only after all the analytes are bound to the ligand, in the method of the present disclosure, the at least two optical signals obtained in S130 are at least two optical signals obtained in steps S110 and S120, respectively reflecting the first-stage reaction and the second-stage reaction, and further a first reaction analysis value of the first reaction system is obtained based on at least one optical signal and a second reaction analysis value of the second reaction system is obtained based on at least another optical signal.

[0149] Further, in S150, a judgment is made based on the first reaction analysis value and / or the second reaction analysis value, and one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or an optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

[0150] Since the concentration of the analyte in the test sample fluctuates within a large range, for different samples, there are different situations in which the detection results of the first-stage reaction can better reflect the concentration of the analyte, and the detection results of the second-stage reaction can better reflect the concentration of the analyte. The method judges the first reaction analysis value and / or the second reaction analysis value, selects one of them according to the judgment result, and further obtains the analysis result of the analyte in the test sample. Compared with conventional methods, this can achieve improved detection accuracy in a wider range of analyte concentrations, thereby significantly expanding the detection linear range of the method.

[0151] As previously mentioned, the reaction analysis value can be a light signal itself, a processed light signal, or a reaction analysis value calculated from multiple light signals. Therefore, in the method, after selecting one of the first and second reaction analysis values, in one embodiment, the analysis result can be obtained using the selected reaction analysis value. Alternatively, in another embodiment, even though the reaction analysis value is not the light signal itself, the analysis result can be obtained using the unprocessed light signal corresponding to the reaction analysis value.

[0152] The method for obtaining the analysis result of the analyte in the sample to be tested by the reaction analysis value or its corresponding light signal can be any conventional method. For example, a standard curve (or calibration curve) can be obtained in advance by testing a series of standard samples containing the analyte at standard concentrations. Corresponding to the method disclosed herein, a first standard curve measured by the reaction of the standard sample with the first reagent, and a second standard curve measured by the reaction of the standard sample with the first reagent and further with the second reagent can be obtained respectively. After selecting one of the first reaction analysis value and the second reaction analysis value of the sample to be tested by the method, the selected reaction analysis value or its corresponding light signal can be used to obtain the concentration of the analyte in the sample to be tested according to the corresponding standard curve. Or when the reaction analysis value itself is the preliminary analysis result (such as concentration) of the analyte, the reaction analysis value can be directly used / output as the final analysis result of the analyte.

[0153] The method disclosed herein can obtain more accurate analysis results and significantly broaden the detection linear range of the method by utilizing the first reaction analysis value and the second reaction analysis value, which respectively reflect the reaction conditions of the two stages.

[0154] In some embodiments, S150, judging based on the first reaction analysis value and / or the second reaction analysis value and further obtaining the analysis result of the analyte in the sample to be tested includes: comparing the first reaction analysis value and the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or, selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0155] In some embodiments, the first reaction analysis value and the second reaction analysis value are compared, and the larger of the first reaction analysis value and the second reaction analysis value is selected based on the comparison result to obtain the analysis result of the analyte in the sample to be tested, or the optical signal corresponding to the larger of the first reaction analysis value and the second reaction analysis value is selected based on the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0156] In other embodiments, based on the first reaction analysis value or the second reaction analysis value, it is determined whether it is within a preset range, and according to the determination result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or according to the determination result, the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested.

[0157] In the different embodiments, the first reaction analysis value and the second reaction analysis value are judged to select the one that more accurately reflects the concentration of the analyte in the sample to be tested. As mentioned above, the concentration of the analyte in the sample to be tested may vary over a large range. Therefore, when the concentration of the analyte is low, the analyte is basically all bound to the first ligand in the first reagent. After the second reagent is added, the change in the light signal is mainly caused by the components of the second reagent and the change in the system volume. In contrast, when the concentration of the analyte is high, there are still more unreacted analytes after the analyte is bound to the first ligand in the first reagent. After the second reagent is added, these unreacted analytes further bind to the second ligand, causing the light signal to continue to increase. Therefore, by judging the first reaction analysis value and the second reaction analysis value, it is possible to select the one that more accurately reflects the concentration of the analyte.

[0158] One method of determining includes comparing a first reaction analysis value and a second reaction analysis value. In a preferred embodiment, the larger value is selected, and the analysis result of the analyte in the test sample is further obtained from this. Another method of determining includes, for example, comparing the first reaction analysis value with a first preset range. If the first reaction analysis value is within the first preset range (or can also be set to be outside the first preset range), the concentration of the analyte in the test sample is further obtained from the first reaction analysis value; if the first reaction analysis value is outside the first preset range (or can also be set to be within the first preset range), the second reaction analysis value is selected and the concentration of the analyte in the test sample is further obtained from the second reaction analysis value. In this determination method, the second reaction analysis value can also be compared with the second preset range. In other embodiments, the first reaction analysis value and the second reaction analysis value can also be compared with corresponding preset ranges, and the appropriate reaction analysis value is selected based on the comparison results to obtain the analysis result of the analyte. The preset range can also be a threshold value. The preset range can be obtained through experience. Generally, the preset range is related to the specific equipment and the detection method set by the equipment, as well as the detection items (i.e., sample type and specific analyte) and the reagents used. Those skilled in the art can determine the appropriate preset range according to actual conditions.

[0159] Further referring to FIG2 , there is shown a sample analysis method according to another embodiment of the present invention, which includes the following steps.

[0160] S210 , controlling the sample to be tested to mix with a first reagent to obtain a first reaction system and allowing the first reaction system to react for a first predetermined time, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested.

[0161] S220, controlling a second reagent to mix with the first reaction system to obtain a second reaction system and allowing the second reaction system to react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte.

[0162] S230: Acquire at least two optical signals.

[0163] S240: Obtain a first reaction analysis value of the first reaction system based on at least one optical signal, and obtain a second reaction analysis value of the second reaction system based on at least another optical signal.

[0164] S250 , obtaining an analysis result of the analyte in the sample to be tested based on the sum of the first reaction analysis value and the second reaction analysis value.

[0165] In this embodiment, S210 to S240 are respectively the same as S110 to S140 in the aforementioned embodiment, and are not described again here.

[0166] Different from the above embodiment in which one of the first and second reaction analysis values ​​is selected by judgment to obtain the final result, in S250 , the final analysis result is obtained based on the sum of the first reaction analysis value and the second reaction analysis value.

[0167] Likewise, the at least two optical signals may be used directly to obtain the sum of the first and second reaction analysis values, or may be processed and optionally further assigned different weights to obtain the sum of the first and second reaction analysis values.

[0168] In this embodiment, the sum of the first reaction analysis value and the second reaction analysis value, which reflect the reaction conditions of the two stages, is utilized to obtain more accurate analysis results and significantly broaden the detection linear range of the method. On the one hand, this method allows the reaction conditions of the two stages to be reflected in the final result, which plays a role in widening the detection range. On the other hand, only one standard curve is required. It is more suitable for this situation: that is, the detection of the first reaction without a severe hook effect. Furthermore, in order to obtain better detection results, the first reaction analysis value and the second reaction analysis value can be assigned weights and then added together.

[0169] In some embodiments, different methods can be used to obtain the analytical result of the analyte in the test sample based on the summed results. One example is to use the summed results to obtain the analyte concentration on a corresponding standard curve. Another example is to perform further calculations on the summed results, such as averaging, weighted averaging, or other calculations, to obtain the analytical result of the analyte in the test sample.

[0170] In other embodiments, illustratively, the analysis result of the analyte in the sample to be tested is obtained by selecting a more reliable reaction analysis value based on relevant information obtained during the reaction, such as interference conditions, antigen excess conditions, or information known before the reaction, such as sample concentration range, interfering substances and analogs contained in the sample.

[0171] In some implementations of the above two embodiments, acquiring at least two optical signals in S130 and S230 includes the following steps.

[0172] After the test sample is controlled to be mixed with the first reagent and before the second reagent is controlled to be mixed with the first reaction system, at least one optical signal is obtained, and after the second reagent is controlled to be mixed with the first reaction system, at least another optical signal is obtained.

[0173] Alternatively, the at least two optical signals are acquired after controlling the mixing of the second reagent and the first reaction system.

[0174] In the method, the at least two optical signals are further used to obtain the first reaction analysis value of the first reaction system and the second reaction analysis value of the second reaction system. Therefore, according to some embodiments, at least one optical signal is obtained after the first reagent and the sample to be tested are mixed but before the second reagent is further added, and at least another optical signal is obtained after the second reagent is added. In this way, the at least two optical signals are obtained from the process of the first stage reaction and the process of the second stage reaction respectively. According to other embodiments, the at least two optical signals are obtained after the second reagent is further added. In this case, when the second reagent is just added to the first reaction system (such as before 1 minute after addition, illustratively such as: 10s, 20s, 30s or 40s), the second ligand in the second reagent has not yet participated in the reaction in large quantities. At this time, compared to the optical signal after the sample to be tested and the first reagent have passed the first predetermined time (i.e., at the end of the first stage reaction), the change in the optical signal of the system mainly comes from the components in the second reagent (such as the second carrier) and the change in the optical signal cited due to the increase in the volume of the system. In some cases, the change in the optical signal of this system is small enough or stable enough not to cause noise. The at least one optical signal acquired at this time primarily includes changes in the system optical signal resulting from the first-stage reaction, thereby obtaining a first reaction analysis value for the first reaction system. During or after the second predetermined time period, at least another optical signal is acquired, further including changes in the system optical signal resulting from the second-stage reaction, thereby obtaining a second reaction analysis value for the second reaction system.

[0175] In some implementations of the above two embodiments, acquiring at least two optical signals in S130 and S230 includes acquiring the at least one optical signal at a first detection wavelength and acquiring the at least another optical signal at a second detection wavelength.

[0176] In the methods disclosed herein, the first ligand and the second ligand in the first and second reagents are respectively bound to the surface of the carrier, or the second ligand may exist in a free form. Therefore, the optimal detection wavelength for the first reaction system after the addition of the first reagent may or may not be suitable for the second reaction system after the further addition of the second reagent. In other words, the optimal detection wavelengths of the first reaction system and the second reaction system may be different.

[0177] Therefore, preferably, the first and second detection wavelengths are different. By setting optimal detection wavelengths suitable for the first and second reaction systems, the sensitivity and accuracy of detection can be further improved, and the linear range of detection can be further expanded. Generally, shorter wavelengths are beneficial for improving detection sensitivity, while longer wavelengths are beneficial for detecting high-concentration samples to prevent excessive optical signals from exceeding the detection limit of the device.

[0178] In traditional detection methods, a fixed wavelength is often used for the detection of the same sample. Therefore, when a reagent contains microspheres of two particle sizes, whether they are contained in one reagent in a mixed manner or contained in two reagents separately as in the method disclosed in the present invention, it is necessary to consider that the particle sizes of the two selected microspheres are roughly suitable for the detection wavelength. This places certain restrictions on the selection of microspheres. In the above embodiment, since different detection wavelengths can be used in the detection process of the same sample, the selection range of the carrier in the first reagent and the second reagent can be expanded, and thus the lower and upper limits of the detection can be further broadened by selecting carriers with larger differences in particle size.

[0179] In some specific embodiments, the first detection wavelength and the second detection wavelength are selected from 320 nm to 860 nm. Preferably, the first detection wavelength and the second detection wavelength are selected from the range of 340 nm to 850 nm.

[0180] In some embodiments, the detection wavelength consists of a primary detection wavelength and a secondary detection wavelength.

[0181] Several exemplary implementations of acquiring optical signals and processing and analyzing optical signals in the above two embodiments are further described below. It should be understood that the sample detection method is not limited to these exemplary implementations.

[0182] According to the first embodiment, acquiring at least two optical signals in S130 and S230 respectively includes the following steps.

[0183] The first optical signal is acquired based on the first reagent or after the sample to be tested is controlled to be mixed with the first reagent and before the first predetermined time begins.

[0184] A second light signal is acquired after the first predetermined time ends and before the second reagent is controlled to mix with the first reaction system.

[0185] A third light signal is acquired after the second reagent is controlled to mix with the first reaction system and before the second predetermined time begins.

[0186] A fourth optical signal is acquired after the second predetermined time expires.

[0187] In S140 and S240, obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal respectively include: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal.

[0188] In this embodiment, the second and fourth light signals are obtained at the end points of the first stage reaction and the second stage reaction, respectively. In this way, the second and fourth light signals respectively contain the concentration information of the measured substance participating in the first stage reaction and the concentration information of the measured substance participating in the first stage reaction and the second stage reaction (that is, the total concentration information of the measured substance). Further, the first light signal just obtained when the first reagent is added, or just after the first reagent is mixed with the sample to be tested, and the third light signal just after the second reagent is mixed with the first reaction system are obtained, so that the first light signal contains the light signal of the first reagent itself, or when the first reagent and the sample to be tested are just mixed, the light signal when the measured substance and the first ligand have not yet reacted in large quantities. The first light signal can be regarded as the blank signal of the first reaction system. The same third light signal can be regarded as the blank signal of the second reaction system.

[0189] Obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal can be, for example, subtracting the first optical signal from the second optical signal, or processing the second optical signal and / or the first optical signal (for example, after correction) and then subtracting the processed first optical signal from the processed second optical signal to obtain the first reaction analysis value.

[0190] Similarly, obtaining the second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal can be, for example, subtracting the second optical signal from the fourth optical signal, or processing the fourth optical signal and / or the second optical signal (for example, after correction) and then subtracting the processed second optical signal from the processed fourth optical signal to obtain the second reaction analysis value.

[0191] In the method, after the sample to be tested is controlled to be mixed with the first reagent and before the first predetermined time begins, and after the second reagent is controlled to be mixed with the first reaction system and before the second predetermined time begins, respectively refers to a certain time point when the first reagent is added to be mixed with the sample to be tested or the second reagent is added to be mixed with the first reaction system for a certain time (such as about 1 minute, or about 50 seconds, or about 40 seconds), for example, 10 seconds, 20 seconds, 30 seconds, 40 seconds or 50 seconds.

[0192] According to the second embodiment, acquiring at least two optical signals in S130 and S230 respectively includes the following steps.

[0193] A second light signal is acquired after the first predetermined time ends and before the second reagent is controlled to mix with the first reaction system.

[0194] A fourth optical signal is acquired after the second predetermined time expires.

[0195] In S140 and S240, obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal respectively include: obtaining the first reaction analysis value of the first reaction system based on the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the second optical signal.

[0196] In this embodiment, the second and fourth optical signals are obtained at the endpoints of the first and second stage reactions, respectively. The second and fourth optical signals can be used directly as the first and second reaction analysis values, respectively, or they can be processed as such and used as the first and second reaction analysis values, respectively. Furthermore, the second optical signal can be used as a blank signal for the second stage reaction and subtracted from the fourth optical signal.

[0197] As mentioned above, after the addition of the second reagent, the optical signal of the system will produce changes that are unrelated to the analyte. This is because the absorbance of the second reagent is inconsistent with the reaction system before the second reagent is added. This phenomenon can be observed by detecting a sample with a concentration of 0. This will cause the optical signal measured in the second stage reaction to include both the reaction between the reagent and the analyte and the background signal that is unrelated to the analyte. This phenomenon reduces the signal-to-noise ratio. That is, the absorbance change caused by the reaction between the analyte and the reagent may be greater than the absorbance change caused by the reaction system itself. Therefore, in conventional methods, it is necessary to balance the blank absorbance of the first and second reagents. In order to reduce the difference between the two, the choice of carrier and carrier particle size is limited.

[0198] This phenomenon can be solved by collecting the light signal as a blank light signal after adding the second reagent (as in the method of the first embodiment).

[0199] When the second light signal is used as the blank signal for the second stage reaction, the second light signal cannot reflect the absorbance change caused by dilution after the addition of the second reagent. However, the influence of this phenomenon can be eliminated by multiplying the second light signal by the volume correction factor. That is, the first reagent volume V R1 and sample volume V S The sum of the first reagent volume V R1 , the volume of the second reagent V R2 and sample volume V S The ratio of the sum.

[0200] According to the third embodiment, acquiring at least two optical signals in S130 and S230 respectively includes the following steps.

[0201] A third light signal is acquired after the second reagent is controlled to mix with the first reaction system and before the second predetermined time begins.

[0202] A fourth optical signal is acquired after the second predetermined time expires.

[0203] In S140 and S240, obtaining the first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining the second reaction analysis value of the second reaction system based on at least another optical signal respectively include: obtaining the first reaction analysis value of the first reaction system based on the third optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the third optical signal.

[0204] In this embodiment, the at least two optical signals are obtained after the addition of the second reagent. As mentioned above, when the second reagent is just added to the first reaction system (such as before 1 minute after addition, illustratively such as: 10s, 20s, 30s, 40s), the second ligand in the second reagent has not yet participated in the reaction in large quantities. At this time, the at least one optical signal obtained mainly includes the change of the system optical signal caused by the first stage reaction, and thus the first reaction analysis value of the first reaction system can be obtained. During or after the second predetermined time, further obtaining at least another optical signal further includes the change of the system optical signal caused by the second stage reaction, and thus the second reaction analysis value of the second reaction system can be obtained. Specifically, the second reaction analysis value of the second reaction system can be obtained based only on the fourth optical signal; or, based on the fourth optical signal and the third optical signal (such as using the third optical signal as the blank signal of the second stage reaction, subtracting the third optical signal from the fourth optical signal) the second reaction analysis value of the second reaction system is obtained.

[0205] According to the fourth embodiment, acquiring at least two optical signals in S130 and S230 respectively includes the following steps.

[0206] The first optical signal is acquired based on the first reagent or after the sample to be tested is controlled to be mixed with the first reagent and before the first predetermined time begins.

[0207] A second light signal is acquired after the first predetermined time ends and before the second reagent is controlled to mix with the first reaction system.

[0208] A fourth optical signal is acquired after the second predetermined time expires.

[0209] In S140 and S240, obtaining the first reaction analysis value of the first reaction system based on the at least one optical signal, and obtaining the second reaction analysis value of the second reaction system based on at least another optical signal respectively include: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the first optical signal and the fourth optical signal or based on the second optical signal and the fourth optical signal.

[0210] This embodiment differs from the aforementioned second embodiment in that a first light signal is further obtained when the first reagent is just added, or after the first reagent is mixed with the sample to be tested. As previously mentioned, the particle size of the first carrier in the first reagent can be larger, so that for the same sample to be tested, the intensity of the light signal can be increased relative to the reagent with a smaller particle size of the carrier contained, thereby improving the detection sensitivity and widening the detection limit. Therefore, the light signal of the first reagent itself is also stronger than the second reagent with a smaller particle size of the carrier contained or even without a carrier. By deducting the light signal of the first reagent itself from the light signal at the end point of the reaction (i.e., the second light signal), or the light signal after the first reagent is mixed with the sample to be tested but before the first predetermined time begins, the first reaction analysis value of the first reaction system is obtained, and the accuracy of the first reaction analysis value can be improved. In one example, the first light signal can be reduced from the fourth light signal to obtain the second reaction analysis value of the second reaction system, and the accuracy of the second reaction analysis value can also be improved.

[0211] According to the fifth embodiment, acquiring at least two optical signals in S130 and S230 respectively includes the following steps.

[0212] A plurality of the optical signals are collected during at least a period from the start of the first predetermined time to the end of the first predetermined time, and a first reaction curve is obtained.

[0213] A plurality of the optical signals are collected during at least a period from the start of the second predetermined time to the end of the second predetermined time, thereby acquiring a second reaction curve.

[0214] In S140 and S240, obtaining the first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining the second reaction analysis value of the second reaction system based on at least another optical signal respectively include: obtaining the first reaction analysis value of the first reaction system based on the first reaction curve, and obtaining the first reaction analysis value of the first reaction system based on the second reaction curve.

[0215] In this embodiment, unlike the point-sampling method described in the first to fourth embodiments, a rate method is used to obtain the reaction analysis value. Generally speaking, when the reactant concentration in the reaction system is high, the reaction rate is faster, and conversely, when the reactant concentration is low, the reaction rate is slower. Therefore, this embodiment utilizes the change in reaction rate (i.e., reaction kinetic information) reflected by the change in the optical signal to obtain the concentration information of the analyte in the sample to be tested.

[0216] By collecting a plurality of the optical signals during at least a period starting from the first predetermined time and ending at the first predetermined time, at least a partial reaction curve (first reaction curve) of the first-stage reaction can be obtained, thereby obtaining reaction kinetic information of the reaction in that stage. Similarly, at least a partial reaction curve (second reaction curve) of the second-stage reaction can be obtained, thereby obtaining reaction kinetic information of the second-stage reaction.

[0217] In a preferred embodiment, a first reaction analysis value of the first reaction system is obtained based on the first reaction curve or based on the characteristic value of the first reaction curve, and the second reaction analysis value of the second reaction system is obtained based on the second reaction curve or based on the characteristic value of the second reaction curve.

[0218] The collecting of the plurality of optical signals includes, for example, collecting the plurality of optical signals at fixed time intervals over a certain period of time. Exemplarily, during the first predetermined time period or the second predetermined time period, or during the "incubation" period, optical signals are continuously collected at fixed time intervals such as 10 seconds or 20 seconds for, for example, 1 to 5 minutes (e.g., 2 minutes, 3 minutes, 4 minutes).

[0219] The characteristic value may be, for example, the slope of a certain curve (the rate of change of the optical signal per unit time), the maximum slope (the maximum value of the rate of change of the optical signal per unit time), the integral of the slope over time, etc., but is not limited thereto.

[0220] The above only uses five preferred implementation methods to illustrate the sample analysis method of obtaining at least two optical signals, further obtaining a first reaction analysis value of the first reaction system and a second reaction analysis value of the second reaction system based on the at least two optical signals, and further obtaining the analysis result of the analyte in the sample to be tested based on the first reaction analysis value and the second reaction analysis value by a judgment method or an addition method.

[0221] It should be understood that the sample analysis method disclosed herein is not limited to the above five embodiments.

[0222] In some embodiments, for example, when different wavelengths are used to detect two stage reactions, a second light signal can be obtained at a first detection wavelength after the first predetermined time ends and before the second reagent is added, and a third light signal can be obtained at a second detection wavelength different from the first detection wavelength. The second light signal serves as the light signal of the end point of the first stage reaction, and the third light signal serves as the blank signal of the second stage reaction. In other embodiments, similarly, after the second reagent is added and mixed and before the second predetermined time begins, a second light signal can also be obtained at a first detection wavelength, and a third light signal can be obtained at a second detection wavelength different from the first detection wavelength. The second light signal serves as the light signal of the end point of the first stage reaction, and the third light signal serves as the blank signal of the second stage reaction.

[0223] For another example, the addition ratio of the sample to be tested and the reagent can be further adjusted based on each embodiment, thereby further adjusting the linear range applicable to the detection method and improving the accuracy of the detection. According to one example, a first reagent with a reduced volume relative to conventional practice can be mixed with a sample to be tested of a conventional volume so that the concentration of the analyte in the first reaction system obtained is relatively increased, thereby further improving the detection sensitivity of the first reagent. In this example, by controlling the amount of reagent and sample added, the concentration of the analyte in the first reaction system is relatively concentrated. According to another example, a sample to be tested with a reduced volume relative to conventional practice can be mixed with a first reagent with a reduced volume in the same proportion. At this time, the concentration of each component in the first reaction system remains unchanged relative to conventional practice, only the system volume is reduced; then a second reagent with an increased volume is further added to reduce the concentration of the analyte in the second reaction system obtained, thereby further improving the detection limit. In this example, by controlling the amount of reagent and sample added, the concentration of the analyte in the second reaction system is relatively diluted. Here, in order to maintain a low reagent cost, the concentration of its ligand (and / or carrier) can be reduced while increasing the volume of the second reagent. Other volume and / or concentration adjustments may also be used to increase the sensitivity of detection and / or the upper limit of linear detection.

[0224] According to some embodiments, the binding ability of the first ligand to the analyte is higher than the binding ability of the second ligand to the analyte. In this way, when the first reagent is mixed with the sample to be tested, the first ligand is more likely to bind to the analyte, which can further improve the sensitivity of the detection method, thereby further broadening the lower limit of the detection method. In addition, by setting the binding ability of the first ligand to the analyte to be higher than the binding ability of the second ligand to the analyte, the detection sensitivity of the first reagent to samples containing low concentrations of the analyte is improved, thereby also making it possible to have more possibilities for the selection of the particle size of the first carrier and (if present) the second carrier. For example, a first carrier with a relatively small particle size can be selected, and the particle size of the first carrier can even be selected to be smaller than the particle size of the second carrier.

[0225] In the method disclosed herein, the second ligand in the second reagent exists in a free form or exists in a form bound to the surface of the second carrier, or the second reagent may include both the free second ligand and the second ligand bound to the surface of the carrier.

[0226] In a preferred embodiment, the carrier is latex microparticles. However, the carrier used in the sample detection method is not limited thereto. For example, the carrier can also be magnetic beads, colloidal gold, nanosilver particles, polymerized proteins, etc. In short, any carrier that can cause a change in the optical signal in the reaction system after forming an aggregated state can be used as a carrier. Those skilled in the art can select the carrier according to actual needs.

[0227] In some embodiments, the first carrier in the first reagent includes latex microspheres having a first particle size, and the second carrier in the second reagent includes latex microspheres having a second particle size. The present disclosure does not particularly limit the selection of the particle size of the first carrier and the second carrier. For example, the two can be the same, or the particle size of the first carrier is different from the particle size of the second carrier. In a preferred embodiment, the second particle size is smaller than the first particle size. As previously mentioned, treating the sample to be tested with such a first reagent and a second reagent can obtain a lower linear detection lower limit and a higher linear detection upper limit.

[0228] The above embodiments are described with respect to each reagent containing particles of only one size. It should be understood that the methods disclosed herein are not limited thereto. For example, each reagent may include particles of two or more sizes. By selecting a combination of particles and ligands having an appropriate size, the first reagent can be adapted for detecting samples of low analyte concentrations to meet the requirements of the lower limit of linear detection, while the second reagent can be adapted for detecting samples of high analyte concentrations to meet the requirements of the upper limit of linear detection.

[0229] In some embodiments, the method may further include further treating the sample with a third reagent.

[0230] According to an example, the 3rd reagent is a buffer, which may optionally include an anti-interference agent. In this example, the 3rd reagent is mixed with the sample to be tested before the first reagent, or after the first reagent adds and reacts the first predetermined time, the 3rd reagent is added. The adding of the 3rd reagent can play a certain dilution effect on the sample to be tested. In addition, if the 3rd reagent contains an anti-interference agent, mixing with the sample to be tested with the 3rd reagent in advance can eliminate interference, which is conducive to improving the accuracy of detection.

[0231] According to another example, the third reagent is a reagent with higher sensitivity. In this example, the third reagent is mixed with the sample to be tested before the first reagent and reacts for a certain period of time, during which a light signal is obtained, and a reaction analysis value is obtained based on the light signal. Then, the first reagent and the second reagent are further added to further react with the analyte in the sample to be tested, and light signals and corresponding reaction analysis values ​​are obtained respectively. In this way, the reaction analysis values ​​of the three-stage reaction can be obtained in this example, and the most suitable one is selected from them to obtain the final analysis result by a similar method as described above, or the three reaction analysis values ​​are calculated, and the final analysis result is obtained according to the calculation result. The sample analysis method of this example can further broaden the detection limit.

[0232] According to another example, a third reagent is suitable for use in samples containing high concentrations of the analyte, extending the upper limit of detection. Similar to the previous example, this third reagent is added to the reaction system after the second reagent reacts to further react, ultimately obtaining three reaction analysis values ​​for the three-stage reaction and ultimately obtaining the final analysis result.

[0233] Of course, the above examples can also be combined to use four or even more reagents for detection.

[0234] According to some embodiments, the first ligand and the second ligand are antigens or antibodies that can bind to the analyte.

[0235] The present disclosure does not particularly limit the type of ligand. In addition to antigens or antibodies, the sample detection method may also employ other substances that have a certain degree of mutual binding ability with the analyte and whose reaction products can change the system's optical signal, thereby being detected, such as aptamers, enzymes, or substrates. Those skilled in the art will be able to select the ligand according to actual needs.

[0236] According to some embodiments, the light signal is a scattered light signal and / or a transmitted light signal.

[0237] According to some embodiments, the sample to be tested is a body fluid sample from a mammal, especially a primate, particularly a human, such as blood, urine, cerebrospinal fluid, saliva, etc.

[0238] The present disclosure does not particularly limit the specific analytical items used in the sample analysis method. Any detection item that uses ligand detection, such as immunoturbidimetry, can use the method of the present disclosure to broaden the linear range of detection, for example, immunoglobulins (IgA, IgG, IgE), complement components (C3, C1q), apolipoproteins (ApoA1, ApoE), haptens (such as antibiotics, vitamin D, digoxin), antibodies (such as anti-streptolysin O antibodies (ASO), anti-cyclic citrullinated peptide antibodies (ACCP), Helicobacter pylori antibodies), tumor markers (such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA)), enzymes (such as creatine kinase isoenzyme (CKMB), lipoprotein-associated phospholipase A2 (LP-PLA2)), acute phase proteins (such as C-reactive protein, ceruloplasmin, haptoglobin), myocardial injury markers (myoglobin, troponin), and common proteins in body fluids such as albumin, prealbumin, hemoglobin, glycated hemoglobin, cystatin C, etc. The method is particularly suitable for detection items with large changes in the concentration of the analyte, such as CRP, MALB, RF, β2-MG, etc., but is not limited thereto.

[0239] The sample analysis method disclosed herein is not limited to the enhanced immunoassay method using latex microspheres. The method can utilize other carriers capable of enhancing the detection signal, such as colloidal gold immunocolorimetry. For example, suitable carrier materials include any inorganic, organic, or polymeric materials for testing of particulate enhanced light scattering. Such materials include, for example: selenium, carbon, gold; nitrides of carbon, silicon, or germanium, such as Si3N4; oxides of iron, titanium, or silicon, such as TiO2, SiO2; and polymeric materials, such as polystyrene, polyvinyl chloride, epoxy resin, polyvinylidene chloride, poly(α-naphthyl methacrylate), polyvinyl naphthylene, or copolymers thereof, particularly copolymers of styrene and ethylenically unsaturated compounds, such as styrene-(meth)acrylate copolymers, core-shell particles composed of a polystyrene core and a shell formed by copolymerization of styrene and ethylenically unsaturated compounds, and the like.

[0240] A second aspect of the present disclosure also provides a sample analyzer.

[0241] Before describing the sample analyzer in detail, the structure of the sample analyzer will be described first.

[0242] 3 , which shows an embodiment of the sample analyzer, includes a sample unit 10 , a reagent unit 20 , a determination unit 30 , and a processor 40 . According to another embodiment, referring to FIG. 4 , the sample analyzer further includes a display unit 50 .

[0243] The sample component 10 is used to carry the sample to be tested, and after absorbing the sample, it is provided to the measuring component 30. Referring to Figure 5, in some embodiments, the sample component 10 includes a sample carrying component 11 and a sample dispensing mechanism 12. The sample carrying component 11 is used to carry the sample. In some examples, the sample carrying component 11 may include a sample delivery module (SDM) and a front track. In other examples - such as Figure 5, the sample carrying component 11 may also be a sample tray, which includes a plurality of sample positions for placing samples such as sample tubes. The sample tray can dispatch the sample to the corresponding position by rotating its tray structure, such as the position for the sample dispensing mechanism 12 to absorb the sample. The sample dispensing mechanism 12 is used to absorb the sample and discharge it into the reaction cup to be loaded. For example, the sample dispensing mechanism 12 may include a sample needle, which performs two-dimensional or three-dimensional movement in space through a two-dimensional or three-dimensional driving mechanism, so that the sample needle can move to absorb the sample carried by the sample carrying component 11, and move to the reaction cup to be loaded, and discharge the sample into the reaction cup.

[0244] The reagent component 20 is used to carry the reagent, and after absorbing the reagent, it is provided to the measuring component 30. In some embodiments, the reagent component 20 may include a reagent carrying component 13 and a reagent dispensing mechanism 14. The reagent carrying component 13 is used to carry the reagent. In one example, the reagent carrying component 13 can be a reagent disk, which is arranged in a disc-shaped structure and has a plurality of positions for carrying reagent containers. The reagent carrying component 13 can rotate and drive the reagent container it carries to rotate, and is used to rotate the reagent container to a specific position, such as a position where the reagent is absorbed by the reagent dispensing mechanism 14. The number of reagent carrying components 13 can be one or more. The reagent dispensing mechanism 14 is used to absorb the reagent and discharge it into a reaction cup to be added with the reagent. In one example, the reagent dispensing mechanism 14 may include a reagent needle, which performs two-dimensional or three-dimensional movement in space through a two-dimensional or three-dimensional driving mechanism, so that the reagent needle can move to absorb the reagent carried by the reagent carrying component 13, and move to the reaction cup to be added with the reagent, and discharge the reagent into the reaction cup.

[0245] The measuring component 30 is used to test the analyte in the sample to obtain test data of the analyte. In some embodiments, the measuring component 30 may include a reaction component 15 and a light measuring component 16. The reaction component 15 has at least one placement position, which is used to place a reaction cup and incubate the reaction liquid in the reaction cup. For example, the reaction component 15 is a reaction disk, which is arranged in a disc-shaped structure and has one or more placement positions for placing reaction cups. The reaction disk can rotate and drive the reaction cups in its placement positions to rotate, and is used to arrange the reaction cups in the reaction disk and incubate the reaction liquid in the reaction cups. The light measuring component 16 is used to perform light measurement on the reaction system obtained by mixing and during or after a predetermined time to obtain the light signal of the reaction system. For example, the light measuring component 16 detects the intensity of the transmitted light and / or scattered light of the reaction system, and calculates the concentration of the analyte in the sample through a standard curve. In one embodiment, the light measuring component 16 is separately arranged outside the reaction component 15.

[0246] 3 to 5 , various embodiments of the sample analyzer disclosed herein will be described in detail.

[0247] According to one embodiment, the sample analyzer includes: a sample component 10 , a reagent component 20 , a measurement component 30 and a controller 40 .

[0248] The sample component 10 includes a sample carrying component 11 for carrying the sample to be tested and a sample dispensing mechanism 12; the reagent component 20 includes a reagent carrying component 13 for carrying the reagent and a reagent dispensing mechanism 14; the measuring component 30 includes a reaction component 15 and a light measuring component 16, wherein the reaction component 15 has at least one placement position for placing a reaction cup.

[0249] The controller 40 is configured to perform the following operations:

[0250] Controlling the reagent dispensing mechanism 14 to draw a first reagent and provide it to the reaction cup, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested; controlling the sample dispensing mechanism 12 to draw the sample to be tested and provide it to the reaction cup to obtain a first reaction system; and controlling the first reaction system to react for a first predetermined time;

[0251] controlling the reagent dispensing mechanism 14 to further draw a second reagent and provide it into the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand capable of binding to the analyte, and controlling the second reaction system to react for a second predetermined time;

[0252] Controlling the optical detection component 16 to obtain at least two optical signals;

[0253] obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and

[0254] A judgment is performed based on the first reaction analysis value and / or the second reaction analysis value, and one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or an optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

[0255] The sample to be tested, the first reagent, and the second reagent are as described in the first aspect above and will not be repeated here.

[0256] The sample analyzer disclosed herein controls the reagent dispensing mechanism 14 to first draw a first reagent, controls the sample dispensing mechanism 12 to draw a sample to be tested into a reaction cup for mixing to obtain a first reaction system, and then controls the reagent dispensing mechanism 14 to further draw a second reagent into the reaction cup for further mixing with the first reaction system and reacting for a second predetermined time. Similar to the sample analysis method described in the first aspect, controlling the optical detection component 16 to acquire at least two optical signals can be performed simultaneously with controlling the sample dispensing mechanism 12 to draw a sample and / or the reagent dispensing mechanism 14 to draw a reagent. Alternatively, the control can be performed while the reagent and sample are mixing and reacting in the reaction cup for a predetermined time, or after the predetermined reaction time has elapsed.

[0257] In some embodiments, controlling the optical detection component 16 to obtain at least two optical signals includes: obtaining the at least one optical signal after controlling the reagent dispensing mechanism 14 to absorb the first reagent and provide it to the reaction cup and before controlling the reagent dispensing mechanism 14 to further absorb the second reagent and provide it to the reaction cup, and obtaining the at least another optical signal after controlling the reagent dispensing mechanism 14 to further absorb the second reagent and provide it to the reaction cup.

[0258] In other embodiments, controlling the optical detection component 16 to obtain at least two optical signals includes: obtaining the at least two optical signals after controlling the reagent dispensing mechanism 14 to further absorb the second reagent and provide it into the reaction cup.

[0259] In some embodiments, the controller 40 is configured to perform the following operations: perform a judgment based on the first reaction analysis value and / or the second reaction analysis value, select one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain an analysis result of the analyte in the sample to be tested, or select an optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain an analysis result of the analyte in the sample to be tested, including:

[0260] The first reaction analysis value and the second reaction analysis value are compared, and one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or the light signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected according to the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0261] In a preferred embodiment, the first reaction analysis value and the second reaction analysis value are compared, and the larger of the first reaction analysis value and the second reaction analysis value is selected based on the comparison result to obtain the analysis result of the analyte in the sample to be tested, or the optical signal corresponding to the larger of the first reaction analysis value and the second reaction analysis value is selected based on the comparison result to obtain the analysis result of the analyte in the sample to be tested.

[0262] According to other embodiments, it is determined whether the first reaction analysis value and / or the second reaction analysis value are within a preset range, and one of the first reaction analysis value and the second reaction analysis value is selected based on the determination result to obtain the analysis result of the analyte in the sample to be tested, or the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected based on the determination result to obtain the analysis result of the analyte in the sample to be tested.

[0263] Another embodiment of the second aspect of the present disclosure provides a sample analyzer, including: a sample component, a reagent component, a measurement component, and a controller.

[0264] The difference from the sample analyzer provided in the above embodiment is that the controller is configured to control the optical detection component to perform the following operations after acquiring at least two optical signals:

[0265] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and obtaining an analysis result of the analyte in the sample to be tested based on the sum of the first reaction analysis value and the second reaction analysis value.

[0266] The operation that the controller is configured to perform to ultimately obtain the analysis result of the analyte in the sample to be tested through the at least two optical signals is the same as that described in the first aspect above, and will not be repeated here.

[0267] In the sample analyzers of the above two embodiments, controlling the optical detection component to acquire at least two optical signals includes acquiring the at least one optical signal at a first detection wavelength and acquiring the at least another optical signal at a second detection wavelength.

[0268] Preferably, the first detection wavelength and the second detection wavelength are different.

[0269] According to some embodiments, the first detection wavelength and the second detection wavelength are selected from 320 nm to 860 nm. Preferably, the first detection wavelength and the second detection wavelength are selected from 340 nm to 850 nm.

[0270] The following further describes some implementation methods of controlling the optical detection component to obtain at least two optical signals in the above two embodiments.

[0271] According to the first embodiment, controlling the optical detection component to acquire at least two optical signals includes the following operations.

[0272] The first optical signal is acquired after the reagent dispensing mechanism is controlled to absorb the first reagent and provide it into the reaction cup, or the first optical signal is acquired after the reagent dispensing mechanism is controlled to absorb the first reagent and provide it into the reaction cup and the sample dispensing mechanism is controlled to absorb the sample and provide it into the reaction cup, and before the first predetermined time starts.

[0273] After the first predetermined time has elapsed and before the reagent dispensing mechanism is controlled to further aspirate the second reagent and provide it into the cuvette, a second optical signal is acquired.

[0274] After the reagent dispensing mechanism is controlled to further aspirate the second reagent and provide it into the cuvette, a third optical signal is acquired before the second predetermined time starts.

[0275] A fourth optical signal is acquired after the second predetermined time expires.

[0276] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal.

[0277] According to the second embodiment, controlling the optical detection component to acquire at least two optical signals includes the following operations.

[0278] After the first predetermined time has elapsed and before the reagent dispensing mechanism is controlled to further aspirate the second reagent and provide it into the cuvette, a second optical signal is acquired.

[0279] A fourth optical signal is acquired after the second predetermined time expires.

[0280] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the second optical signal.

[0281] According to a third embodiment, controlling the optical detection component to acquire at least two optical signals includes the following operations.

[0282] After the reagent dispensing mechanism is controlled to further aspirate the second reagent and provide it into the cuvette, a third optical signal is acquired before the second predetermined time starts.

[0283] A fourth optical signal is acquired after the second predetermined time expires.

[0284] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the third optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the third optical signal.

[0285] According to a fourth embodiment, controlling the optical detection component to acquire at least two optical signals includes the following operations.

[0286] The first optical signal is acquired after the reagent dispensing mechanism is controlled to absorb the first reagent and provide it into the reaction cup, or the first optical signal is acquired after the reagent dispensing mechanism is controlled to absorb the first reagent and provide it into the reaction cup and the sample dispensing mechanism is controlled to absorb the sample and provide it into the reaction cup, and before the first predetermined time starts.

[0287] After the first predetermined time has elapsed and before the reagent dispensing mechanism is controlled to further aspirate the second reagent and provide it into the cuvette, a second optical signal is acquired.

[0288] A fourth optical signal is acquired after the second predetermined time expires.

[0289] Obtaining a first reaction analysis value of the first reaction system based on the at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the first optical signal and the fourth optical signal or based on the second optical signal and the fourth optical signal.

[0290] According to the fifth embodiment, controlling the optical detection component to acquire at least two optical signals includes the following operations.

[0291] A plurality of the optical signals are collected during at least a period from the start of the first predetermined time to the end of the first predetermined time, thereby acquiring a first reaction curve.

[0292] A plurality of the optical signals are collected during at least a period from the start of the second predetermined time to the end of the second predetermined time, thereby obtaining a second response curve.

[0293] Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: obtaining the first reaction analysis value of the first reaction system based on the first reaction curve, and obtaining the second reaction analysis value of the second reaction system based on the second reaction curve.

[0294] In a preferred embodiment, a first reaction analysis value of the first reaction system is obtained based on the first reaction curve or based on the characteristic value of the first reaction curve, and a second reaction analysis value of the second reaction system is obtained based on the second reaction curve or based on the characteristic value of the second reaction curve.

[0295] The operations in the first to fifth implementations of the sample analyzers of the above two embodiments correspond to the steps in the first to fifth implementations of the sample analysis method described in the first aspect, and therefore the operations in the above implementations are not described in detail.

[0296] Similarly, corresponding to the sample analysis method described in the first aspect above, the operation mode of the sample analyzer disclosed herein is not limited to the above-described embodiments. Those skilled in the art can further obtain other operation modes of the sample analyzer based on the above-described sample analysis methods.

[0297] Another embodiment of the second aspect of the present disclosure provides a sample analyzer, comprising: a sample unit 10, a reagent unit 20, a measurement unit 30, and a controller 40. Similar to the aforementioned embodiments, the sample unit 10 comprises a sample carrier 11 for carrying a sample to be tested and a sample dispensing mechanism 12; the reagent unit 20 comprises a reagent carrier 13 for carrying a reagent and a reagent dispensing mechanism 14; and the measurement unit 30 comprises a reaction unit 15 and a light detection unit 16, wherein the reaction unit 15 has at least one placement position for a reaction cup.

[0298] The controller 40 is configured to perform the following operations:

[0299] The reagent dispensing mechanism 14 is controlled to absorb the first reagent and provide it to the reaction cup, wherein the first reagent includes a first carrier having a first ligand bound to the surface thereof that can bind to the analyte in the sample to be tested; the sample dispensing mechanism 12 is controlled to absorb the sample to be tested and provide it to the reaction cup to obtain a first reaction system; and the first reaction system is controlled to react for a first predetermined time.

[0300] The light detecting component 16 is controlled to obtain at least one light signal.

[0301] A first reaction analysis value of the first reaction system is acquired based on the at least one optical signal.

[0302] Based on the first reaction analysis value, the following is judged:

[0303] When the judgment result meets the preset condition, the analysis result of the analyte in the sample to be tested is obtained based on the first reaction analysis value.

[0304] When the judgment result does not meet the preset condition, the reagent dispensing mechanism 14 is controlled to further absorb a second reagent and provide it into the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand capable of binding to the analyte, and the second reaction system is controlled to react for a second predetermined time;

[0305] controlling the optical detection component 16 to obtain at least another optical signal;

[0306] obtaining a second reaction analysis value of the second reaction system based at least on the at least another optical signal;

[0307] An analysis result of the analyte in the test sample is obtained based at least on the second reaction analysis value.

[0308] In this embodiment, the controller 40 is configured to first control the various components of the sample analyzer to perform various operations for detecting an analyte in the sample using a first reagent, causing the first reagent to mix with the sample to form a first reaction system and react for a first predetermined time. The controller then obtains at least one optical signal reflecting the reaction between the analyte in the sample and the first ligand in the first reagent, and obtains a first reaction analysis value of the first reaction system based on the at least one optical signal. A determination is then made based on the first reaction analysis value, and if the determination result satisfies a preset condition, an analysis result of the analyte in the sample is obtained based on the first reaction analysis value.

[0309] In this way, the sample analyzer of this embodiment can avoid further testing with the second reagent. Therefore, when the sample to be tested can be accurately tested using only the first reagent, the second reagent is not required. This sample analyzer can save testing time and also save the second reagent.

[0310] When the judgment result does not meet the preset conditions, the various components of the sample analyzer are controlled to further add a second reagent into the reaction cup to obtain a second reaction system, and the second reaction system is controlled to react for a second predetermined time. During this process, the optical detection component controls to obtain at least another optical signal.

[0311] According to some embodiments, determining based on the first reaction analysis value includes determining whether the first reaction analysis value is within a preset range.

[0312] According to one embodiment, the controller 40 is configured to perform the following operations: Controlling the reagent dispensing mechanism 14 to aspirate a first reagent and deliver it to a cuvette. The first reagent includes a first carrier having a first ligand bound to its surface that can bind to an analyte in the sample to be tested. Controlling the sample dispensing mechanism 12 to aspirate the sample to be tested and deliver it to the cuvette to obtain a first reaction system, and controlling the first reaction system to react for a first predetermined time. Controlling the optical detection component 16 to acquire at least one optical signal. A first reaction analysis value of the first reaction system is obtained based on the at least one optical signal. A determination is made based on the first reaction analysis value. When the determination result satisfies a preset condition, an analysis result of the analyte in the sample to be tested is obtained based on the first reaction analysis value. When the determination result does not satisfy the preset condition, controlling the reagent dispensing mechanism 14 to further aspirate a second reagent and deliver it to the cuvette to obtain a second reaction system. The second reagent includes a second carrier having a second ligand bound to its surface that can bind to an analyte in the sample to be tested. The particle size of the first carrier is larger than that of the second carrier. Controlling the second reaction system to react for a second predetermined time. Controlling the optical detection component to acquire at least another optical signal. A second reaction analysis value of the second reaction system is obtained based at least on the at least another optical signal, and an analysis result of the analyte in the sample to be tested is obtained based at least on the second reaction analysis value.

[0313] According to some embodiments, obtaining the analysis result of the analyte in the sample to be tested based at least on the second reaction analysis value includes: obtaining the analysis result of the analyte in the sample to be tested based on the second reaction analysis value.

[0314] According to other embodiments, obtaining the analysis result of the analyte in the sample to be tested based at least on the second reaction analysis value includes: obtaining the analysis result of the analyte in the sample to be tested based on the first reaction analysis value and the second reaction analysis value. This embodiment is the same as the embodiments of obtaining the analysis result of the analyte in the sample to be tested based on the first reaction analysis value and the second reaction analysis value in the two aforementioned embodiments. For example, the analysis result of the analyte in the sample to be tested can be obtained by judging the first reaction analysis value and the second reaction analysis value, and then selecting one of them; or obtaining the analysis result of the analyte in the sample to be tested by summing the first reaction analysis value and the second reaction analysis value. The specific embodiments will not be repeated here.

[0315] Unlike the sample analyzers of the two aforementioned embodiments, in this embodiment, the specific implementation of controlling the optical measurement component 16 to acquire at least one optical signal and obtaining a first reaction analysis value for the first reaction system based on the at least one optical signal may differ from the specific implementation of controlling the optical measurement component 16 to acquire at least another optical signal and obtaining a second reaction analysis value for the second reaction system based on the at least another optical signal. That is, at least one optical signal may be acquired and the first reaction analysis value for the first reaction system may be obtained based on the at least one optical signal by any of the aforementioned first to fifth embodiments, and at least another optical signal may be acquired and the second reaction analysis value for the second reaction system may be obtained based on the at least another optical signal by any of the aforementioned first to fifth embodiments. For example, the first and second optical signals of the first-stage reaction may be acquired using the point-sampling method described in the first embodiment, and the first reaction analysis value may be further obtained from them. Simultaneously, a second reaction curve may be acquired using the rate method described in the fifth embodiment, and the second reaction analysis value may be further obtained from the second reaction curve or a portion thereof.

[0316] In various embodiments, the light signal is a scattered light signal and / or a transmitted light signal.

[0317] The sample analyzers of each of the above embodiments may further include a user interface. According to some embodiments, the user interface is configured to display a sample analysis mode for user selection and initiate the corresponding analysis mode based on the user selection. According to some embodiments, the user interface is configured to display a signal processing mode for user selection and perform corresponding signal processing based on the user selection. According to some embodiments, the user interface is configured to output the analysis results of the analyte in the sample to be tested. The above embodiments may be combined in any manner.

[0318] A third aspect of the present disclosure provides an immunoturbidimetric reagent kit comprising a first reagent and a second reagent. The first reagent comprises a first carrier having a first ligand bound to its surface; the second reagent comprises a second ligand; the first and second ligands may be the same or different and may bind to the same analyte in the same sample.

[0319] As mentioned above, the first reagent and the second reagent in the reagent kit of the present disclosure include a first ligand and a second ligand, respectively. That is, both reagents contain a ligand that can react with the analyte in the sample.

[0320] The second ligand in the second reagent may exist in a free form or may be bound to the surface of the second carrier.

[0321] The first carrier and the second carrier can be the same or different. In a preferred embodiment, the particle size of the first carrier is larger than the particle size of the second carrier. However, the embodiments of the reagent kit disclosed herein are not limited thereto. For example, the first carrier and the second carrier can be the same, or the particle size of the first carrier can be smaller than the particle size of the second carrier, as long as the first reagent is more suitable for detecting samples with lower analyte concentrations and the second reagent is more suitable for detecting samples with higher analyte concentrations.

[0322] As mentioned above, the first reagent may include carriers with different particle sizes; the second reagent may also include carriers with different particle sizes, or further include a second ligand in a free form.

[0323] The carrier is preferably, but not limited to, latex microspheres. For example, the carrier may also be magnetic beads, colloidal gold, nanosilver particles, polymerized proteins, etc. In short, any carrier that can cause a change in the optical signal in the reaction system after forming an aggregated state can be used as a carrier. Those skilled in the art can select the carrier according to actual needs.

[0324] According to some specific embodiments, the first carrier includes first latex microspheres, and the particle size of the first latex microspheres is 40 nm to 500 nm, preferably 80 nm to 400 nm.

[0325] In other embodiments, the second reagent does not contain a carrier, and the second ligand exists in the second reagent in a free form.

[0326] There is no particular limitation on the type of ligands for each reagent in the reagent kit of the present disclosure.

[0327] According to some embodiments, the first ligand and the second ligand are the same. According to other embodiments, the first ligand has a stronger binding ability to the analyte than the second ligand has a stronger binding ability to the analyte.

[0328] According to some embodiments, the first ligand and the second ligand are antigens or antibodies that can bind to the analyte in the test sample. According to other embodiments, the first ligand and the second ligand can be substances that can bind to the analyte in the test sample, and the reaction products can change the system light signal so as to be detected. For example, the first ligand and the second ligand can be, for example, aptamers, enzymes or substrates. Those skilled in the art can make a selection according to actual needs.

[0329] The selection of each ligand can be determined by those skilled in the art based on the actual analyte.

[0330] The amounts of the first ligand and the second ligand in the first reagent and the second reagent can also be determined by those skilled in the art based on the actual analyte.

[0331] In some embodiments, the first reagent further comprises a first buffer and an optional anti-interference agent; and the second reagent further comprises a second buffer.

[0332] The present disclosure does not particularly limit the type and pH value of the first and second buffers. Conventional buffers used for detecting analytes in samples can be used. The selection and determination can be based on the specific sample and analyte.

[0333] Described anti-interference agent can be the material that eliminates for example rheumatoid factor, chylomicron interference, for example blocking agent, surfactant etc.The disclosure is not restricted to the kind of anti-interference agent and the concentration in the first reagent.Can adopt conventional anti-interference agent and consumption thereof, prerequisite is, anti-interference agent is added in the first reagent and can not affect the reaction and detection of measurand in the first reagent and the testing sample.

[0334] If anti-interference agent is not suitable for being added in the first reagent, then described reagent kit further comprises the 3rd reagent.According to an example, the 3rd reagent is a pre-treatment reagent, and described pre-treatment reagent comprises the 3rd buffer agent, and optional anti-interference agent.Can use the 3rd reagent to carry out pre-treatment to the sample to be tested, with for example dilution sample, and eliminate interference alternatively.

[0335] The reagent kit uses three reagents to process the sample to be tested more flexibly without causing adverse effects on the detection, and is more conducive to improving the sensitivity of the detection and widening the linear range of the detection.

[0336] The third buffer can also be any suitable buffer having any suitable pH value.

[0337] In other embodiments, the reagent kit further includes a fourth reagent and / or a fifth reagent.

[0338] The fourth reagent, similar to the first reagent, includes a third ligand bound to the surface of a third microsphere. By selecting the appropriate third microsphere and third ligand, the fourth reagent has a relatively higher sensitivity, making it suitable for detecting samples with low analyte concentrations, thereby further broadening the detection limit.

[0339] The fifth reagent, similar to the second reagent, includes a free fourth ligand or a fourth ligand bound to the surface of a fourth microsphere. By selecting an appropriate fourth ligand, or a combination of fourth microspheres and fourth ligand, the fifth reagent has a relatively high upper limit of detection, making it suitable for detecting samples with high analyte concentrations, thereby further broadening the upper limit of detection.

[0340] The following describes further the features and advantages of various aspects of the present disclosure through specific embodiments.

[0341] Example

[0342] The reagents and sample analyzers used in the Examples and Comparative Examples are as follows:

[0343] Reagents: All reagents not specified are commercially available conventional reagents.

[0344] Sample analyzer: Mindray BS-2800

[0345] Samples to be tested: Calibrators are homemade samples containing the analyte that have been determined by a standard detection system; clinical samples are collected samples; high-concentration samples are samples obtained by diluting the pure sample.

[0346] Example 1. Detection of β2-MG concentration

[0347] The R1 reagent (ie, the first reagent) and the R2 reagent (ie, the second reagent) were prepared according to the following formula.

[0348] Reagent R1: 50 mM Tris buffer pH 7.5, 180 nm latex microspheres conjugated to β2-MG antibody, 40 mg / L

[0349] R2 reagent: 50 mM Tris buffer pH 7.5, 100 nm latex microspheres conjugated to β2-MG antibody 320 mg / L

[0350] A series of standards A to H were tested using a sample analyzer, with water used as a blank control (β2-MG concentrations are shown in Table 1 below). The specific method is as follows: 100 μL of R1 reagent was added to the reaction cup, followed by 2 μL of sample. After 0.5 minutes, the blank absorbance S0L (i.e., the first light signal) was read at a wavelength of 570 nm. After a further 4 minutes of incubation at 37°C, the absorbance S1L (i.e., the second light signal) was read at a wavelength of 570 nm. 100 μL of R2 reagent was added to the reaction cup, and after 0.5 minutes, the blank absorbance S0H (i.e., the third light signal) was read at a wavelength of 570 nm. After a further 5 minutes of incubation, the absorbance S1H (i.e., the fourth light signal) was read at a wavelength of 570 nm. The absorbance and the signal value calculated from the absorbance are both expressed in units of 0.0001A, and units are omitted in the following references.

[0351] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0352] Low concentration segment signal value SL = S1L-S0L;

[0353] The high concentration section signal value SH=S1H-S0H.

[0354] The sum of the first and second reaction analysis values ​​(SL + SH) was obtained, and the two were compared to select the larger one (SL or SH). The test results for each sample are shown in Table 1 below.

[0355] The two sets of signal values ​​(SL and SH) are obtained above and the following three processing methods are performed.

[0356] Method 1: Using multi-point fitting (e.g., spline fitting), the functional relationship between the standard concentration and the signal value SL (calibration data 1) and the functional relationship between the calibrator concentration and the signal value SH (calibration data 2) are obtained, thereby obtaining calibration curves 1 and 2, respectively. See Table 2 below, which shows the relationship between concentration and signal value. After obtaining the SL and SH signal values ​​(i.e., the first and second reaction analysis values, the same below) for the test sample, it is determined whether SL is less than 2098. If so, SL is substituted into calibration curve 1 to obtain the concentration of β2-MG in the test sample. If not, SH is substituted into calibration curve 2 to obtain the concentration of β2-MG in the test sample.

[0357] Method 2: Calibration Curve 3 is generated by summing the signal values ​​SL and SH. The relationship between concentration and signal value is shown in Table 2. After the SL and SH signal values ​​are obtained from the test sample, they are similarly summed. The summed result is then applied to Calibration Curve 3 to determine the concentration of β2-MG in the test sample.

[0358] Method 3: Comparing the signal values ​​SL and SH, the larger of these two values ​​is used to generate calibration curve 4. The relationship between concentration and signal value is shown in Table 2 below. After testing the sample to obtain the SL and SH signal values, the comparison is similarly performed. The larger of these two values ​​is then substituted into calibration curve 4 to determine the β2-MG concentration in the sample.

[0359] Comparative Example 1. Detection of β2-MG concentration

[0360] Prepare R1 reagent (i.e., buffer reagent) and R2 reagent according to the following formula:

[0361] R1 reagent: 50 mM Tris buffer pH 7.5 R2 reagent: 50 mM Tris buffer pH 7.5 180 nm latex microspheres conjugated to β2-MG antibody 40 mg / L 100 nm latex microspheres conjugated to β2-MG antibody 320 mg / L

[0362] A series of standard samples were tested using a sample analyzer. Specifically, 100 μL of R1 reagent was added to the reaction cup, followed by 2 μL of sample, incubated for 4 minutes, and then 100 μL of R2 reagent was added. The blank absorbance, S0, was read at a wavelength of 570 nm 0.5 minutes after addition. After a further 5 minutes of incubation, the absorbance, S1, was read at a wavelength of 570 nm.

[0363] The final signal value obtained according to the two absorbances is: signal value S=S1-S0, as shown in Table 1.

[0364] Further, based on the signal value S, the relationship between the concentration of the sample with known concentration and the signal value S is established to obtain a standard curve. The corresponding relationship between the concentration and the signal value is shown in Table 2 below.

[0365] Table 1 Detected signal values ​​and signal value processing results

[0366] Table 2 Correspondence between concentration and signal value (standard curve table)

[0367] Clinically tested:

[0368] 40 clinical samples were tested using the reagents of Example 1 and Comparative Example 1, and the signal values ​​SL, SH, and S were calculated according to the methods of Example 1 and Comparative Example 1, respectively. The signal values ​​SL and SH were processed according to the three methods in Example 1, and the concentration values ​​of each clinical sample were further obtained on the corresponding standard curves. For the signal value S, the concentration values ​​of each clinical sample were obtained on the corresponding standard curves according to the method in Comparative Example 1. The specific results are shown in Tables 3 and 4 below.

[0369] Table 3 Signal values ​​of clinical samples and signal values ​​after treatment according to the methods of Example 1 and Comparative Example 1

[0370] Table 4. Concentrations and relative deviations of clinical samples obtained based on signal values ​​or signal values ​​after treatment according to the method of Example 1

[0371] As shown in Tables 3-4 above, accurate test results can be obtained by using various signal value processing methods in Example 1. The deviations from the control samples are all within 10%, indicating good consistency.

[0372] Repeatability of low concentration sample detection:

[0373] The above method was used to perform 20 parallel tests on samples with β2-MG concentrations of 0.2 mg / L, 1.0 mg / L, and 20 mg / L, respectively. The detection concentrations of each method were obtained according to the three methods in Comparative Example 1 and Example 1, and the mean, standard deviation SD, and coefficient of variation CV were calculated, as shown in Table 5 below.

[0374] Table 5 Test results of the tested samples

[0375] It can be seen from the above coefficient of variation CV that the detection accuracy and precision of each method in Example 1 are better, especially the sensitivity for low concentration is significantly improved, thereby broadening the linear detection range.

[0376] Example 2. Detection of β2-MG

[0377] Prepare R1 reagent (i.e., the first reagent) and R2 reagent (i.e., the second reagent) according to the following formula:

[0378] Reagent R1: 25 mM phosphate buffer pH 7.4, 190 nm latex microspheres conjugated to rabbit anti-human β2-MG antibody 50 mg / L, blocking agent (rabbit IgG) 1 g / L

[0379] R2 reagent: 25 mM phosphate buffer pH 7.5, 800 mg / L of 80 nm latex microspheres conjugated to goat anti-human β2-MG antibody

[0380] Use a sample analyzer to test each sample. The specific method is: add 100 μL of R1 reagent to the reaction cup, further add 2 μL of sample, read the blank absorbance S0L (i.e., the first light signal) at a wavelength of 570nm 0.5 minutes after addition, continue incubating at 37°C for 4 minutes, and then read the absorbance S1L (i.e., the second light signal). Continue to add 100 μL of R2 reagent to the reaction cup, read the blank absorbance S0H (i.e., the third light signal) at a wavelength of 570nm 0.5 minutes after addition, continue incubating for 5 minutes, and then read the absorbance S1H (i.e., the fourth light signal) at a wavelength of 570nm.

[0381] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0382] Low concentration segment signal value SL = S1L-S0L;

[0383] The high concentration section signal value SH=S1H-S0H.

[0384] The first reaction analysis value SL was compared with three times the second reaction analysis value 3*SH. If SL > 3*SH, SL was used as the signal value for the output result; otherwise, SH was used as the signal value for the output result. The test results for each sample are shown in Table 6 below.

[0385] Further, according to the selected signal value (SL or SH), the concentration of β2-MG in each sample is obtained from the corresponding calibration curve (the corresponding relationship between signal value and concentration is established by calibrators).

[0386] Example 3. Detection of β2-MG

[0387] The first and second reagents of Example 3 were used to test the same samples. The specific method was as follows: 100 μL of R1 reagent was added to the reaction cup, and 2 μL of sample was further added. 0.5 minutes after the addition, the blank absorbance S0L (i.e., the first light signal) was immediately read at a wavelength of 412 nm. After incubation at 37°C for 4 minutes, the absorbance S1L (i.e., the second light signal) was read. 100 μL of R2 reagent was further added to the reaction cup. 0.5 minutes after the addition, the blank absorbance S0H (i.e., the third light signal) was immediately read at a wavelength of 605 nm. After incubation for 5 minutes, the absorbance S1H (i.e., the fourth light signal) was further read.

[0388] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0389] Low concentration segment signal value SL = S1L-S0L;

[0390] The high concentration section signal value SH=S1H-S0H.

[0391] The first reaction analysis value SL was compared with three times the second reaction analysis value 3*SH. If SL > 3*SH, SL was used as the signal value for the output result; otherwise, SH was used as the signal value for the output result. The test results for each sample are shown in Table 6 below.

[0392] Further, according to the selected signal value (SL or SH), the concentration of β2-MG in each sample is obtained from the corresponding calibration curve (the corresponding relationship between signal value and concentration is established by calibrators).

[0393] Example 4. Detection of β2-MG

[0394] The same samples were tested using the first and second reagents of Example 3. Specifically, 100 μL of R1 reagent was added to the reaction cup, followed by 2 μL of sample. After mixing, the mixture was incubated at 37°C for 4 minutes, during which the absorbance was continuously read at 570 nm to obtain the first reaction curve. 100 μL of R2 reagent was then added to the reaction cup, mixed, and incubated at 37°C for 5 minutes. During this time, the absorbance was continuously read at 570 nm to obtain the second reaction curve.

[0395] The absorbance S was obtained at 18 s intervals around 2 minutes of the first reaction curve. 11 and S 12 , calculate the absorbance change rate per minute SL=(S 12 -S 11 ) / (18*60) (i.e., the first reaction analysis value). The absorbance S was obtained at intervals of 18 s around 1.5 minutes of the second reaction curve. 21 and S 22 , calculate the absorbance change rate per minute SH=(S 21 -S 22 ) / (18*60) (i.e., the first reaction analysis value).

[0396] The first reaction analysis value SL was compared with 2.8 times the second reaction analysis value 2.8*SH. If SL > 2.8*SH, SL was used as the signal value for the output result; otherwise, SH was used as the signal value for the output result. The test results for each sample are shown in Table 6 below.

[0397] Further, according to the selected signal value (SL or SH), the concentration of β2-MG in each sample is obtained from the corresponding calibration curve (the corresponding relationship between signal value and concentration is established by calibrators).

[0398] Example 5. Detection of β2-MG

[0399] Using the first reagent and the second reagent of Example 3, the same samples were detected. The specific method is as follows: Add 100 μL of R1 reagent to the reaction cup, further add 2 μL of the sample to the reaction cup, mix and incubate at 37 °C for 4 minutes. During this period, continuously read the absorbance at a wavelength of 570 nm to obtain the first reaction curve. Then continue to add 100 μL of R2 reagent to the reaction cup, mix and incubate at 37 °C for 5 minutes. During this period, continuously read the absorbance at a wavelength of 570 nm to obtain the second reaction curve.

[0400] On the first reaction curve, at an interval of 18 s, calculate the difference between the absorbances Sn and Sn-1 at two adjacent time points. n is the ordinal number of the monitoring points after mixing the R1 reagent and the sample and before adding the R2 reagent. In this example, 5 < n < 16, and n is a natural number. Calculate the absorbance change rate per minute at each monitoring point (Sn - Sn-1) / (18 * 60), and take SL = MAX[(Sn - Sn-1) / (18 * 60)] (i.e., the first reaction analysis value). On the second reaction curve, at an interval of 18 s, calculate the difference between the absorbances Sn and Sn-1 at two adjacent time points. n is the ordinal number of the monitoring points after adding the R2 reagent and until the end of incubation. In this example, 18 < n < 33, and n is a natural number. Calculate the absorbance change rate per minute at each monitoring point (Sn - Sn-1) / (18 * 60), and take SH = MAX[(Sn - Sn-1) / (18 * 60)] (i.e., the second reaction analysis value).

[0401] Compare the first reaction analysis value SL with the second reaction analysis value SH. When SL > SH, use SL as the signal value of the output result; otherwise, use SH as the signal value of the output result. The detection results of each sample are shown in Table 6 below.

[0402] Further, according to the selected signal value (SL or SH), obtain the concentration of β2-MG in each sample from the corresponding calibration curve (establishing the corresponding relationship between the signal value and the concentration through calibration samples).

[0403] Comparative Example 2. Detection of β2-MG

[0404] Prepare the R1 reagent (i.e., buffer reagent) and the R2 reagent according to the following formula

[0405] R1 reagent: 50 mM Tris buffer solution, pH 7.5

[0406] R2 reagent: 50 mM Tris buffer pH 7.5 210 nm latex microspheres conjugated to β2-MG antibody 100 mg / L 80 nm latex microspheres conjugated to β2-MG antibody 800 mg / L

[0407] Each sample was tested using a sample analyzer. Specifically, 100 μL of R1 reagent was added to the reaction cup, followed by 2 μL of sample. The mixture was incubated at 37°C for 4 minutes. Then, 100 μL of R2 reagent was added. The blank absorbance (S0) was immediately read at 570 nm 0.5 minutes after addition. After a further 5 minutes of incubation at 37°C, the absorbance (S1) was read at 570 nm.

[0408] The final signal value obtained according to the two absorbances is: signal value S=S1-S0, as shown in Table 6.

[0409] Further, according to the signal value S, the concentration of β2-MG in each sample is obtained from a calibration curve (the corresponding relationship between signal value and concentration is established by using a calibrator).

[0410] Table 6

[0411] Generally speaking, for the same low-concentration sample, the higher the signal value (minus the signal when the sample concentration is 0), the higher the sensitivity of the method used; for high-concentration samples, the signal value can continue to increase when the concentration increases (that is, the concentration-signal curve is monotonically increasing), which reflects that the detection upper limit of the method used is higher. As can be seen from the above table, the detection sensitivity of each embodiment is significantly improved compared with Comparative Example 2, thereby improving the overall detection range.

[0412] Example 6. Detection of β2-MG

[0413] Prepare R1 reagent (i.e., the first reagent) and R2 reagent (i.e., the second reagent) according to the following formula:

[0414] Reagent R1: 50 mM Tris buffer pH 7.5, 100 nm latex microspheres conjugated to β2-MG antibody, 200 mg / L

[0415] R2 reagent: 50 mM Tris buffer pH 7.5, 100 nm latex microspheres conjugated to β2-MG antibody 200 mg / L

[0416] Determination of the optimal detection wavelength:

[0417] The absorbance of a sample containing approximately 0.375 mg / L of β2-MG was measured 20 times using multiple detection wavelengths within the range of 340 nm to 850 nm. The mean value, standard deviation SD, and coefficient of variation CV of the detection at each wavelength were calculated and shown in Table 7 below.

[0418] Table 7

[0419] According to Table 7 above, 412 nm, which has the smallest coefficient of variation, was used as the detection wavelength after adding the first reagent in the low concentration range. A longer wavelength was used after adding the second reagent to avoid exceeding the instrument's detection limit for high-concentration samples, so 570 nm was used as the detection wavelength.

[0420] Each sample was tested using a sample analyzer. Specifically, 100 μL of R1 reagent was added to the reaction cuvette, followed by 2 μL of sample. After 0.5 minutes, the blank absorbance S0L (i.e., the first light signal) was immediately read at 412 nm. After incubation at 37°C for approximately 4 minutes, the absorbance S1L (i.e., the second light signal) was read. 100 μL of R2 reagent was then added to the reaction cuvette. After 0.5 minutes, the blank absorbance S0H (i.e., the third light signal) was immediately read at 505 nm. After incubation for approximately 5 minutes, the absorbance S1H (i.e., the fourth light signal) was read at 570 nm.

[0421] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0422] Low concentration segment signal value SL = S1L-S0L;

[0423] The high concentration section signal value SH=S1H-S0H.

[0424] The first reaction analysis value SL is compared with the signal threshold value 6000. If SL < 6000, SL is used as the signal value of the output result. Otherwise, SH is used as the signal value of the output result. The test results of each sample are shown in Table 8 below.

[0425] Further, according to the selected signal value (SL or SH), the concentration of β2-MG in each sample can be obtained from the corresponding calibration curve (the corresponding relationship between signal value and concentration is established by calibrators).

[0426] Comparative Example 3. Detection of β2-MG

[0427] Prepare R1 reagent (i.e., buffer reagent) and R2 reagent according to the following formula:

[0428] Reagent R1: 50 mM Tris buffer pH 7.5

[0429] R2 reagent: 50 mM Tris buffer pH 7.5, 100 nm latex microspheres conjugated to β2-MG antibody, 1 g / L

[0430] Each sample was tested using a sample analyzer. Specifically, 160 μL of R1 reagent was added to the reaction cup, followed by 2 μL of sample. The mixture was incubated at 37°C for 4 minutes, followed by 40 μL of R2 reagent. The blank absorbance (S0) was immediately read at 450 nm 0.5 minutes after addition. After a further 5 minutes of incubation at 37°C, the absorbance (S1) was read at 450 nm. (Note: At the optimal detection wavelength of 412 nm determined in the previous example, high-concentration samples exceeded the instrument's detection limit, so 450 nm was selected for testing.)

[0431] The final signal value obtained according to the two absorbances is: signal value S=S1-S0, as shown in Table 8.

[0432] Further, according to the signal value S, the concentration of β2-MG in each sample is obtained from a calibration curve (the corresponding relationship between signal value and concentration is established by using a calibrator).

[0433] Table 8

[0434] Example 7. Detection of CRP

[0435] The R1 reagent (ie, the first reagent) and the R2 reagent (ie, the second reagent) were prepared according to the following formula.

[0436] R1 reagent: 20 mM phosphate buffer pH 7.5, 210 nm latex microspheres conjugated to CRP antibody, 100 mg / L

[0437] R2 reagent: 20 mM phosphate buffer pH 7.5, 60 nm latex microspheres conjugated to CRP antibody, 600 mg / L

[0438] Use a sample analyzer to test each sample. The specific method is: add 180 μL of R1 reagent to the reaction cup, add 3.6 μL of sample and mix, immediately read the blank absorbance S0L (i.e., the first light signal) at a wavelength of 570 nm after 0.5 minutes, continue incubating at 37°C for 4 minutes, and then read the absorbance S1L (i.e., the second light signal) at a wavelength of 570 nm. Continue to add 60 μL of R2 reagent to the reaction cup and mix, incubate at 37°C for 5 minutes, and then read the absorbance S1H (i.e., the fourth light signal) at a wavelength of 570 nm.

[0439] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0440] Low concentration segment signal value SL = S1L-S0L;

[0441] The high concentration segment signal value SH=S1H-S0L.

[0442] The specific signal values ​​are shown in Table 9.

[0443] Example 8. Detection of CRP

[0444] The reagents were prepared according to the ligands of Example 7, and each sample was tested using a sample analyzer. Specifically, 180 μL of R1 reagent was added to the reaction cup, and 3.6 μL of sample was added and mixed. After 0.5 minutes, the blank absorbance S0L (i.e., the first light signal) was immediately read at a wavelength of 450 nm. After incubation at 37°C for 4 minutes, the absorbance S1L (i.e., the second light signal) was read at a wavelength of 450 nm, and the absorbance S0H (i.e., the third light signal) was read at a wavelength of 700 nm. 60 μL of R2 reagent was then added to the reaction cup, mixed, and after incubation at 37°C for 5 minutes, the absorbance S1H (i.e., the fourth light signal) was read at a wavelength of 700 nm.

[0445] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0446] Low concentration segment signal value SL = S1L-S0L;

[0447] The high concentration section signal value SH=S1H-S0H.

[0448] The specific signal values ​​are shown in Table 9.

[0449] Example 9. Detection of CRP

[0450] The reagents were prepared according to the ligands of Example 7, and each sample to be tested was tested using a sample analyzer. The specific method was as follows: 80 μL of R1 reagent was added to the reaction cup, and 3.6 μL of sample was added and mixed. After 0.5 minutes, the blank absorbance S0L (i.e., the first light signal) was immediately read at a wavelength of 570 nm. After incubation at 37°C for 4 minutes, the absorbance S1L (i.e., the second light signal) was read at a wavelength of 570 nm. 160 μL of R2 reagent was further added to the reaction cup and mixed. After 0.5 minutes, the blank absorbance S0H (i.e., the third light signal) was immediately read at a wavelength of 570 nm. After incubation at 37°C for 5 minutes, the absorbance S1H (i.e., the fourth light signal) was read at a wavelength of 570 nm.

[0451] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0452] Low concentration segment signal value SL = S1L-S0L;

[0453] The high concentration section signal value SH=S1H-S0H.

[0454] The specific signal values ​​are shown in Table 9.

[0455] Example 10. Detection of CRP

[0456] The R1 reagent (ie, the first reagent) and the R2 reagent (ie, the second reagent) were prepared according to the following formula: Compared with Example 7, the content of latex microspheres in the R2 reagent was reduced by 62.5%.

[0457] R1 reagent: 20 mM phosphate buffer pH 7.5, 210 nm latex microspheres conjugated to CRP antibody, 100 mg / L

[0458] R2 reagent: 20 mM phosphate buffer pH 7.5, 60 nm latex microspheres conjugated to CRP antibody 225 mg / L

[0459] Use a sample analyzer to test each sample to be tested. The specific method is: add 80 μL of R1 reagent to the reaction cup, add 1.6 μL of sample and mix, read the blank absorbance S0L (i.e., the first light signal) at a wavelength of 570 nm immediately after 0.5 minutes, incubate at 37°C for 4 minutes, and then read the absorbance S1L (i.e., the second light signal) at a wavelength of 570 nm. Continue to add 160 μL of R2 reagent to the reaction cup and mix, read the blank absorbance S0H (i.e., the third light signal) at a wavelength of 570 nm immediately after 0.5 minutes, continue to incubate at 37°C for 5 minutes, and then read the absorbance S1H (i.e., the fourth light signal) at a wavelength of 570 nm.

[0460] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0461] Low concentration segment signal value SL = S1L-S0L;

[0462] The high concentration segment signal value SH=S1H-S0L.

[0463] The specific signal values ​​are shown in Table 9.

[0464] Comparative Example 4. Detection of CRP

[0465] Reagents were prepared according to the recipe in Example 7, and each sample was tested using a sample analyzer. Specifically, 180 μL of R1 reagent was added to a reaction cup, followed by 3.6 μL of sample, and the mixture was mixed. After 0.5 minutes, the blank absorbance S0 (i.e., the first light signal) was immediately read at a wavelength of 570 nm. After a further 4 minutes of incubation at 37°C, 60 μL of R2 reagent was added to the reaction cup, mixed, and after 5 minutes of incubation at 37°C, the absorbance S1 (i.e., the fourth light signal) was read at a wavelength of 570 nm.

[0466] According to the above absorbance, the signal value S is obtained:

[0467] Signal value S=S1-S0.

[0468] The specific signal values ​​are shown in Table 9.

[0469] Table 9

[0470] As can be seen from Table 9 above, Comparative Example 4 only detects the absorbance S0 when the sample is mixed with the first reagent and detects the absorbance S1 after the second reagent is added and the incubation is completed, and the signal value is obtained by the difference between the two. When detecting samples containing high concentrations of the analyte, a hook effect occurs. However, Examples 7 to 10 respectively detect the signal value of the first stage reaction after adding the first reagent and the signal value of the second stage reaction after further adding the second reagent. A more flexible detection method (such as Example 8 using two wavelengths for detection, Examples 9 and 10 adjusting the volume of the added reagent and sample to increase the analyte concentration of the first stage reaction, or reducing the analyte concentration of the second stage reaction) can be used to improve the sensitivity of detection of low-concentration analyte samples (the SL signal value is significantly increased relative to Comparative Example 4), and / or avoid the hook effect when detecting high-concentration analyte samples, thereby expanding the linear range of detection.

[0471] Comparative Example 5. Detection of CRP

[0472] The R1 reagent (buffer) and the R2 reagent without latex particles were prepared according to the following formula.

[0473] R1 reagent: 50mM Tris buffer pH7.5 PEG (PEG6000) 55g / L

[0474] R2 reagent: 50mM Tris buffer pH 7.5 CRP antibody 10g / L

[0475] Each sample was tested using a sample analyzer. Specifically, 200 μL of R1 reagent was added to a reaction cup, followed by 8 μL of sample, followed by incubation at 37°C for 4 minutes, and then the absorbance (S0) was read at 340 nm. Furthermore, 60 μL of R2 reagent was added to the reaction cup, mixed, and then the absorbance (S1) was read at 340 nm after incubation at 37°C for 4 minutes.

[0476] According to the above absorbance, the signal value S is obtained:

[0477] Signal value S=S1-S0.

[0478] The results are shown in Table 10.

[0479] Comparative Example 6. Detection of CRP

[0480] The R1 reagent (buffer) and the R2 reagent containing latex particles of two sizes were prepared according to the following formula.

[0481] R1 reagent: 20mM phosphate buffer pH7.5 PEG (PEG6000) 55g / L

[0482] R2 reagent: 20 mM phosphate buffer pH 7.5, 190 nm latex microspheres conjugated to CRP antibody at 100 mg / L, 70 nm latex microspheres conjugated to CRP antibody at 1000 mg / L

[0483] Each sample was tested using a sample analyzer. Specifically, 100 μL of R1 reagent was added to a reaction cup, followed by 2 μL of sample, and the mixture was mixed. After incubation at 37°C for 4 minutes, 100 μL of R2 reagent was added to the reaction cup and mixed thoroughly. After 0.5 minutes, the absorbance (S0) was immediately read at a wavelength of 570 nm. After incubation at 37°C for 5 minutes, the absorbance (S1) was read at a wavelength of 570 nm.

[0484] According to the above absorbance, the signal value S is obtained:

[0485] Signal value S=S1-S0.

[0486] The results are shown in Table 10.

[0487] Example 11. Detection of CRP

[0488] The R1 reagent (ie, the first reagent) and the R2 reagent (ie, the second reagent) not containing latex particles were prepared according to the following formulas.

[0489] R1 reagent: 20mM phosphate buffer pH 7.5, PEG (PEG6000) 15g / L, 100nm latex microspheres conjugated to CRP antibody 150mg / L

[0490] R2 reagent: 20mM phosphate buffer pH 7.5 CRP antibody 10g / L

[0491] Each sample was tested using a sample analyzer. Specifically, 150 μL of R1 reagent was added to a reaction cuvette, followed by 10 μL of sample, and the mixture was immediately mixed. After 0.5 minutes, the blank absorbance (S0L) was read at a wavelength of 570 nm. After incubation at 37°C for 4 minutes, the absorbance (S1L) was read at a wavelength of 570 nm, and the absorbance (S0H) was read at a wavelength of 340 nm. Furthermore, 50 μL of R2 reagent was added to the reaction cuvette, mixed, and after incubation at 37°C for 5 minutes, the absorbance (S1H) was read at a wavelength of 340 nm.

[0492] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0493] Low concentration segment signal value SL = S1L-S0L;

[0494] The high concentration section signal value SH=S1H-S0H×160 / 210.

[0495] 160 / 210 is the volume correction factor

[0496] The test results are shown in Table 10 below.

[0497] Table 10

[0498] As can be seen from the table above, Comparative Example 5 uses a non-latex-enhanced immunoturbidimetric method with poor sensitivity; Comparative Example 6 uses latex microspheres of two particle sizes, which significantly increases sensitivity but exhibits a hook effect at high concentrations. However, the method of Example 11 improves both sensitivity and the upper limit of detection.

[0499] Example 12. Detection of CRP

[0500] The R1 reagent (ie, the first reagent), the R2 reagent (ie, the second reagent), and the R3 reagent (ie, the third reagent) were prepared according to the following formula.

[0501] R1 reagent: 20 mM phosphate buffer pH 8.0, 100 nm latex microspheres conjugated to CRP antibody, 100 mg / L

[0502] R2 reagent: 50mM Tris buffer pH 7.5 CRP antibody 10g / L

[0503] R3 reagent: 50mM Tris buffer pH 7.0 PEG (PEG6000) 55g / L Blocking agent (rabbit IgG) 1g / L

[0504] Use a sample analyzer to test each sample to be tested. The specific method is: add 160 μL of R3 reagent to the reaction cup, add 10 μL of sample, mix well, incubate at 37°C for 4 minutes, add 50 μL of R1 reagent and mix, immediately read the blank absorbance S0L (i.e., the first light signal) at a wavelength of 340nm after 0.5 minutes, continue to incubate at 37°C for 5 minutes, and then read the absorbance S1L (i.e., the second light signal) at a wavelength of 340nm. Continue to add 50 μL of R2 reagent to the reaction cup and mix well. After incubating at 37°C for 4 minutes, read the absorbance S1H (i.e., the fourth light signal) at a wavelength of 340nm.

[0505] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0506] Low concentration segment signal value SL = S1L-S0L;

[0507] The high concentration section signal value SH=S1H-S0L×220 / 270.

[0508] Where 220 / 270 is the volume correction factor.

[0509] The test results are shown in Table 11 below.

[0510] Example 13. Detection of CRP

[0511] According to the same formula as in Example 12, the R1 reagent (ie, the first reagent), the R2 reagent (ie, the second reagent), and the R3 reagent (ie, the third reagent) were prepared.

[0512] Use a sample analyzer to detect each sample to be tested. The specific method is: add 80 μL of R1 reagent to the reaction cup, read the blank absorbance S0L (i.e., the first light signal) at a wavelength of 570 nm, then add 10 μL of sample to the reaction cup, mix, incubate at 37 ° C for 4 minutes, and read the absorbance S1L (i.e., the second light signal) at a wavelength of 570 nm. Continue to add 130 μL of R3 reagent to the reaction cup and mix, incubate at 37 ° C for 5 minutes, and read the absorbance S0H (i.e., the third light signal) at a wavelength of 340 nm. Further add 50 μL of R2 reagent to the reaction cup and mix, incubate at 37 ° C for 4 minutes, and read the absorbance S1H (i.e., the fourth light signal) at a wavelength of 340 nm.

[0513] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the second reaction analysis value) are obtained respectively:

[0514] Low concentration signal value SL = S1L - S0L × 80 / 90. ;

[0515] The high concentration section signal value SH=S1H-S0L×220 / 270.

[0516] Among them, 80 / 90 and 220 / 270 are volume correction factors.

[0517] The test results are shown in Table 11 below.

[0518] Example 14. Detection of CRP

[0519] The R1 reagent (ie, the first reagent), the R2 reagent (ie, the second reagent), and the R3 reagent (ie, the third reagent) were prepared according to the following formula.

[0520] Reagent R1: 50 mM Tris buffer pH 7.5, 210 nm latex microspheres conjugated to CRP antibody 60 mg / L

[0521] R2 reagent: 50 mM Tris buffer pH 7.5, 60 nm latex microspheres conjugated to CRP antibody 500 mg / L

[0522] R3 reagent: 50mM Tris buffer pH 7.5 CRP antibody 5g / L

[0523] Use a sample analyzer to test each sample to be tested. The specific method is: add 120 μL of R1 reagent to the reaction cup, add 10 μL of sample, mix well, and immediately read the blank absorbance S0L (i.e., the first light signal) at a wavelength of 570 nm after 0.5 minutes. After incubation at 37 ° C for 4 minutes, read the absorbance S1L (i.e., the second light signal) at a wavelength of 570 nm. Add 40 μL of R2 reagent and mix, and immediately read the blank absorbance S0M (i.e., the third light signal) at a wavelength of 570 nm after 0.5 minutes. After continuing to incubate at 37 ° C for 5 minutes, read the absorbance S1M (i.e., the fourth light signal) at a wavelength of 570 nm, and at the same time read the absorbance S0H (i.e., the fifth light signal) at a wavelength of 340 nm. 50 μL of R3 reagent was added to the reaction cup and mixed. After incubation at 37° C. for 4 minutes, the absorbance S1H (ie, the sixth light signal) was read at a wavelength of 340 nm.

[0524] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value), the medium concentration segment signal value SM (i.e., the second reaction analysis value) and the high concentration segment signal value SH (i.e., the third reaction analysis value) are obtained respectively:

[0525] Low concentration segment signal value SL = S1L-S0L;

[0526] The signal value of the medium concentration section SM=S1M-S0M;

[0527] The high concentration section signal value SH=S1H-S0H×170 / 220.

[0528] 170 / 220 is the volume correction factor

[0529] The test results are shown in Table 11 below.

[0530] Table 11

[0531] As can be seen from Table 11 above, the use of three reagents can more flexibly detect samples, thereby achieving the effects of eliminating interference, diluting samples, and further broadening the detection limit.

[0532] Comparative Example 7. Non-latex enhancement method for detecting RF

[0533] Each sample was tested using the Mindray Rheumatoid Factor (RF II) Assay Kit (Immunoturbidimetry) 105-004670-00 using a sample analyzer. The specific method is as follows: 180 μL of R1 reagent was added to a reaction cuvette, followed by 6 μL of sample. The mixture was incubated at 37°C for 4 minutes, and the absorbance (S0) was read at a wavelength of 340 nm. Furthermore, 36 μL of R2 reagent was added to the reaction cuvette, and the mixture was incubated at 37°C for 4 minutes. The absorbance (S1) was read at a wavelength of 340 nm.

[0534] Signal value S = S1 - S0 × 186 / 222

[0535] The test results are shown in Table 12 below.

[0536] Comparative Example 8. Detection of RF by Latex Enhancement Method

[0537] Each sample was tested using a Mindray rheumatoid factor (RF) assay kit (latex-enhanced immunoturbidimetry) 105-001546-00 using a sample analyzer. The specific method is as follows: 120 μL of R1 reagent was added to a reaction cup, followed by 4 μL of sample. The mixture was incubated at 37°C for 4 minutes. 40 μL of R2 reagent was then added to the reaction cup. The absorbance (S0) was measured at 570 nm. The mixture was incubated at 37°C for 4 minutes, and the absorbance (S1) was measured at 570 nm.

[0538] Signal value S = S1 - S0

[0539] The test results are shown in Table 12 below.

[0540] Example 15. Detection of RF using two reagents

[0541] The R1 reagent (ie, the first reagent) and the R2 reagent (ie, the second reagent) were prepared as follows.

[0542] Reagent R1 was prepared by mixing reagent R1 and reagent R2 in the kit of Comparative Example 8 at a volume ratio of 7:1. Reagent R2 was also prepared by mixing reagent R2 in the kit of Comparative Example 8. The resulting reagent R1 was a reagent containing latex microspheres diluted with a diluent, while reagent R2 was an undiluted reagent containing latex microspheres.

[0543] Each sample was tested using a sample analyzer. Specifically, 120 μL of R1 reagent was added to the reaction cup, and the absorbance (S0L) was read at 380 nm. Then, 4 μL of sample was added, mixed, and incubated at 37°C for 4 minutes. The absorbance (S1L) (i.e., the second light signal) was read at 380 nm. 40 μL of R2 reagent was added, mixed, and incubated at 37°C for 5 minutes. The absorbance (S1H) (i.e., the fourth light signal) was read at 380 nm.

[0544] According to the above absorbance, the low concentration segment signal value SL (i.e., the first reaction analysis value) and the high concentration segment signal value SH (i.e., the third reaction analysis value) are obtained respectively:

[0545] Low concentration segment signal value SL = S1L-S0L×120 / 124;

[0546] The high-concentration segment signal value SH=S1H-S0H×124 / 164.

[0547] Among them, 120 / 124 and 124 / 164 are volume correction factors

[0548] The signal value of SL+SH is used as the output result.

[0549] The test results are shown in Table 12 below.

[0550] Table 12

[0551] As can be seen from Table 12 above, the detection sensitivity of Comparative Example 7 using the non-latex enhancement method is low, while the hook effect of Comparative Example 8 using the conventional latex enhancement method is obvious for high-concentration samples. However, Example 15 uses the method of the present disclosure and achieves both high sensitivity and a high detection limit.

[0552] The above description is only a preferred embodiment of the present disclosure and does not limit the scope of the present disclosure. All equivalent structural transformations made by using the contents of the present disclosure and the drawings under the inventive concept of the present disclosure, or direct / indirect application in other related technical fields are included in the protection scope of the present disclosure.

Claims

1. A sample analyzer, comprising: A sample component, a reagent component, a measurement component, and a controller, wherein, the sample component includes a sample carrier component for carrying a sample to be measured and a sample dispensing mechanism; the reagent component includes a reagent carrier component for carrying a reagent and a reagent dispensing mechanism; the measurement component includes a reaction component and an optical measurement component, wherein the reaction component has at least one placement position for placing a reaction cup; the controller is configured to perform the following operations: control the reagent dispensing mechanism to aspirate a first reagent and provide it to the reaction cup, wherein the first reagent includes a first carrier with a first ligand bound to its surface that can bind to the analyte in the sample to be measured, control the sample dispensing mechanism to aspirate the sample to be measured and provide it to the reaction cup to obtain a first reaction system, and control the first reaction system to react for a first predetermined time; control the reagent dispensing mechanism to further aspirate a second reagent and provide it to the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand that can bind to the analyte, and control the second reaction system to react for a second predetermined time; control the optical measurement component to obtain at least two optical signals; obtain a first reaction analysis value of the first reaction system based on at least one optical signal, and obtain a second reaction analysis value of the second reaction system based on at least another optical signal; and make a judgment based on the first reaction analysis value and / or the second reaction analysis value, and select one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be measured, or select the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be measured.

2. A sample analyzer, comprising: A sample component, a reagent component, a measurement component, and a controller, wherein, the sample component includes a sample carrier component for carrying a sample to be measured and a sample dispensing mechanism; the reagent component includes a reagent carrier component for carrying a reagent and a reagent dispensing mechanism; the measurement component includes a reaction component and an optical measurement component, wherein the reaction component has at least one placement position for placing a reaction cup; the controller is configured to perform the following operations: control the reagent dispensing mechanism to aspirate a first reagent and provide it to the reaction cup, wherein the first reagent includes a first carrier with a first ligand bound to its surface that can bind to the analyte in the sample to be measured, control the sample dispensing mechanism to aspirate the sample to be measured and provide it to the reaction cup to obtain a first reaction system, and control the first reaction system to react for a first predetermined time; control the reagent dispensing mechanism to further aspirate a second reagent and provide it to the reaction cup to obtain a second reaction system, wherein the second reagent includes a second ligand that can bind to the analyte, and control the second reaction system to react for a second predetermined time; control the optical measurement component to obtain at least two optical signals; obtain a first reaction analysis value of the first reaction system based on at least one optical signal, and obtain a second reaction analysis value of the second reaction system based on at least another optical signal; and An analysis result of the analyte in the sample to be tested is obtained based on the sum of the first reaction analysis value and the second reaction analysis value.

3. The sample analyzer according to any one of claims 1 or 2, wherein, The controlling the optical measurement component to obtain at least two optical signals includes: obtaining the at least one optical signal after controlling the reagent dispensing mechanism to aspirate the first reagent and provide it to the reaction cup and before further controlling the reagent dispensing mechanism to aspirate the second reagent and provide it to the reaction cup, and obtaining the at least another optical signal after controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it to the reaction cup; or, obtaining the at least two optical signals after controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it to the reaction cup.

4. The sample analyzer according to claim 1, wherein, The making a judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested includes: comparing the first reaction analysis value and the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested; Preferably, comparing the first reaction analysis value and the second reaction analysis value, and selecting the larger one of the first reaction analysis value and the second reaction analysis value according to the comparison result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to the larger one of the first reaction analysis value and the second reaction analysis value to obtain the analysis result of the analyte in the sample to be tested.

5. The sample analyzer according to claim 1, wherein, The making a judgment based on the first reaction analysis value and / or the second reaction analysis value, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested includes: judging whether the first reaction analysis value and / or the second reaction analysis value is within a preset range, and selecting one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested, or selecting the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value according to the judgment result to obtain the analysis result of the analyte in the sample to be tested.

6. The sample analyzer according to any one of claims 1 to 5, wherein The controlling the optical measurement component to obtain at least two optical signals includes: Obtain the at least one optical signal at a first detection wavelength and obtain the at least one other optical signal at a second detection wavelength; Preferably, the first detection wavelength and the second detection wavelength are different; More preferably, the first detection wavelength and the second detection wavelength are selected from 320 nm to 860 nm.

7. The sample analyzer according to any one of claims 1 to 6, wherein, The controlling the optical measurement component to obtain at least two optical signals includes: Obtaining a first optical signal after controlling the reagent dispensing mechanism to aspirate the first reagent and provide it into the reaction cup, or, after controlling the reagent dispensing mechanism to aspirate the first reagent and provide it into the reaction cup and controlling the test sample dispensing mechanism to aspirate the test sample and provide it into the reaction cup, and before the start of the first predetermined time, obtain the first optical signal, Obtaining a second optical signal after the end of the first predetermined time and before controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it into the reaction cup, Obtaining a third optical signal after controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it into the reaction cup and before the start of the second predetermined time, and Obtaining a fourth optical signal after the end of the second predetermined time; and The obtaining the first reaction analysis value of the first reaction system based on at least one optical signal and obtaining the second reaction analysis value of the second reaction system based on at least one other optical signal includes: Obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal.

8. The sample analyzer according to any one of claims 1 to 6, wherein, The controlling the optical measurement component to obtain at least two optical signals includes: Obtaining a second optical signal after the end of the first predetermined time and before controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it into the reaction cup, and Obtaining a fourth optical signal after the end of the second predetermined time; and The obtaining the first reaction analysis value of the first reaction system based on at least one optical signal and obtaining the second reaction analysis value of the second reaction system based on at least one other optical signal includes: Obtaining the first reaction analysis value of the first reaction system based on the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the second optical signal.

9. The sample analyzer according to any one of claims 1 to 6, wherein, The controlling the optical measurement component to obtain at least two optical signals includes: Obtaining a third optical signal after controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it into the reaction cup and before the start of the second predetermined time, and Obtaining a fourth optical signal after the end of the second predetermined time; and Obtaining the first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining the second reaction analysis value of the second reaction system based on at least another optical signal, includes: Obtaining the first reaction analysis value of the first reaction system based on the third optical signal, and obtaining the second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the third optical signal.

10. The sample analyzer according to any one of claims 1 to 6, wherein Controlling the optical measurement component to obtain at least two optical signals includes: Obtaining a first optical signal after controlling the reagent dispensing mechanism to aspirate the first reagent and provide it to the reaction cup, or, after controlling the reagent dispensing mechanism to aspirate the first reagent and provide it to the reaction cup and controlling the test sample dispensing mechanism to aspirate the test sample and provide it to the reaction cup, and before the start of the first predetermined time, obtaining the first optical signal, Obtaining a second optical signal after the end of the first predetermined time and before controlling the reagent dispensing mechanism to further aspirate the second reagent and provide it to the reaction cup, and Obtaining a fourth optical signal after the end of the second predetermined time; and Obtaining the first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining the second reaction analysis value of the second reaction system based on at least another optical signal, includes: Obtaining the first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining the second reaction analysis value of the second reaction system based on the first optical signal and the fourth optical signal or based on the second optical signal and the fourth optical signal.

11. The sample analyzer according to any one of claims 1 to 6, wherein Controlling the optical measurement component to obtain at least two optical signals includes: Collecting a plurality of the optical signals during at least one period from the start to the end of the first predetermined time, so as to obtain a first reaction curve, and Collecting a plurality of the optical signals during at least one period from the start to the end of the second predetermined time, so as to obtain a second reaction curve; and Obtaining the first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining the second reaction analysis value of the second reaction system based on at least another optical signal, includes: Obtaining the first reaction analysis value of the first reaction system based on the first reaction curve, and obtaining the second reaction analysis value of the second reaction system based on the second reaction curve, Preferably, obtaining the first reaction analysis value of the first reaction system based on the first reaction curve or based on a characteristic value of the first reaction curve, and obtaining the second reaction analysis value of the second reaction system based on the second reaction curve or based on a characteristic value of the second reaction curve.

12. A sample analyzer, comprising: A sample component, a reagent component, a measurement component, and a controller, wherein The sample component includes a sample carrier component for carrying a test sample and a sample dispensing mechanism; The reagent component includes a reagent carrier component for carrying reagents and a reagent dispensing mechanism; The measurement component includes a reaction component and an optical measurement component, wherein the reaction component has at least one placement position for placing reaction cups; The controller is configured to perform the following operations: Control the reagent dispensing mechanism to aspirate a first reagent and provide it into the reaction cup, wherein the first reagent includes a first carrier with a first ligand bound to its surface that can bind to the analyte in the test sample, control the sample dispensing mechanism to aspirate the test sample and provide it into the reaction cup to obtain a first reaction system, and control the first reaction system to react for a first predetermined time; Control the optical measurement component to obtain at least one optical signal; Obtain a first reaction analysis value of the first reaction system based on the at least one optical signal; Make a judgment based on the first reaction analysis value, When the judgment result meets the preset conditions, obtain the analysis result of the analyte in the test sample based on the first reaction analysis value; When the judgment result does not meet the preset conditions, control the reagent dispensing mechanism to further aspirate a second reagent and provide it into the reaction cup to obtain a second reaction system, the second reagent includes a second ligand that can bind to the analyte, control the second reaction system to react for a second predetermined time, Control the optical measurement component to obtain at least another optical signal, Obtain a second reaction analysis value of the second reaction system based on at least the at least another optical signal, and Obtain the analysis result of the analyte in the test sample based on at least the second reaction analysis value.

13. The sample analyzer according to claim 12, wherein, The making a judgment based on the first reaction analysis value includes: Judge whether the first reaction analysis value is within a preset range, If so, obtain the analysis result of the analyte in the test sample based on the first reaction analysis value or the optical signal corresponding to the first reaction analysis value; If not, control the reagent dispensing mechanism to further aspirate a second reagent and provide it into the reaction cup to obtain a second reaction system, the second reagent includes a second ligand that can bind to the analyte, control the second reaction system to react for a second predetermined time, Control the optical measurement component to obtain the at least another optical signal, Obtain a second reaction analysis value of the second reaction system based on at least the at least another optical signal, and Obtain the analysis result of the analyte in the test sample based on at least the second reaction analysis value.

14. The sample analyzer according to claim 12 or 13, wherein, The obtaining the analysis result of the analyte in the test sample based on at least the second reaction analysis value includes: Obtain the analysis result of the analyte in the test sample based on the first reaction analysis value and the second reaction analysis value.

15. The sample analyzer according to claim 14, wherein, The obtaining the analysis result of the analyte in the test sample based on at least the first reaction analysis value and the second reaction analysis value includes: Judgment is made based on the first reaction analysis value and / or the second reaction analysis value, and according to the judgment result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the judgment result, the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested.

16. The sample analyzer according to claim 14, wherein, The obtaining of the analysis result of the analyte in the sample to be tested based on the first reaction analysis value and the second reaction analysis value includes: Obtaining the analysis result of the analyte in the sample to be tested based on the sum result of the first reaction analysis value and the second reaction analysis value.

17. The sample analyzer according to any one of claims 1 to 16, wherein, The optical signal is a scattered light signal and / or a transmitted light signal.

18. A sample analysis method, the method includes: Controlling the sample to be tested to be mixed with a first reagent to obtain a first reaction system and allowing the first reaction system to react for a first predetermined time, wherein the first reagent includes a first carrier with a first ligand capable of binding to the analyte in the sample to be tested bound to its surface; Controlling a second reagent to be mixed with the first reaction system to obtain a second reaction system and allowing the second reaction system to react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte; Obtaining at least two optical signals; Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and Judgment is made based on the first reaction analysis value and / or the second reaction analysis value, and according to the judgment result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the judgment result, the optical signal corresponding to one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested.

19. A sample analysis method, the method includes: Controlling the sample to be tested to be mixed with a first reagent to obtain a first reaction system and allowing the first reaction system to react for a first predetermined time, wherein the first reagent includes a first carrier with a first ligand capable of binding to the analyte in the sample to be tested bound to its surface; Controlling a second reagent to be mixed with the first reaction system to obtain a second reaction system and allowing the second reaction system to react for a second predetermined time, wherein the second reagent includes a second ligand capable of binding to the analyte; Obtaining at least two optical signals; Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal; and Obtaining the analysis result of the analyte in the sample to be tested based on the sum result of the first reaction analysis value and the second reaction analysis value.

20. The sample analysis method according to claim 18 or 19, wherein, The obtaining of at least two optical signals includes: After controlling the mixing of the sample to be tested and the first reagent and before controlling the mixing of the second reagent and the first reaction system, at least one optical signal is obtained, and after controlling the mixing of the second reagent and the first reaction system, at least another optical signal is obtained; or, After controlling the mixing of the second reagent and the first reaction system, the at least two optical signals are obtained.

21. The sample analysis method according to claim 18, wherein, Based on the first reaction analysis value and / or the second reaction analysis value for judgment, according to the judgment result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the judgment result, one of the optical signals corresponding to the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, including: Comparing the first reaction analysis value and the second reaction analysis value, and according to the comparison result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the comparison result, one of the optical signals corresponding to the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested; Preferably, the first reaction analysis value and the second reaction analysis value are compared, and according to the comparison result, the larger one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the comparison result, the optical signal corresponding to the larger one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested.

22. The sample analysis method according to claim 18, wherein, Based on the first reaction analysis value and / or the second reaction analysis value for judgment, according to the judgment result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the judgment result, one of the optical signals corresponding to the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, including: Based on the first reaction analysis value or the second reaction analysis value, it is judged whether it is within a preset range, according to the judg ment result, one of the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested, or, according to the judgment result, one of the optical signals corresponding to the first reaction analysis value and the second reaction analysis value is selected to obtain the analysis result of the analyte in the sample to be tested.

23. The sample analysis method according to any one of claims 18 to 22, wherein, The obtaining of at least two optical signals includes: Obtaining the at least one optical signal at a first detection wavelength and obtaining the at least another optical signal at a second detection wavelength; Preferably, the first detection wavelength and the second detection wavelength are different; More preferably, the first detection wavelength and the second detection wavelength are selected from 320 nm to 860 nm.

24. According to the sample analysis method according to any one of claims 18 to 23, wherein, The obtaining of at least two optical signals includes: Obtain a first optical signal based on the first reagent or obtain a first optical signal after controlling the mixing of the sample to be tested and the first reagent and before the start of the first predetermined time, Obtain a second optical signal after the end of the first predetermined time and before controlling the mixing of the second reagent and the first reaction system, Obtain a third optical signal after controlling the mixing of the second reagent and the first reaction system and before the start of the second predetermined time, and Obtain a fourth optical signal after the end of the second predetermined time; and Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, including: Obtaining a first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining a second reaction analysis value of the second reaction system based on the third optical signal and the fourth optical signal.

25. The sample analysis method according to any one of claims 18 to 23, wherein, The obtaining of at least two optical signals includes: Obtaining a second optical signal after the end of the first predetermined time and before controlling the mixing of the second reagent and the first reaction system, and Obtaining a fourth optical signal after the end of the second predetermined time; and Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, including: Obtaining a first reaction analysis value of the first reaction system based on the second optical signal, and based on the Fourth optical signal or obtaining a second reaction analysis value of the second reaction system based on the fourth optical signal and the second optical signal.

26. The sample analysis method according to any one of claims 18 to 23, wherein, The obtaining of at least two optical signals includes: Obtaining a third optical signal after controlling the mixing of the second reagent and the first reaction system and before the start of the second predetermined time, Obtaining a fourth optical signal after the end of the second predetermined time; and Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, including: Obtaining a first reaction analysis value of the first reaction system based on the third optical signal, and obtaining a second reaction analysis value of the second reaction system based on the fourth optical signal or based on the fourth optical signal and the third optical signal.

27. The sample analysis method according to any one of claims 18 to 23, wherein, The obtaining of at least two optical signals includes: Obtaining a first optical signal based on the first reagent or obtaining a first optical signal after controlling the mixing of the sample to be tested and the first reagent and before the start of the first predetermined time, Obtaining a second optical signal after the end of the first predetermined time and before controlling the mixing of the second reagent and the first reaction system, and Obtaining a fourth optical signal after the end of the second predetermined time; and Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: Obtaining a first reaction analysis value of the first reaction system based on the first optical signal and the second optical signal, and obtaining a second reaction analysis value of the second reaction system based on the first optical signal and the fourth optical signal or based on the second optical signal and the fourth optical signal.

28. The sample analysis method according to any one of claims 18 to 23, wherein The obtaining of at least two optical signals includes: Collecting a plurality of the optical signals during at least one period starting from and ending at the first predetermined time, and obtaining a first reaction curve, and Collecting a plurality of the optical signals during at least one period starting from and ending at the second predetermined time, thereby obtaining a second reaction curve; and Obtaining a first reaction analysis value of the first reaction system based on at least one optical signal, and obtaining a second reaction analysis value of the second reaction system based on at least another optical signal, includes: Obtaining a first reaction analysis value of the first reaction system based on the first reaction curve, and obtaining a first reaction analysis value of the first reaction system based on the second reaction curve, Preferably, obtaining a first reaction analysis value of the first reaction system based on the first reaction curve or based on a characteristic value of the first reaction curve, and obtaining the first reaction analysis value of the first reaction system based on the second reaction curve or based on a characteristic value of the second reaction curve.

29. The sample analysis method according to any one of claims 18 to 28, wherein, The binding ability of the first ligand to the analyte is higher than the binding ability of the second ligand to the analyte.

30. The sample analysis method according to any one of claims 18 to 29, wherein, The second ligand in the second reagent exists in a free form and / or in a form bound to the surface of the second carrier.

31. The sample analysis method according to claim 30, wherein, The first carrier in the first reagent includes latex microspheres having a first particle size, and the second carrier in the second reagent includes latex microspheres having a second particle size, and the second particle size is smaller than the first particle size.

32. The sample analysis method according to any one of claims 18 to 31, wherein, The first ligand and the second ligand are antigens or antibodies capable of binding to an analyte.

33. The sample analysis method according to any one of claims 18 to 32, wherein, The optical signal is a scattered light signal and / or a transmitted light signal.

34. A reagent kit, including a first reagent and a second reagent, wherein The first reagent includes a first carrier with a first ligand bound to its surface; The second reagent includes a free second ligand; and The first ligand and the second ligand are the same or different, and can bind to the same analyte in the same sample.

35. The reagent kit according to claim 34, wherein The first carrier includes first latex microspheres, and the particle size of the first latex microspheres is 40 nm to 500 nm, preferably 80 nm to 400 nm.

36. The reagent kit according to claim 34 or 35, wherein The first ligand and the second ligand are antigens or antibodies capable of binding to an analyte in a test sample.

37. The reagent kit according to any one of claims 34 to 36, wherein The binding ability of the first ligand to the analyte is higher than the binding ability of the second ligand to the analyte.

38. The reagent kit according to any one of claims 34 to 37, wherein, The first reagent further includes a first buffer and an optional anti-interference agent; the second reagent further includes a second buffer.

39. The reagent kit according to any one of claims 34 to 38, further comprising a pretreatment reagent, wherein the pretreatment reagent comprises a third buffer and, optionally, an anti-interference agent.

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