EP-4741830-A1 - SAMPLE ANALYZER, PROTEIN ANALYSIS METHOD, AND PROTEIN ANALYSIS REAGENT

EP4741830A1EP 4741830 A1EP4741830 A1EP 4741830A1EP-4741830-A1

Abstract

The present application relates to a sample analyzer, a protein analysis method, and a protein analysis reagent. The protein analysis method comprises: preparing a first test solution by using a sample to be tested and a colorimetric reagent; testing the first test solution by using a colorimetric method, so as to acquire a colorimetric detection result for protein in said sample; on the basis of the colorimetric detection result, determining whether to perform a turbidimetric test; if a turbidimetric test is not performed, determining the concentration of the protein in said sample on the basis of the colorimetric detection result; and if a turbidimetric test is performed, preparing a second test solution by using said sample and a turbidimetric reagent, detecting the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in said sample, and determining the concentration of the protein in said sample on the basis of the turbidimetric detection result and the colorimetric detection result, optionally. The present application can integrate a colorimetric method with a turbidimetric method to measure protein in a sample, thereby enlarging the linear detection range of a single protein assay.

Inventors

HUANG, BIN
WANG, JIN
JIANG, MING

Assignees

Shenzhen Mindray Bio-Medical Electronics Co., Ltd.

Dates

Publication Date: 20260513
Application Date: 20240705

Claims (20)

A sample analyzer, comprising: a sample preparation apparatus configured to prepare a test solution to be tested from a sample and a detection reagent; a detection device configured to detect the test solution to be tested, so as to obtain a detection result for protein in the test solution to be tested; a controller configured to: control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a colorimetric reagent, wherein the colorimetric reagent comprises at least a coloring agent, and control the detection device to detect the first test solution by using a colorimetric method, so as to acquire a colorimetric detection result for protein in the sample to be tested; characterized in that the controller is further configured to: determine, on the basis of the colorimetric detection result, whether to perform a turbidimetric test, if no, then determine a concentration of the protein in the sample to be tested on the basis of the colorimetric detection result, and if yes, then control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, and control the detection device to detect the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in the sample to be tested, and determine a concentration of the protein in the sample to be tested on the basis of the turbidimetric detection result and optionally the colorimetric detection result; or, control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, and control the detection device to detect the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in the sample to be tested, and select, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested.
The sample analyzer of claim 1, characterized in that the turbidimetric reagent comprises at least an antibody reagent; the controller further configured to determine, on the basis of the colorimetric detection result, whether to perform a turbidimetric test, comprises: the controller further configured to: determine that the turbidimetric test is not required to be performed, if the colorimetric detection result is in a first predetermined range, for example greater than a predetermined threshold value; and determine that the turbidimetric test is required to be performed, if the colorimetric detection result is in a second predetermined range, for example not greater than the predetermined threshold value.
The sample analyzer of claim 1, characterized in that the turbidimetric reagent comprises at least an antibody reagent; the controller further configured to select, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested, comprises: the controller further configured to: calculate the concentration of the protein in the sample to be tested only on the basis of the colorimetric detection result, if the colorimetric detection result is in a first predetermined range, for example greater than a predetermined threshold value; calculate the concentration of the protein in the sample to be tested only on the basis of the turbidimetric detection result, if the colorimetric detection result is in a second predetermined range, for example not greater than the predetermined threshold value.
The sample analyzer of claim 1, characterized in that the turbidimetric reagent comprises at least an antibody reagent; and the controller further configured to select, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested, comprises: the controller further configured to: calculate the concentration of the protein in the sample to be tested only on the basis of the colorimetric detection result, if the colorimetric detection result is in a first predetermined range, for example greater than a predetermined threshold value by a first difference value; calculate the concentration of the protein in the sample to be tested only on the basis of the turbidimetric detection result, if the colorimetric detection result is in a second predetermined range, for example less than the predetermined threshold value by a second difference value; calculate the concentration of the protein in the sample to be tested on the basis of the turbidimetric detection result and the colorimetric detection result, if the colorimetric detection result is in a third predetermined range, for example, an absolute difference between the colorimetric detection result and the predetermined threshold value is not greater than the first difference value and the second difference value.
The sample analyzer of claim 1, characterized in that the turbidimetric reagent comprises at least a protein precipitation reagent; the controller further configured to determine, on the basis of the colorimetric detection result, whether to perform a turbidimetric test, comprises: the controller further configured to: determine that the turbidimetric test is not required to be performed, if the colorimetric detection result is in a first predetermined range, for example less than a predetermined threshold value; and determine that the turbidimetric test is required to be performed, if the colorimetric detection result is in a second predetermined range, for example not less than the predetermined threshold value.
The sample analyzer of claim 1, characterized in that the turbidimetric reagent comprises at least a protein precipitation reagent; the controller further configured to select, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested, comprises: the controller further configured to: calculate the concentration of the protein in the sample to be tested only on the basis of the colorimetric detection result, if the colorimetric detection result is in a first predetermined range, for example less than a predetermined threshold value; calculate the concentration of the protein in the sample to be tested only on the basis of the turbidimetric detection result, if the colorimetric detection result is in a second predetermined range, for example not less than the predetermined threshold value.
The sample analyzer of claim 1, characterized in that the turbidimetric reagent comprises at least a protein precipitation reagent; and the controller further configured to select, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested, comprises: the controller further configured: calculate the concentration of the protein in the sample to be tested only on the basis of the colorimetric detection result, if the colorimetric detection result is in a first predetermined range, for example less than a predetermined threshold value by a first difference value; calculate the concentration of the protein in the sample to be tested only on the basis of the turbidimetric detection result, if the colorimetric detection result is in a second predetermined range, for example greater than the predetermined threshold value by a second difference value; calculate the concentration of the protein in the sample to be tested on the basis of the turbidimetric detection result and the colorimetric detection result, if the colorimetric detection result is in a third predetermined range, for example, an absolute difference between the colorimetric detection result and the predetermined threshold value is not greater than the first difference value and the second difference value.
The sample analyzer of any one of claims 1 to 7, characterized in that the controller configured to control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a colorimetric reagent, comprises: the controller configured to control the sample preparation apparatus to mix at least a portion of the sample to be tested with the colorimetric reagent to prepare the first test solution; and the controller further configured to control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, comprises: the controller further configured to control the sample preparation apparatus to mix at least a portion of the first test solution with the turbidimetric reagent to prepare the second test solution.
The sample analyzer of any one of claims 1 to 7, characterized in that the controller configured to control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a colorimetric reagent, comprises: the controller configured to control the sample preparation apparatus to mix at least a portion of the sample to be tested with the colorimetric reagent to prepare the first test solution; and the controller further configured to control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, comprises: the controller further configured to control the sample preparation apparatus to mix at least another portion of the sample to be tested with the turbidimetric reagent to prepare the second test solution.
The sample analyzer of any one of claims 1 to 9, characterized in that the protein is albumin or total protein, preferably the protein is albumin; and/or the sample to be tested is urine or serum or cerebrospinal fluid, preferably the sample to be tested is urine; preferably, the sample to be tested is urine and the protein is albumin or total protein.
A sample analyzer, comprising: a sample preparation apparatus configured to prepare a test solution to be tested from a sample; a detection device configured to detect the test solution to be tested, so as to obtain a detection result for protein in the test solution to be tested; a controller configured to: on the basis of a first detection method, control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a first detection reagent, and control the detection device to detect the first test solution, so as to acquire a first detection result for protein in the sample to be tested; characterized in that the controller is further configured to: determine, on the basis of the first detection result, whether to perform a test on the basis of a second detection method, if no, then determine a concentration of the protein in the sample to be tested on the basis of the first detection result, if yes, then on the basis of the second detection method, control the sample preparation apparatus to prepare a second test solution by using the sample to be tested, and control the detection device to detect the second test solution, so as to acquire a second detection result for the protein in the sample to be tested, and determine a concentration of the protein in the sample to be tested on the basis of the second detection result and the first detection result; or, on the basis of the second detection method, control the sample preparation apparatus to prepare a second test solution by using the sample to be tested, and control the detection device to detect the second test solution, so as to acquire a second detection result for the protein in the sample to be tested, and select, on the basis of the first detection result, at least one of the first detection result and the second detection result to determine a concentration of the protein in the sample to be tested.
A sample analyzer, comprising: a sample preparation apparatus configured to prepare a test solution to be tested from a sample; a detection device configured to detect the test solution to be tested, so as to obtain a detection result for protein in the test solution to be tested; a controller configured to: on the basis of a first detection method, control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a first detection reagent, and control the detection device to detect the first test solution, so as to acquire a first detection result for protein in the sample to be tested; characterized in that the controller is further configured to: determine, on the basis of the first detection result, whether to perform a test on the basis of a second detection method, if no, then determine a concentration of the protein in the sample to be tested on the basis of the first detection result, if yes, then on the basis of the second detection method, control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a second detection reagent, and control the detection device to detect the second test solution, so as to acquire a second detection result for the protein in the sample to be tested, and determine a concentration of protein in the sample to be tested on the basis of the second detection result and optionally the first detection result; or, on the basis of the second detection method, control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a second detection reagent, and control the detection device to detect the second test solution, so as to acquire a second detection result for the protein in the sample to be tested, and select, on the basis of the first detection result, at least one of the first detection result and the second detection result to determine a concentration of the protein in the sample to be tested.
The sample analyzer of claim 11 or 12, characterized in that a protein concentration detection upper limit of the first detection method is greater than a protein concentration detection upper limit of the second detection method; the controller further configured to determine, on the basis of the first detection result, whether to perform a test on the basis of a second detection method, comprises: controller further configured to: determine that the test on the basis of the second detection method is not required to be performed, if the first detection result is greater than a predetermined threshold value; and determine that the test on the basis of the second detection method is required to be performed, if the first detection result is not greater than the predetermined threshold value; or, characterized in that a protein concentration detection upper limit of the first detection method is less than a protein concentration detection upper limit of the second detection method; the controller further configured to determine, on the basis of the first detection result, whether to perform a test on the basis of a second detection method, comprises: controller further configured to: determine that the test on the basis of the second detection method is not required to be performed, if the first detection result is less than a predetermined threshold value; and determine that the test on the basis of the second detection method is required to be performed, if the first detection result is not less than the predetermined threshold value.
The sample analyzer of any one of claims 11 to 13, characterized in that a calibration curve corresponding to the first detection method and a calibration curve corresponding to the second detection method are different; the controller is further configured to: obtain the first detection result from a first calibration curve and first optical signals obtained by detecting the first test solution; obtain the second detection result from a second calibration curve and second optical signals obtained by detecting the second test solution; wherein the first calibration curve is different from the second calibration curve, preferably a linear range of the first calibration curve is different from that of the second calibration curve, and the linear range of the first calibration curve and the linear range of the second calibration curve partially overlap with each other.
The sample analyzer of any one of claims 11 to 13, characterized in that the first detection method and the second detection method are based on different methodologies; or, the first detection reagent used in the first detection method and the second detection reagent used in the second detection method belong to different categories; or, the first detection reagent used in the first detection method and the second detection reagent used in the second detection method belong to a same category, but the first detection reagent used in the first detection method and the second detection reagent used in the second detection method differ in formulation, especially in concentration; or, a detector used for optical signal measurement of the first test solution in the first detection method and a detector used for optical signal measurement of the second test solution in the second detection method belong to different categories or have different linear detection ranges; or, a detection wavelength used for optical signal measurement of the first test solution in the first detection method is different from a detection wavelength used for optical signal measurement of the second test solution in the second detection method.
A protein analysis method for a sample analyzer, wherein the sample analyzer comprises a sample preparation apparatus, a detection device, and a controller, and the protein analysis method comprises: controlling, by the controller, the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a colorimetric reagent, wherein the colorimetric reagent comprises at least a coloring agent; and controlling, by the controller, the detection device to detect the first test solution by using a colorimetric method, so as to acquire a colorimetric detection result for protein in the sample to be tested; characterized in that the protein analysis method further comprises performing the following steps by the controller: determining, on the basis of the colorimetric detection result, whether to perform a turbidimetric test, if no, then determining a concentration of the protein in the sample to be tested on the basis of the colorimetric detection result, and if yes, then controlling the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, and controlling the detection device to detect the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in the sample to be tested, and determining a concentration of the protein in the sample to be tested on the basis of the turbidimetric detection result and optionally the colorimetric detection result; or, controlling the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, and controlling the detection device to detect the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in the sample to be tested, selecting, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested.
A protein analysis method for a sample analyzer, wherein the sample analyzer comprises a sample preparation apparatus, a detection device, and a controller, and the protein analysis method comprises: controlling, by the controller, the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a turbidimetric reagent; and controlling by the controller, the detection device to detect the first test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for protein in the sample to be tested; characterized in that the protein analysis method further comprises performing the following steps by the controller: determining, on the basis of the turbidimetric detection result, whether to perform a colorimetric test, if no, then determining a concentration of the protein in the sample to be tested on the basis of the colorimetric detection result, and if yes, then controlling the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a colorimetric reagent, and controlling the detection device to detect the second test solution by using a colorimetric method, so as to acquire a colorimetric detection result for the protein in the sample to be tested, and determining a concentration of the protein in the sample to be tested on the basis of the colorimetric detection result and optionally the turbidimetric detection result, wherein the colorimetric reagent comprises at least a coloring agent; or, controlling the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a colorimetric reagent, controlling the detection device to detect the second test solution by using a colorimetric method, so as to acquire a colorimetric detection result for the protein in the sample to be tested, wherein the colorimetric reagent comprises at least a coloring agent, and selecting, on the basis of the turbidimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested.
A protein analysis reagent, characterized in that the protein analysis reagent comprises: a colorimetric reagent comprising a coloring agent; and a turbidimetric reagent comprising an antibody reagent or a protein precipitation reagent.
The protein analysis reagent of claim 18, characterized in that the colorimetric reagent further comprises a turbidity-enhancing reagent comprising a hydrophilic polymer; the turbidimetric reagent comprises an antibody reagent.
The protein analysis reagent of claim 18, characterized in that the turbidimetric reagent comprises an antibody reagent, wherein the antibody reagent comprises a solid-phase carrier with an antibody attached to a surface thereof, wherein the solid-phase carrier is preferably latex microspheres.

Description

TECHNICAL FIELD The present disclosure relates to the field of in vitro diagnostics, and in particular to a sample analyzer, a protein analysis method and a protein analysis reagent. BACKGROUND Currently, in an automated biochemical analyzer, there are mainly two methods, colorimetric method and turbidimetric method, which are used to measure protein in a sample, such as albumin in urine. The basic principle of the colorimetric method is that: a dye (or coloring agent, chromogen) binds to protein, such as albumin, under specific conditions to produce a color change, thereby performing protein detection, for example, albumin detection. However, the colorimetric method has a low sensitivity and is generally used only to determine albumin content in serum, but usually not used to detect albumin in urine. The basic principle of the turbidimetric method, such as immunoturbidimetric method, which is conventionally used to detect urinary albumin (urinary microalbumin) is that: an antibody binds to protein, such as albumin, to form turbidity for detection. However, the detection upper limit of the immunoturbidimetric method usually only covers a lower detection range, for example less than 1000 mg/L, with a hook effect. The concentration range of urinary albumin in a patient can reach a level of 30000 mg/L. Therefore, for a high-concentration urine sample, the immunoturbidimetric method is prone to a hook effect, resulting in misjudgment of results. In order to avoid the misjudgment caused by the hook effect, frequent dilution and retesting are required, resulting in a significant additional investment of resources, such as reagents. SUMMARY In order to at least partially solve the technical problems described above, an object of the disclosure is to provide a sample analyzer, a protein analysis method and a protein analysis reagent, which are capable of combining two protein assay methods with different detection ranges to broaden the linear detection range of a single protein assay, for example, combining the low detection lower limit of the immunoturbidimetric method and the high detection upper limit of the colorimetric method to broaden the linear detection range for the protein assay. In order to achieve the above object of the disclosure, a first aspect of the disclosure provides a sample analyzer, including: a sample preparation apparatus configured to prepare a test solution to be tested from a sample and a detection reagent;a detection device configured to detect the test solution to be tested, so as to obtain a detection result for protein in the test solution to be tested;a controller configured to: control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a colorimetric reagent, where the colorimetric reagent includes at least a coloring agent, and control the detection device to detect the first test solution by using a colorimetric method, so as to acquire a colorimetric detection result for protein in the sample to be tested;characterized in that the controller is further configured to: determine, on the basis of the colorimetric detection result, whether to perform a turbidimetric test, if no, then determine a concentration of the protein in the sample to be tested on the basis of the colorimetric detection result, and if yes, then control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, and control the detection device to detect the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in the sample to be tested, and determine a concentration of the protein in the sample to be tested on the basis of the turbidimetric detection result and optionally the colorimetric detection result; or,control the sample preparation apparatus to prepare a second test solution by using the sample to be tested and a turbidimetric reagent, and control the detection device to detect the second test solution by using a turbidimetric method, so as to acquire a turbidimetric detection result for the protein in the sample to be tested, and select, on the basis of the colorimetric detection result, at least one of the colorimetric detection result and the turbidimetric detection result to determine a concentration of the protein in the sample to be tested. A second aspect of the disclosure provides another sample analyzer, including: a sample preparation apparatus configured to prepare a test solution to be tested from a sample and a detection reagent;a detection device configured to detect the test solution to be tested, so as to obtain a detection result for protein in the test solution to be tested;a controller configured to: control the sample preparation apparatus to prepare a first test solution by using a sample to be tested and a turbidimetric reagent; and control the detection device to detect the first test solution by