Method for reducing cross interference of detection item reagents and sample analyzer

Abstract

The invention relates to a method for reducing cross interference of detection item reagents and a sample analyzer. The method comprises the following steps: receiving detection tasks of at least two to-be-detected items; judging an associated project group in the to-be-detected project; and determining a detection sequence of the to-be-detected items in the associated item group according to the association strength of the to-be-detected items in the associated item group. According to the scheme provided by the invention, the cross interference of different detection items can be reduced or avoided while the experimental period is not prolonged and the interference of washing liquid is avoided.

Description

Technical Field

[0001] This application relates to the technical field of sample analysis, and particularly to a method for reducing cross-interference of reagents for detection items and a sample analyzer. Background Art

[0002] A sample analyzer is an essential inspection instrument in a clinical laboratory, with the characteristics of high accuracy, high precision, and high efficiency. A sample analyzer generally uses a pipetting needle of a pipettor to aspirate reagents and inject the reagents into a sample to achieve detection. Between performing different detection items, the pipetting needle will be cleaned. However, it is very difficult to ensure 100% cleanliness during this cleaning, so interference will be carried.

[0003] In related technologies, generally, the pipetting needle is cleaned by increasing the washing time or using a washing solution with stronger cleaning power to reduce the risk of cross-interference between different detection items.

[0004] However, increasing the washing time will increase the experimental cycle, and using a washing solution with stronger cleaning power will pose a risk of washing solution interference.

[0005] Therefore, there is an urgent need for a new method to reduce or avoid cross-interference between different detection items without increasing the experimental cycle and avoiding washing solution interference. Summary of the Invention

[0006] To solve or partially solve the problems existing in related technologies, this application provides a method for reducing cross-interference of reagents for detection items and a sample analyzer, which can reduce or avoid cross-interference between different detection items without increasing the experimental cycle and avoiding washing solution interference.

[0007] The first aspect of this application provides a method for reducing cross-interference of reagents for detection items, including:

[0008] Receiving detection tasks for at least two items to be detected;

[0009] Judging associated item groups among the items to be detected;

[0010] Determining the detection order of each of the items to be detected in the associated item group according to the association strength of the items to be detected in the associated item group.

[0011] As an optional embodiment, the target molecules to which the detection molecules in the detection reagents corresponding to any two of the items to be detected in the associated item group specifically bind have partially the same molecular structure.

[0012] As an optional embodiment, the detection molecule in the detection reagent corresponding to one of the items to be detected in the associated item group will bind to the target molecule of another item to be detected.

[0013] As an optional embodiment, determining the detection order of each of the items to be detected in the associated item group according to the association strength of the items to be detected in the associated item group includes:

[0014] According to the association strength of the items to be detected in the associated item group, filter out the item to be detected in the associated item group with the highest association strength with other items to be detected, and rank the detection order of this item to be detected at the nth position, where n is the total number of items to be detected in the associated items;

[0015] Filter out the item to be detected with the weakest association strength with the item to be detected at the mth position from other items to be detected, and rank the detection order of this item to be detected at the m - 1th position. Starting from m = n until m = 3, sequentially complete the sorting of n - 1 items to be detected in the associated item group, and rank the last item to be detected at the first position, where m is a natural number from 3 to n.

[0016] The second aspect of the present application provides a method for determining the above-mentioned association strength, including:

[0017] Equally mix the samples of all items to be detected in the associated item group to configure a mixed sample;

[0018] Split and combine the paired detection reagents of the items to be detected in the associated item group to form multiple groups of paired reagents to be detected;

[0019] Mix the paired reagents to be detected with the mixed sample and detect the luminescence signal;

[0020] According to the luminescence signal, determine the association strength of the items to be detected in the associated item group.

[0021] As an optional embodiment, splitting and combining the paired detection reagents of the items to be detected in the associated item group to form multiple groups of paired reagents to be detected includes:

[0022] One by one, mix one reagent in the paired detection reagent of any one of the items to be detected in the associated item group with the other reagent in the paired detection reagents of other items to be detected to form multiple groups of paired reagents to be detected.

[0023] As an optional embodiment, determining the association strength of the items to be detected in the associated item group according to the luminescence signal includes:

[0024] Mix the paired detection reagent of any one of the items to be detected in the associated item group with the mixed sample as a control detection item, detect the luminescence signal of the control item and use it as a control signal;

[0025] Calculate the ratio of the luminescence signal of the test pairing reagent to the corresponding control signal, and use the ratio as the cross-reaction intensity of the test pairing reagent.

[0026] Determine the correlation intensity between the two corresponding test items according to the cross-reaction intensity of the test pairing reagent.

[0027] As an optional embodiment, the determining the correlation intensity between the two corresponding test items according to the cross-reaction intensity of the test pairing reagent includes:

[0028] Sum and calculate the luminescence signals of each group of test pairing reagents formed by splitting and combining the two test items to obtain the correlation intensity between the two test items.

[0029] The third aspect of the present application provides a readable storage medium, on which a computer program is stored. When the computer program is executed, the steps of the method for reducing cross-interference of reagents for test items described above are executed.

[0030] The fourth aspect of the present application provides a sample analyzer, including:

[0031] A reagent unit, including a reagent warehouse for storing detection reagents and a pipette for sucking detection reagents;

[0032] A sample unit, including a sample warehouse for storing samples and a sampling arm for sucking samples;

[0033] An analysis unit for analyzing the mixture of the sample and the reagent;

[0034] A control device for controlling the sample analyzer. The control device includes the readable storage medium described above and is used to execute the steps of the method for reducing cross-interference of reagents for test items described above.

[0035] The technical solution provided by the present application may include the following beneficial effects:

[0036] When there is an associated item group in the received test items, the present application will determine and adjust the detection order of each test item in the associated item group according to the correlation intensity between the test items in the associated item group. The test items with high correlation intensity can be sorted at intervals, and the test items with weak correlation intensity can be sorted continuously, reducing the cross-reaction between each test item in the associated item group. Therefore, the embodiments of the present application can reduce or avoid cross-interference between different test items without increasing the cleaning of the pipette needle and the cleaning time of the pipette needle, which is beneficial to improving the accuracy of the detection results while avoiding the interference of the washing solution and without increasing the experimental period.

[0037] It should be understood that the above general description and the following detailed description are merely exemplary and explanatory, and do not limit this application. Description of the Drawings

[0038] By describing the exemplary embodiments of this application in more detail in conjunction with the drawings, the above and other objects, features, and advantages of this application will become more apparent. Among them, in the exemplary embodiments of this application, the same reference numerals generally represent the same components.

[0039] Figure 1 is a flowchart of the method for reducing reagent cross-interference in detection items shown in the embodiments of this application.

[0040] Figure 2 is a flowchart of the method for determining the association strength of the items to be detected in the associated item group shown in the embodiments of this application. Detailed Embodiments

[0041] The embodiments of this application will be described in more detail below with reference to the drawings. Although the embodiments of this application are shown in the drawings, it should be understood that this application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to make this application more thorough and complete, and to fully convey the scope of this application to those skilled in the art.

[0042] It should be understood that although the terms "first", "second", "third", etc. may be used in this application to describe various information, such information should not be limited to these terms. These terms are only used to distinguish the same type of information from each other. For example, without departing from the scope of this application, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of this application, "a plurality" means two or more unless otherwise specifically defined.

[0043] In the description of this application, it should be understood that the orientation or positional relationship indicated by the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing this application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation of this application.

[0044] Unless otherwise clearly defined and limited, terms such as "install", "connect", "join", "fix", etc. should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two components or the interaction relationship between two components. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0045] In the related art, generally, the washing time is increased or a washing solution with stronger detergency is used to clean the pipette needle to reduce the risk of cross-interference between different detection items. However, increasing the washing time will increase the experimental cycle, and using a washing solution with stronger detergency will have the risk of washing solution interference. Therefore, there is an urgent need for a new method to reduce or avoid cross-interference between different detection items while not increasing the experimental cycle and avoiding washing solution interference.

[0046] In view of the above problems, the embodiment of the present application provides a method for reducing cross-interference of detection item reagents, which can reduce or avoid cross-interference between different detection items while not increasing the experimental cycle and avoiding washing solution interference.

[0047] The technical solutions of the embodiments of the present application will be described in detail below with reference to the accompanying drawings.

[0048] Figure 1 is a flowchart of the method for reducing cross-interference of detection item reagents shown in the embodiment of the present application. This method can run on any sample analyzer that uses detection reagents to analyze blood samples. For example, the sample analyzer can be a biochemical analyzer, a chemiluminescence analyzer, etc. Further, the sample analyzer can be a sample analyzer based on different detection methodologies, such as a biochemical analyzer based on latex turbidimetry detection, a chemiluminescence analyzer based on enzyme-linked immunosorbent assay, a chemiluminescence analyzer based on amplified luminescent proximity homogeneous assay technology.

[0049] The details of the method for reducing cross-interference of detection item reagents will be described below based on the sample analyzer provided in the embodiment of the present application. Figure 1 The sample analyzer provided by the embodiment of the present application is designed based on amplified luminescent proximity homogeneous assay technology and uses the corresponding detection kit of amplified luminescent proximity homogeneous assay technology.

[0050] The luminescent oxygen channeling immunoassay (LOCI) is a homogeneous chemiluminescence assay that detects the concentration of the analyte in a blood sample to be tested based on the interaction between biomolecules. The detection kit for the LOCI method includes a variety of reagents, which respectively include photosensitive microspheres and luminescent microspheres. Usually, the antigen or antibody used to label the analyte is coated on the luminescent microspheres to prepare the first reagent R1 containing the luminescent microspheres. The surface of the photosensitive microspheres is coated with avidin to prepare the second reagent R2. During the detection process, the first reagent R1 containing the luminescent microspheres and the second reagent R2 are successively combined with the sample to be tested. When the sample contains the analyte, the photosensitive microspheres and the luminescent microspheres are combined within a certain range through the biotin-avidin reaction system, generating the transfer of ionic oxygen energy and emitting a light signal, thereby detecting the sample to be tested. Among them, the photosensitive microspheres are filled with a photosensitive compound inside, while the luminescent microspheres are filled with a luminescent compound and a lanthanide element. Under the excitation of a red laser (600 - 700 nm), the photosensitive microspheres release high-energy singlet oxygen ions, and the propagation distance is about 200 nm. When the distance between the photosensitive microspheres and the luminescent microspheres is close enough, the singlet oxygen ions released by the photosensitive microspheres can reach the luminescent microspheres and emit light with a high energy level of 520 - 620 nm through a series of chemical reactions, which is detected by the detection unit of the instrument. When the sample does not contain the analyte, an immune complex cannot be formed between the two types of microspheres, the distance between the two types of microspheres exceeds the propagation range of ionic oxygen, and the ionic oxygen is rapidly quenched in the liquid phase, so no high-energy red light is generated during detection.

[0051] Although the embodiments of the present application take the luminescent oxygen channeling immunoassay analyzer and the luminescent oxygen channeling immunoassay detection reagent as examples, the present application is not limited thereto, but can run on any sample analyzer that uses a detection reagent to analyze a blood sample, as long as the microspheres contained in the detection reagent are coated with an antigen or antibody, or a biotin-labeled antigen or antibody.

[0052] The sample analyzer provided by the embodiment of the present application has a reagent unit, which includes a reagent storage for storing detection reagents required for detection and a pipette for aspirating detection reagents. The detection reagents are, for example, follicle-stimulating hormone antigen (FSH antigen), luteinizing hormone antigen (LH antigen), thyroid-stimulating hormone antigen (TSH antigen), and β-human chorionic gonadotropin antigen (β-HCG antigen). The sample analyzer also has a sample unit, which includes a sample storage for storing blood samples to be detected and a sampling arm for aspirating samples. The blood samples are, for example, patient blood samples or animal blood samples. A scanner (not shown) for reading sample codes is provided in the sample storage. The sample analyzer also has an analysis unit for analyzing the mixture of the sample and the reagent. The analysis unit includes an incubation tray for carrying reaction cups required for detection and providing the temperature required for the reaction, for example, heating the reaction container through a heating sheet. The analysis unit also includes a detection unit (not shown) for detecting the signal generated by the reaction liquid in the reaction cup. The sample analyzer also has a cup handler for storing reaction cups required for detection analysis and transporting the reaction cups to the incubation tray.

[0053] The sample analyzer is equipped with a control device that controls the execution of the actions of each component. The control device obtains the sample code from the sample storage. The sample code is a specific identifier used to identify the sample. After obtaining the sample code, the control device obtains the detection items of the sample to be detected according to the sample code. The user can pre-enter the detection items corresponding to the sample code into the sample analyzer. The detection items can also be obtained by the control device from a superior information management system (such as a laboratory information management system LIS or a hospital information management system HIS) communicatively connected to the sample analyzer.

[0054] Samples to be detected are usually placed in the sample storage in batches, for example, five or ten at a time. In addition, each sample to be detected may correspond to multiple items to be detected, for example, one sample needs to be detected for 3 kinds of infectious diseases. The control device determines the final execution order of each item to be detected and controls each component of the sample analyzer to perform corresponding actions.

[0055] In the embodiment of the present application, the control device receives detection tasks for at least two items to be detected; determines the associated item groups among the items to be detected; and determines the detection order of each item to be detected in the associated item group according to the association strength of the items to be detected in the associated item group.

[0056] See Figure 1 , the embodiment of the present application provides a method for reducing cross-interference of reagents for detection items, including:

[0057] S110: Receive detection tasks for at least two items to be detected;

[0058] S120: Determine the associated item groups in the items to be detected;

[0059] S130: Determine the detection order of each item to be detected in the associated item group according to the association strength of the items to be detected in the associated item group.

[0060] The reagent cross-interference of the detection items in the sample analyzer means that the residual part of the reagent or sample of the measured item affects the measurement result of the subsequent detection item. Due to incomplete cleaning of the shared part of the sample analyzer, there is cross-interference during its use, which will affect the accuracy of the test result and even cause a large measurement error. For example, the sample addition needle of this analyzer is washed with deionized water between two samples or between two detection items. If the cleaning is not thorough, the residual part of the reagent needle or sample needle of the previous detection item will affect the next detection item. One of the common reasons for the influence is that the reagent of the previous detection item contains the component to be measured in the next detection item or a certain substance in the reagent can participate in the reaction of the next detection item, thereby interfering with the subsequent detection item and affecting the repeatability and accuracy of the measurement of the subsequent detection item. And the influence on calibration and low-value samples may be more serious.

[0061] The applicant found that although there are cross-reactions between the items to be detected in the associated item group, due to the different binding forces of the paired detection reagents for each item to be detected and the different selection of diluents, the cross-reaction intensities between each item to be detected are also different. Based on this discovery, in the embodiments of the present application, through the above steps, when there is an associated item group in the received items to be detected, the detection order of each item to be detected in the associated item group will be determined and adjusted according to the association strength of the items to be detected in the associated item group. The items to be detected with high association strength can be sorted at intervals, and the items to be detected with weak association strength can be sorted continuously, reducing the cross-reaction between each item to be detected in the associated item group. Therefore, in the embodiments of the present application, without strengthening the cleaning of the pipetting needle and increasing the cleaning time of the pipetting needle, it is possible to reduce or avoid the cross-interference between different detection items while not increasing the experimental period and avoiding the interference of the washing solution, which is beneficial to improving the accuracy of the detection result.

[0062] Furthermore, the target molecules specifically bound by the detection molecules in the detection reagents corresponding to any two items to be detected in the associated item group have partially the same molecular structure.

[0063] Taking four test items of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and β-human chorionic gonadotropin (β-HCG) as examples, since these four heterodimeric glycoprotein hormones are all composed of a common α subunit and their respective different β subunits, the common α subunit may cause the target molecule of one test reagent for these four test items to specifically bind to the target molecules of other test reagents, which may lead to possible cross-interference among these four test items. Therefore, when receiving a test task containing these four test items to be detected, it is determined that the associated item group in the test items to be detected includes these four test items to be detected.

[0064] Further, the detection molecule in the test reagent corresponding to one of the test items in the associated item group binds to the target molecule of another test item.

[0065] Taking two test items of follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) as examples, the first reagent R1 (luminescent microspheres coated with FSH antibody) in the test reagent corresponding to the FSH test item binds to the target molecule (TSH antigen) of the TSH test item.

[0066] Preferably, step S130 further includes:

[0067] S131: According to the association strength of the test items in the associated item group, screen out the test item in the associated item group with the highest association strength with other test items, and arrange the detection order of this test item in the nth position, where n is the total number of test items in the associated items;

[0068] S132: Screen out the test item with the weakest association strength with the test item in the mth position from other test items, and arrange the detection order of this test item in the (m - 1)th position. Starting from m = n until m = 3, sequentially complete the sorting of n - 1 test items in the associated item group. The last test item is arranged in the first position, where m is a natural number from 3 to n.

[0069] Taking four detection items of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and β-human chorionic gonadotropin (β-HCG) as examples, if it is determined that the TSH detection item has the highest correlation strength with other items, then the detection order of the TSH detection item is ranked 4th; among the other three detection items, since the β-HCG detection item has the weakest correlation strength with the TSH detection item, the detection order of the β-HCG detection item is placed before the TSH detection item and ranked 3rd; among the remaining LH detection item and FSH detection item, the correlation strength of the LH detection item with the β-HCG detection item is less than that of the FSH detection item with the β-HCG detection item, so the detection order of the LH detection item is placed before the β-HCG detection item and ranked 2nd; the last FSH detection item is ranked 1st.

[0070] By determining the detection order of each item to be detected in the associated item group through the above steps, so that the correlation strength between two adjacent items to be detected is the weakest, the cross-interference between two adjacent detection items can be greatly reduced, thereby reducing or even avoiding the cross-interference of all items to be detected in the entire associated item group.

[0071] See Figure 2 , the embodiment of the present application also provides a method for determining the correlation strength of items to be detected in an associated item group, including:

[0072] S210: Mix the samples of all items to be detected in the associated item group in equal proportion to configure a mixed sample;

[0073] S220: Split and combine the paired detection reagents of the items to be detected in the associated item group to form multiple groups of paired reagents to be detected;

[0074] S230: Mix the paired reagents to be detected with the mixed sample and detect the luminescence signal;

[0075] S240: Determine the correlation strength of the items to be detected in the associated item group according to the luminescence signal.

[0076] Since it is difficult to clean the sample needle or reagent needle 100%, the sample remaining from the previous detection item will form a mixed sample with the sample of the next detection item, and the paired detection reagent remaining from the previous detection item will form a paired reagent with the paired detection reagent of the next detection item. The paired reagent will react with the mixed sample, thus affecting the detection result of the next detection item. Through the above steps, the embodiment of the present application can experimentally simulate the cross-reaction of the items to be detected in the associated item group, thereby determining the correlation strength of the items to be detected in the associated item group.

[0077] Preferably, step S220 further includes: mixing one reagent in the paired detection reagents of any one of the to-be-detected items in the associated item group with the other reagent in the paired detection reagents of the other to-be-detected items one by one to form multiple groups of to-be-detected paired reagents.

[0078] In the embodiments of the present application, the paired detection reagents for the to-be-detected items may refer to the first reagent R1 and the second reagent R2. Taking four detection items of follicle-stimulating hormone FSH, luteinizing hormone LH, thyroid-stimulating hormone TSH, and β-human chorionic gonadotropin β-HCG as examples, the paired detection reagents for the FSH detection item are the first reagent R1 containing FSH antibody-coated luminescent microspheres and the second reagent R2 containing avidin-coated photosensitive microspheres; the paired detection reagents for the LH detection item are the first reagent R1 containing LH antibody-coated luminescent microspheres and the second reagent R2 containing avidin-coated photosensitive microspheres; the paired detection reagents for the TSH detection item are the first reagent R1 containing TSH antibody-coated luminescent microspheres and the second reagent R2 containing avidin-coated photosensitive microspheres; the paired detection reagents for the β-HCG detection item are the first reagent R1 containing β-HCG antibody-coated luminescent microspheres and the second reagent R2 containing avidin-coated photosensitive microspheres.

[0079] In the embodiments of the present application, the first reagent R1 of any one of the to-be-detected items can be mixed and paired with the second reagent R2 in the paired detection reagents of the other to-be-detected items one by one to form multiple groups of to-be-detected paired reagents, or the second reagent R2 of any one of the to-be-detected items can be mixed and paired with the first reagent R1 in the paired detection reagents of the other to-be-detected items one by one to form multiple groups of to-be-detected paired reagents. For example: mixing the second reagent R2 of the FSH detection item with the first reagent R1 of the LH detection item, TSH detection item, and β-HCG detection item one by one, mixing the second reagent R2 of the LH detection item with the first reagent R1 of the FSH detection item, TSH detection item, and β-HCG detection item one by one, mixing the second reagent R2 of the TSH detection item with the first reagent R1 of the FSH detection item, LH detection item, and β-HCG detection item one by one, and mixing the second reagent R2 of the β-HCG detection item with the first reagent R1 of the FSH detection item, LH detection item, and FSH detection item one by one to form 12 groups of to-be-detected paired reagents.

[0080] Preferably, step S240 further includes:

[0081] S241: Mixing the paired detection reagents of any one of the to-be-detected items in the associated item group with the mixed sample as a control detection item, detecting the luminescence signal of the control item and using it as a control signal;

[0082] S242: Calculate the ratio of the luminescence signal of the paired reagent to be tested to the corresponding control signal, and use the ratio as the cross-reaction intensity of the paired reagent to be tested;

[0083] S243: Determine the correlation strength of the two corresponding test items according to the cross-reaction intensity of the paired reagent to be tested.

[0084] Taking the FSH test item and the LH test item as examples, first mix the first reagent R1 and the second reagent R2 of the FSH test item with the mixed sample as the control test item, and label it as FSH-R1 / R2. Mix the first reagent R1 and the second reagent R2 of the LH test item with the mixed sample as the control test item, and label it as LH-R1 / R2; then label the paired reagent to be tested formed by mixing the second reagent R2 of the FSH test item with the first reagent R1 of the LH test item as FSH-R2 / LH-R1, and label the paired reagent to be tested formed by mixing the second reagent R2 of the LH test item with the first reagent R1 of the FSH test item as LH-R2 / FSH-R1. Among them, FSH-R1 / R2 is used as the control test item for FSH-R2 / LH-R1, and LH-R1 / R2 is used as the control test item for LH-R2 / FSH-R1. Then calculate the ratio of the luminescence signal of FSH-R2 / LH-R1 to the luminescence signal of FSH-R1 / R2, and use the ratio as the cross-reaction intensity of FSH-R2 / LH-R1; then calculate the ratio of the luminescence signal of LH-R2 / FSH-R1 to the luminescence signal of LH-R1 / R2, and use the ratio as the cross-reaction intensity of LH-R2 / FSH-R1; finally, determine the correlation strength of the FSH test item and the LH test item according to the cross-reaction intensities of FSH-R2 / LH-R1 and LH-R2 / FSH-R1.

[0085] Step S243 further includes: adding and calculating the luminescence signals of each group of paired reagents to be tested formed by splitting and combining the two test items to obtain the correlation strength of the two test items.

[0086] Based on the above description, add and calculate the cross-reaction intensities of FSH-R2 / LH-R1 and LH-R2 / FSH-R1 to obtain the correlation strength of the FSH test item and the LH test item.

[0087] To make the present invention easier to understand, the following will further elaborate on the present application in conjunction with embodiments. These embodiments are only illustrative and are not limited to the application scope of the present application. The raw materials or components used in the present application can be obtained through commercial channels or conventional methods without special instructions.

[0088] Example 1

[0089] Determine the detection order of the items to be detected in the associated project group.

[0090] 1. Main experimental raw materials and equipment

[0091] (1) Reagents: Select the finished product reagent kits of FSH, LH, TSH, and β-HCG produced by KeMei Diagnostic Technology Co., Ltd.

[0092] (2) Samples: Select high-value samples for the detection items of FSH, LH, TSH, and β-HCG, and configure them into a mixed sample according to the ratio of 1:1:1:1.

[0093] (3) Instruments: Select the LiCA800 fully automatic chemiluminescence immunoassay system.

[0094] 2. Experimental procedures

[0095] (1) Pair the second reagent R2 of the LH detection item with the first reagent R1 of the FSH detection item, the first reagent R1 of the TSH detection item, and the first reagent R1 of the β-HCG detection item one by one.

[0096] (2) Repeat step (1), and pair the second reagent R2 of the FSH detection item, the second reagent R2 of the TSH detection item, and the second reagent R2 of the β-HCG detection item with the first reagent R1 of the other three detection items respectively to form multiple groups of paired reagents to be tested.

[0097] (3) Mix the multiple groups of paired reagents to be tested with the mixed sample and detect the luminescence signal.

[0098] (4) Query the experimental results after the operation ends.

[0099] (5) Exit the host computer software after the experiment ends.

[0100] 3. Statistical analysis

[0101] (1) Take the luminescence signal of the paired reagent in the finished product reagent kit (for example, the first reagent R1 and the second reagent R2 of the LH detection item) as the control signal, calculate the ratio of the luminescence signal of the paired reagent to be tested composed of the second reagent R2 (or the first reagent R1) of the LH detection item and the first reagent R1 (or the second reagent R2) of other detection items to the control signal, and define this ratio as the cross-reaction intensity of the paired reagent to be tested. The higher the ratio, the stronger the affinity, that is, the stronger the cross-reactivity. Among them, the ratio not greater than 0.5 can be defined as weak cross-reaction, and the ratio greater than 0.5 can be defined as strong cross-reaction.

[0102] (2) Sum the luminescence signals of each group of paired reagents to be detected formed by splitting and combining two items to be detected, and obtain the correlation strength between the two items to be detected. For example, sum the cross-reaction strengths of the paired reagents to be detected formed by combining the second reagent R2 of the LH detection item with the first reagent R1 of the FSH detection item, and the cross-reaction strengths of the paired reagents to be detected formed by combining the first reagent R1 of the LH detection item with the second reagent R2 of the FSH detection item, to obtain the correlation strength between the LH detection item and the FSH detection item.

[0103] 4. Experimental data

[0104] Table 1 Test results of cross-reaction strengths between paired reagents to be detected

[0105] Reagent components LH reagent 2 FSH reagent 2 TSH reagent 2 β-HCG reagent 2 LH reagent 1 1.00 0.23 0.93 0.22 FSH reagent 1 0.52 1.00 0.73 0.91 TSH reagent 1 1.06 0.37 1.00 0.27 β-HCG reagent 1 0.05 0.10 0.08 1.00

[0106] Table 2 Test results of correlation strengths of items to be detected in the associated item group

[0107] LH FSH TSH β-HCG LH / 0.75 1.99 0.27 FSH 0.75 / 1.10 1.01 TSH 1.99 1.10 / 0.35 β-HCG 0.27 1.01 0.35 /

[0108] 5. Analysis of experimental data

[0109] According to the test results of the correlation strengths of the items to be detected in the associated item group in Table 2, it can be known that: the correlation strength between the TSH detection item and other items is the highest, so the detection order of the TSH detection item is ranked 4th; among the other three detection items, since the correlation strength between the β-HCG detection item and the TSH detection item is the weakest, the detection order of the β-HCG detection item is placed before the TSH detection item, ranked 3rd; among the remaining LH detection item and FSH detection item, the correlation strength between the LH detection item and the β-HCG detection item is less than the correlation strength between the FSH detection item and the β-HCG detection item, so the detection order of the LH detection item is placed before the β-HCG detection item, ranked 2nd; the last FSH detection item is ranked 1st.

[0110] 6. Experimental conclusion

[0111] It can be seen from the result analysis that running in the detection order of FSH > LH > β-HCG > TSH can reduce the risk of cross-interference between the detection items in the associated items.

[0112] Example 2

[0113] Verify whether the detection order determined in Example 1 can reduce cross-interference.

[0114] 1. Main experimental raw materials and equipment

[0115] (1) Reagents: finished product kits for FSH, LH, TSH, and β-HCG.

[0116] (2) Samples: For each test item, select 5 samples from the low value to the high value, including 1 - 2 samples at the medical decision levels, and label them as Sample 1, Sample 2, Sample 3, Sample 4, and Sample 5.

[0117] (3) Instrument: Select the LiCA800 fully automated chemiluminescence immunoassay system.

[0118] 2. Experimental Procedures

[0119] (1) Repeat the detection of the 5 samples for each of the LH, β - HCG, and TSH test items 10 times respectively, and calculate the theoretical values of the samples.

[0120] (2) Edit 1 worksheet: Submit the detection tasks in the detection order of FSH > LH > β - HCG > TSH.

[0121] (3) Load Sample 1 of each test item onto the instrument and repeat the detection of this group of samples 3 times.

[0122] (4) Repeat Step (4) for Samples 2 - 5 of each test item.

[0123] (6) Query the experimental results after the operation ends.

[0124] 3. Statistical Analysis

[0125] (1) Calculate the standard deviation SD of the detection results of each group of samples repeated 3 times, and the ratio CV of the standard deviation SD to the mean, with the requirement that CV is not higher than 8%.

[0126] (2) Calculate the percentage deviation of the mean of the detection results of each group of samples repeated 3 times from the theoretical value, with the requirement that the percentage deviation is not higher than 10%.

[0127] 4. Experimental Data

[0128] Table 5 Statistics of LH Operation Results

[0129]

[0130] Table 6 Statistics of β - HCG Operation Results

[0131]

[0132] Table 7 Statistics of TSH Operation Results

[0133]

[0134] 5. Analysis of Experimental Data

[0135] The test results show that when detecting in the order of FSH > LH > β-HCG > TSH, the CV of each sample detection is not higher than 8%, and the percentage deviation of the mean value from the theoretical value is not higher than 10%.

[0136] 6. Experimental conclusion

[0137] According to the solution of Embodiment 1, determining the detection order of detection items according to the cross-reaction intensity can reduce the cross-interference between detection items.

[0138] Corresponding to the foregoing method embodiments for realizing application functions, the present application further provides a control device, a readable storage medium, a sample analyzer for reducing cross-interference of detection item reagents, and corresponding embodiments.

[0139] This embodiment provides a control device for reducing cross-interference of detection item reagents, which is applied to a sample analyzer and includes: a receiving module for receiving detection tasks of at least two items to be detected; a judging module for judging associated item groups in the items to be detected; and a determining module for determining the detection order of each item to be detected in the associated item group according to the association intensity of the items to be detected in the associated item group.

[0140] The control device of the embodiment of the present application may further include a processor and a memory. The processor is used to execute the above-mentioned various program modules stored in the memory to realize the operation control of detection items, and control each item to be detected in the associated item group to execute according to the determined detection order.

[0141] The processor may be a central processing unit (CPU), or may also be other general-purpose processors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor may be a microprocessor or the processor may also be any conventional processor, etc.

[0142] The memory may include various types of storage units, such as system memory, read-only memory (ROM), and permanent storage devices. Among them, the ROM can store static data or instructions required by the processor or other modules of the computer. The permanent storage device can be a readable and writable storage device. The permanent storage device can be a non-volatile storage device that does not lose the stored instructions and data even when the computer is powered off. In some embodiments, the permanent storage device uses a mass storage device (such as a magnetic or optical disk, flash memory) as the permanent storage device. In some other embodiments, the permanent storage device can be a removable storage device (such as a floppy disk, optical drive). The system memory can be a readable and writable storage device or a volatile readable and writable storage device, such as dynamic random access memory. The system memory can store some or all of the instructions and data required by the processor during operation. In addition, the memory can include any combination of computer-readable storage media, including various types of semiconductor storage chips (such as DRAM, SRAM, SDRAM, flash memory, programmable read-only memory), and magnetic disks and / or optical disks can also be used. In some embodiments, the memory can include a removable storage device that is readable and / or writable, such as a compact disc (CD), read-only digital versatile disc (such as DVD-ROM, dual-layer DVD-ROM), read-only Blu-ray disc, super density disc, flash memory card (such as SD card, min SD card, Micro-SD card, etc.), magnetic floppy disk, etc. The computer-readable storage medium does not include carrier waves and instantaneous electronic signals transmitted wirelessly or wiredly.

[0143] Executable code is stored on the memory, and when the executable code is processed by the processor, it can cause the processor to execute some or all of the methods described above.

[0144] In addition, the method according to the present application can also be implemented as a computer program or computer program product, which includes computer program code instructions for executing some or all of the above steps of the method according to the present application.

[0145] Alternatively, the present application can also be implemented as a computer-readable storage medium (or non-transitory machine-readable storage medium or machine-readable storage medium) on which executable code (or computer program or computer instruction code) is stored. When the executable code (or computer program or computer instruction code) is executed by the processor of an electronic device (or server, etc.), it causes the processor to execute some or all of the steps of the method according to the present application.

[0146] It should be noted that although several units / modules or sub-units / modules of the operation control device for the detection items are mentioned in the above detailed description, this division is merely exemplary and not mandatory. In fact, according to the embodiments of the present invention, the features and functions of two or more units / modules described above can be embodied in one unit / modules. Conversely, the features and functions of one unit / modules described above can also be further divided and embodied by multiple units / modules.

[0147] The embodiment of the present application also provides a sample analyzer, including:

[0148] A reagent unit, including a reagent bin for storing detection reagents and a pipette for aspirating detection reagents;

[0149] A sample unit, including a sample bin for storing samples and a sampling arm for aspirating samples;

[0150] An analysis unit for analyzing the mixture of the sample and the reagent;

[0151] A control device for controlling the sample analyzer, the control device includes the aforementioned readable storage medium for executing the steps of the method for reducing the reagent cross-interference of the detection items.

[0152] The solution of the present application has been described in detail above with reference to the accompanying drawings. In the above embodiments, the descriptions of the respective embodiments have their own emphases. For the parts not described in detail in a certain embodiment, reference can be made to the relevant descriptions of other embodiments. Those skilled in the art should also be aware that the actions and modules involved in the specification are not necessarily essential to the present application. In addition, it can be understood that the steps in the method embodiments of the present application can be adjusted, combined, and deleted according to actual needs, and the modules in the device embodiments of the present application can be combined, divided, and deleted according to actual needs.

[0153] The above has described the embodiments of the present application. The above description is exemplary and not exhaustive, and is not limited to the disclosed embodiments. Many modifications and changes are obvious to those of ordinary skill in the art in the technical field without departing from the scope and spirit of the described embodiments. The selection of the terms used herein is intended to best explain the principles of the embodiments, the practical application, or the improvement of the technology in the market, or to enable other ordinary technicians in the technical field to understand the disclosed embodiments.

Claims

1. A method for reducing cross-interference of detection reagents for detection items, characterized in that, it includes: Receiving detection tasks for at least two detection items to be detected; Judging the associated item groups in the detection items to be detected; Determining the detection order of each of the detection items to be detected in the associated item group according to the association strength of the detection items to be detected in the associated item group.

2. The method according to claim 1, characterized in that, The target molecules specifically bound by the detection molecules in the detection reagents corresponding to any two of the detection items to be detected in the associated item group have partially identical molecular structures.

3. The method according to claim 1 or 2, characterized in that, The detection molecule in the detection reagent corresponding to one of the detection items to be detected in the associated item group will bind to the target molecule of another detection item to be detected.

4. The method according to claim 1, characterized in that, The determining the detection order of each of the detection items to be detected in the associated item group according to the association strength of the detection items to be detected in the associated item group includes: According to the association strength of the detection items to be detected in the associated item group, screening out the detection item to be detected with the highest association strength with other detection items to be detected in the associated item group, and arranging the detection order of this detection item in the nth place, where n is the total number of detection items to be detected in the associated item; Screening out the detection item to be detected with the weakest association strength with the detection item to be detected in the mth place from other detection items to be detected, and arranging the detection order of this detection item in the (m - 1)th place. Starting from m = n until m = 3, sequentially complete the sorting of n - 1 detection items to be detected in the associated item group, and arrange the last detection item in the first place, where m is a natural number from 3 to n.

5. A method for determining the association strength according to claim 1, characterized in that, it includes: Equally mixing the samples of all detection items to be detected in the associated item group to prepare a mixed sample; Splitting and combining the paired detection reagents of the detection items to be detected in the associated item group to form multiple groups of paired reagents to be detected; Mixing the paired reagents to be detected with the mixed sample and detecting the luminescence signal; Determining the association strength of the detection items to be detected in the associated item group according to the luminescence signal.

6. The method according to claim 5, characterized in that, The splitting and combining the paired detection reagents of the detection items to be detected in the associated item group to form multiple groups of paired reagents to be detected includes: Mixing one reagent in the paired detection reagent of any one of the detection items to be detected in the associated item group with the other reagent in the paired detection reagents of other detection items to be detected one by one to form multiple groups of paired reagents to be detected.

7. The method according to claim 5 or 6, characterized in that, The determining the association strength of the detection items to be detected in the associated item group according to the luminescence signal includes: Mixing the paired detection reagent of any one of the detection items to be detected in the associated item group with the mixed sample as a control detection item, detecting the luminescence signal of the control item and using it as a control signal; Calculate the ratio of the luminescence signal of the test pairing reagent to the corresponding control signal, and use the ratio as the cross-reaction intensity of the test pairing reagent. Determine the association strength between the two test items corresponding to the cross-reaction intensity of the test pairing reagent.

8. The method according to claim 7, wherein, the determining the association strength between the two test items corresponding to the cross-reaction intensity of the test pairing reagent includes: Performing an additive calculation on the luminescence signals of each group of test pairing reagents formed by splitting and combining the two test items to obtain the association strength between the two test items.

9. A readable storage medium, on which a computer program is stored. When the computer program is executed, the steps of the method for reducing cross-interference of reagents for test items as described in any one of claims 1 to 4 are performed.

10. A sample analyzer, wherein, comprising: A reagent unit, including a reagent bin for storing detection reagents and a pipette for aspirating detection reagents; A sample unit, including a sample bin for storing samples and a sampling arm for aspirating samples; An analysis unit for analyzing the mixture of the sample and the reagent; A control device for controlling the sample analyzer. The control device includes the readable storage medium as described in claim 9 and is used to perform the steps of the method for reducing cross-interference of reagents for test items as described in any one of claims 1 to 4.

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