Allergen detection task generation method, detection method and sample analyzer

Abstract

This application relates to a method for generating allergen testing tasks, a testing method, and a sample analyzer. The method includes: identifying the testing information on a test order and determining the allergen testing type; displaying a test work order indicating the testing items based on the allergen testing type, wherein the testing items include a fixed test item group and a candidate test item group; determining multiple candidate test items corresponding to the testing information from the candidate test item group based on the user's selection instructions, and forming a flexible test item group; and generating an allergen testing task based on the fixed test item group, the flexible test item group, and a reference test item. The solution provided by this application enables flexible combination testing of allergens, reducing testing costs for patients.

Description

Technical Field

[0001] This application relates to the field of biomedical detection technology, and in particular to a method for generating allergen detection tasks, a detection method, and a sample analyzer. Background Technology

[0002] Allergen testing falls under the category of etiological testing. It involves detecting allergen-specific antibodies (sIgE) in a patient's body. By detecting sIgE, clinical diagnosis can be aided, and patients can be guided to take measures to avoid exposure to these allergens, thereby alleviating clinical symptoms. Furthermore, allergic diseases exhibit significant geographical and racial characteristics. Epidemiological studies show that due to differences in climate, dietary habits, customs, and the frequency of different allergens varies across different regions or ethnic groups.

[0003] In related technologies, sIgE detection employs an indirect analysis mode. This involves coating a solid-phase material with a known antigen, binding it to the antibody to be tested, washing it, and then using a signal-labeled anti-human IgE antibody to report the antigen-antibody reaction intensity, ultimately determining the result. Depending on the detection method, sIgE detection is divided into two types: single-item detection with arbitrary combination mode and fixed-combination combined detection mode. The single-item detection with arbitrary combination mode means that one reaction cup detects only one type of sIgE antibody. Based on clinical manifestations and medical history, the types and quantities of allergens can be arbitrarily combined. The fixed-combination combined detection mode often uses a nitrocellulose membrane as the solid-phase carrier. The membrane strip is sequentially coated with multiple allergen components according to different physical positions, and then incubated with the serum to be tested. The sIgE to be tested binds to specific antigens on the surface of the solid-phase membrane. After washing, the signal-labeled anti-human IgE antibody reports the antigen-antibody reaction intensity. Depending on the color development location, the result is obtained by photographing or scanning.

[0004] However, the two sIgE detection modes mentioned above have some drawbacks: in the single-item detection mode, registration and production are based on a single allergen, resulting in high registration and production costs. In the fixed-combination detection mode, the allergen is pre-fixed on the membrane strip surface, and can only accept fixed combinations during use, failing to meet the detection needs of random combinations. Summary of the Invention

[0005] To address or partially address the problems existing in related technologies, this application provides an allergen detection task generation method, a detection method, and a sample analyzer, which can flexibly combine and detect allergens, reducing detection costs.

[0006] The first aspect of this application provides a method for generating an allergen detection task, comprising: Identify the test information on the test report to determine the type of allergen test; Based on the allergen detection type, a test order is displayed to indicate the test items, which includes a fixed test item group and a candidate test item group; Based on the user's selection instructions, multiple candidate detection items corresponding to the detection information are determined from the candidate detection item group and formed into a flexible detection item group; An allergen detection task is generated based on the fixed detection item group, the flexible detection item group, and the reference detection item.

[0007] As an optional embodiment, the allergen detection type includes at least one of inhaled allergen detection and ingested allergen detection.

[0008] As an optional embodiment, it further includes: a multi-hole detection mode, the multi-hole detection mode including multiple holes for fixed detection item group detection, multiple holes for elastic detection item group detection, and a single hole for reference detection item detection.

[0009] As an optional embodiment, the interconnected hole detection mode is an eight-hole interconnected hole detection mode, which includes four holes for fixed detection item group detection, three holes for flexible detection item group detection, and one hole for reference detection item detection.

[0010] As an optional embodiment, the candidate detection items include at least one of the following: allergen detection based on regional differences, allergen detection based on seasonal differences, allergen detection based on age differences, and allergen detection based on dietary differences.

[0011] A second aspect of this application provides a detection kit for the allergen detection task generation method described above, comprising: Multiple test reagent sets are provided, with different test reagent sets matched for different allergen detection tasks; each test reagent set includes multiple fixed test reagents and multiple flexible test reagents. A testing container includes multiple testing holes and a reference hole. The multiple testing holes include a fixed testing hole group and a flexible testing hole group. The fixed testing hole group is used to match multiple fixed testing reagents in the testing reagent group, and the flexible testing hole group is used to match multiple flexible testing items in the testing reagent group.

[0012] As an optional embodiment, the detection steps of the test kit include: Based on the allergen detection task, select the reagents required for the first step reaction; A sample, reagents required for the first step reaction, and reagents required for the second step reaction are sequentially added into multiple detection wells and reference wells of the detection container, and a luminescent complex to be detected is formed in the detection wells, and a reference luminescent complex is formed in the reference wells. The chemiluminescent signals of the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well are detected. Analyze the chemiluminescent signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction.

[0013] As an optional embodiment, analyzing the chemiluminescence signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction includes: Based on the relationship between the chemiluminescent signal of the reference luminescent complex in the reference well and the first threshold, it is determined whether it is an allergic reaction; If the chemiluminescence signal of the reference luminescent complex in the reference well is greater than the first threshold, it is determined to be an allergic reaction, and the allergen causing the allergic reaction is determined according to the relationship between the chemiluminescence signal of the luminescent complex to be detected in the detection well and the second threshold. If the chemiluminescence signal of the luminescent complex to be detected in the detection well is greater than the second threshold, then the allergic reaction is determined to be caused by the allergen detected in the detection well.

[0014] As an optional embodiment, the detection reagent set includes reagent R1, which includes detection reagent R1 and reference reagent R1; the detection reagent R1 contains luminescent microparticles coated with allergens, and the reference reagent R1 contains luminescent microparticles coated with anti-hIgE antibodies; the detection reagent R1 and the reference reagent R1 are respectively added to the detection well and the reference well.

[0015] As an optional embodiment, the detection reagent kit further includes reagent R2 and reagent R3, wherein reagent R2 contains a biotin-labeled anti-hIgE antibody and reagent R3 contains avidin-coated photosensitive microparticles.

[0016] A third aspect of this application provides a readable storage medium having a computer program stored thereon, which, when executed, performs the steps of the allergen detection task generation method described above.

[0017] A fourth aspect of this application provides a sample analyzer, comprising: The acquisition unit is used to acquire the aforementioned allergen detection task; The testing container includes multiple testing holes and reference holes; The reagent unit includes a reagent compartment for storing test reagents and a pipette for drawing test reagents into the test well and the reference well; The sample unit includes a sample compartment for storing samples and a sample dispensing arm for drawing samples into the detection well and the reference well; An analysis unit is used to analyze the mixture of sample and reagent in the detection well and the reference well; A control device for controlling the sample analyzer, the control device including the aforementioned readable storage medium, for executing the steps of the aforementioned allergen detection task generation method.

[0018] The technical solution provided in this application may include the following beneficial effects: The allergen testing task generation method of this application allows for flexible combination of testing items based on the needs of the region or different departments, enabling the testing to be performed as a single task. Furthermore, the method allows the combined testing reagents corresponding to a testing task to be used as a single diagnostic reagent, thus solving the problem of high testing costs associated with arbitrary combinations of single testing items and minimizing testing costs. Simultaneously, the testing reagents corresponding to the allergen testing tasks generated by this application can be flexibly combined according to regional and departmental needs, addressing the issue that fixed-combination reagents cannot meet the needs of randomized combination testing.

[0019] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and do not limit this application. Attached Figure Description

[0020] The above and other objects, features and advantages of this application will become more apparent from the more detailed description of exemplary embodiments thereof in conjunction with the accompanying drawings, wherein the same reference numerals generally represent the same components in the exemplary embodiments thereof.

[0021] Figure 1 This is a schematic flowchart illustrating the allergen detection task generation method in an embodiment of this application; Figure 2 This is a schematic flowchart illustrating the detection method for an allergen detection task as shown in the embodiments of this application; Figure 3 This is a schematic diagram illustrating the principle of the detection method ("4+3X+1" allergen screening mode) for allergen detection tasks shown in the embodiments of this application. Figure 4 This is the calibration curve of tIgE shown in the embodiments of this application; Figure 5 This is the calibration curve of sIgE shown in the embodiments of this application; Figure 6 This is a schematic diagram of the structure of an electronic device shown in an embodiment of this application. Detailed Implementation

[0022] Embodiments of this application will now be described in more detail with reference to the accompanying drawings. While embodiments of this application are shown in the drawings, it should be understood that this application may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, 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.

[0023] The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The singular forms “a,” “the,” and “the” used in this application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and includes any or all possible combinations of one or more of the associated listed items.

[0024] It should be understood that although the terms "first," "second," "third," etc., may be used in this application to describe various information, this information should not be limited to these terms. These terms are only used to distinguish information of the same type from one another. For example, without departing from the scope of this application, first information may also be referred to as second information, and similarly, second information may also be referred to as first information. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this application, "multiple" means two or more, unless otherwise explicitly specified.

[0025] In related technologies, sIgE detection employs an indirect analysis mode. Depending on the detection method, sIgE detection is divided into two types: single-item detection with arbitrary combinations and fixed-item combination detection. However, both single-item detection with arbitrary combinations and fixed-item combination detection have some drawbacks: in the single-item detection mode, registration and production are based on a single allergen, resulting in high registration and production costs. In the fixed-item combination detection mode, the allergen is pre-fixed on the membrane strip surface, meaning clinical laboratories can only accept fixed combinations and cannot meet the needs of randomized combination detection.

[0026] To address the aforementioned issues, this application provides an allergen detection task generation method that enables flexible combination detection of allergens, thereby reducing detection costs.

[0027] The technical solutions of the embodiments of this application are described in detail below with reference to the accompanying drawings.

[0028] Figure 1 This is a schematic flowchart illustrating the allergen detection task generation method shown in the embodiments of this application.

[0029] See Figure 1This application provides a method for generating an allergen detection task, including steps S101 to S104: Step S101: Identify the test information on the test form and determine the allergen test type.

[0030] The testing form in step S101 is a test form issued by a doctor after clinical diagnosis. The form must at least include patient information, allergen testing type, and testing items. Patient information may include patient name, gender, ID, etc.; the allergen testing type may include at least one of inhaled allergen testing and ingested allergen testing; the testing items may include a fixed testing item group, a flexible testing item group, and a reference testing item. The test form may only include the flexible testing items. Different allergen testing types correspond to different testing items. The flexible testing item group can be selected by the clinician from the candidate testing item group based on the patient's symptoms, subjective feelings, living and residential conditions, combined with the geographical characteristics and climate conditions of the patient's residence, to form a flexible testing item group for personalized testing. The reference testing item is used to detect tIgE, which is used to detect the patient's overall allergic reaction and serves as an indicator for drug use and monitoring its effectiveness.

[0031] This application uses inhaled allergen detection and food allergen detection as examples to illustrate the detection items included in these two types: For example, the fixed detection item group in inhaled allergen detection may include at least one allergen detection among house dust mites, flour mites, cat hair, and dog hair; the optional detection item group in inhaled allergen detection may include at least one allergen detection among artemisia, hops, cockroaches, house dust, Aspergillus fumigatus, ragweed, and trees; the fixed detection item group in food allergen detection may include at least one allergen detection among milk, eggs, soybeans, and peanuts; the optional detection item group in food allergen detection may include at least one allergen detection among shrimp, crab, scallops, beef, mutton, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts.

[0032] The detection information in step S101 can usually be obtained from the hospital's customer information system (HIS) after the sample analyzer scans the test order.

[0033] Step S102: Based on the allergen testing type, display the test order to indicate the test items, which includes a fixed test item group and a candidate test item group.

[0034] The sample analyzer's database contains test orders displayed on the human-computer interface. These test orders are matched to the allergen testing type and can include inhaled allergen test orders and ingested allergen test orders. For example, an inhaled allergen test order includes a fixed test item group and a candidate test item group. The fixed test item group can include at least one allergen test among house dust mites, flour mites, cat dander, and dog dander, while the candidate test item group can include at least one allergen test among artemisia, hops, cockroaches, house dust, Aspergillus fumigatus, ragweed, and tree sap. Similarly, an ingested allergen test order includes a fixed test item group and a candidate test item group. The fixed test item group can include at least one allergen test among milk, eggs, soybeans, and peanuts, while the candidate test item group can include at least one allergen test among shrimp, crab, scallops, beef, lamb, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts.

[0035] Step S103: Based on the user's selection instructions, determine multiple candidate detection items corresponding to the detection information from the candidate detection item group, and form a flexible detection item group.

[0036] In the test order displayed on the human-computer interface of the sample analyzer, fixed test item groups are unselectable buttons (e.g., gray boxes), while selectable test item groups are selectable buttons (e.g., white boxes). Users select the corresponding candidate test items from the candidate test item groups based on the test information recorded in the test order. The selected candidate test items form a flexible test item group. For example, if a doctor prescribes a test order after clinical consultation for inhaled allergen testing (Artemisia argyi, Humulus scandens, and Ragweed), the user will select Artemisia argyi, Humulus scandens, and Ragweed from the candidate test item groups; these test items form a flexible test item group.

[0037] Step S104: Generate an allergen testing task based on the fixed testing item group, the flexible testing item group, and the reference testing item.

[0038] After determining the flexible testing item group, the fixed testing item group, the flexible testing item group, and the reference testing item group are combined into an allergen testing task. The sample analyzer determines the corresponding testing reagents based on the allergen testing task.

[0039] The allergen detection task generation method of this application embodiment allows for flexible combination of detection items based on the needs of the region or different departments, enabling them to be combined into a single detection task. Furthermore, the combined detection reagents corresponding to the detection task can be used as a single diagnostic reagent. This not only solves the problem of high cost associated with arbitrary combinations of single test items but also addresses the issue that fixed combination testing methods cannot meet the needs of random combination testing. Therefore, the detection reagents corresponding to the allergen detection tasks generated in this application embodiment can be used as single diagnostic reagents, and by combining regional and departmental flexible combination requirements, testing costs can be minimized.

[0040] As an optional embodiment, the allergen detection type includes at least one of inhaled allergen detection and ingested allergen detection.

[0041] Allergens are classified according to their route of entry into the body: inhaled allergens (such as pollen and animal dander), ingested allergens (such as milk and eggs), and intradermal contact allergens (such as mosquito bites), or other routes. This application's embodiments only illustrate inhaled and ingested allergen detection; other types of allergen detection are similar and will not be elaborated upon further.

[0042] As an optional embodiment, the allergen detection task generation method further includes: It is equipped with a multi-hole detection mode, which includes multi-holes for fixed detection item groups, multi-holes for elastic detection item groups, and single holes for reference detection item groups.

[0043] The embodiments of this application can achieve the simultaneous addition of samples and reagents in fixed detection project groups, flexible detection project groups and reference detection projects through the interconnected detection mode (for example, samples and reagents can be added by one aspiration and multiple dispensing), as well as simultaneous detection of multiple projects, which can greatly improve detection efficiency.

[0044] As a preferred embodiment, the interconnected hole detection mode is an eight-hole interconnected hole detection mode, which includes four holes for fixed detection item group detection, three holes for elastic detection item group detection, and one hole for reference detection item detection.

[0045] The eight-well detection mode of this application embodiment can be a "4+3X+1" mode, where four wells are used for fixed test item group detection, three wells are used for flexible test item group detection, and one well is used for reference test item detection, forming a total of 8 test wells. The eight-well strip of Komei Diagnostics Technology Co., Ltd. can be used as a test unit, and the sample to be tested and the test reagent are added by one aspiration and multiple dispensing, which can realize the six-strip joint detection mode to meet the needs of high-speed detection.

[0046] This application provides a novel method for clinical allergen screening using a "4+3X+1" combined detection mode based on photoluminescence homogeneous emission technology. In this detection mode, the fixed wells ("4+1": fixed detection well group + reference well) can detect common sIgE and total IgE of allergens, while the flexible detection wells ("3X") allow for personalized testing based on the patient's specific needs. Therefore, this combined detection mode shortens the detection time, improves detection efficiency, and requires only a small amount of serum to achieve automated detection.

[0047] As an optional embodiment, the candidate detection items include at least one of the following: allergen detection based on regional differences, allergen detection based on seasonal differences, allergen detection based on age differences, and allergen detection based on dietary differences.

[0048] While allergic diseases can affect people of almost any age and in any region, the incidence and type of allergic diseases can vary across different ages and regions. For example, people with a family history of allergic diseases are more likely to develop them, indicating that genetic factors play an important role in their development. Lifestyle factors, such as diet, living environment, and frequency of allergen exposure, are also associated with the incidence of allergic diseases. Urban living, poor indoor air quality, and changes in dietary structure are considered to increase the risk of allergic diseases. In terms of age, the incidence of allergic diseases is generally higher in childhood and may then decline or stabilize in adulthood. In terms of gender, some allergic diseases show significant differences between men and women; for example, asthma is more common in men in childhood but more common in women in adulthood. The occurrence of allergic diseases is closely related to the frequency and type of allergen exposure. For example, the occurrence of seasonal allergic rhinitis is associated with the seasonal release of pollen allergens. Environmental factors, such as air pollution, climate change, and chemical exposure, may also be associated with the prevalence of allergic diseases. Climate change can affect the distribution and release of allergens.

[0049] This application's embodiments, targeting the characteristics of allergic diseases, set different conditions for the fixed and optional test items in the testing program. For example, the allergens in the fixed test item group in this application's embodiments meet the following characteristics: high probability of occurrence, no obvious regionality, no obvious seasonality, and no significant age difference. The allergens in the optional test item group in this application's embodiments meet the following characteristics: obvious regional characteristics, obvious seasonal characteristics, obvious dietary differences, and significant age differences.

[0050] The following section explains the testing items using inhaled allergen testing and ingested allergen testing as examples: The test items for inhaled allergen testing include: Based on literature review and epidemiological statistical analysis, four common allergens that are not easily affected by seasons or regions were selected as fixed testing items. Screening revealed that among people with inhalant allergies, 25% to 35% are allergic to house dust mites and flour mites, and 5% to 10% are allergic to cat and dog dander. Because these are less affected by seasons and are generally more prevalent, they were selected as fixed testing items. Allergens that are prevalent in spring and autumn, such as artemisia, ragweed, and Aspergillus fumigatus, and allergens that are easily affected by regional differences, such as hops, cockroaches, and trees, were selected as candidate testing items to provide targeted and accurate testing for patients and reduce testing costs.

[0051] Test items for food allergen testing: Based on literature review and epidemiological statistical analysis, high-frequency food allergens were selected as fixed testing items, with eggs and milk being the most common. Considering common food types in China and nutritional sources, soybeans and peanuts were also selected as four fixed allergens for testing. Based on regional dietary differences and differences in coastal and inland geographical locations, shrimp, crab, scallops, beef, lamb, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts were selected as candidate testing items, covering a variety of nutritional needs. Doctors can flexibly combine testing methods after consulting with patients about their dietary habits.

[0052] Figure 2 This is a schematic flowchart illustrating the detection method for an allergen detection task as shown in the embodiments of this application.

[0053] See Figure 2 This application also provides a detection method for an allergen detection task, including steps S201 to S204: Step S201: Select the reagents required for the first step reaction according to the allergen detection task.

[0054] This application embodiment combines photo-induced chemiluminescence (PET) analysis to complete the allergen detection task. PET analysis belongs to homogeneous immunoassay, which eliminates the need for separation and washing, and directly performs signal detection. The analysis system includes luminescent microparticles coated with antigens or antibodies, biotin-labeled antigens or antibodies, and photosensitive microparticles coated with streptavidin. The PET process includes two steps: the analyte in the sample first reacts with the luminescent microspheres coated with antigens or antibodies and the biotin-labeled antigens or antibodies in the reagents required for the first step reaction, generating an immunoreaction complex. Subsequently, the immunoreaction complex reacts with the streptavidin-coated photosensitive microparticles in the reagents required for the second step reaction, generating a chemiluminescent complex. The binding of biotin and avidin shortens the distance between the luminescent and photosensitive microspheres (<200 nm), allowing the photosensitive microspheres to release singlet oxygen under excitation light, enabling the luminescent microspheres to emit light. Finally, the concentration of the analyte in the sample solution is calculated by detecting the luminescence signal.

[0055] In step S201, since the test reagents for the fixed test item group and the reference test item can be determined after the allergen test type is determined, this step mainly involves selecting the reagents required for the first step reaction corresponding to the flexible test item group.

[0056] Step S202: The sample, the reagents required for the first step reaction, and the reagents required for the second step reaction are sequentially added into the multiple detection wells and reference wells of the detection container, and the luminescent complex to be detected is formed in the detection wells, and the reference luminescent complex is formed in the reference wells.

[0057] In step S202, the detection container can be an eight-well strip from Komei Biotechnology Co., Ltd., in which the samples in the detection wells and reference wells, as well as the reagents required for the second step reaction, are all shared reagents.

[0058] The first step of the reaction requires reagents R1 and R2, while the second step requires reagent R3. Reagent R1 includes detection reagent R1 and reference reagent R1, which are added to the detection well and reference well, respectively. Detection reagent R1 contains luminescent microparticles coated with allergens, reference reagent R1 contains luminescent microparticles coated with anti-hIgE antibodies, reagent R2 contains biotin-labeled anti-hIgE antibodies, and reagent R3 contains avidin-coated photosensitive microparticles. The luminescent complex to be detected and the reference luminescent complex both contain chemiluminescent complexes.

[0059] Step S203: Detect the chemiluminescence signals of the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well.

[0060] The luminescence information of the reference luminescent complex is used to assist clinicians in making a more definitive diagnosis, while the luminescent complex to be tested is used to identify the allergen, which helps guide patients to take measures to avoid contact with these allergens and alleviate clinical symptoms.

[0061] Step S204: Analyze the chemiluminescence signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction.

[0062] Figure 3 This is a schematic diagram illustrating the principle of the detection method ("4+3X+1" allergen screening mode) for allergen detection tasks shown in the embodiments of this application.

[0063] In the diagram, ABCD represents the fixed detection well group, used for the detection of fixed test items; EFG represents the elastic detection well group, used for the detection of elastic test items; H represents the reference well, used for the detection of reference items; GG represents photosensitive microspheres; FG represents luminescent microspheres; Bio represents biotin; Ag represents allergens; SA represents streptavidin; and Ab represents the sIgE antibody to be detected.

[0064] The following combination Figure 3 The principles of the detection methods for allergen testing are explained: 1. Based on the allergen detection task, determine the detection reagents corresponding to EFG.

[0065] 2. Add 1:10 diluted sample (containing the sIgE antibody and tIgE to be tested) 50 μL / well to each test well and reference well of the test container, and use a one-pipe-multiple-split sample addition method; 3. Add the corresponding allergen-coated luminescent microparticle solution (test reagent R1) to each of ABCD, 25 μL / Well; add the corresponding allergen-coated luminescent microparticle solution (test reagent R1) to each of EFG according to the flexible test items determined by the user's selected instructions, 25 μL / Well; add anti-hIgE antibody-coated luminescent microparticle solution (reference reagent R1) to H, 25 μL / Well. 4. Add biotin-labeled anti-hIgE antibody solution (reagent R2) to each well, 25 μL / well, and use a single aspirator to add multiple samples at a time; 5. Incubate at 42°C for 30 minutes to allow the first step reaction to occur in the detection well and reference well; 6. Add streptavidin-coated photosensitive microparticle solution (reagent R3) to each well, 25 μL / well, and use a single aspiration and multiple dispensing method; 7. The second reaction occurs in the detection well and the reference well at 42°C for 10 minutes, forming the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well. 8. Detect the optical signal and output the result.

[0066] This application utilizes photo-induced chemiluminescence analysis, which offers advantages such as no need for separation and washing, the use of a single biotin-labeled secondary antibody, and a universal photosensitive solution. It also provides convenient combination of total immunoglobulin E (tIgE) levels. Furthermore, the "4+3X+1" allergen screening model proposed in this application can be used as a single diagnostic reagent to meet the flexible combination needs of different regions and departments, minimizing testing costs.

[0067] As an optional embodiment, step S204 may include: S214: Determine whether it is an allergic reaction based on the relationship between the chemiluminescent signal of the reference luminescent complex in the reference well and the first threshold.

[0068] In step S214, the chemiluminescent signal of the reference luminescent complex is mainly used to indicate whether the patient has an allergic reaction, wherein the first threshold can be 70 IU / mL.

[0069] S224: If the chemiluminescence signal of the reference luminescent complex in the reference well is greater than the first threshold, it is determined to be an allergic reaction, and the allergen causing the allergic reaction is determined based on the relationship between the chemiluminescence signal of the luminescent complex to be tested in the detection well and the second threshold.

[0070] If the chemiluminescent signal of the reference luminescent complex is greater than 70 IU / mL, an allergic reaction is identified. Further analysis is then performed based on the relationship between the chemiluminescent signal of the tested luminescent complex and a second threshold to determine the allergen causing the allergic reaction. The second threshold can be 0.35 kU. A / L.

[0071] S234: If the chemiluminescence signal of the luminescent complex to be detected in the detection well is greater than the second threshold, then the allergic reaction is determined to be caused by the allergen to be detected in the detection well.

[0072] If the chemiluminescence signal of the luminescent complex to be detected in a certain detection well is greater than 0.35 kU A If the result is / L, then the allergic reaction is determined to be caused by the corresponding allergen detected in that test well.

[0073] This application also provides a detection kit, comprising: Multiple test kits are available, with different kits designed for different allergen detection tasks. Each kit includes multiple fixed test kits and multiple flexible test kits.

[0074] The testing container includes multiple testing holes and a reference hole. The multiple testing holes include a fixed testing hole group and a flexible testing hole group. The fixed testing hole group is used to match multiple fixed testing reagents in the testing reagent group, and the flexible testing hole group is used to match multiple flexible testing reagents in the testing reagent group.

[0075] In this application embodiment, one test kit is matched with one allergen detection task, and the flexible test reagents in the test kit can be flexibly combined according to the allergen detection task. Not only can each test kit be applied for registration as a single diagnostic reagent, but it also meets the needs of flexible combination in different regions and departments.

[0076] As an optional embodiment, the test reagent set includes reagent R1, which includes test reagent R1 and reference reagent R1; test reagent R1 contains luminescent microparticles coated with allergens, and reference reagent R1 contains luminescent microparticles coated with anti-hIgE antibody; test reagent R1 and reference reagent R1 are respectively added to the test well and the reference well.

[0077] As an optional embodiment, the detection reagent kit also includes reagent R2 and reagent R3, wherein reagent R2 contains a biotin-labeled anti-hIgE antibody and reagent R3 contains avidin-coated photosensitive microparticles.

[0078] The detection wells in the allergen detection kit of this application embodiment can employ an indirect detection mode: FG-Ag (reagent R1), Bio-anti-hIgE (reagent R2), and a photosensitive solution (GG-SA) form a detection system. FG-Ag contains multiple reagents applicable to the detection of different allergens. Furthermore, the reference wells in the allergen detection kit can employ a double-antibody sandwich detection mode: FG-anti-hIgE (reagent R1), Bio-anti-hIgE (reagent R2), and a photosensitive solution (GG-SA) form a detection system.

[0079] To make the present invention easier to understand, the following describes the allergen detection method and allergen detection kit of this application using two types of allergen detection as examples: I. Types of Allergen Detection Kits The allergen detection kits in this application are divided into two categories: inhaled allergen kits and ingested allergen kits.

[0080] (1) Inhalation allergen kit: Based on literature review and epidemiological statistical analysis, four common allergens that are not easily affected by seasons and regions were selected as fixed testing items. Screening revealed that among people with inhalant allergies, 25% to 35% were allergic to house dust mites and flour mites, and 5% to 10% were allergic to cat and dog dander. Because these are less affected by seasons and are generally more prevalent, they were selected as fixed testing items. Allergens that are prevalent in spring and autumn, such as artemisia, ragweed, and Aspergillus fumigatus, and allergens that are easily affected by regional differences, such as hops, cockroaches, and trees, were selected as candidate testing items to provide targeted and accurate testing for patients and reduce testing costs. The "4+3X+1" allergen testing kit was limited based on the characteristics of inhalant allergens. 4 indicates fixed testing items: house dust mites, flour dust mites, cat hair, and dog hair.

[0081] 3X indicates the items to be tested: Artemisia argyi, Hops, cockroaches, house dust, Aspergillus fumigatus, ragweed, and trees.

[0082] 1 indicates the reference test item: tIgE.

[0083] (2) Food allergen test kit: Based on literature review and epidemiological statistical analysis, high-frequency food allergens were selected as fixed testing items, with eggs and milk being the most common. Considering common food types in China and nutritional sources, soybeans and peanuts were also selected as fixed testing items. Based on regional dietary differences and differences in coastal and inland geographical locations, shrimp, crab, scallops, beef, mutton, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts were selected as candidate testing items, covering a variety of nutritional needs. Doctors can flexibly combine testing methods after consulting with patients about their dietary habits.

[0084] 4 indicates fixed testing items: milk, eggs, soybeans, peanuts 3X indicates the items to be tested: shrimp, crab, scallops, beef, lamb, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts. 1 indicates the reference test item: tIgE.

[0085] II. Allergen-coupled luminescent microspheres Using carboxyl-based luminescent microspheres as carriers, 11 inhalant allergens (house dust mite, flour dust mite, cat dander, dog dander, artemisia, hops, cockroach, house dust, Aspergillus fumigatus, ragweed, tree dust), 17 food allergens (milk, eggs, soybeans, peanuts, shrimp, crab, scallops, beef, mutton, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, hazelnuts) and tIgE were coated onto the surface of the luminescent microspheres using conventional coating methods (EDC activation). The microspheres were stored at 4°C.

[0086] III. 4+3X+1 Detection Mode Combination To meet the flexible testing needs of different regions, seasons, and departments, four fixed testing items are selected: inhaled allergens (house dust mites, flour mites, cat dander, dog dander) and ingested allergens (milk, eggs, soy, peanuts). Doctors can choose allergen testing combinations from a 3X range, taking into account seasonally prevalent allergens (such as high incidence of allergies to mugwort, ragweed, and mold in autumn), age-related prevalent allergens (such as high incidence of shrimp, crab, and peanut allergies in infancy), and symptom assessment and medical history of the patient, thereby reducing the testing cost for patients.

[0087] IV. Testing Process Detection steps The serum sample was diluted 1:10. 25 μL of serum, 25 μL of biotinylated anti-human IgE antibody, and 25 μL of the corresponding FG-Ag solution (antigen-coated luminescent microparticle solution) for the fixed / flexible test item were added to each well of the eight-well strip. The strip was incubated at 37°C for 30 minutes. If the serum contained the target IgE antibody, an FG-Ag-target IgE antibody-biotinylated anti-human IgE antibody complex was formed. After the first incubation period, 150 μL of universal photosensitive solution (streptavidin-coated photosensitive microparticle solution SA-GG) was added to each well. After incubation for 15 minutes, the patient's allergic reaction was determined based on the intensity of the detection signal.

[0088] Establish calibration curves Calibration curve for total IgE (tIgE) (see) Figure 4 The calibration curves for tIgE (sIgE) were generated using six different concentrations of calibrators from the tIgE kit, while the calibration curves for specific IgE (sIgE) are shown in (see [link to calibrator]). Figure 5 The calibration curve is generated by diluting low-value calibrators. The generated calibration curve can be used to calibrate the detection values ​​for each allergen, thereby creating a standardized measurement pattern.

[0089] Performance testing As shown in Table 2, three different grades of serum (high, medium, and low) were selected for repeated assays of house dust mite sIgE to assess accuracy, and the mean, SD, and CV values ​​were calculated. The CV values ​​characterizing repeatability ranged from 3.46% to 8.37%, and the CV values ​​characterizing intermediate precision ranged from 4.51% to 9.48%, both below 10%, meeting the requirements for repeatability and high precision detection.

[0090] Table 2 Repeatability and intermediate precision of house dust mite sIgE assay

[0091] Limit of Quantification (LoQ) Sixty blank samples were tested, and the test results of the 60 blank samples were sorted from smallest to largest. The percentiles (Pct) of the blank sample results distribution were calculated, where α=0.05, Pct=0.95, and the index corresponding to the percentile of 0.95 is 0.5+60×0.95=57.5, that is, the value of the percentile of 0.95 is the mean of the 57th and 58th percentile values.

[0092] According to LoB = X57 + 0.5(X58) Calculate LoB using X57, where X57 = 0.035 and X58 = 0.036. Therefore, the calculated LoB is 0.035 kU. A / L.

[0093] Four low-concentration samples with concentrations ranging from 1 to 4 times the LoB were selected, and the LoD was used as the median of these four samples, yielding a LoD of 0.092 kU. A / L.

[0094] Select 3-5 samples with concentrations between 1 and 4 times the LoD, and perform at least 5 batches of measurements. Obtain at least 40 replicate results for each concentration sample, and calculate the LoQ as 0.172 kU. A / L. LoQ is not less than LoD, and CV is less than 15%, indicating that the detection method of this application embodiment can achieve accurate quantitative detection.

[0095] V. Clinical Sample Testing (1) Inhalant allergen detection The test results are as follows: Inhalant allergen test, Artemisia argyi, Humulus scandens, and Ragweed.

[0096] The instrument's testing items are as follows: Fixed testing item group: house dust mites, flour dust mites, cat hair, dog hair; Elasticity testing item group: artemisia, hops, ragweed; Reference testing item: tIgE.

[0097] The test results are shown in the table below:

[0098] The unit of sIgE is kU A / L, tIgE is in IU / mL.

[0099] A tIgE test result >70 IU / mL is considered an allergic reaction, and a sIgE test result >0.35kU is considered an allergic reaction. A The result was positive for / L, therefore the allergens were dust mites and mugwort.

[0100] (2) Detection of food allergens The test results are as follows: Food allergen test, shrimp, crab, and mutton.

[0101] The instrument was designed to detect the following items: fixed test items group: milk, eggs, soybeans, peanuts; elastic test items group: shrimp, crab, mutton; and reference test item: tIgE.

[0102] The test results are shown in the table below:

[0103] The unit of sIgE is kU A / L, tIgE is in IU / mL.

[0104] A tIgE test result >70 IU / mL is considered an allergic reaction, and a sIgE test result >0.35 kU is considered an allergic reaction. AThe result was positive for / L, therefore the allergens were milk and shrimp.

[0105] This application also provides a readable storage medium storing a computer program thereon, which, when executed, performs the steps of the aforementioned allergen detection method.

[0106] This application also provides a sample analyzer, including: The acquisition unit is used to acquire the aforementioned allergen detection task.

[0107] The testing container includes multiple testing holes and reference holes.

[0108] The reagent unit includes a reagent compartment for storing test reagents and a pipette for drawing test reagents into test wells and reference wells.

[0109] The sample unit includes a sample compartment for storing samples and a sample dispensing arm for drawing samples into the detection well and reference well.

[0110] The analysis unit is used to analyze the mixture of sample and reagent in the detection well and reference well.

[0111] A control device for controlling a sample analyzer, the control device including the aforementioned readable storage medium, for performing the steps of the aforementioned allergen detection method.

[0112] The detection method of this application embodiment can be run on any sample analyzer that analyzes blood samples using detection reagents. For example, the sample analyzer can be a biochemical analyzer, a chemiluminescence analyzer, etc. Furthermore, the sample analyzer can be a sample analyzer based on different detection methodologies, such as a biochemical analyzer based on latex turbidimetry, a chemiluminescence analyzer based on enzyme-linked immunosorbent assay (ELISA), or a chemiluminescence analyzer based on photo-induced chemiluminescence.

[0113] Although the embodiments of this application use a photochemiluminescence analyzer and a photochemiluminescence detection reagent as examples, this application is not limited to these. Rather, it can be run on any sample analyzer that uses the detection reagent to analyze blood samples, as long as the microspheres contained in the detection reagent are coated with antigens or antibodies, or biotin-labeled antigens or antibodies.

[0114] The sample analyzer provided in this application embodiment includes a detection container, which may be an eight-well strip from Komei Biotechnology Co., Ltd., and a reagent unit. The reagent unit includes a reagent compartment for storing the detection reagents required for the test and a pipette for aspirating the detection reagents into the detection wells and reference wells. The sample analyzer also includes a sample unit, which includes a sample compartment for storing a blood sample to be tested and a pipette for aspirating the detection reagents into the detection wells and reference wells. The blood sample may be, for example, a patient's blood sample or an animal's blood sample. A scanner (not shown) for reading sample codes is provided in the sample compartment. The sample analyzer also includes an analysis unit for analyzing the mixture of sample and reagents in the detection wells and reference wells. The analysis unit includes an incubation tray for holding the detection container and providing the temperature required for the reaction, for example, by heating the reaction container with a heating element. The analysis unit also includes a detection unit (not shown) for detecting the signal generated by the reaction liquid in the detection container. The sample analyzer also includes a cup unscrambler for storing the detection containers required for the analysis and transferring the detection containers to the incubation tray.

[0115] The sample analyzer is equipped with a control device that controls the operation of each component. The control device obtains the sample code from the sample compartment. The sample code is a specific identifier used to identify the sample. After obtaining the sample code, the control device retrieves the test items for the sample to be tested based on the sample code. Users can pre-input the test items corresponding to the sample code into the sample analyzer. The test items can also be obtained by the control device from a higher-level information management system (such as a Laboratory Information System (LIS) or Hospital Information System (HIS)) that is connected to the sample analyzer.

[0116] Samples to be tested are typically placed into the sample chamber in batches, such as five or ten at a time. Furthermore, each sample may correspond to multiple tests; for example, one sample may need to be tested for three infectious diseases. The control unit determines the testing reagents and controls the various components of the sample analyzer to perform the corresponding actions.

[0117] Corresponding to the aforementioned application function implementation method embodiments, this application also provides a control device, electronic device, and corresponding embodiments for an allergen detection task generation method.

[0118] This embodiment provides a control device for an allergen detection task generation method, applied to a sample analyzer, including: an identification module for identifying the detection information on a test order and determining the allergen detection type; a display module for displaying a test order indicating the detection items according to the allergen detection type, wherein the detection items include a fixed test item group and a candidate test item group; a combination module for determining multiple candidate test items corresponding to the detection information from the candidate test item group based on the user's selection instructions, and forming a flexible test item group; and a generation module for generating an allergen detection task based on the fixed test item group, the flexible test item group, and the reference test items.

[0119] The control device in this application embodiment may further include a processor and a memory. The processor is used to execute the above-mentioned program modules stored in the memory to realize the operation control of the detection items and control the generation of allergen detection tasks.

[0120] Regarding the apparatus in the above embodiments, the specific manner in which each module performs its operation has been described in detail in the embodiments related to the method, and will not be elaborated further here.

[0121] Figure 6 This is a schematic diagram of the structure of an electronic device shown in an embodiment of this application.

[0122] See Figure 6 The electronic device 400 includes a memory 410 and a processor 420.

[0123] The processor 420 can be a Central Processing Unit (CPU), or 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 can be a microprocessor or any conventional processor.

[0124] Memory 410 may include various types of storage units, such as system memory, read-only memory (ROM), and permanent storage devices. ROM may store static data or instructions required by processor 420 or other modules of the computer. Permanent storage devices may be read-write storage devices. Permanent storage devices may be non-volatile storage devices that retain stored instructions and data even when the computer is powered off. In some embodiments, permanent storage devices use mass storage devices (e.g., magnetic or optical disks, flash memory) as permanent storage devices. In other embodiments, permanent storage devices may be removable storage devices (e.g., floppy disks, optical drives). System memory may be a read-write storage device or a volatile read-write storage device, such as dynamic random access memory. System memory may store some or all of the instructions and data required by the processor during operation. Furthermore, memory 410 may include any combination of computer-readable storage media, including various types of semiconductor memory chips (e.g., DRAM, SRAM, SDRAM, flash memory, programmable read-only memory), and disks and / or optical disks may also be used. In some embodiments, memory 410 may include a removable storage device that is readable and / or writable, such as a laser disc (CD), a read-only digital multifunction optical disc (e.g., DVD-ROM, dual-layer DVD-ROM), a read-only Blu-ray disc, an ultra-high density optical disc, a flash memory card (e.g., SD card, mini SD card, Micro-SD card, etc.), a magnetic floppy disk, etc. Computer-readable storage media do not contain carrier waves or transient electronic signals transmitted wirelessly or via wired connections.

[0125] The memory 410 stores executable code, which, when processed by the processor 420, can cause the processor 420 to execute part or all of the methods described above.

[0126] Furthermore, the method according to this application can also be implemented as a computer program or computer program product, which includes computer program code instructions for performing some or all of the steps in the method described above.

[0127] Alternatively, this application may be implemented as a computer-readable storage medium (or a non-transitory machine-readable storage medium or a machine-readable storage medium) storing executable code (or computer program or computer instruction code) thereon, which, when executed by a processor of an electronic device (or server, etc.), causes the processor to perform part or all of the steps of the methods described above according to this application.

[0128] The various embodiments of this application have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or improvement of the technology in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. A method for generating an allergen detection task, characterized in that, include: Identify the test information on the test report to determine the type of allergen test; Based on the allergen detection type, a test order is displayed to indicate the test items, which includes a fixed test item group and a candidate test item group; Based on the user's selection instructions, multiple candidate detection items corresponding to the detection information are determined from the candidate detection item group and formed into a flexible detection item group; An allergen detection task is generated based on the fixed detection item group, the flexible detection item group, and the reference detection item.

2. The method according to claim 1, characterized in that, The allergen detection types include at least one of inhaled allergen detection and ingested allergen detection.

3. The method according to claim 1, characterized in that, Also includes: It is configured with a multi-hole detection mode, which includes multiple holes for fixed detection item groups, multiple holes for elastic detection item groups, and a single hole for reference detection item groups.

4. The method according to claim 3, characterized in that, The interconnected hole detection mode is an eight-hole interconnected hole detection mode, which includes four holes for fixed detection item group detection, three holes for elastic detection item group detection, and one hole for reference detection item detection.

5. The method according to claim 1, characterized in that, The optional testing items include at least one of the following: allergen testing based on regional differences, allergen testing based on seasonal differences, allergen testing based on age differences, and allergen testing based on dietary differences.

6. A test kit for use in the allergen detection task generation method according to any one of claims 1 to 5, characterized in that, include: Multiple test kits, with different test kits matched for different allergen detection tasks; The test reagent set includes multiple fixed test reagents and multiple flexible test reagents; A testing container, the testing container including a plurality of testing holes and a reference hole, the plurality of testing holes including a fixed testing hole group and an elastic testing hole group; The fixed detection well group is used to match multiple fixed detection reagents in the detection reagent group, and the flexible detection well group is used to match multiple flexible detection items in the detection reagent group.

7. The detection kit according to claim 6, characterized in that, The detection steps of the test kit include: Based on the allergen detection task, select the reagents required for the first step reaction; A sample, reagents required for the first step reaction, and reagents required for the second step reaction are sequentially added into multiple detection wells and reference wells of the detection container, and a luminescent complex to be detected is formed in the detection wells, and a reference luminescent complex is formed in the reference wells. The chemiluminescent signals of the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well are detected. Analyze the chemiluminescent signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction.

8. The detection kit according to claim 7, characterized in that, The analysis of the chemiluminescent signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction includes: Based on the relationship between the chemiluminescent signal of the reference luminescent complex in the reference well and the first threshold, it is determined whether it is an allergic reaction; If the chemiluminescence signal of the reference luminescent complex in the reference well is greater than the first threshold, it is determined to be an allergic reaction, and the allergen causing the allergic reaction is determined according to the relationship between the chemiluminescence signal of the luminescent complex to be detected in the detection well and the second threshold. If the chemiluminescence signal of the luminescent complex to be detected in the detection well is greater than the second threshold, then the allergic reaction is determined to be caused by the allergen detected in the detection well.

9. The detection kit according to claim 6, characterized in that, The detection reagent set includes reagent R1, which includes detection reagent R1 and reference reagent R1; detection reagent R1 contains luminescent microparticles coated with allergens, and reference reagent R1 contains luminescent microparticles coated with anti-hIgE antibody; detection reagent R1 and reference reagent R1 are respectively added to the detection well and the reference well.

10. The detection kit according to claim 9, characterized in that, The detection reagent kit also includes reagent R2 and reagent R3, wherein reagent R2 contains a biotin-labeled anti-hIgE antibody and reagent R3 contains avidin-coated photosensitive microparticles.

11. A readable storage medium having a computer program stored thereon, which, when executed, performs the steps of the allergen detection task generation method as described in any one of claims 1 to 5.

12. A sample analyzer, characterized in that, include: The acquisition unit is configured to acquire the allergen detection task as described in any one of claims 1 to 5; The testing container includes multiple testing holes and reference holes; The reagent unit includes a reagent compartment for storing test reagents and a pipette for drawing test reagents into the test well and the reference well; The sample unit includes a sample compartment for storing samples and a sample dispensing arm for drawing samples into the detection well and the reference well; An analysis unit is used to analyze the mixture of sample and reagent in the detection well and the reference well; A control device for controlling the sample analyzer, the control device comprising a readable storage medium as described in claim 11, for performing the steps of the allergen detection task generation method as described in any one of claims 1 to 5.

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