Allergen detection task generation method, detection method and sample analyzer

Abstract

The invention relates to an allergen detection task generation method, a detection method and a sample analyzer. The method comprises the following steps: identifying detection information of a detection sheet, and determining an allergen detection type; according to the allergen detection type, a detection work order used for indicating detection items is displayed, and the detection items comprise a fixed detection item group and a to-be-selected detection item group; based on a selection instruction of a user, determining a plurality of to-be-selected detection items corresponding to the detection information from the to-be-selected detection item group, and forming an elastic detection item group; and generating an allergen detection task according to the fixed detection item group, the elastic detection item group and the reference detection item. According to the scheme provided by the invention, the allergen can be subjected to elastic combined detection, and the detection cost of a patient is reduced.

Description

Technical Field

[0001] The present application relates to the field of biomedical detection technology, and in particular to an allergen detection task generation method, a detection method, and a sample analyzer. Background Art

[0002] Allergen testing, part of etiology testing, involves detecting allergen-specific antibodies (sIgE) in patients. sIgE testing aids in making a more definitive diagnosis and guides patients in avoiding these allergens to alleviate symptoms. Furthermore, allergic diseases exhibit significant regional and ethnic characteristics. Epidemiological studies show that the frequency of allergens varies across regions and populations due to differences in climate, dietary habits, and customs.

[0003] In the related art, sIgE detection adopts an indirect analysis mode, that is, a solid phase material is coated with a known antigen, combined with the antibody to be tested, and after washing, the antigen-antibody reaction intensity is reported by the anti-human IgE antibody labeled with a signal molecule, and the result is finally determined. According to different detection methods, sIgE detection is divided into two types: single detection arbitrary combination mode and fixed combination joint detection mode. The single detection arbitrary combination mode means that one reaction cup only detects one sIgE antibody. According to the clinical manifestations and medical history characteristics, the type and quantity of allergens can be arbitrarily combined. The fixed combination joint detection mode often uses nitrocellulose membrane as a solid phase carrier. The membrane strip is coated with multiple allergen components in sequence according to different physical positions, and then incubated with the serum to be tested. The sIgE to be tested is respectively bound to the specific antigen on the surface of the solid phase membrane. After washing, the antigen-antibody reaction intensity is reported by the anti-human IgE antibody labeled with a signal molecule. According to the different color development positions, the allergen detection results are given by taking pictures or scanning.

[0004] However, the two aforementioned sIgE testing models have some drawbacks: In the single-item testing model, registration and production are based on a single allergen, resulting in high registration and production costs. In the fixed-combination testing model, allergens are pre-fixed on the membrane strip surface, so only fixed combinations can be used, which cannot meet the needs of random combination testing. Summary of the Invention

[0005] In order to solve or partially solve the problems existing in the related art, the present application provides an allergen detection task generation method, a detection method and a sample analyzer, which can perform flexible combination detection of allergens and reduce detection costs.

[0006] In a first aspect, the present application provides a method for generating an allergen detection task, comprising:

[0007] Identify the test information on the test form and determine the allergen test type;

[0008] Displaying a test work order indicating test items according to the allergen test type, wherein the test items include a fixed test item group and a selectable test item group;

[0009] Based on a user's selection instruction, a plurality of to-be-selected test items corresponding to the test information are determined from the to-be-selected test item group, and the to-be-selected test items are formed into a flexible test item group;

[0010] An allergen detection task is generated according to the fixed detection item group, the elastic detection item group and the reference detection items.

[0011] As an optional embodiment, the allergen detection type includes at least one of inhaled allergen detection and ingested allergen detection.

[0012] As an optional embodiment, it further includes: configuring a joint hole detection mode, wherein the joint hole detection mode includes multiple holes for detecting a fixed detection item group, multiple holes for detecting an elastic detection item group, and a single hole for detecting a reference detection item.

[0013] As an optional embodiment, the linked hole detection mode is an eight-linked hole detection mode, which includes four holes for detecting a fixed detection item group, three holes for detecting an elastic detection item group, and one hole for detecting a reference detection item.

[0014] As an optional embodiment, the selected detection items include at least one of regional difference allergen detection, seasonal difference allergen detection, age difference allergen detection and dietary difference allergen detection.

[0015] A second aspect of the present application provides a detection method for the above-mentioned allergen detection task, comprising:

[0016] According to the allergen detection task, select the reagents required for the first step reaction;

[0017] Sequentially adding samples, reagents required for the first step reaction, and reagents required for the second step reaction into a plurality of detection wells and reference wells of the detection container, and forming a luminescent complex to be detected in the detection wells and a reference luminescent complex in the reference wells;

[0018] detecting chemiluminescent signals of the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well;

[0019] The chemiluminescent signal is analyzed to determine whether it is an allergic reaction and the allergen causing the allergic reaction.

[0020] As an optional embodiment, analyzing the chemiluminescent signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction includes:

[0021] determining whether it is an allergic reaction based on a relationship between a chemiluminescent signal of the reference luminescent complex in the reference well and a first threshold;

[0022] If the chemiluminescent 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 chemiluminescent signal of the luminescent complex to be tested in the detection well and the second threshold;

[0023] If the chemiluminescent signal of the luminescent complex to be detected in the detection well is greater than the second threshold, it is determined that the allergic reaction is caused by the corresponding allergen to be detected in the detection well.

[0024] In a third aspect, the present application provides a detection kit for the above-mentioned allergen detection method, comprising:

[0025] Multiple detection reagent sets, different detection reagent sets are matched with different allergen detection tasks; the detection reagent sets include multiple fixed detection reagents and multiple flexible detection reagents;

[0026] A detection container, comprising a plurality of detection holes and reference holes, wherein the plurality of detection holes comprises a fixed detection hole group and an elastic detection hole group; the fixed detection hole group is used to match a plurality of fixed detection reagents in the detection reagent group, and the elastic detection hole group is used to match a plurality of elastic detection items in the detection reagent group.

[0027] As an optional embodiment, the detection reagent group includes reagent R1, and the reagent R1 includes detection reagent R1 and reference reagent R1; the detection reagent R1 contains luminescent particles coated with allergens, and the reference reagent R1 contains luminescent particles coated with anti-hIgE antibodies; the detection reagent R1 and reference reagent R1 are respectively added to the detection well and the reference well.

[0028] As an optional embodiment, the detection reagent set further includes reagent R2 and reagent R3, wherein the reagent R2 includes biotin-labeled anti-hIgE antibodies, and the reagent R3 includes avidin-coated photosensitive particles.

[0029] In a fourth aspect, the present application provides a readable storage medium having a computer program stored thereon. When the computer program is executed, the steps of the detection method for the allergen detection task described above are performed.

[0030] A fifth aspect of the present application provides a sample analyzer, comprising:

[0031] an acquisition unit, configured to acquire the aforementioned allergen detection task;

[0032] A detection container, comprising a plurality of detection holes and a reference hole;

[0033] a reagent unit, comprising a reagent reservoir for storing a detection reagent and a pipette for aspirating the detection reagent into the detection well and the reference well;

[0034] The sample unit comprises a sample chamber for storing the sample and a sample loading arm for drawing the sample into the detection well and the reference well;

[0035] an analysis unit, configured to analyze the mixture of the sample and the reagent in the detection well and the reference well;

[0036] A control device is used to control the sample analyzer, and the control device includes the readable storage medium mentioned above, and is used to execute the steps of the detection method of the allergen detection task mentioned above.

[0037] The technical solution provided by this application may have the following beneficial effects:

[0038] The allergen detection task generation method of the present application can flexibly combine the detection items according to the needs of the use area or different departments and can be tested as a detection task. In addition, the combination detection reagents corresponding to the detection task can be used as a single diagnostic reagent, which solves the problem of high detection costs of arbitrary combination modes of single test items and reduces the detection costs as much as possible. At the same time, the detection reagents corresponding to the allergen detection tasks generated by the present application can be combined with regionality and the flexible combination needs of different departments, and also solves the problem that fixed combination joint detection reagents cannot meet the needs of random combination detection.

[0039] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The above and other objects, features and advantages of the present application will become more apparent by describing in more detail exemplary embodiments of the present application in conjunction with the accompanying drawings, wherein the same reference numerals generally represent the same components in the exemplary embodiments of the present application.

[0041] Figure 1 is a flowchart of a method for generating an allergen detection task according to an embodiment of the present application;

[0042] Figure 2 1 is a flow chart of a detection method for an allergen detection task shown in an embodiment of the present application;

[0043] Figure 3 Schematic diagram of the principle of the detection method for allergen detection tasks ("4+3X+1" allergen screening mode) shown in an embodiment of the present application;

[0044] Figure 4 is the calibration curve of tIgE shown in the examples of the present application;

[0045] Figure 5 is the calibration curve of sIgE shown in the examples of this application;

[0046] Figure 6 It is a structural diagram of an electronic device shown in an embodiment of the present application. DETAILED DESCRIPTION

[0047] The following describes embodiments of the present application in more detail with reference to the accompanying drawings. Although the accompanying drawings illustrate embodiments of the present application, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. Rather, these embodiments are provided to make the present application more thorough and complete, and to fully convey the scope of the present application to those skilled in the art.

[0048] The terms used in this application are for the purpose of describing specific embodiments only and are not intended to limit this application. As used in this application and the appended claims, the singular forms "a," "an," "the," and "the" are 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 encompasses any and all possible combinations of one or more of the associated listed items.

[0049] 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 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, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0050] In related technologies, sIgE testing uses an indirect analysis mode. Depending on the detection method, sIgE testing is divided into two types: a single-item test with any combination mode and a fixed-combination joint detection mode. However, both the single-item test with any combination mode and the fixed-combination joint detection mode have some defects: in the single-item test mode, registration and production are based on a single allergen as a unit, which will result in higher registration and production costs. In the fixed-combination joint detection mode, allergens are fixed on the surface of the membrane strip in advance. Clinical laboratories can only accept the fixed combination method, which cannot meet the detection needs of random combinations.

[0051] In response to the above problems, an embodiment of the present application provides an allergen detection task generation method, which can perform flexible combination detection of allergens and reduce detection costs.

[0052] The technical solutions of the embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0053] Figure 1 This is a flow chart of the allergen detection task generation method shown in an embodiment of the present application.

[0054] See also Figure 1 , this embodiment of the application provides a method for generating an allergen detection task, including steps S101 to S104:

[0055] Step S101: Identify the test information of the test order and determine the allergen test type.

[0056] The test form in step S101 is a test form issued by a doctor after clinical diagnosis. The test form contains at least patient information, allergen test type and test items. Among them, patient information may include the patient's name, gender, ID, etc.; the allergen test type may include at least one of inhaled allergen test and ingested allergen test; the test items may include a fixed test item group, a flexible test item group and a reference test item, and the test form may only record the flexible test items; different allergen test types correspond to different test items, and the flexible test item group can be a clinician who asks the patient about the symptoms, subjective feelings, life and living conditions, and combines the geographical characteristics and climatic conditions of the patient's residence to select the most likely allergen combination from the candidate test item group to form a flexible test item group for personalized testing of the patient. The reference test 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 the effect of use.

[0057] The embodiments of the present application take inhalation allergen detection and ingestion allergen detection as examples to illustrate the detection items included in these two types: for example, the fixed detection item group in inhalation allergen detection may include at least one allergen detection of house dust mites, dust mites, cat hair and dog hair, and the optional detection item group in inhalation allergen detection may include at least one allergen detection of artemisia, humulus, cockroaches, house dust, Aspergillus fumigatus, ragweed, and trees; the fixed detection item group in ingestion allergen detection may include at least one allergen detection of milk, eggs, soybeans, and peanuts, and the optional detection item group in ingestion allergen detection may include at least one allergen detection of shrimp, crab, scallops, beef, mutton, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts.

[0058] The test information in step S101 can usually be obtained from the hospital's customer information management system (HIS) based on the hospital's laboratory information system (LIS) after the sample analyzer scans the test order.

[0059] Step S102: Displaying a test work order indicating test items according to the allergen test type. The test items include a fixed test item group and a to-be-selected test item group.

[0060] The database of the sample analyzer is provided with a test work order for displaying on the human-computer interaction interface. The test work order matches the allergen test type and can include an inhalation allergen test work order and an ingestion allergen test work order. For example, the inhalation allergen test work order includes a fixed test item group and a to-be-selected test item group, wherein the fixed test item group can include at least one allergen test among house dust mites, dust mites, cat hair and dog hair, and the to-be-selected test item group can include at least one allergen test among mugwort, humulus, cockroaches, house dust, Aspergillus fumigatus, ragweed and trees; the ingestion allergen test work order includes a fixed test item group and a to-be-selected test item group, wherein the fixed test item group can include at least one allergen test among milk, eggs, soybeans and peanuts, and the to-be-selected 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.

[0061] Step S103: Based on the user's selection instruction, a plurality of to-be-selected test items corresponding to the test information are determined from the to-be-selected test item group and form a flexible test item group.

[0062] In the test work order displayed on the human-computer interaction interface of the sample analyzer, the fixed test item group is an unselectable button, such as a "gray box", and the selectable test item group is an selectable button, such as a "white box". The user selects the corresponding test items from the selectable test item group based on the test items recorded in the test information of the test order. The selected test items form the flexible test item group. For example, if a doctor issues a test order after a clinical consultation for inhalation allergen testing, including mugwort, humulus, and ragweed, the user will select mugwort, humulus, and ragweed from the selectable test item group, and these test items will form the flexible test item group.

[0063] Step S104: Generate an allergen detection task based on the fixed detection item group, the flexible detection item group and the reference detection items.

[0064] After the elasticity detection item group is determined, the fixed detection item group, the elasticity detection item group and the reference detection items are combined into an allergen detection task, and the sample analyzer determines the corresponding detection reagent according to the allergen detection task.

[0065] The allergen detection task generation method of the present embodiment allows for flexible combination of test items based on the needs of the region or different departments, allowing for testing as a single test task. Furthermore, the combined test reagents corresponding to the test task can be used as a single diagnostic reagent. This not only addresses the high cost of arbitrary combinations of individual test items, but also addresses the inability of fixed-combination joint testing models to meet the needs of random combination testing. Therefore, the test reagents corresponding to the allergen detection tasks generated by the present embodiment can be used as a single diagnostic reagent, minimizing testing costs by combining regionality and the flexible combination needs of different departments.

[0066] As an optional embodiment, the allergen detection type includes at least one of inhaled allergen detection and ingested allergen detection.

[0067] Allergens are categorized by their route of entry into the body: inhaled allergens (e.g., pollen, animal dander), ingested allergens (e.g., milk, eggs), intradermal contact allergens (e.g., insect bites), and other routes. This application's examples illustrate inhaled and ingested allergen detection, and the same principles apply to other allergen types, which will not be discussed in detail.

[0068] As an optional embodiment, the allergen detection task generation method further includes:

[0069] A combined hole detection mode is configured, which includes multiple holes for detecting a fixed detection item group, multiple holes for detecting an elastic detection item group, and a single hole for detecting a reference detection item.

[0070] The embodiment of the present application can realize the simultaneous addition of samples and reagents in the fixed detection item group, elasticity detection item group and reference detection item through the linked hole detection mode (for example, samples and reagents can be added by a one-absorption-multiple-distribution method), as well as simultaneous detection of multiple items, which can greatly improve the detection efficiency.

[0071] As a preferred embodiment, the linked hole detection mode is an eight-linked hole detection mode, which includes four holes for detecting a fixed detection item group, three holes for detecting an elastic detection item group, and one hole for detecting a reference detection item.

[0072] The eight-hole detection mode of the embodiment of the present application can be a "4+3X+1" mode, where four holes are used for fixed detection item group detection, three holes are used for elastic detection item group detection, and one hole is used for reference detection item detection, totaling 8 detection holes. The eight-hole strip of Comed Diagnostics Technology Co., Ltd. can be selected as a detection unit, and the sample to be tested and the detection reagent are added in a one-absorption-multiple-distribution method, which can realize a 6-strip joint detection mode and meet the demand for high-speed detection.

[0073] The embodiment of the present application uses the "4+3X+1" combined detection mode based on the photoexcitation homogeneous luminescence technology as a platform to provide a new method for clinical allergen screening. In this detection mode, the fixed wells ("4+1": fixed detection well group + reference well) can detect common sIgE and total IgE of allergens, and also allow flexible detection wells ("3X") to perform personalized testing according to the specific needs of the patient. Therefore, this combined detection mode shortens the detection time, improves the detection efficiency, and only requires the use of less serum to achieve automated detection.

[0074] As an optional embodiment, the selected detection items include at least one of regional difference allergen detection, seasonal difference allergen detection, age difference allergen detection and dietary difference allergen detection.

[0075] Although allergic diseases can affect people of almost any age and region, the incidence and types of allergic diseases can vary across age groups and regions. For example, people with a family history are more likely to develop allergic diseases, suggesting that genetic factors play a significant role in the development of the disease. 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 dietary changes are thought to increase the risk of allergic diseases. Regarding age, the incidence of allergic diseases is generally higher in childhood and may then decline or stabilize in adulthood. Regarding gender, certain allergic diseases exhibit significant differences between men and women. For example, asthma is more common in men during childhood and 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 contribute to the prevalence of allergic diseases. Climate change can affect the distribution and release of allergens.

[0076] In this embodiment of the present application, different conditions are set for the fixed test items and the optional test items in the test items based on the characteristics of allergic diseases. For example, the allergens in the fixed test item group in this embodiment of the present application meet the following characteristics: high probability of occurrence, no obvious regional characteristics, no obvious seasonality, and no significant age difference. The allergens in the optional test item group in this embodiment of the present application meet the following characteristics: obvious regional characteristics, obvious seasonal characteristics, obvious dietary differences, and significant age differences.

[0077] The following describes the test items based on inhaled allergen testing and ingested allergen testing:

[0078] Inhalant allergen testing items:

[0079] Combining literature research and epidemiological statistical analysis, we selected four common allergens that are less susceptible to seasonal and regional allergies as fixed testing items. Screening revealed that among people with inhalant allergies, allergies to house dust mites and dust mites can reach as high as 25% to 35%, and allergies to cat and dog hair can reach 5% to 10%. Because these allergens are less susceptible to seasonal changes and are universally susceptible, we selected them as fixed testing items. Spring and autumn allergens that are susceptible, such as mugwort, ragweed, and Aspergillus fumigatus, as well as allergens that are susceptible to regional variations, such as humulus, cockroaches, and trees, were selected as candidate testing items. This allows for targeted and accurate testing of patients, reducing testing costs.

[0080] Test items for food allergen detection:

[0081] Combining literature research and epidemiological statistical analysis, we selected high-frequency food allergens as fixed testing items, with eggs and milk being the most common. Based on common domestic food types and comprehensive consideration of nutritional sources, we also selected soy and peanuts as four fixed allergens for testing. Based on regional dietary differences and coastal and inland geographical locations, shrimp, crab, scallops, beef, lamb, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts were selected as potential testing items to cover a variety of nutritional intake needs. Doctors can flexibly combine testing methods after consulting with patients on their dietary habits.

[0082] Figure 2 It is a flowchart of the detection method for the allergen detection task shown in the embodiment of the present application.

[0083] See also Figure 2 The present embodiment also provides a method for detecting allergens, including steps S201 to S204:

[0084] Step S201: According to the allergen detection task, the reagents required for the first step reaction are selected.

[0085] The embodiment of the present application combines photochemiluminescence analysis to complete the allergen detection task. Photochemiluminescence analysis belongs to homogeneous immunoassay and does not require 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 photochemiluminescence process includes a two-step reaction: the substance to be tested in the sample to be tested first reacts with the luminescent microspheres coated with antigens or antibodies and biotin-labeled antigens or antibodies in the reagents required for the first step reaction to generate an immune reaction complex, and then the immune reaction complex reacts with the streptavidin-coated photosensitive microparticles in the reagents required for the second step reaction to generate a chemiluminescent complex. The combination of biotin and avidin shortens the distance between the luminescent microspheres and the photosensitive microspheres (<200nm), so that the photosensitive microspheres release singlet oxygen under the excitation of the excitation light, which can make the luminescent microspheres emit light. Finally, the concentration of the substance to be tested in the sample liquid is inferred by detecting the luminescent signal.

[0086] In step S201, since the detection reagents for the fixed detection item group and the reference detection item can be determined after the allergen detection type is determined, this step mainly selects the reagents required for the first step reaction corresponding to the elastic detection item group.

[0087] Step S202: Samples, reagents required for the first step reaction, and reagents required for the second step reaction are sequentially added to the multiple detection wells and reference wells of the detection container, and luminescent complexes to be detected are formed in the detection wells, and reference luminescent complexes are formed in the reference wells.

[0088] In step S202, the detection container can be an eight-well strip produced by Kemei Biotechnology Co., Ltd., in which the samples in the detection wells and reference wells and the reagents required for the second step reaction are all shared reagents.

[0089] The reagents required for the first step of the reaction include reagent R1 and reagent R2, and the reagents required for the second step of the reaction include 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 contain chemiluminescent complexes.

[0090] Step S203: Detecting the chemiluminescent signals of the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well.

[0091] The luminescence information of the reference luminescent complex is used to assist the clinician in making a clearer diagnosis, and the luminescent complex to be tested is used to identify allergens, so as to guide patients to take measures to avoid contact with these allergens and alleviate clinical symptoms.

[0092] Step S204: Analyze the chemiluminescent signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction.

[0093] Figure 3 Schematic diagram of the principle of the detection method (“4+3X+1” allergen screening mode) for allergen detection tasks shown in an embodiment of the present application.

[0094] In the figure, ABCD is a fixed detection well group, which is used for the detection of fixed detection items; EFG is an elastic detection well group, which is used for the detection of elastic detection items; H is a reference well, which is used for the detection of reference items; GG represents photosensitive microspheres; FG represents luminescent microspheres; Bio represents biotin; Ag represents allergen; SA represents streptavidin; and sIgE Ab to be detected represents sIgE antibody to be detected.

[0095] The following combination Figure 3 The principle of the detection method for allergen detection tasks is explained:

[0096] 1. Determine the detection reagent corresponding to EFG based on the allergen detection task.

[0097] 2. Add 1:10 diluted sample (including sIgE antibody and tIgE) to each test well and reference well of the test container, 50 μL / Well, and use a single aspiration multiple aspiration method;

[0098] 3. Add the corresponding allergen-coated luminescent microparticle solution (detection reagent R1) to ABCD, 25 μL / Well respectively; add the corresponding allergen-coated luminescent microparticle solution (detection reagent R1) to EFG according to the elasticity detection item determined by the user selection instruction, 25 μL / Well; add the anti-hIgE antibody-coated luminescent microparticle solution (reference reagent R1) to H, 25 μL / Well;

[0099] 4. Add biotin-labeled anti-hIgE antibody solution (reagent R2) to each well, 25 μL / Well, and use a single-aspiration, multiple-dispensing method;

[0100] 5. Incubate at 42°C for 30 minutes to allow the first reaction to occur in the test and reference wells.

[0101] 6. Add 25 μL / well of streptavidin-coated photosensitive microparticle solution (reagent R3) to each well and use a single-aspiration, multiple-dispensing method.

[0102] 7. Incubate at 42°C for 10 minutes. A second reaction occurs in the detection well and the reference well, forming a luminescent complex to be detected in the detection well and a reference luminescent complex in the reference well.

[0103] 8. Detect the optical signal and output the result.

[0104] This embodiment utilizes photochemiluminescence analysis, which offers advantages such as eliminating the need for separation and washing, sharing a biotinylated secondary antibody, and utilizing a universal photosensitive solution. It also facilitates combining total immunoglobulin E (tIgE) levels. Furthermore, the "4+3X+1" allergen screening model proposed in this embodiment can be used as a single diagnostic reagent to meet the flexible combination needs of different regions and departments, minimizing testing costs.

[0105] As an optional embodiment, step S204 may include:

[0106] 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.

[0107] The chemiluminescent signal of the reference luminescent complex in step S214 is mainly used to indicate whether the patient has an allergic reaction, wherein the first threshold value may be 70 IU / mL.

[0108] S224: If the chemiluminescent 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 chemiluminescent signal of the luminescent complex to be tested in the detection well and the second threshold.

[0109] If the chemiluminescent signal of the reference luminescent complex is greater than 70 IU / mL, it is determined to be an allergic reaction, and the allergen causing the allergic reaction is further determined based on the relationship between the chemiluminescent signal of the luminescent complex to be tested and the second threshold. The second threshold can be 0.35 kU A / L.

[0110] S234: If the chemiluminescent signal of the luminescent complex to be detected in the detection well is greater than a second threshold value, it is determined that the allergic reaction is caused by the corresponding allergen to be detected in the detection well.

[0111] If the chemiluminescent signal of the luminescent complex to be detected in a certain detection well is greater than 0.35kU A / L, it is determined that the allergic reaction is caused by the corresponding allergen in the test hole.

[0112] The present invention also provides a detection kit comprising:

[0113] Multiple detection reagent groups, different detection reagent groups match different allergen detection tasks; the detection reagent group includes multiple fixed detection reagents and multiple flexible detection reagents.

[0114] The detection container includes multiple detection holes and reference holes, and the multiple detection holes include a fixed detection hole group and an elastic detection hole group; the fixed detection hole group is used to match multiple fixed detection reagents in the detection reagent group, and the elastic detection hole group is used to match multiple elastic detection reagents in the detection reagent group.

[0115] A detection kit in the embodiment of the present application matches one allergen detection task, and the flexible detection reagents in the detection kit can be flexibly combined according to the allergen detection task. Not only can each detection kit be registered as a single diagnostic reagent, but it also meets the flexible combination requirements of regionality and different departments.

[0116] As an optional embodiment, the detection reagent set includes reagent R1, which includes detection reagent R1 and reference reagent R1; detection reagent R1 contains luminescent particles coated with allergens, and reference reagent R1 contains luminescent particles coated with anti-hIgE antibodies; detection reagent R1 and reference reagent R1 are added to the detection well and reference well, respectively.

[0117] As an optional embodiment, the detection reagent set further includes reagent R2 and reagent R3, wherein reagent R2 includes biotin-labeled anti-hIgE antibody, and reagent R3 includes avidin-coated photosensitive particles.

[0118] The detection wells in the allergen detection kits of the present invention can utilize an indirect detection method: FG-Ag (reagent R1), Bio-anti-hIgE (reagent R2), and a photosensitive solution (GG-SA) form a detection system. FG-Ag contains multiple reagents for detecting different allergens. Furthermore, the reference wells in the allergen detection kits can utilize a double-antibody sandwich method: FG-anti-hIgE (reagent R1), Bio-anti-hIgE (reagent R2), and a photosensitive solution (GG-SA) form a detection system.

[0119] To make the present invention easier to understand, the following describes the allergen detection method and allergen detection kit according to the embodiments of the present application, taking two types of allergen detection as examples:

[0120] 1. Types of Allergen Detection Kits

[0121] The allergen detection kits in the embodiments of the present application are divided into two categories of products: inhalation allergen kits and ingestion allergen kits.

[0122] (1) Inhalation allergen test kit:

[0123] Combining literature research and epidemiological statistical analysis, four common allergens that are not easily affected by seasons and regions were selected as fixed detection items. After screening, among people with inhalation allergies, the number of people allergic to house dust mites and dust mites can be as high as 25% to 35%, and the number of people allergic to cat hair and dog hair can be as high as 5% to 10%. Because they are less affected by seasons and are generally susceptible, they are used as fixed detection items. Allergens that are susceptible to allergens in spring and autumn, such as Artemisia, ragweed, and Aspergillus fumigatus, and allergens that are easily affected by regional differences, such as Humulus, cockroaches, and trees, were selected as candidate detection items to conduct targeted and accurate testing on patients and reduce detection costs. The "4+3X+1" allergen detection kit is limited by the characteristics of inhalation allergens:

[0124] 4 indicates fixed detection items: house dust mites, dust mites, cat hair, and dog hair.

[0125] 3X indicates items to be tested: Artemisia, Humulus, Cockroach, House Dust, Aspergillus fumigatus, Ragweed, and Tree.

[0126] 1 indicates reference test item: tIgE.

[0127] (2) Food allergen test kit:

[0128] Combining literature research and epidemiological statistical analysis, we selected high-frequency food allergens as fixed testing items, with eggs and milk being the most common. Based on common domestic food types and comprehensive consideration of nutritional sources, we also selected soybeans and peanuts as fixed testing items. Based on regional dietary differences and 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 to cover a variety of nutritional intake needs. Doctors can flexibly combine testing methods after consulting with patients on their dietary habits.

[0129] 4 indicates fixed test items: milk, eggs, soybeans, peanuts

[0130] 3X indicates items to be tested: shrimp, crab, scallops, beef, lamb, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, hazelnuts

[0131] 1 indicates reference test item: tIgE.

[0132] 2. Allergen-coupled luminescent microspheres

[0133] Using carboxyl luminescent microspheres as carriers, a conventional coating method (EDC activation) was used to coat 11 inhalation allergens (house dust mites, dust mites, cat hair, dog hair, Artemisia, Humulus, cockroaches, house dust, Aspergillus fumigatus, ragweed, and trees), 17 food allergens (milk, eggs, soybeans, peanuts, shrimp, crab, scallops, beef, lamb, sesame, honey, wheat flour, coffee, pineapple, mango, almonds, and hazelnuts) and tIgE on the surface of the luminescent microspheres. The microspheres were stored at 4°C.

[0134] 3. 4+3X+1 detection mode combination

[0135] To meet the flexible testing needs of different regions, seasons, and departments, four fixed test items are available: inhaled allergens for house dust mites, dust mites, cat hair, and dog hair, and ingested allergens for milk, eggs, soy, and peanuts. Doctors select allergen testing combinations from a 3X range based on seasonal allergens (e.g., autumn allergies to mugwort, ragweed, and mold are more common), age-related allergens (e.g., infant allergies to shrimp, crab, and peanuts are more common), and patient symptom assessment and consultation, reducing testing costs.

[0136] 4. Testing process

[0137] Detection steps

[0138] The test sample (serum) is diluted at a ratio of 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 test item / elasticity test item are added to each well of an eight-well strip. The eight-well strip is incubated at 37°C for 30 minutes. If the serum contains the test IgE antibody, a FG-Ag-test IgE antibody-biotinylated anti-human IgE antibody complex is formed. After the first incubation period, 150 μL of universal photosensitive solution (streptavidin-coated photosensitive microparticle solution SA-GG) is added to each well. After incubation for 15 minutes, the patient's allergy status is determined based on the intensity of the test signal.

[0139] Create a calibration curve

[0140] Calibration curve for total IgE (tIgE) (see Figure 4 ) was generated using the six different concentrations of the calibrator in the tIgE kit, while the calibration curve for specific IgE (sIgE) (see Figure 5 ) is generated by diluting a low-value calibrator. The resulting calibration curve can be used to calibrate the detection value for each allergen, thereby creating a standardized measurement mode.

[0141] Performance Testing

[0142] As shown in Table 2, three different levels of sera (high, intermediate, and low) were selected for repeated measurements of D. farinae sIgE to assess precision, and the mean, SD, and CV values ​​were calculated. The CV values, representing repeatability, ranged from 3.46% to 8.37%, and the CV values, representing intermediate precision, ranged from 4.51% to 9.48%, both below 10%, meeting the requirements for repeatability and high precision.

[0143] Table 2 Repeatability and intermediate precision of dust mite sIgE determination

[0144]

[0145] Limit of quantitation (LoQ)

[0146] 60 blank samples were tested, and the test results of the 60 blank samples were sorted from smallest to largest, and the percentile (Pct) of the blank sample result distribution was calculated, where α = 0.05, Pct = 0.95, the sequence number corresponding to the percentage of 0.95 = 0.5 + 60 × 0.95 = 57.5, that is, the value of the percentage of 0.95 is the average of the 57th and 58th digit values.

[0147] LoB is calculated according to LoB = X57 + 0.5 (X58 - X57), where X57 = 0.035 and X58 = 0.036. Therefore, the calculated LoB is 0.035 kU. A / L.

[0148] Four low-concentration samples with concentrations ranging from 1 to 4 times the LoB were selected, and the LoD was taken as the median of the four test samples, resulting in an LoD of 0.092 kU. A / L.

[0149] Select 3 to 5 samples with concentrations between 1 and 4 times the LoD and measure them in at least 5 batches. Obtain at least 40 replicates for each concentration. Calculate the LoQ to be 0.172 kU. A / L. The LoQ is not less than the LoD, and the CV is less than 15%, indicating that the detection method of the embodiment of the present application can achieve quantitative and accurate detection.

[0150] 5. Clinical Sample Testing

[0151] (1) Inhalant allergen detection

[0152] The test list is as follows: Inhalation allergen test, Artemisia, Humulus, and Ragweed.

[0153] The instrument determines the detection items as follows: fixed detection item group: house dust mites, dust mites, cat hair, dog hair, elastic detection item group: Artemisia, Humulus, Amomum villosum, Reference detection item: tIgE.

[0154] The test results are shown in the following table:

[0155] Hole position A B C D E F G H Test items House dust mites Dust mites Cat hair dog hair mugwort Humulus Ragweed tIgE Interpretation of results - 3.8 - - 4.6 - - 1680

[0156] sIgE unit is kU A / L, the unit of tIgE is IU / mL.

[0157] A tIgE test result of >70 IU / mL is considered an allergic reaction, and a sIgE test result of >0.35 kU is considered an allergic reaction. A / L is positive, so the allergens are dust mites and mugwort.

[0158] (2) Detection of ingested allergens

[0159] The test list is as follows: Food allergen test, shrimp, crab, and lamb.

[0160] The instrument determines the test items as follows: fixed test item group: milk, eggs, soybeans, peanuts, elasticity test item group: shrimp, crab, lamb, reference test item: tIgE.

[0161] The test results are shown in the following table:

[0162] Hole position A B C D E F G H Test items milk egg soybeans peanut shrimp crab mutton tIgE Interpretation of results 1.08 - - - 0.75 - - 890

[0163] sIgE unit is kU A / L, the unit of tIgE is IU / mL.

[0164] A tIgE test result of >70 IU / mL is considered an allergic reaction, and a sIgE test result of >0.35 kU is considered an allergic reaction. A / L is positive, so the allergens are milk and shrimp.

[0165] The embodiment of the present application further provides a readable storage medium having a computer program stored thereon. When the computer program is executed, the steps of the detection method of the aforementioned allergen detection task are performed.

[0166] The present application also provides a sample analyzer, comprising:

[0167] The acquisition unit is used to acquire the aforementioned allergen detection task.

[0168] The detection container includes a plurality of detection holes and reference holes.

[0169] The reagent unit includes a reagent tank for storing the detection reagent and a pipette for aspirating the detection reagent into the detection well and the reference well.

[0170] The sample unit includes a sample chamber for storing samples and a sample adding arm for drawing samples into the detection well and the reference well.

[0171] The analysis unit is used to analyze the mixture of the sample and the reagent in the detection well and the reference well.

[0172] A control device is used to control the sample analyzer. The control device includes the aforementioned readable storage medium and is used to execute the steps of the detection method for the aforementioned allergen detection task.

[0173] The detection methods of the embodiments of the present application can be 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. 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, or a chemiluminescence analyzer based on photoluminescence.

[0174] Although the embodiments of the present application use a photochemiluminescence analyzer and a photochemiluminescence detection reagent as an example, the present application is not limited thereto. Instead, the present application can be 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.

[0175] The sample analyzer provided in the embodiment of the present application has a detection container, which can be an eight-hole strip of Kemei Biotechnology Co., Ltd., and also has a reagent unit, which includes a reagent compartment for storing the detection reagent required for detection and a pipette for drawing the detection reagent into the detection hole and the reference hole. The sample analyzer also has a sample unit, which includes a sample compartment for storing a blood sample to be detected and a pipette for drawing the detection reagent into the detection hole and the reference hole, wherein the blood sample is, for example, a patient blood sample or an animal blood sample. A scanner (not shown) for reading the sample code is provided in the sample compartment. The sample analyzer also has an analysis unit, which is used to analyze the mixture of the sample and the reagent in the detection hole and the reference hole. The analysis unit includes an incubation tray, which is used to carry the detection container required for detection and provide the temperature required for reaction, such as heating the reaction container by heating the reaction vessel. The analysis unit also includes a detection unit not shown, which detects the signal generated by the reaction liquid in the detection container. The sample analyzer also has a cup sorter, which is used to store the detection container required for detection analysis and transfer the detection container to the incubation tray.

[0176] The sample analyzer is equipped with a control device that controls the execution of the actions of each component. The control device obtains a sample code from the sample bin. The sample code is a specific identifier used to identify the sample. After obtaining the sample code, the control device obtains the test items of the sample to be tested according to the sample code. The user can input the test items corresponding to the sample code into the sample analyzer in advance. The test 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) that is in communication with the sample analyzer.

[0177] Samples to be tested are typically placed in batches of five or ten at a time into the sample chamber. Furthermore, each sample may correspond to multiple tests, such as testing a single sample for three infectious diseases. A control unit determines the test reagents and controls the various components of the sample analyzer to perform the corresponding actions.

[0178] Corresponding to the aforementioned application function implementation method embodiment, the present application also provides a control device, electronic device and corresponding embodiments of an allergen detection task generation method.

[0179] This embodiment provides a control device for an allergen detection task generation method, which is applied to a sample analyzer and includes: an identification module for identifying detection information of a detection order and determining the allergen detection type; a display module for displaying a detection work order for indicating detection items according to the allergen detection type, where the detection items include a fixed detection item group and a to-be-selected detection item group; a combination module for determining, based on a user's selection instruction, multiple to-be-selected detection items corresponding to the detection information from the to-be-selected detection item group and forming a flexible detection item group; and a generation module for generating an allergen detection task based on the fixed detection item group, the flexible detection item group, and the reference detection items.

[0180] The control device of the embodiment of the present application may further include a processor and a memory, and 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.

[0181] Regarding the apparatus in the above embodiment, the specific manner in which each module performs operations has been described in detail in the embodiment of the method, and will not be elaborated again here.

[0182] Figure 6 It is a structural diagram of an electronic device shown in an embodiment of the present application.

[0183] See also Figure 6 , the electronic device 400 includes a memory 410 and a processor 420.

[0184] The processor 420 may be a central processing unit (CPU), or other general-purpose processors, digital signal processors (DSP), application-specific integrated circuits (ASIC), field-programmable gate arrays (FPGA), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor may be a microprocessor or any conventional processor.

[0185] Memory 410 may include various types of storage units, such as system memory, read-only memory (ROM), and permanent storage. ROM may store static data or instructions required by processor 420 or other modules of the computer. Permanent storage may be a readable and writable storage device. A permanent storage device may be a non-volatile storage device that retains stored instructions and data even when the computer is powered off. In some embodiments, the permanent storage device uses a large-capacity storage device (e.g., a magnetic or optical disk, flash memory) as the permanent storage device. In other embodiments, the permanent storage device may be a removable storage device (e.g., a floppy disk, optical drive). System memory may be a readable and writable storage device or a volatile readable and writable storage device, such as dynamic random access memory. System memory may store some or all instructions and data required by the processor during operation. In addition, 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 magnetic disks and / or optical disks may also be used. In some embodiments, the memory 410 may include a readable and / or writable removable storage device, such as a compact disc (CD), a read-only digital versatile disc (e.g., DVD-ROM, dual-layer DVD-ROM), a read-only Blu-ray disc, an ultra-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 include carrier waves and transient electronic signals transmitted wirelessly or wired.

[0186] The memory 410 stores executable codes. When the executable codes are processed by the processor 420 , the processor 420 may execute part or all of the above-mentioned methods.

[0187] In addition, the method according to the present application may also be implemented as a computer program or a computer program product, which includes computer program code instructions for executing some or all of the steps in the above method of the present application.

[0188] 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 a processor of an electronic device (or server, etc.), the processor executes part or all of the steps of the above-mentioned method according to the present application.

[0189] The embodiments of the present application have been described above. The above description is exemplary, not exhaustive, and is not 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 selected to best explain the principles of the embodiments, their practical applications, or improvements to the technology in the market, or to enable other persons 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 form and determine the allergen test type; Displaying a test work order indicating test items according to the allergen test type, wherein the test items include a fixed test item group and a selectable test item group; Based on a user's selection instruction, a plurality of to-be-selected test items corresponding to the test information are determined from the to-be-selected test item group, and the to-be-selected test items are formed into a flexible test item group; An allergen detection task is generated according to the fixed detection item group, the elastic detection item group and the reference detection items.

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

3. The method according to claim 1, characterized in that Also includes: A linked hole detection mode is configured, the linked hole detection mode includes multiple holes for detecting a fixed detection item group, multiple holes for detecting an elasticity detection item group, and a single hole for detecting a reference detection item; preferably, the linked hole detection mode is an eight-hole detection mode, the eight-hole detection mode includes four holes for detecting a fixed detection item group, three holes for detecting an elasticity detection item group, and one hole for detecting a reference detection item; And / or, the selected detection items include at least one of regional difference allergen detection, seasonal difference allergen detection, age difference allergen detection and dietary difference allergen detection.

4. A method for detecting allergens according to any one of claims 1 to 3, characterized in that: include: According to the allergen detection task, select the reagents required for the first step reaction; Sequentially adding samples, reagents required for the first step reaction, and reagents required for the second step reaction into a plurality of detection wells and reference wells of the detection container, and forming a luminescent complex to be detected in the detection wells and a reference luminescent complex in the reference wells; detecting chemiluminescent signals of the luminescent complex to be detected in the detection well and the reference luminescent complex in the reference well; The chemiluminescent signal is analyzed to determine whether it is an allergic reaction and the allergen causing the allergic reaction.

5. The method according to claim 4, characterized in that The analyzing the chemiluminescent signal to determine whether it is an allergic reaction and the allergen causing the allergic reaction includes: determining whether it is an allergic reaction based on a relationship between a chemiluminescent signal of the reference luminescent complex in the reference well and a first threshold; If the chemiluminescent 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 chemiluminescent signal of the luminescent complex to be tested in the detection well and the second threshold; If the chemiluminescent signal of the luminescent complex to be detected in the detection well is greater than the second threshold, it is determined that the allergic reaction is caused by the corresponding allergen to be detected in the detection well.

6. A detection kit for the allergen detection method according to any one of claims 4 to 5, characterized in that: include: Multiple detection reagent sets, different detection reagent sets are matched with different allergen detection tasks; The detection reagent set includes a plurality of fixed detection reagents and a plurality of elastic detection reagents; A detection container, the detection container comprising a plurality of detection holes and a reference hole, the plurality of detection holes comprising a fixed detection hole group and an elastic detection hole group; The fixed detection hole group is used to match multiple fixed detection reagents in the detection reagent group, and the elasticity detection hole group is used to match multiple elasticity detection items in the detection reagent group.

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

8. The detection kit according to claim 7, characterized in that The detection reagent set further includes reagent R2 and reagent R3, wherein the reagent R2 comprises biotin-labeled anti-hIgE antibody, and the reagent R3 comprises avidin-coated photosensitive particles.

9. A readable storage medium having a computer program stored thereon, which, when executed, performs the steps of the detection method for the allergen detection task according to claim 4 or 5.

10. A sample analyzer, characterized in that: include: an acquiring unit, configured to acquire the allergen detection task according to any one of claims 1 to 3; A detection container, comprising a plurality of detection holes and a reference hole; a reagent unit, comprising a reagent reservoir for storing a detection reagent and a pipette for aspirating the detection reagent into the detection well and the reference well; The sample unit comprises a sample chamber for storing the sample and a sample loading arm for drawing the sample into the detection well and the reference well; an analysis unit, configured to analyze the mixture of the sample and the reagent in the detection well and the reference well; A control device for controlling the sample analyzer, wherein the control device comprises the readable storage medium according to claim 9 and is used to execute the steps of the detection method for the allergen detection task according to any one of claims 4 or 5.

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