Magnetic separation liquid for improving magnetic separation cleaning effect

Abstract

The invention provides a magnetic separation liquid for improving magnetic separation cleaning effect, the magnetic separation liquid comprises a defoaming agent, a surfactant and a metal chelate, the surfactant comprises an anionic surfactant, a cationic surfactant and a nonionic surfactant, the anionic surfactant, the cationic surfactant and the nonionic surfactant are combined according to a specific proportion, and the metal chelate is a metal chelate. And a strong synergistic effect can be achieved. By using the magnetic separation liquid on the chemiluminescence instrument, a more thorough cleaning effect can be realized, a value jumping phenomenon caused by incomplete magnetic separation in a cleaning process in a detection process is effectively reduced, the repeatability of a detection result is remarkably improved, and the accuracy and reproducibility of a measured value are ensured.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemiluminescence immunoassay, and particularly relates to a magnetic separation liquid for improving magnetic separation and cleaning effect. BACKGROUND

[0002] Direct chemiluminescence (CLIA) is a highly sensitive analytical technique widely used in biomedical, environmental monitoring and food safety fields. Its working principle is to excite 430nm visible light by using the energy released in the chemical reaction, and the concentration of the sample is determined by the different light signal values. In the field of biomedicine, direct chemiluminescence is often used for immunoassay. After the luminescent marker such as antifoam ester is directly labeled on the antibody, and the corresponding antigen in the sample to be measured is immunoreacted, a solid-phase coated antibody-sample antigen-antifoam ester labeled antibody complex is formed. After adding oxidizing agent (such as hydrogen peroxide) and alkaline environment (such as sodium hydroxide), the antifoam ester is decomposed and emits light without catalyst, and the light signal intensity is proportional to the amount of the antigen to be measured, so that the quantitative detection of the target analyte is realized.

[0003] In the reaction process, magnetic separation and cleaning is a key step, and its principle is as follows: after the immunoreaction is completed, the solid carrier (such as magnetic beads coated with antibody) is specifically combined with the antigen in the sample to be measured by using magnetic separation technology. Through the action of the magnet, the magnetic beads are adsorbed to one side of the reaction cup, and the uncombined components remain in the solution. Subsequently, the magnetic separation liquid is injected, and the added magnetic separation liquid can help to remove the non-specific adsorbents and residual samples on the surface of the magnetic beads.

[0004] In the process of magnetic separation and cleaning, the magnetic beads repeatedly perform magnetic adsorption and release in the magnetic separation liquid, so that the magnetic separation liquid fully contacts the surface of the magnetic beads, and effectively removes various impurities. If the cleaning is not complete, not only the non-specific signal interference will be introduced, resulting in the jump value phenomenon of the detection result, affecting the accuracy and repeatability of the detection data. At the same time, it also aggravates the loss of magnetic beads, and further shortens the service life of the instrument.

[0005] Therefore, it is necessary to further optimize the magnetic separation liquid, and further improve the repeatability of the measured value of chemiluminescence immunoassay, and ensure the accuracy and reproducibility of the measured value concentration. SUMMARY

[0006] The present application relates to a magnetic separation liquid for improving the magnetic separation and cleaning effect in chemiluminescence immunoassay. The magnetic separation liquid is applied in the process of magnetic separation and cleaning in the chemiluminescence immunoassay, which can significantly improve the cleaning efficiency and effect of the magnetic beads. By optimizing the composition of the magnetic separation liquid, the magnetic separation liquid can reduce various non-specific adsorption and cross contamination in the reaction process, reduce the generation of jump value phenomenon, improve the repeatability and accuracy of the detection result, and ensure that stable and reliable results can be obtained in each detection.

[0007] The present invention provides a magnetic separation liquid, which contains, by weight, 0.1 to 2.0 parts of a defoaming agent, 0.05 to 0.45 parts of a surfactant, and 0.1 to 0.5 parts of a metal chelating agent, wherein the surfactant is composed of an anionic surfactant, a cationic surfactant, and a nonionic surfactant.

[0008] Specifically, the magnetic separation liquid also includes a solvent, such as water, especially purified water.

[0009] Specifically, the magnetic separation liquid contains 500 to 1500 parts by mass of water (for example, 500 parts, 550 parts, 600 parts, 650 parts, 700 parts, 750 parts, 800 parts, 850 parts, 900 parts, 1000 parts, 1050 parts, 1100 parts, 1150 parts, 1200 parts, 1250 parts, 1300 parts, 1350 parts, 1400 parts, 1450 parts or 1500 parts, etc.), and especially contains 1000 parts of water.

[0010] Specifically, the pH range of the magnetic separation liquid is 7.20-7.40 (eg, 7.20, 7.25, 7.30, 7.35, 7.40).

[0011] Specifically, the defoaming agent includes silicone and alcohol reagents.

[0012] Specifically, the organic silicones include one or more of dimethyl silicone oil, fluorosilicone, glycol siloxane, dimethylsiloxane or polydimethylsiloxane.

[0013] Specifically, the alcohol reagent includes one or more of methanol, ethanol, isopropanol, ethylene glycol, glycerol or n-octanol.

[0014] In a specific embodiment of the present invention, the defoaming agent is selected from dimethyl silicone oil and n-octanol.

[0015] Specifically, the magnetic separation liquid contains 0.1 to 3.0 parts of defoaming agent by mass (for example, 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1.0 part, 1.1 part, 1.2 parts, 1.3 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts, 2.0 parts, 2.1 parts, 2.2 parts, 2.3 parts, 2.4 parts, 2.5 parts, 2.6 parts, 2.7 parts, 2..8 parts, 2.9 parts or 3.0 parts, etc.).

[0016] Specifically, the surfactant consists of a nonionic surfactant, a cationic surfactant and an anionic surfactant.

[0017] Specifically, the non-ionic surfactant includes one or more than two of nonylphenol polyoxyethylene ether, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, fatty acid polyoxyethylene ester or polyoxyethylene.

[0018] Specifically, the cationic surfactant includes one or more than two of cetyltrimethylammonium bromide, benzyl dodecyl dimethyl ammonium chloride, benzalkonium bromide or benzalkonium chloride.

[0019] Specifically, the anionic surfactant includes one or more than two of sodium fatty acid methyl ester sulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, or sodium fatty acid methyl ester ethoxylate sulfonate.

[0020] Specifically, the magnetic separation liquid contains 0.05-0.75 parts (for example, 0.05 parts, 0.06 parts, 0.07 parts, 0.08 parts, 0.09 parts, 0.1 parts, 0.11 parts, 0.12 parts, 0.14 parts, 0.16 parts, 0.18 parts, 0.20 parts, 0.22 parts, 0.24 parts, 0.26 parts, 0.27 parts, 0.28 parts, 0.29 parts, 0.30 parts, 0.31 parts, 0.32 parts, 0.34 parts, 0.36 parts, 0.38 parts, 0.40 parts, 0.41 parts, 0.42 parts, 0.43 parts, 0.44 parts, 0.45 parts, 0.46 parts, 0.47 parts, 0.48 parts, 0.49 parts, 0.50 parts, 0.51 parts, 0.52 parts, 0.53 parts, 0.54 parts, 0.55 parts, 0.56 parts, 0.57 parts, 0.58 parts, 0.59 parts, 0.60 parts, 0.61 parts, 0.62 parts, 0.63 parts, 0.64 parts, 0.65 parts, 0.66 parts, 0.67 parts, 0.68 parts, 0.69 parts, 0.70 parts, 0.71 parts, 0.72 parts, 0.73 parts, 0.74 parts or 0.75 parts, etc.) of surfactant by mass.

[0021] In one specific embodiment of the present application, the surfactant is nonylphenol polyoxyethylene ether, sodium fatty acid methyl ester sulfonate and cetyltrimethylammonium bromide.

[0022] When nonylphenol polyoxyethylene ether, sodium fatty acid methyl ester sulfonate and cetyltrimethylammonium bromide are combined in a specific ratio (for example, 1:1:1, mass ratio), a clear and strong synergistic effect can be produced by reducing the critical micelle concentration, enhancing the solubilizing ability, improving the wetting and spreading properties, improving the emulsification stability, and combining the antistatic and foam regulating effects, which can significantly improve the cleaning effect, especially for specific high-efficiency cleaning occasions.

[0023] Among them, nonylphenol polyoxyethylene ether plays an indispensable role in stabilizing the anion / cation pair and the overall synergy of the magnetic separation liquid system.

[0024] Specifically, the metal chelating agent includes one or more of diethylenetriaminepentaacetic acid, ethylenediaminetetraacetic acid, tetrasodium dimethyl aspartate or trisodium ethylenediamine disuccinate.

[0025] Specifically, the magnetic separation liquid contains 0.1 to 1.0 parts of metal chelating agent by mass (for example, 0.1 parts, 0.15 parts, 0.20 parts, 0.25 parts, 0.30 parts, 0.35 parts, 0.40 parts, 0.45 parts, 0.50 parts, 0.55 parts, 0.60 parts, 0.65 parts, 0.70 parts, 0.75 parts, 0.80 parts, 0.85 parts, 0.90 parts, 0.95 parts or 1.0 parts, etc.).

[0026] Furthermore, a preservative needs to be added to the magnetic separation liquid.

[0027] Specifically, the preservative is selected from one or more of methyl parahydroxybenzoate, potassium sorbate, sodium benzoate, benzoic acid, ethyl hydroxybenzoate, propyl hydroxybenzoate, butyl hydroxybenzoate or chlorobutanol.

[0028] Specifically, the magnetic separation liquid contains 0.5 to 5.0 parts of preservatives by mass (for example, 0.5 parts, 1.0 parts, 1.5 parts, 2.0 parts, 2.5 parts, 3.0 parts, 3.5 parts, 4.0 parts, 4.5 parts, or 5.0 parts, etc.).

[0029] In a specific embodiment of the present invention, the magnetic separation liquid comprises, by mass: 0.1-1.5 parts of n-octanol (such as 0.1 part, 0.2 part, 0.4 part, 0.5 part, 0.6 part, 0.8 part, 1.0 part, 1.1 part, 1.2 parts, 1.3 parts, 1.4 parts or 1.5 parts, etc.); 0.1-1.5 parts of dimethyl silicone oil (such as 0.1 part, 0.2 part, 0.4 part, 0.5 part, 0.6 part, 0.8 part, 1.0 part, 1.1 part, 1.2 parts, 1.3 parts, 1.4 parts or 1.5 parts, etc.); 0.05-0.25 parts of nonylphenol polyoxyethylene ether (such as 0.05 parts, 0.06 parts, 0.08 parts, 0.1 parts, 0.12 parts, 0.14 parts, 0.15 parts, 0.16 parts, 0.17 parts, 0.18 parts, 0.19 parts, 0.20 parts, 0.21 parts, 0.22 parts, 0.23 parts, 0.24 parts or 0.25 parts, etc.); Fatty acid methyl ester sulfonate sodium 0.05-0.25 parts (such as 0.05 parts, 0.06 parts, 0.08 parts, 0.1 parts, 0.12 parts, 0.14 parts, 0.15 parts, 0.16 parts, 0.17 parts, 0.18 parts, 0.19 parts, 0.20 parts, 0.21 parts, 0.22 parts, 0.23 parts, 0.24 parts, or 0.25 parts, etc.); Cetyltrimethylammonium bromide 0.05-0.25 parts (such as 0.05 parts, 0.06 parts, 0.08 parts, 0.1 parts, 0.12 parts, 0.14 parts, 0.15 parts, 0.16 parts, 0.17 parts, 0.18 parts, 0.19 parts, 0.20 parts, 0.21 parts, 0.22 parts, 0.23 parts, 0.24 parts, or 0.25 parts, etc.); Diethylenetriamine pentaacetic acid 0.1-1.0 parts (such as 0.1 parts, 0.15 parts, 0.20 parts, 0.25 parts, 0.3 parts, 0.35 parts, 0.4 parts, 0.45 parts, 0.5 parts, 0.6 parts, 0.7 parts, 0.8 parts, 0.9 parts, or 1.0 parts, etc.); Methyl paraben 0.5-2.5 parts (such as 0.5 parts, 0.6 parts, 0.8 parts, 1.0 parts, 1.2 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts, 2.0 parts, 2.1 parts, 2.2 parts, 2.3 parts, 2.4 parts, or 2.5 parts, etc.); Potassium sorbate 0.5-2.5 parts (such as 0.5 parts, 0.6 parts, 0.8 parts, 1.0 parts, 1.2 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts, 2.0 parts, 2.1 parts, 2.2 parts, 2.3 parts, 2.4 parts, or 2.5 parts, etc.).

[0030] More specifically, the magnetic separation fluid includes, by mass fraction: n-Octanol 0.4-1.2 parts; Dimethyl silicone oil 0.4-1.2 parts; Nonylphenol polyoxyethylene ether 0.08-0.20 parts; Fatty acid methyl ester sulfonate sodium 0.08-0.20 parts; Cetyltrimethylammonium bromide 0.08-0.20 parts; Diethylenetriamine pentaacetic acid 0.2-0.8 parts; Methyl paraben 0.8-2.0 parts; Potassium sorbate 0.8-2.0 parts.

[0031] Specifically, the magnetic separation fluid includes a solvent (such as water), and the concentration ranges of the components are: n-octanol 1-15 mg / mL (e.g., 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, or 15 mg / mL, etc.), preferably 4-12 mg / mL; dimethicone 1-15 mg / mL (e.g., 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, or 15 mg / mL, etc.), preferably 4-12 mg / mL; nonylphenol ethoxylate 0.5-2.5 mg / mL (e.g., 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1.0 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1.6 mg / mL, 1.7 mg / mL, 1.8 mg / mL, 1.9 mg / mL, 2.0 mg / mL, 2.1 mg / mL, 2.2 mg / mL, 2.3 mg / mL, 2.4 mg / mL, or 2.5 mg / mL, etc.), preferably 0.8-2.0 mg / mL; fatty acid methyl ester sodium sulfonate 0.5-2.5 mg / mL (e.g., 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1.0 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1.6 mg / mL, 1.7 mg / mL, 1.8 mg / mL, 1.9 mg / mL, 2.0 mg / mL, 2.1 mg / mL, 2.2 mg / mL, 2.3 mg / mL, 2.4 mg / mL, or 2.5 mg / mL, etc.), preferably 0.8-2.0 mg / mL; Cetyltrimethylammonium bromide 0.5-2.5 mg / mL (e.g. 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1.0 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1.6 mg / mL, 1.7 mg / mL, 1.8 mg / mL, 1.9 mg / mL, 2.0 mg / mL, 2.1 mg / mL, 2.2 mg / mL, 2.3 mg / mL, 2.4 mg / mL or 2.5 mg / mL, etc.), preferably 0.8-2.0 mg / mL; Diethylenetriaminepentaacetic acid 1-10 mg / mL (e.g. 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL or 10 mg / mL, etc.), preferably 2-8 mg / mL; Methylparaben 5-25 mg / mL (e.g. 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL or 25 mg / mL, etc.), preferably 8-20 mg / mL; Potassium sorbate 5-25 mg / mL (e.g. 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL or 25 mg / mL, etc.), preferably 8-20 mg / mL.

[0032] In one specific embodiment of the present application, the magnetic separation fluid comprises, by mass fraction: n-Octanol 0.5 parts; Dimethyl silicone oil 0.5 parts; Nonylphenol polyoxyethylene ether 0.1 parts; Fatty acid methyl ester sulfonate sodium 0.1 parts; Cetyltrimethylammonium bromide 0.1 parts; Diethylenetriaminepentaacetic acid 0.25 parts; 1.0 part of methyl parahydroxybenzoate; 1.0 part of potassium sorbate.

[0033] In a specific embodiment of the present invention, the magnetic separation liquid comprises, by mass: 1.0 part of n-octanol; 1.0 part of dimethyl silicone oil; 0.15 parts of nonylphenol polyoxyethylene ether; 0.15 parts of sodium fatty acid methyl ester sulfonate; 0.15 parts of hexadecyltrimethylammonium bromide; 0.5 parts of diethylenetriaminepentaacetic acid; 1.5 parts of methyl parahydroxybenzoate; 1.5 parts of potassium sorbate.

[0034] Specifically, in the above magnetic separation liquid composition, the balance is water.

[0035] Specifically, in one embodiment of the present invention, the concentration of each component in the magnetic separation liquid is (with water as the solvent): n-Octanol 5 mg / mL; Dimethicone 5 mg / mL; Nonylphenol polyoxyethylene ether 1mg / mL; Sodium fatty acid methyl ester sulfonate 1 mg / mL; Cetyltrimethylammonium bromide 1 mg / mL; Diethylenetriaminepentaacetic acid 2.5 mg / mL; Methyl paraben 10 mg / mL; Potassium sorbate 10mg / mL.

[0036] Specifically, in one embodiment of the present invention, the concentration of each component in the magnetic separation liquid is (with water as the solvent): n-Octanol 10 mg / mL; Dimethicone 10 mg / mL; Nonylphenol polyoxyethylene ether 1.5 mg / mL; Sodium fatty acid methyl ester sulfonate 1.5 mg / mL; Hexadecyltrimethylammonium bromide 1.5 mg / mL; Diethylenetriaminepentaacetic acid 5 mg / mL; Methylparaben 15 mg / mL; Potassium sorbate 15mg / mL.

[0037] Another aspect of the present invention provides a method for preparing a magnetic separation liquid, the method comprising: The magnetic separation liquid is prepared by sequentially adding defoaming agent, surfactant, metal chelating agent and preservative into water, and mixing uniformly.

[0038] Specifically, the magnetic separation liquid needs to be stored at low temperature.

[0039] Specifically, the storage temperature is 2-8℃ (for example, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃ or 8℃, etc.).

[0040] In a third aspect, the application provides application of the magnetic separation liquid in chemiluminescence immunoassay.

[0041] Specifically, the chemiluminescence immunoassay is divided into direct chemiluminescence immunoassay and enzyme catalytic chemiluminescence immunoassay according to principle.

[0042] In a fourth aspect, the application provides a magnetic particle chemiluminescence immunoassay detection method, which comprises the step of washing and separating the magnetic particle-immune complex by using the magnetic separation liquid.

[0043] Specifically, the magnetic particle chemiluminescence immunoassay detection method comprises the steps of forming a combination of the to-be-detected substance in the test item sample and the magnetic beads in the magnetic bead reagent, performing magnetic adsorption, then removing the reaction solution and adding the magnetic separation liquid, washing the combination in the magnetic separation liquid, and then removing the magnetic separation liquid.

[0044] Specifically, the operation of removing the reaction solution and adding the magnetic separation liquid in the magnetic particle chemiluminescence immunoassay detection method can be repeated one or more times.

[0045] Specifically, the detection items include, but are not limited to, high-sensitivity troponin (hs-cTnI), D-dimer (D-Dimer), interleukin 10 (IL-10), creatine kinase isoenzyme (CK-MB), N-terminal pro brain natriuretic peptide (NT-proBNP), anti-double-stranded DNA antibody (anti-dsDNA antibody), anti-cyclic citrullinated peptide antibody (anti-CCP antibody), procalcitonin (PCT), and hepatitis B five items (HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb).

[0046] The application has the following beneficial effects: By using the magnetic separation liquid in the magnetic separation and washing of the chemiluminescence immunoassay instrument, the problem of jumping value caused by incomplete washing in the magnetic separation process can be effectively solved, the problem of false positive caused by jumping value can be effectively avoided, and the accuracy of the measured value is ensured. DETAILED DESCRIPTION

[0047] The technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application. Example 1: Preparation of magnetic separation liquid

[0048] 0.1% of dimethyl silicone oil, 0.1% of n-octanol, 0.05% of nonylphenol polyoxyethylene ether, 0.05% of sodium fatty acid methyl ester sulfonate, 0.05% of cetyltrimethylammonium bromide, 0.1% of diethylene triamine pentaacetic acid, 0.5% of methyl p-hydroxybenzoate and 0.5% of potassium sorbate, and then the mixture is uniformly mixed and stored at 5°C. Example 2: Preparation of magnetic separation liquid

[0049] 0.5% of dimethyl silicone oil, 0.5% of n-octanol, 0.1% of nonylphenol polyoxyethylene ether, 0.1% of sodium fatty acid methyl ester sulfonate, 0.1% of cetyltrimethylammonium bromide, 0.25% of diethylene triamine pentaacetic acid, 1.0% of methyl p-hydroxybenzoate and 1.0% of potassium sorbate, and then the mixture is uniformly mixed and stored at 5°C. Example 3: Preparation of magnetic separation liquid

[0050] 1.0% of dimethyl silicone oil, 1.0% of n-octanol, 0.15% of nonylphenol polyoxyethylene ether, 0.15% of sodium fatty acid methyl ester sulfonate, 0.15% of cetyltrimethylammonium bromide, 0.5% of diethylene triamine pentaacetic acid, 1.5% of methyl p-hydroxybenzoate and 1.5% of potassium sorbate, and then the mixture is uniformly mixed and stored at 5°C. Effect verification

[0051] An instrument that has passed factory inspection without problems is selected as the experimental machine to verify the magnetic separation and cleaning effects of the magnetic separation liquids prepared in different embodiments. The control group is a non-optimized magnetic separation liquid (0.5 mol / L PBS buffer).

[0052] The magnetic separation liquids in Examples 1-3 and the control group are tested on the same instrument. The test items include: high-sensitivity troponin (hs-cTnI), D-dimer (D-Dimer) and interleukin 10 (IL-10). For each test item, 20 test samples are taken, and the jump value probability is calculated to determine whether the magnetic separation liquid meets the standard (the standard is a jump value probability of 0.00%).

[0053] At the same time, after each change of magnetic separation liquid, the instrument pipeline needs to be fully filled and cleaned. Experimental testing can only be started after ensuring that there is no liquid residue from the previous batch of magnetic separation liquid in the pipeline.

[0054] 1) High-sensitivity troponin (hs-cTnI) test results The experimental results of detecting high-sensitivity cardiac troponin (hs-cTnI) using magnetic separation fluid are shown in Table 1. It can be seen that the probability of high-sensitivity cardiac troponin (hs-cTnI) value jump when detecting using the control group (unoptimized magnetic separation fluid) is 35%, the probability of high-sensitivity cardiac troponin (hs-cTnI) value jump when detecting using the magnetic separation fluid prepared in Example 1 is 10%, and there is no value jump when detecting using the magnetic separation fluids prepared in Examples 2 and 3, and the probability of value jump is 0.00%.

[0055] Table 1 High-sensitivity cardiac troponin (hs-cTnI) test results

[0056] 2) D-Dimer test results The experimental results of detecting D-dimer using magnetic separation fluid are shown in Table 2. It can be seen that the probability of D-dimer jumping value when detecting using the control group (unoptimized magnetic separation fluid) is 45%, the probability of D-dimer jumping value when detecting using the magnetic separation fluid prepared in Example 1 is 20%, and there is no jumping value when detecting using the magnetic separation fluids prepared in Examples 2 and 3, and the jumping value probability is 0.00%.

[0057] Table 2 D-Dimer experimental results

[0058] 3) Interleukin-10 (IL-10) experimental results The experimental results of interleukin 10 (IL-10) detection using magnetic separation fluid are shown in Table 3. It can be seen that the jump value probability of interleukin 10 (IL-10) when detected using the control group (unoptimized magnetic separation fluid) is 20%, the jump value probability of interleukin 10 (IL-10) when detected using the magnetic separation fluid prepared in Example 1 is 5%, and there is no jump value when detected using the magnetic separation fluids prepared in Examples 2 and 3, and the jump value probability is 0.00%.

[0059] Table 3 Interleukin 10 (IL-10) experimental results

[0060] In summary, the jump value probability is high, easily leads to false positive, and in three embodiments, embodiment 1 also has jump value, but compared with the control group, the jump value number is a lot less, and the concentration measured by the jump value is also relatively low, with certain improvement. And embodiment 2 and embodiment 3 do not have jump value in three projects, completely solve the jump value phenomenon caused by the incomplete cleaning of magnetic separation, and the effect is obvious. Consider again in conjunction with cost aspect, the cost of embodiment 2 is lower than the cost of embodiment 3, but the effect is the same, so the magnetic separation liquid prepared by embodiment 2 is the best effect, and can meet market use while saving cost, and ensure product quality.

[0061] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details of the above embodiments. Within the technical concept of the present invention, various simple variations can be made to the technical solution of the present invention, and these simple variations all fall within the scope of protection of the present invention. It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A magnetic separation liquid, characterized in that The magnetic separation liquid contains, by weight, 0.1 to 3.0 parts of a defoaming agent, 0.05 to 0.75 parts of a surfactant, and 0.1 to 1.0 parts of a metal chelating agent; wherein the surfactant is composed of an anionic surfactant, a cationic surfactant, and a nonionic surfactant; Preferably, the magnetic separation liquid further comprises a solvent, preferably water, in an amount of 500 to 1500 parts.

2. The magnetic separation liquid according to claim 1, characterized in that The pH range of the magnetic separation liquid is 7.20 to 7.40; Preferably, the defoaming agent includes silicone and alcohol reagents.

3. The magnetic separation liquid according to claim 2, characterized in that The organosilicon includes one or more of dimethyl silicone oil, fluorosilicone, glycol siloxane, dimethyl siloxane or polydimethyl siloxane; Preferably, the alcohol reagent includes one or more of methanol, ethanol, isopropanol, ethylene glycol, glycerol or n-octanol; More preferably, the defoaming agent includes dimethyl silicone oil and n-octanol.

4. The magnetic separation liquid according to claim 1, characterized in that The nonionic surfactant includes one or more of nonylphenol polyoxyethylene ether, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, fatty acid polyoxyethylene ester or polyoxyethylene amine; Preferably, the cationic surfactant includes one or more of cetyltrimethylammonium bromide, benzyldodecyldimethylammonium chloride, benzalkonium bromide or benzalkonium chloride; Further preferably, the anionic surfactant includes one or more of sodium fatty acid methyl ester sulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, or sodium fatty acid methyl ester ethoxylate sulfonate; More preferably, the surfactant includes nonylphenol polyoxyethylene ether, sodium fatty acid methyl ester sulfonate, and cetyltrimethylammonium bromide.

5. The magnetic separation liquid according to claim 1, characterized in that The metal chelating agent comprises one or more of diethylenetriamine pentaacetic acid, ethylenediamine tetraacetic acid, tetrasodium dimethyl aspartate or trisodium ethylenediamine disuccinate.

6. The magnetic separation liquid according to any one of claims 1 to 5, characterized in that The magnetic separation liquid also includes a preservative; Preferably, the preservative is selected from one or more of methyl parahydroxybenzoate, potassium sorbate, sodium benzoate, benzoic acid, ethyl hydroxybenzoate, propyl hydroxybenzoate, butyl hydroxybenzoate or chlorobutanol.

7. The magnetic separation liquid according to any one of claims 1 to 6, characterized in that The magnetic separation liquid comprises, by mass: 0.1-1.5 parts of n-octanol; 0.1-1.5 parts of dimethyl silicone oil; 0.05-0.25 parts of nonylphenol polyoxyethylene ether; 0.05-0.25 parts of sodium fatty acid methyl ester sulfonate; 0.05-0.25 parts of hexadecyltrimethylammonium bromide; 0.1-1.0 parts of diethylenetriaminepentaacetic acid; 0.5-2.5 parts of methyl parahydroxybenzoate; 0.5-2.5 parts of potassium sorbate; Preferably, the magnetic separation liquid comprises, by mass: 0.5 parts of n-octanol; 0.5 parts of dimethyl silicone oil; 0.1 part of nonylphenol polyoxyethylene ether; 0.1 part of sodium fatty acid methyl ester sulfonate; 0.1 parts of hexadecyltrimethylammonium bromide; 0.25 parts of diethylenetriaminepentaacetic acid; 1.0 part of methyl parahydroxybenzoate; 1.0 part of potassium sorbate; Preferably, the magnetic separation liquid comprises, by mass: 1.0 part of n-octanol; 1.0 part of dimethyl silicone oil; 0.15 parts of nonylphenol polyoxyethylene ether; 0.15 parts of sodium fatty acid methyl ester sulfonate; 0.15 parts of hexadecyltrimethylammonium bromide; 0.5 parts of diethylenetriaminepentaacetic acid; 1.5 parts of methyl parahydroxybenzoate; 1.5 parts of potassium sorbate.

8. The magnetic separation liquid according to claim 7, characterized in that The concentration of each component in the magnetic separation liquid is: n-Octanol 5 mg / mL; Dimethicone 5 mg / mL; Nonylphenol polyoxyethylene ether 1mg / mL; Sodium fatty acid methyl ester sulfonate 1 mg / mL; Cetyltrimethylammonium bromide 1 mg / mL; Diethylenetriaminepentaacetic acid 2.5 mg / mL; Methyl paraben 10 mg / mL; Potassium sorbate 10 mg / mL; or The concentration of each component in the magnetic separation liquid is: n-Octanol 10 mg / mL; Dimethicone 10 mg / mL; Nonylphenol polyoxyethylene ether 1.5 mg / mL; Sodium fatty acid methyl ester sulfonate 1.5 mg / mL; Hexadecyltrimethylammonium bromide 1.5 mg / mL; Diethylenetriaminepentaacetic acid 5 mg / mL; Methylparaben 15 mg / mL; Potassium sorbate 15mg / mL.

9. Use of the magnetic separation solution according to any one of claims 1 to 8 in chemiluminescent immunoassay.

10. A magnetic particle chemiluminescence immunoassay detection method, comprising the step of washing and separating the magnetic particle-immune complex using the magnetic separation solution according to any one of claims 1 to 8.

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