CN114200133A - Anti-extractable nuclear antigen antibody quality control product and preparation method and application thereof - Google Patents
Anti-extractable nuclear antigen antibody quality control product and preparation method and application thereof Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Rheumatology (AREA)
- Rehabilitation Therapy (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention relates to an anti-extractable nuclear antigen antibody quality control product, a preparation method and application thereof, comprising the following steps: providing a plasma sample containing anti-extractable nuclear antigen antibodies; mixing the plasma sample with soluble calcium chloride, freezing and thawing, and taking supernatant; mixing the supernatant with perchloric acid, incubating, and then adding an alkali solution for neutralization to obtain an antibody solution; and mixing the antibody solution with a protective solution to obtain a liquid quality control product. The preparation method of the quality control product of the anti-extractable nuclear antigen antibody utilizes the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid for treatment, can reduce the interference of impurities such as organic micromolecular substances, fibrin, lipoprotein and the like to the maximum extent, can reduce non-specific binding reaction, can reduce the risk of infection, can solve the problem that the plasma raw material is easy to precipitate, and improves the stability.
Description
Technical Field
The invention relates to the technical field of immunodetection, in particular to an anti-extractable nuclear antigen antibody quality control product and a preparation method and application thereof.
Background
Ena (extractable Nuclear antigen), the chinese name, which is extractable Nuclear antigen, does not contain histone and can be extracted by dissolving in saline. Antibodies against ENA, namely, anti-extractable nuclear antigen antibodies (anti-ENA antibodies), belong to the anti-ENA antibody spectrum among the antinuclear antibody spectrum, and there are mainly 6: the anti-SS-A antibody, the anti-SS-B antibody, the anti-Sm antibody, the anti-ribonucleoprotein 70(RNP70) antibody, the anti-Jo-1 antibody and the anti-Scl-70 antibody are mainly used for qualitatively detecting the autoantibodies in human serum or plasmA, have important significance for diagnosis and differential diagnosis of connective tissue diseases and have no obvious correlation with the severity and activity of the diseases.
For the detection of related items of the anti-ENA autoantibody, immunological detection technologies on the market comprise an immunoblotting method, an enzyme-linked immunosorbent assay, a chemiluminescence method and the like, and a chemiluminescence immunoassay detection technology has higher sensitivity and specificity and gradually replaces detection technologies of an immunoblotting method, an enzyme-linked immunosorbent assay and the like. In the detection, a liquid quality control substance of the anti-ENA autoantibody or a freeze-dried powder quality control substance of the anti-ENA autoantibody and the like are required to be used for quality control in the detection of related items of the anti-ENA autoantibody in a laboratory.
However, the quality control of the anti-extractable nuclear antigen antibodies prepared by the conventional methods is poor, and the antibodies are prone to non-specific binding reactions and have poor stability.
Disclosure of Invention
Accordingly, there is a need for a method for preparing a quality control product of anti-extractable nuclear antigen antibodies that can reduce non-specific binding reactions and improve stability.
A method for preparing quality control products of anti-extractable nuclear antigen antibodies comprises the following steps:
providing a plasma sample containing anti-extractable nuclear antigen antibodies;
mixing the plasma sample with soluble calcium chloride, freezing and thawing, and taking supernatant;
mixing the supernatant with perchloric acid, incubating, and then adding an alkali solution for neutralization to obtain an antibody solution;
and mixing the antibody solution with a protective solution to obtain a liquid quality control product.
The preparation method of the quality control product of the anti-extractable nuclear antigen antibody utilizes the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid for treatment, can reduce the interference of impurities such as organic micromolecular substances, fibrin, lipoprotein and the like to the maximum extent, can reduce non-specific binding reaction, can reduce the risk of infection, can solve the problem that the plasma raw material is easy to precipitate, and improves the stability.
In one embodiment, the protective solution comprises 9-13 g/L of MOPS sodium salt, 7-11 g/L of sodium chloride, 2-5 g/L of disodium ethylene diamine tetraacetate, 15-23 g/L of trehalose, 75-85 g/L of mannitol, 38-42 g/L of bovine serum albumin and 28-32 mL/L of tert-butyl alcohol.
In one embodiment, the protective solution further comprises 8-12 g/L glucose, 3-7 g/L glycine and 1.5-3.5 g/L casein.
In one embodiment, the soluble calcium chloride is used in an amount of: 2.5-3 mg of the soluble calcium chloride is added into each milliliter of the plasma sample.
In one embodiment, the perchloric acid is used in an amount of: and adding 150-250 microliter of perchloric acid into every 100 microliter of the supernatant.
In one embodiment, the method further comprises the following steps: and (3) freeze-drying the liquid quality control product to obtain a dry powder quality control product.
In one embodiment, the freeze drying comprises prefreezing, primary drying and secondary drying, and the condition parameters of the prefreezing step are as follows: treating at 3-5 ℃ for 3-7 min and at-50 to-40 ℃ for 20-40 min; the condition parameters of the primary drying step are as follows in sequence: treating for 5-10 s at the temperature of minus 50 to minus 40 ℃ and the vacuum degree of 0.2-0.4 mbar, treating for 50-70 min at the temperature of minus 50 to minus 40 ℃ and the vacuum degree of 0.05-0.15 mbar, treating for 22-24 h at the temperature of minus 35 to minus 25 ℃ and the vacuum degree of 0.05-0.15 mbar, and treating for 40-80 min at the temperature of minus 15 to minus 5 ℃ and the vacuum degree of 0.05-0.15 mbar; the condition parameters of the secondary drying step are as follows: treating for 2-3 hours at 5-15 ℃ and 0.0005-0.0015 mbar vacuum degree.
In one embodiment, the anti-extractable nuclear antigen antibody includes an anti-SS-A antibody, an anti-SS-B antibody, an anti-Sm antibody, an anti-RNP 70 antibody, an anti-Jo-1 antibody, and an anti-Scl-70 antibody.
The invention also provides an anti-extractable nuclear antigen antibody quality control product which is prepared according to the preparation method.
The invention also provides an anti-extractable nuclear antigen antibody detection kit, which comprises an immunoassay reagent and the quality control product of the anti-extractable nuclear antigen antibody.
Detailed Description
In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The preparation method of the anti-extractable nuclear antigen antibody quality control product of the embodiment of the invention comprises the following steps of S1-S4:
s1, providing a plasma sample containing the anti-extractable nuclear antigen antibody.
And S2, mixing the plasma sample with soluble calcium chloride, freezing and thawing, and taking supernatant. Recalcification, introduction of calcium ions, removal of impurities such as fibrinogen in blood plasma, and obtaining of blood plasma material with less impurities.
And S3, mixing the supernatant with perchloric acid, incubating, and then adding an alkali solution for neutralization to obtain an antibody solution. The perchloric acid is added into the supernatant of the blood plasma, so that the interference of components such as hemoglobin or triglyceride can be effectively overcome, the recovery rate is improved, a plurality of proteases, blood coagulation factors and the like can be removed, and the anti-interference capability is greatly improved.
And S4, mixing the antibody solution with the protective solution to obtain the liquid quality control product.
The preparation method of the quality control product of the anti-extractable nuclear antigen antibody utilizes the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid for treatment, can reduce the interference of impurities such as organic micromolecular substances, fibrin, lipoprotein and the like to the maximum extent, can reduce non-specific binding reaction, can reduce the risk of infection, can solve the problem that the plasma raw material is easy to precipitate, and improves the stability.
In a specific example, the protective solution comprises 9-13 g/L of MOPS sodium salt, 7-11 g/L of sodium chloride, 2-5 g/L of disodium ethylene diamine tetraacetic acid (EDTA disodium), 15-23 g/L of trehalose, 75-85 g/L of mannitol, 38-42 g/L of bovine serum albumin and 28-32 mL/L of tert-butyl alcohol. The stability of each analyte of the quality control product is enhanced by adding a certain proportion of tert-butyl alcohol as a freeze-drying acceleration solvent, adding bovine serum albumin as an excipient, and adding EDTA disodium, trehalose, sucrose and other components as freeze-drying stabilizers and protective agents.
In a specific example, the protective solution further comprises 8-12 g/L glucose, 3-7 g/L glycine and 1.5-3.5 g/L casein. The stability of each analyte of the quality control product can be obviously improved by further adding glucose, glycine and casein on the basis of the formula, and the dosage proportion of each component is applied to the quality control product, so that the stability of each analyte can be improved, the storage is convenient, and the active ingredients can be ensured to be hardly damaged in the freeze-drying process.
In one embodiment, the protective solution further comprises a preservative. The bovine serum albumin and other substances in the protective solution are rich in nutrition and are easy to breed microorganisms, so that the preservative is added into the protective solution to prevent the pollution. Preferably, the protective solution comprises two preservatives, namely ProClin 300 and PS-3, and the concentrations of the ProClin 300 and the PS-3 are 0.4-0.6 mL/L and 0.1-0.3 g/L respectively.
In one specific example, the amount of soluble calcium chloride used is: 2.5-3 mg of soluble calcium chloride is added to each ml of plasma sample.
In one specific example, perchloric acid is used in an amount of: adding 150-250 microliter perchloric acid into every 100 microliter of supernatant.
In one specific example, the anti-extractable nuclear antigen antibody includes an anti-SS-A antibody, an anti-SS-B antibody, an anti-Sm antibody, an anti-RNP 70 antibody, an anti-Jo-1 antibody, and an anti-Scl-70 antibody. It can be understood that after the corresponding antibody solutions are respectively obtained by processing the plasma samples containing different antibodies, different amounts of the corresponding antibody solutions are respectively taken according to the target concentration and mixed with the protective solution, and the anti-ENA autoantibody composite quality control product can be obtained. Optionally, the plasma sample is a plasma material of jaundice, hemolysis, lipemia, or the like.
In one specific example, the preparation method further comprises the following steps: and (4) freeze-drying the liquid quality control product to obtain a dry powder quality control product. The quality control product in liquid form is greatly influenced by factors such as temperature, microorganisms and the like, and the active ingredients are more easily degraded and are inconvenient to store for a long time; the quality control product in the form of the freeze-dried powder has less moisture, is not beneficial to the growth of microorganisms, has a compact crystal structure, is not beneficial to the movement of internal molecules, is not easy to degrade active substances, has better stability and is more convenient to store for a long time. The single liquid quality control product has the defects of short validity period, instability and the like, the single freeze-dried powder quality control product has the defects of difficult redissolution, easy influence on the active structure of raw materials and the like, and the single quality control product cannot be simultaneously used for detecting all items contained in the anti-ENA autoantibody, so the efficiency can be improved and the cost can be reduced by adopting the composite quality control product.
In one specific example, the freeze drying includes prefreezing, primary drying and secondary drying, and the condition parameters of the prefreezing step are as follows: treating at 3-5 ℃ for 3-7 min and at-50 to-40 ℃ for 20-40 min; the condition parameters of the primary drying step are as follows in sequence: treating for 5-10 s at the temperature of minus 50 to minus 40 ℃ and the vacuum degree of 0.2-0.4 mbar, treating for 50-70 min at the temperature of minus 50 to minus 40 ℃ and the vacuum degree of 0.05-0.15 mbar, treating for 22-24 h at the temperature of minus 35 to minus 25 ℃ and the vacuum degree of 0.05-0.15 mbar, and treating for 40-80 min at the temperature of minus 15 to minus 5 ℃ and the vacuum degree of 0.05-0.15 mbar; the condition parameters of the secondary drying step are as follows: treating for 2-3 hours at 5-15 ℃ and 0.0005-0.0015 mbar vacuum degree. The ENA-resisting autoantibody composite quality control product obtained by adopting the improved freeze-drying program freeze-drying can keep the original physicochemical property and biological activity of the product, has the advantages of little loss of effective components, little water, loose crystal structure in appearance, low water content, easy long-term storage, long storage period, good redissolution stability, small matrix effect and the like, can be simultaneously used for indoor quality control of a plurality of analytes, and improves the efficiency.
In conclusion, the plasma treatment process adopted in the preparation method of the invention can reduce impurity interference, reduce non-specific binding reaction, save preparation time, reduce labor cost and the like, and the improved formula of the protective solution and the freeze-drying procedure are more advantageous, can protect the active ingredients of the analyte from being damaged, improve the stability of the analyte and facilitate long-term storage and transportation.
The present invention will be described in further detail below mainly with reference to specific embodiments.
Example 1 Positive Material treatment
Taking out positive materials of six items (SS-A IgG, SS-B IgG, Sm IgG, RNP70 IgG, Jo-1 IgG and Scl-70 IgG) from A refrigerator at the temperature of minus 80 ℃, unfreezing, cooling to 0-5 ℃, centrifuging, using A centrifuged precipitate layer for cryopreservation, and collecting A supernatant layer for subsequent treatment. 1% of diatomaceous earth was added to the supernatant, and the mixture was stirred slowly for 4 hours, left to stand for half an hour, and then filtered. Weighing 0.5% of activated carbon, adding the activated carbon into the positive material, carrying out magnetic stirring treatment for 5 hours at room temperature, then carrying out aseptic filtration for multiple times by using an aseptic device so as to separate out the activated carbon, collecting the separated positive material, and sampling for mass spectrometry detection. The antibiotic detection result in the treated plasma material is negative.
Adding 2.5-3 mg of calcium chloride into 1mL of the treated plasma material to obtain a first experimental group; adding 2.5-3 mg of magnesium chloride into 1mL of the treated plasma material to obtain an experiment group II; 2.5-3 mg of ferric chloride was added to 1mL of the treated plasma material, and the mixture was set as experiment group III. The influence of different chloride salts on the fibrinogen content of the plasma material was verified, and the results are shown in table 1. It can be seen that the fibrinogen content detected in the plasma material with calcium chloride added is lower than 0.02g/L, and the fibrinogen removal effect is significantly better than that with magnesium chloride or ferric chloride.
Taking 1mL of plasma material, adding 2.5-3 mg of calcium chloride, mixing, repeatedly freezing and thawing the mixed solution, taking supernatant, and setting three experimental groups, namely an experimental group I: adding 200 μ L of 0.2mol/L HClO per 100 μ L plasma4And water bath at 37 ℃ for 5 min. 200. mu.L of 0.2mol/L NaOH + 500. mu.L of 0.2mol/L PBS buffer was added to obtain an antibody material. Two additional control experimental groups were set, experimental group two: adding 200 mu L of 0.2mol/L HCl into every 100 mu L of plasma, carrying out water bath at 37 ℃ for 5min, and then adding 200 mu L of 0.2mol/L NaOH +500 mu L of 0.2mol/L PBS buffer solution; experiment group three: mu.L of 0.2mol/L acetic acid was added to 100. mu.L of plasma, and water bath was carried out at 37 ℃ for 5min, followed by 200. mu.L of 0.2mol/L NaOH + 500. mu.L of 0.2mol/L PBS buffer. The influence of different treated plasma materials on the interference bias and recovery of different concentrations of bilirubin and triglyceride samples was verified and the results are shown in tables 2 and 3. Therefore, the interference deviation of the plasma material treated by adding perchloric acid on bilirubin and triglyceride samples with different concentrations is controlled within 8.89%, the recovery rate is kept within the range of 90-115%, and the recovery rate is relatively stable.
Compared with the traditional calcium chloride treatment technology, the plasma material obtained by the technical means of mixing the soluble calcium chloride with the plasma sample and then treating the mixture by perchloric acid can greatly reduce the combination of nonspecific components. The antibody materials after the 6 items of treatment are tested on a chemiluminescence tester to determine the concentration, and the concentration requirements of the antibody materials of the six items are respectively as follows: SS-A IgG is more than or equal to 1000AU/mL, SS-B IgG is more than or equal to 1000AU/mL, Sm IgG is more than or equal to 1000AU/mL, RNP70 IgG is more than or equal to 1000AU/mL, Jo-1 IgG is more than or equal to 500AU/mL, Scl-70IgG is more than or equal to 500 AU/mL; RF, RF IgG and RF IgM were simultaneously measured, and the results are shown in Table 4. It can be seen that plasma materials obtained from the calcium chloride-perchloric acid treatment showed RF <0.5AU/mL, RF IgG <0.5AU/mL, and RF IgM <1AU/mL, with significantly less non-specifically bound components than the conventional methods. After screening the appropriate antibody material, the antibody material is filtered through a filter membrane with the aperture of 0.45 mu m and then is labeled for standby.
TABLE 1 results of the Effect of different chloride salts on the fibrinogen content of plasma materials
| Different treatment | Fibrinogen concentration |
| 2.5mg/L calcium chloride | 0.01g/L |
| 2.5mg/L magnesium chloride | 8.4g/L |
| 2.5mg/L ferric chloride | 10.5g/L |
TABLE 2 results of the influence of different treated plasma materials on the interference deviation and recovery of bilirubin samples of different concentrations
TABLE 3 results of the influence of different treated plasma materials on the interfering deviation and recovery of triglyceride samples of different concentrations
TABLE 4 results of plasma Material specificity determination (unit: AU/mL) for different treatments
EXAMPLE 2 preparation of the protective solution
The materials were added in the following proportion and order according to the matrix formulation table shown in table 5 below to prepare quality control matrix solution a.
TABLE 5 base fluid A formulation
| Name of material | Per L of the active ingredient |
| MOPS sodium salt | 11.6g |
| Sodium chloride | 9.0g |
| EDTA-2 sodium salt | 3.72g |
| Trehalose (dihydrate) | 20.0g |
| D-mannitol | 80.0g |
| Bovine serum albumin (Proliant) | 40.0g |
| Tert-butyl alcohol | 30mL |
| ProClin 300 (for luminescence) | 0.500mL |
| PS-3 | 0.200g |
Taking 1L of the matrix solution A as an example, firstly weighing 11.6g of MOPS sodium salt, 9.0g of sodium chloride, 3.72g of EDTA-2 sodium and 0.200g of PS-3, adding 800mL of water, and adjusting the pH after dissolving the sodium chloride, the EDTA-2 sodium and the PS-3; then 20.0g trehalose (dihydrate), 80.0g D-mannitol, 40.0g bovine serum albumin are weighed, 0.500mL ProClin 300 is sucked by a pipette, 30mL tertiary butanol is weighed by a measuring cylinder, and after all the components are dissolved, the pH is adjusted. Filtering with 0.45 μm filter membrane for use. Optimizing on the basis of the formula A, adding glucose, glycine and casein as protective agents to prepare a matrix liquid B, wherein the formula B is as follows: 1L of the substrate solution A +10g of glucose +5g of glycine +2.5g of casein, and after all the solution was dissolved, the pH was adjusted. Filtering with 0.45 μm filter membrane for use.
EXAMPLE 3 Freeze-drying of ENA autoantibody composite quality control
And respectively adding the six antibody materials into the matrix solution A and the matrix solution B, and mixing and blending to obtain a negative quality control product and a positive quality control product with target concentrations. And (2) subpackaging the raw materials into 7mL brown glass bottles by using subpackaging equipment, wherein the packaging amount of each bottle of the essential control product is 2.0mL, subpackaging the quality control product by using an electric continuous liquid distributor during small-batch production, subpackaging the quality control product by using a filling machine during large-batch production, putting the subpackaged product into a freeze dryer, performing low-temperature vacuum drying according to a set program, and capping the freeze dryer in a vacuum state to obtain the ENA autoantibody composite quality control product.
And (3) respectively placing the negative quality control product and the positive quality control product prepared by respectively blending the matrix solution A and the matrix solution B at 37 ℃, 2-8 ℃ and-20 ℃ for 10 days, and carrying out stability comparison verification, wherein the results are shown in table 6. Therefore, the deviation of the thermal stability and the redissolution stability of each analyte of the quality control product prepared by the matrix liquid B is small and is within the range of +/-5%.
TABLE 6 comparative validation of stability of base solution A and base solution B (Unit: AU/mL)
The negative quality control product and the positive quality control product prepared by using the matrix liquid B are subjected to freeze drying by using a conventional freeze-drying procedure 2 and a freeze-drying procedure 1 of the present invention, and specific parameters of the freeze-drying procedure 1 and the freeze-drying procedure 2 are shown in Table 7. Placing the obtained non-redissolved dry powder quality control product at 37 ℃ for 10 days, adding pure water for redissolving, placing the product at 2-8 ℃ and-20 ℃ for 10 days, placing the non-redissolved dry powder quality control product at 2-8 ℃ as a reference, taking out the quality control product at 10 days, adding water to the non-redissolved dry powder quality control product for dissolving, fully dissolving, and performing stability comparison verification when the redissolved quality control product is recovered to room temperature, wherein the result is shown in Table 8. It can be seen that lyophilization procedure 1 of the present invention was selected for lyophilization with minimal deviation in thermal stability and reconstitution stability, both within acceptable limits.
Table 7 parameters of lyophilization program 1 and lyophilization program 2
TABLE 8 stability comparison verification results of lyophilization program 1 and lyophilization program 2 (unit: AU/mL)
Example 4 evaluation of the Performance of ENA autoantibody composite quality control Material
Taking 10 bottles of negative quality control products and positive quality control products of the ENA autoantibody prepared by the method, detecting each of six items for 10 times, calculating the average value (M) and the Standard Deviation (SD) of 10 measurement results of each item, obtaining the variation Coefficient (CV) in the bottle according to the formula CV (SD/M multiplied by 100 percent), and finding that the results are shown in table 9 and the uniformity in the bottle is very good. Taking 10 bottles of negative quality control materials and positive quality control materials in the same batch, respectively measuring six items of each bottle of quality control materials on a detection system for 1 time, and calculating the average value of 10 detection results
And Standard Deviation (SD)1) (ii) a Continuously detecting 10 times with 1 package of the above 10 bottles of negative and positive quality control materials, and calculating the average value of 10 detection results
And Standard Deviation (SD)2) (ii) a Calculating the coefficient of variation between bottles (CV) when SD is given by the following equations (1) to (2)1<SD2When, CV isBottle roomThe results are shown in table 10, with 0, indicating that the uniformity between bottles is also good.
TABLE 9 in-bottle homogeneity test results (unit: AU/mL)
TABLE 10 results of uniformity test between bottles (unit: AU/mL)
Storing the negative quality control material and the positive quality control material of the same batch at 37 ℃ in a dark place, taking out after 10 days, redissolving with a control sample, detecting on a chemiluminescence determinator, and calculating the deviation from the control sample, wherein the result is shown in a table 11. And (3) redissolving the negative quality control products and the positive quality control products in the same batch, placing the products in an environment of 20-25 ℃ for 3 days, placing the products in an environment of 2-8 ℃ for 30 days, placing the products in an environment of-20 ℃ for 30 days, taking the products out the same day after the expiration, redissolving the products together with the control samples, detecting the products on a chemiluminescence determinator, calculating the deviation between the products and the control samples, and obtaining results shown in table 12, wherein the thermal stability and the redissolution stability are excellent.
TABLE 11 results of thermal stability test (unit: AU/mL)
TABLE 12 reconstitution stability test results (Unit: AU/mL)
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. A preparation method of an anti-extractable nuclear antigen antibody quality control product is characterized by comprising the following steps:
providing a plasma sample containing anti-extractable nuclear antigen antibodies;
mixing the plasma sample with soluble calcium chloride, freezing and thawing, and taking supernatant;
mixing the supernatant with perchloric acid, incubating, and then adding an alkali solution for neutralization to obtain an antibody solution;
and mixing the antibody solution with a protective solution to obtain a liquid quality control product.
2. The preparation method of claim 1, wherein the protective solution comprises 9-13 g/L of LMOPS sodium salt, 7-11 g/L of sodium chloride, 2-5 g/L of disodium ethylenediaminetetraacetate, 15-23 g/L of trehalose, 75-85 g/L of mannitol, 38-42 g/L of bovine serum albumin and 28-32 mL/L of tert-butyl alcohol.
3. The preparation method according to claim 2, wherein the protective solution further comprises 8-12 g/L glucose, 3-7 g/L glycine and 1.5-3.5 g/L casein.
4. The method according to claim 1, wherein the soluble calcium chloride is used in an amount of: 2.5-3 mg of the soluble calcium chloride is added into each milliliter of the plasma sample.
5. The method according to claim 1, wherein the perchloric acid is used in an amount of: and adding 150-250 microliter of perchloric acid into every 100 microliter of the supernatant.
6. The method according to any one of claims 1 to 5, further comprising the steps of: and (3) freeze-drying the liquid quality control product to obtain a dry powder quality control product.
7. The preparation method according to claim 6, wherein the freeze drying comprises prefreezing, primary drying and secondary drying, and the condition parameters of the prefreezing step are as follows in sequence: treating at 3-5 ℃ for 3-7 min and at-50 to-40 ℃ for 20-40 min; the condition parameters of the primary drying step are as follows in sequence: treating for 5-10 s at the temperature of minus 50 to minus 40 ℃ and the vacuum degree of 0.2-0.4 mbar, treating for 50-70 min at the temperature of minus 50 to minus 40 ℃ and the vacuum degree of 0.05-0.15 mbar, treating for 22-24 h at the temperature of minus 35 to minus 25 ℃ and the vacuum degree of 0.05-0.15 mbar, and treating for 40-80 min at the temperature of minus 15 to minus 5 ℃ and the vacuum degree of 0.05-0.15 mbar; the condition parameters of the secondary drying step are as follows: treating for 2-3 hours at 5-15 ℃ and 0.0005-0.0015 mbar vacuum degree.
8. The method according to any one of claims 1 to 5, wherein the anti-extractable nuclear antigen antibody comprises an anti-SS-A antibody, an anti-SS-B antibody, an anti-Sm antibody, an anti-ribonucleoprotein 70 antibody, an anti-Jo-1 antibody and an anti-Scl-70 antibody.
9. An anti-extractable nuclear antigen antibody quality control product, characterized by being prepared by the preparation method of any one of claims 1 to 8.
10. An anti-extractable nuclear antigen antibody detection kit, characterized by comprising an immunodetection reagent for extractable nuclear antigen and the quality control product for anti-extractable nuclear antigen antibody of claim 9.
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