CN114200133B - 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
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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
- G01N33/531—Production of immunochemical test materials
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- Life Sciences & Earth Sciences (AREA)
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- Cell Biology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
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- Microbiology (AREA)
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- Biochemistry (AREA)
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- Rehabilitation Therapy (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention relates to an extractable nuclear antigen resistant antibody quality control product and a preparation method and application thereof, and the extractable nuclear antigen resistant antibody quality control product comprises the following steps: providing a plasma sample containing anti-extractable nuclear antigen antibodies; mixing the plasma sample with soluble calcium chloride, and taking supernatant after freeze thawing; 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 the liquid quality control product. The preparation method of the anti-extractable nuclear antigen antibody quality control product utilizes the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid for treatment, can furthest reduce the interference of organic micromolecular substances, fibrin, lipoprotein and other impurities, can reduce non-specific binding reaction, can reduce infection risk, 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, a preparation method and application thereof.
Background
ENA (Extractable Nuclear Antibody) Chinese name is extractable nuclear antigen, which is histone free and can be extracted in saline. Antibodies against ENA, namely, anti-extractable nuclear antigen antibodies (anti-ENA antibodies), belong to the anti-ENA antibody profile in the anti-nuclear antibody profile, and there are mainly 6: the anti-SS-A antibody, the anti-SS-B antibody, the anti-Sm antibody, the anti-ribonucleoprotein 70 (RNP 70) antibody, the anti-Jo-1 antibody and the anti-Scl-70 antibody are mainly used for qualitatively detecting autoantibodies in human serum or blood plasmse:Sup>A, have important significance for connective tissue disease diagnosis and differential diagnosis, and have no obvious correlation with disease severity and activity.
For the detection of anti-ENA autoantibody related projects, immunological detection technologies on the market include an immunoblotting method, an enzyme-linked immunosorbent assay, a chemiluminescence method and the like, and the chemiluminescence immunoassay detection technology has higher sensitivity and specificity and gradually replaces detection technologies such as the immunoblotting method, the enzyme-linked immunosorbent assay and the like. In the detection, a liquid quality control product of the anti-ENA autoantibody or a freeze-dried powder quality control product of the anti-ENA autoantibody and the like are required to be used for quality control in the detection of related items of the laboratory anti-ENA autoantibody.
However, the quality of the anti-extractable nuclear antigen antibody prepared by the traditional method is good and uneven, the non-specific binding reaction is easy to occur, and the stability is poor.
Disclosure of Invention
Based on this, it is necessary to provide a method for preparing an anti-extractable nuclear antigen antibody quality control product which can reduce the nonspecific binding reaction and improve the stability.
A preparation method of an anti-extractable nuclear antigen antibody quality control product comprises the following steps:
providing a plasma sample containing anti-extractable nuclear antigen antibodies;
mixing the plasma sample with soluble calcium chloride, and taking supernatant after freeze thawing;
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 the liquid quality control product.
The preparation method of the anti-extractable nuclear antigen antibody quality control product utilizes the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid for treatment, can furthest reduce the interference of organic micromolecular substances, fibrin, lipoprotein and other impurities, can reduce non-specific binding reaction, can reduce infection risk, 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 MOPS sodium salt, 7-11 g/L sodium chloride, 2-5 g/L disodium ethylenediamine tetraacetate, 15-23 g/L trehalose, 75-85 g/L mannitol, 38-42 g/L bovine serum albumin and 28-32 mL/L tertiary butanol.
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 soluble calcium chloride is added to each milliliter of the plasma sample.
In one embodiment, the perchloric acid is used in an amount of: 150 to 250 microliters of the perchloric acid was added per 100 microliters of the supernatant.
In one embodiment, the method further comprises the steps of: and freeze-drying the liquid quality control product to obtain the dry powder quality control product.
In one embodiment, the freeze-drying comprises pre-freezing, primary drying and secondary drying, and the condition parameters of the pre-freezing step are as follows: treating at 3-5 deg.c for 3-7 min and at-50 to-40 deg.c for 20-40 min; the condition parameters of the primary drying step are as follows: the treatment is carried out for 5 to 10 seconds under the conditions of the temperature of-50 to-40 ℃ and the vacuum degree of 0.2 to 0.4mbar, the treatment is carried out for 50 to 70 minutes under the conditions of the temperature of-50 to-40 ℃ and the vacuum degree of 0.05 to 0.15mbar, the treatment is carried out for 22 to 24 hours under the conditions of the temperature of-35 to-25 ℃ and the vacuum degree of 0.05 to 0.15mbar, and the treatment is carried out for 40 to 80 minutes under the conditions of the temperature of-15 to-5 ℃ and the vacuum degree of 0.05 to 0.15 mbar; the condition parameters of the secondary drying step are as follows: the treatment is carried out for 2 to 3 hours at the temperature of 5 to 15 ℃ and the vacuum degree of 0.0005 to 0.0015 mbar.
In one embodiment, the anti-extractable nuclear antigen antibodies include anti-SS-A antibodies, anti-SS-B antibodies, anti-Sm antibodies, anti-RNP 70 antibodies, anti-Jo-1 antibodies, and anti-Scl-70 antibodies.
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 immunodetection reagent and the anti-extractable nuclear antigen antibody quality control product.
Detailed Description
The present invention will be described more fully hereinafter in order to facilitate an understanding of the present invention, and preferred embodiments of the present invention are set forth. 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 herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
The preparation method of the extractable nuclear antigen resistant antibody quality control product comprises the following steps of S1 to S4:
s1, providing a plasma sample containing an anti-extractable nuclear antigen antibody.
S2, mixing the plasma sample with soluble calcium chloride, and taking supernatant after freeze thawing. The recalcification and the introduction of calcium ions can remove impurities such as fibrinogen and the like in the blood plasma, and the blood plasma material with less impurities can be obtained.
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, coagulation factors and the like can be removed, and the anti-interference capability is greatly improved.
S4, mixing the antibody solution with the protective solution to obtain the liquid quality control product.
The preparation method of the anti-extractable nuclear antigen antibody quality control product utilizes the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid for treatment, can furthest reduce the interference of organic micromolecular substances, fibrin, lipoprotein and other impurities, can reduce non-specific binding reaction, can reduce infection risk, 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 MOPS sodium salt, 7-11 g/L sodium chloride, 2-5 g/L disodium ethylenediamine tetraacetate (EDTA disodium), 15-23 g/L trehalose, 75-85 g/L mannitol, 38-42 g/L bovine serum albumin and 28-32 mL/L tertiary butanol. The stability of each analyte of the quality control product is enhanced by adding a certain proportion of tertiary butanol as a freeze-drying accelerating 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, the dosage proportion of each component is applied to the quality control product, the stability of each analyte can be improved, the storage is convenient, and the active ingredients are hardly damaged in the freeze-drying process.
In a specific example, the protective solution further contains a preservative. The protecting liquid contains rich nutrients, including bovine serum albumin, and is easy to grow microbe, so that preservative is added to the protecting liquid to prevent pollution. Preferably, the protective solution comprises two preservatives of ProClin300 and PS-3, and the concentrations of ProClin300 and PS-3 are respectively 0.4-0.6 mL/L and 0.1-0.3 g/L.
In one specific example, the soluble calcium chloride is used in an amount of: 2.5-3 mg of soluble calcium chloride is added to each milliliter of plasma sample.
In one specific example, the amount of perchloric acid used is: 150 to 250 microliters of perchloric acid is added per 100 microliters of supernatant.
In se:Sup>A specific example, the anti-extractable nuclear antigen antibodies include anti-SS-A antibodies, anti-SS-B antibodies, anti-Sm antibodies, anti-RNP 70 antibodies, anti-Jo-1 antibodies, and anti-Scl-70 antibodies. It can be understood that the anti-ENA autoantibody composite quality control product can be obtained by respectively processing plasma samples containing different antibodies to obtain corresponding antibody solutions, and then respectively mixing the corresponding antibody solutions with a protective solution according to different amounts of target concentrations. Alternatively, the plasma sample is a plasma material of jaundice, hemolysis, lipidemia, etc.
In a specific example, the preparation method further comprises the steps of: and freeze-drying the liquid quality control product to obtain the 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 active ingredients are easier to degrade and inconvenient to store for a long time; the quality control product in the form of the freeze-dried powder has less water, 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 good stability and is more convenient for long-term storage. 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 used for detecting all projects contained in the anti-ENA autoantibody at the same time, so that the efficiency can be improved and the cost can be reduced by adopting the composite quality control product.
In a specific example, the freeze-drying includes prefreezing, primary drying and secondary drying, and the condition parameters of the prefreezing step are in order: treating at 3-5 deg.c for 3-7 min and at-50 to-40 deg.c for 20-40 min; the condition parameters of the primary drying step are as follows: the treatment is carried out for 5 to 10 seconds under the conditions of the temperature of-50 to-40 ℃ and the vacuum degree of 0.2 to 0.4mbar, the treatment is carried out for 50 to 70 minutes under the conditions of the temperature of-50 to-40 ℃ and the vacuum degree of 0.05 to 0.15mbar, the treatment is carried out for 22 to 24 hours under the conditions of the temperature of-35 to-25 ℃ and the vacuum degree of 0.05 to 0.15mbar, and the treatment is carried out for 40 to 80 minutes under the conditions of the temperature of-15 to-5 ℃ and the vacuum degree of 0.05 to 0.15 mbar; the condition parameters of the secondary drying step are: the treatment is carried out for 2 to 3 hours at the temperature of 5 to 15 ℃ and the vacuum degree of 0.0005 to 0.0015 mbar. The anti-ENA autoantibody composite quality control product obtained by adopting the improved freeze-drying procedure in 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 content, 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 summary, 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 liquid and the freeze-drying procedure have more advantages, can protect the active ingredients of the analyte from being damaged almost, improve the stability of the analyte, and are convenient for long-term storage and transportation.
The present invention will be described in further detail below mainly with reference to specific embodiments.
Example 1 treatment of Positive materials
Taking out positive materials of six items (SS-A IgG, SS-B IgG, sm IgG, RNP70 IgG, jo-1 IgG and Scl-70 IgG) at se:Sup>A refrigerator of-80 ℃, thawing, cooling to 0-5 ℃ for centrifugation, freezing the centrifuged precipitate layer, and collecting supernatant for subsequent treatment. Adding 1% diatomite into the supernatant, slowly stirring for 4 hours, standing for half an hour, and filtering. Weighing 0.5% of active carbon, adding the active carbon into a positive material, magnetically stirring the positive material for 5 hours at room temperature, performing sterile filtration for a plurality of times by adopting a sterile device, separating the active carbon, collecting the separated positive material, and sampling for mass spectrum 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 experiment group; adding 2.5-3 mg of magnesium chloride into 1mL of the treated plasma material to obtain a second experimental group; to 1mL of the treated plasma material, 2.5 to 3mg of ferric chloride was added, and the mixture was set as experiment group III. The effect 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 below 0.02g/L, and the fibrinogen removal effect is significantly better than that with magnesium chloride or ferric chloride added.
Taking 1mL of plasma material, adding 2.5-3 mg of calcium chloride, mixing, repeatedly freezing and thawing the mixed solution, taking the supernatant, and setting three experimental groups I: 200 mu L of 0.2mol/L HClO is added to 100 mu L of plasma 4 Water bath at 37 ℃ for 5min. 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: 200. Mu.L of 0.2mol/L HCl is added to 100. Mu.L of plasma, water bath is carried out for 5min at 37 ℃, and 200. Mu.L of 0.2mol/L NaOH and 500. Mu.L of 0.2mol/L PBS buffer are added; experimental group three: 200. Mu.L of 0.2mol/L acetic acid was added to 100. Mu.L of plasma, and the mixture was subjected to a water bath at 37℃for 5 minutes, followed by 200. Mu.L of 0.2mol/L NaOH+500. Mu.L of 0.2mol/L PBS buffer. The effect of different treatments of plasma material on interference bias and recovery of different concentrations of bilirubin and triglyceride samples was verified and the results are shown in tables 2 and 3. It can be seen that the addition of perchloric acid treated plasma material was effective against various concentrations of bilirubin and glycerolThe interference deviation of the triester sample is controlled within 8.89%, the recovery rate is kept in the range of 90% -115%, and the triester sample is stable.
The plasma material obtained by the technical means of mixing soluble calcium chloride with a plasma sample and then adding perchloric acid treatment can greatly reduce the combination of nonspecific components compared with the traditional calcium chloride treatment technology. The 6 items of treated antibody materials are tested on a chemiluminescent analyzer, and the concentration is determined, wherein the concentration requirements of the six items of antibody materials are as follows: SS-A IgG is more than or equal to 1000AU/m, SS-B IgG is more than or equal to 1000AU/m, sm IgG is more than or equal to 1000AU/m, RNP70 IgG is more than or equal to 1000AU/m, jo-1 IgG is more than or equal to 500AU/m, scl-70IgG is more than or equal to 500 AU/m; RF, RF IgG and RF IgM were also measured and the results are shown in Table 4. It can be seen that the plasma material obtained from the calcium chloride-perchloric acid treatment process has a RF <0.5AU/mL, RF IgG <0.5AU/mL, RF IgM <1AU/mL, and significantly less non-specifically bound components than the conventional process. After screening the appropriate antibody material, the antibody material is filtered by a filter membrane with a pore diameter of 0.45 μm and then is labeled for standby.
TABLE 1 Effect of different chloride salts on fibrinogen content of plasma Material results
| Different treatments | 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 influence of different treated plasma materials on interference bias and recovery of bilirubin samples at different concentrations
TABLE 3 results of influence of different treated plasma materials on the interference bias and recovery of triglyceride samples at different concentrations
TABLE 4 results of specific measurements of plasma materials of different treatments (unit: AU/mL)
EXAMPLE 2 preparation of protective liquid
Materials were added according to the ratios and corresponding sequences in accordance with the matrix formulation table shown in table 5 below to prepare a quality control matrix solution a.
Table 5 matrix liquid a formulation
| Material name | The amount per L |
| 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-butanol | 30mL |
| ProClin300 (for luminescence) | 0.500mL |
| PS-3 | 0.200g |
Taking 1L of matrix liquid 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 pH after the solution is dissolved; then 20.0g of trehalose (dihydrate), 80.0g of g D-mannitol and 40.0g of bovine serum albumin are weighed, a pipette sucks 0.500mL ProClin300, a measuring cylinder measures 30mL of tertiary butanol, and after all dissolution, the pH is adjusted. Filtering with 0.45 μm filter membrane for use. Optimizing the formula A, adding glucose, glycine and casein as protective agents, and preparing a matrix liquid B, wherein the formula B is as follows: 1L of matrix solution A+10g of glucose+5 g of glycine+2.5 g of casein, and after all dissolution, the pH was adjusted. Filtering with 0.45 μm filter membrane for use.
EXAMPLE 3 lyophilization of ENA autoantibody Complex quality control
And respectively adding the six antibody materials into the matrix liquid A and the matrix liquid B, and mixing and blending to obtain negative quality control products and positive quality control products with target concentrations. And (3) using split charging equipment to split charging into 7mL brown glass bottles, wherein the amount of each bottle of the essential control product is 2.0mL, using an electric continuous liquid dispenser to split charging the quality control product during small-batch production, using a filling machine to split charging the quality control product during large-batch production, putting the split charging product into a freeze dryer after split charging, carrying out low-temperature vacuum drying according to a set program, and capping in a vacuum state after freeze drying, thus obtaining the ENA autoantibody composite quality control product.
And respectively placing the negative quality control product and the positive quality control product prepared by the matrix liquid A and the matrix liquid 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 thermal stability and the redissolution stability of each analyte of the quality control product prepared by the matrix liquid B have smaller deviation within a range of +/-5 percent.
TABLE 6 comparison of stability of matrix solution A and matrix solution B results (Unit: AU/mL)
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The negative and positive quality control prepared using matrix liquid B were freeze-dried using conventional lyophilization procedure 2 and lyophilization procedure 1 of the present invention, respectively, and the specific parameters of lyophilization procedure 1 and lyophilization 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 obtained non-redissolved dry powder quality control product at 2-8 ℃ and-20 ℃ for 10 days, taking the non-redissolved dry powder quality control product out on the 10 th day, adding water into the non-redissolved dry powder quality control product for dissolving, and recovering the re-dissolved dry powder quality control product to room temperature after the non-redissolved dry powder quality control product is fully dissolved, and carrying out stability comparison verification, wherein the results are shown in Table 8. It can be seen that the lyophilization procedure 1 of the present invention was selected for lyophilization with minimal deviation in thermal stability and reconstitution stability, both within the accepted limits.
Table 7 parameters of lyophilization procedure 1 and lyophilization procedure 2
TABLE 8 stability comparison verification results for lyophilization procedure 1 and lyophilization procedure 2 (Unit: AU/mL)
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Example 4 evaluation of Performance of ENA autoantibody Complex quality control
Taking the negative quality control product and the positive quality control product of the ENA autoantibody prepared by the method of the invention, wherein the two concentrations are respectively10 bottles were repeatedly tested 10 times for each of the six items, and the average value (M) and Standard Deviation (SD) of the 10 measurements for each item were calculated to give the Coefficient of Variation (CV) in the bottle according to the formula cv=sd/mx100%, and the results are shown in table 9, and it was found that the uniformity in the bottle was good. Taking 10 bottles of negative quality control products and positive quality control products of the same batch, measuring each bottle of quality control products for 1 time on six items on a detection system, and calculating the average value of detection results of 10 timesAnd Standard Deviation (SD) 1 ) The method comprises the steps of carrying out a first treatment on the surface of the Further, the above 10 bottles of negative and positive quality control were continuously tested 10 times with 1 package, and the average value of the 10 test results was calculated +.>And Standard Deviation (SD) 2 ) The method comprises the steps of carrying out a first treatment on the surface of the The Coefficient of Variation (CV) between bottles was calculated as SD according to the following formulas (1) to (2) 1 <SD 2 CV at the time Bottle room The results are shown in table 10, and the inter-bottle uniformity is also good. />
TABLE 9 in-bottle uniformity test results (Unit: AU/mL)
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TABLE 10 results of uniformity test between bottles (Unit: AU/mL)
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The negative quality control product and the positive quality control product of the same batch are stored in a dark place at 37 ℃ for 10 days, taken out, re-dissolved with the control sample, detected on a chemiluminescent analyzer, and the deviation with the control sample is calculated, and the result is shown in Table 11. And after redissolving the negative quality control product and the positive quality control product in the same batch, placing the mixture in an environment of 20-25 ℃ for 3 days, placing the mixture in an environment of 2-8 ℃ for 30 days, placing the mixture in an environment of-20 ℃ for 30 days, taking out the mixture on the same day after expiration, detecting the mixture on a chemiluminescent analyzer together with a control sample, and calculating the deviation from the control sample, wherein the result is shown in Table 12, and the heat stability and the redissolving stability are excellent.
TABLE 11 thermal stability test results (Unit: AU/mL)
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TABLE 12 reconstitution stability test results (Unit: AU/mL)
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The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (10)
1. The preparation method of the anti-extractable nuclear antigen antibody quality control product is characterized by comprising the following steps of:
providing a plasma sample containing anti-extractable nuclear antigen antibodies;
mixing the plasma sample with soluble calcium chloride, and taking supernatant after freeze thawing;
mixing the supernatant with perchloric acid, incubating, and then adding an alkali solution for neutralization to obtain an antibody solution;
mixing the antibody solution with a protective solution to obtain a liquid quality control product; the protective solution comprises 9-13 g/LMOPS sodium salt, 7-11 g/L sodium chloride, 2-5 g/L disodium ethylenediamine tetraacetate, 15-23 g/L trehalose, 75-85 g/L mannitol, 38-42 g/L bovine serum albumin, 28-32 mL/L tertiary butanol, 8-12 g/L glucose, 3-7 g/L glycine and 1.5-3.5 g/L casein.
2. The method of claim 1, wherein the protective liquid further comprises a preservative.
3. The method of claim 2, wherein the preservative comprises ProClin300 and PS-3.
4. The method according to claim 1, wherein the soluble calcium chloride is used in an amount of: 2.5-3 mg of soluble calcium chloride is added to each milliliter of the plasma sample.
5. The method according to claim 1, wherein the perchloric acid is used in an amount of: 150 to 250 microliters of the perchloric acid was added per 100 microliters of the supernatant.
6. The method according to any one of claims 1 to 5, further comprising the steps of: and freeze-drying the liquid quality control product to obtain the dry powder quality control product.
7. The 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: treating at 3-5 deg.c for 3-7 min and at-50 to-40 deg.c for 20-40 min; the condition parameters of the primary drying step are as follows: the treatment is carried out for 5 to 10 seconds under the conditions of the temperature of-50 to-40 ℃ and the vacuum degree of 0.2 to 0.4mbar, the treatment is carried out for 50 to 70 minutes under the conditions of the temperature of-50 to-40 ℃ and the vacuum degree of 0.05 to 0.15mbar, the treatment is carried out for 22 to 24 hours under the conditions of the temperature of-35 to-25 ℃ and the vacuum degree of 0.05 to 0.15mbar, and the treatment is carried out for 40 to 80 minutes under the conditions of the temperature of-15 to-5 ℃ and the vacuum degree of 0.05 to 0.15 mbar; the condition parameters of the secondary drying step are as follows: the treatment is carried out for 2 to 3 hours at the temperature of 5 to 15 ℃ and the vacuum degree of 0.0005 to 0.0015 mbar.
8. The method according to any one of claims 1 to 5, wherein the anti-extractable nuclear antigen antibody comprises an anti-SS-se:Sup>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 according to any one of claims 1 to 8.
10. An anti-extractable nuclear antigen antibody detection kit, comprising an immunodetection reagent for extractable nuclear antigen and the anti-extractable nuclear antigen antibody quality control of claim 9.
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| CH615512A5 (en) * | 1970-06-01 | 1980-01-31 | Hoffmann La Roche | Method for the determination of carcinoembryonic antigen |
| CN107478477A (en) * | 2017-08-04 | 2017-12-15 | 福州新北生化工业有限公司 | A kind of jaundice, haemolysis, the serum processing method of piarhemia |
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