CN1388378A - Tubercle mycobaterium detecting reagent - Google Patents
Tubercle mycobaterium detecting reagent Download PDFInfo
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- CN1388378A CN1388378A CN 02113890 CN02113890A CN1388378A CN 1388378 A CN1388378 A CN 1388378A CN 02113890 CN02113890 CN 02113890 CN 02113890 A CN02113890 A CN 02113890A CN 1388378 A CN1388378 A CN 1388378A
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- 239000003153 chemical reaction reagent Substances 0.000 title description 5
- 108091007433 antigens Proteins 0.000 claims abstract description 26
- 102000036639 antigens Human genes 0.000 claims abstract description 26
- 239000000427 antigen Substances 0.000 claims abstract description 23
- 101001057048 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) ESAT-6-like protein EsxB Proteins 0.000 claims abstract description 12
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims abstract description 11
- 101710166488 6 kDa early secretory antigenic target Proteins 0.000 claims abstract description 10
- 230000004927 fusion Effects 0.000 claims abstract description 5
- 210000002966 serum Anatomy 0.000 claims abstract description 4
- 241001465754 Metazoa Species 0.000 claims abstract description 3
- 238000009007 Diagnostic Kit Methods 0.000 claims abstract 2
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 10
- 238000002965 ELISA Methods 0.000 claims description 8
- 241000186359 Mycobacterium Species 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 238000011895 specific detection Methods 0.000 claims 3
- 241000588722 Escherichia Species 0.000 claims 1
- 241000238631 Hexapoda Species 0.000 claims 1
- 241000186366 Mycobacterium bovis Species 0.000 claims 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 230000000890 antigenic effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000000763 evoking effect Effects 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
- 201000008827 tuberculosis Diseases 0.000 abstract description 26
- 238000001514 detection method Methods 0.000 abstract description 7
- 238000003745 diagnosis Methods 0.000 abstract description 6
- 206010070834 Sensitisation Diseases 0.000 abstract description 3
- 238000010353 genetic engineering Methods 0.000 abstract description 3
- 230000008313 sensitization Effects 0.000 abstract description 3
- 238000002255 vaccination Methods 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 2
- 208000031998 Mycobacterium Infections Diseases 0.000 abstract 1
- 108020001507 fusion proteins Proteins 0.000 abstract 1
- 102000037865 fusion proteins Human genes 0.000 abstract 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 abstract 1
- 230000000405 serological effect Effects 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 108700020164 Mycobacterium tuberculosis ESAT-6 Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 1
- 208000036981 active tuberculosis Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000005267 amalgamation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003141 anti-fusion Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 101710135378 pH 6 antigen Proteins 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000037972 tropical disease Diseases 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
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Abstract
本发明是一种结核分枝杆菌的诊断试剂盒,能特异性地检测结核分枝杆菌的抗体及抗原,用于结核病的临床血清学诊断。检测所采用的抗原是通过基因工程手段所获得的两种结核分枝杆菌特异性抗原ESAT－6和CFP－10,以及以ESAT－6和CFP－10融合表达所产生的融合蛋白经纯化而得。检测抗体是以上述抗原免疫动物所产生的免疫血清经纯化得到的IgG。本发明操作简单,特异性强,能区分是因为接种卡介苗、以及与环境中多种非结核性分枝杆菌接触后造成的致敏还是真正的结核分枝杆菌感染。The invention is a diagnostic kit for mycobacterium tuberculosis, which can specifically detect the antibody and antigen of mycobacterium tuberculosis, and is used for clinical serological diagnosis of tuberculosis. The antigens used in the detection are two Mycobacterium tuberculosis specific antigens ESAT-6 and CFP-10 obtained through genetic engineering, and the fusion protein produced by fusion expression of ESAT-6 and CFP-10 is obtained by purification . The detection antibody is the purified IgG obtained from the immune serum produced by the animal immunized with the above antigen. The invention is simple in operation and strong in specificity, and can distinguish between sensitization caused by BCG vaccination and contact with various non-tuberculous mycobacteria in the environment, or real tuberculosis mycobacterium infection.
Description
1. technical field the invention belongs to medical immunology diagnostics technical field, specifically is detection kit and the application in clinical diagnosis lungy thereof about a kind of Much's bacillus.
2. background of invention tuberculosis is a kind of communicable disease that is caused by Much's bacillus, once occurs being very popular in the whole world.Along with the appearance of effective antituberculotic, taking a turn for the better appears in the tuberculosis popularity.But, surplus in the of nearly ten year over owing to the occur together reasons such as increase of infection and movement of population of appearance, HIV and the tubercle bacillus of tubercle bacillus multi-drug resistant bacterial strain, the tuberculosis epidemic situation is gone up once again, degradating trend has appearred in global tuberculosis situation.WHO announced " the tuberculosis whole world emergency circumstance " in 1993, and WHO in 1998 reaffirms again to contain that action lungy is very urgent.The whole world has 2,000,000,000 people to be subjected to mycobacterium tuberculosis infection approximately at present, existing 2,000 ten thousand tuberculosis patients, and wherein 95% in developing country.Annual neopathy number is 800-1000 ten thousand, and death toll is about 3,000,000, has surpassed the summation of acquired immune deficiency syndrome (AIDS), malaria, diarrhoea, tropical disease death toll.The tuberculosis popularity of China is also very serious always, it is one of the high burden of 22 tuberculosis in whole world country, according to the 4th the national tuberculosis epidemiological random sampling survey resulting estimate that carried out in 2000, China has 4,500,000 active tuberculosis patients approximately, the tuberculosis patient numerical digit occupies the second place of the world, account for 1/4th of global tuberculosis patient, the infectiousness pulmonary tuberculosis patient is about 1,500,000, has every year 12.7 ten thousand people to die from tuberculosis approximately.Tuberculosis has become one of main global disease of current threat human health, also is to cause dead common cause by single infectious agent.The key that reduces tuberculosis mortality rate is early diagnosis, thus formulation that can be accurately and timely rationally, the therapeutic scheme of science.
The main means of diagnosis of tuberculosis have smear staining microscopy and separation and Culture, tuberculin skin test and the serology detection etc. of pathogen at present.The acid-fast stain characteristic that smear staining microscopy method is based on tubercle bacillus reaches the purpose of calibrating, and sensitivity is low, the shortcoming of poor specificity but this method exists.The isolated culture inspection often needs 4-8 week or longer time, often incurs loss through delay clinical diagnosis and treatment.Tulase purified protein derivative (PPD) is the reagent that is widely used in diagnosis of tuberculosis at present, but owing to contain the common antigen molecule of many Mycobacteriums (comprising pathogenic mycobacterium, environment mycobacterium and Bacille Calmette-Guerin) among the PPD, therefore the poor specificity of PPD diagnosis of tuberculosis, actually or can not accurately distinguish the PPD test findings positive because bcg vaccination, with due to the real mycobacterium tuberculosis infection of the sensitization that causes after multiple non tuberculous Mycobacterium in the environment contacts.That the serology detection method has is quick, easy, be convenient to promote, the characteristics that need not special exact instrument are a kind of very potential diagnosis of tuberculosis means, but currently used diagnostic antigen (as PPD, 38KD, 30KD, 14KD, 19KD albumen etc.) exists the shortcoming that specificity is relatively poor, false positive rate is high, is badly in need of a kind of have strong specificity and immunogenic diagnostic antigen.
Mycobacterium tuberculosis ESAT-6-6 is promptly produced by the bacterium secretion in early days at mycobacterium tuberculosis infection, and is discerned by host immune system as a kind of low-molecular-weight secretion property antigen protein.Mycobacterium tuberculosis ESAT-6 antigen protein molecule epi-position is numerous (to have B cell epitope, CD
4 +, CD
8 +T cell epitope and DTH epi-position), and only in pathogenic mycobacterium, express, and be not present in Bacille Calmette-Guerin and other non-pathogenic mycobacterium, thereby be a kind of extremely promising tuberculosis specific diagnostic antigen.CFP-10 also is a kind of secretion antigen, and gene and the ESAT-6 of coding CFP-10 are adjacent, are in the same operon, all are positioned at the genomic RD1 section of Much's bacillus, lack equally in Bacille Calmette-Guerin.Coupling ESAT-6 and CFP-10 diagnosis tubercle bacillus affection can improve the susceptibility and the specificity that detect.
3. summary of the invention the present invention is by genetic engineering means, with mycobacterium tuberculosis ESAT-6-6 and CFP-10 albumen at vivoexpression, purifying and prepare the antibody and the antigen detecting agent box of Much's bacillus; And the fusion that ESAT-6 and CFP-10 amalgamation and expression are produced purified after, the antibody and the antigen detecting agent box of preparation Much's bacillus.This kit can detect the antibody and the antigen of Much's bacillus specifically, can distinguish be because bcg vaccination and with sensitization that causes after multiple non tuberculous Mycobacterium in the environment contacts or real m tuberculosis infection, can be used for clinical serodiagnosis lungy.
4. embodiment 1) classify template as with Much's bacillus H37Rv genome sequence, design the primer of ESAT-6 and CFP-10 gene respectively, clone ESAT-6 and CFP-10 gene.2) by genetic engineering means, the ESAT-6 and the CFP-10 gene end of cloning added joining peptide, obtain antigen-4 fusion protein gene.3) change each clone gene over to expression vector, express corresponding protein, carry out identification and analysis by gel electrophoresis and Western Blotting.4) the separation and purification of protein technology of employing standard, each expressing protein of purifying.As: centrifugal, ion-exchange chromatography, hydrophobic chromatography, affinity chromatography etc.5) each expressing protein adopts the immune programme for children immune animal of standard, as: rabbit, cavy, goat etc.Prepare two kinds of corresponding antibody, and its IgG of purifying.6), determine the concentration of envelope antigen (detection albumen), and be equipped with other related reagents that preparation mycobacterium tuberculosis antibody ELISA detects (indirect method) kit through the square formation titration.7), determine the concentration of coated antibody (detection protein antibodies), second antibody (the enzyme mark detects protein antibodies), and be equipped with other related reagents that preparation antigen of mycobacterium tuberculosis ELISA detects (double antibody sandwich method) kit through the square formation titration.
EXAMPLE Example 1:ELISA indirect method detects mycobacterium tuberculosis antibody and gets blood serum sample 0.1ml to be checked, adding has been coated with in the ELISA Plate of fusion antigen, hatches 30 minutes for 37 ℃, and every block of plate is established three hole negative controls, two hole positive controls, a hole blank.Hatch end, discard the liquid in the plate hole, wash plate five times with cleansing solution, button is done.Add anti-human IgG enzyme labelled antibody, fully mixing was hatched 30 minutes for 37 ℃.The same wash plate after, add colour developing liquid 0.1ml, pat mixing, 37 ℃ of lucifuges colour developings 30 minutes.Every hole adds one of stop buffer, pats mixing, surveys with 450nm wavelength microplate reader and reads OD value, result of determination.Embodiment 2:ELISA double antibody sandwich method detects antigen of mycobacterium tuberculosis and gets blood serum sample 0.1ml to be checked, adding has been coated with in the ELISA Plate of fusion antibody (first antibody), hatches 30 minutes for 37 ℃, and every block of plate is established three hole negative controls, two hole positive controls, a hole blank.Hatch end, discard the liquid in the plate hole, wash plate five times with cleansing solution, button is done.Add second antibody (the anti-fusion antibody of rabbit), fully mixing was hatched 30 minutes for 37 ℃.The same washing adds anti-rabbit igg enzyme labelled antibody behind the plate, and fully mixing was hatched 30 minutes for 37 ℃.Wash plate, add colour developing liquid 0.1ml, pat mixing, 37 ℃ of lucifuges developed the color 30 minutes.Every hole adds one of stop buffer, pats mixing, surveys with 450nm wavelength microplate reader and reads OD value, result of determination.
Claims (9)
1. the diagnostic kit of a Much's bacillus is characterized in that adopting specific detection antigen of Much's bacillus and antibody, can be used for clinical serodiagnosis lungy.
2. described specific detection antigen of claim 1 and antibody are two species-specific antigen ESAT-6 of Much's bacillus and the potpourri of CFP-10, and with the immune serum that this hybrid antigen immune animal was produced purified and antibody.
3. described specific detection antigen of claim 2 and antibody also can be a kind of fusions, and this albumen has the antigenic determinant of ESAT-6 and CFP-10 simultaneously, and with the antibody of this protein Preparation.They can combine with antigen with the antibody of mycobacterium respectively specifically.
4. the described antigen protein of claim 2 and claim 3 is to adopt escherichia expression system, expression of recombinant virus system, insect cell expression system, yeast expression system and mammalian cell expression system etc. to express to produce purified obtaining.
5. the described antigen protein of claim 2 and claim 3 also can be used for interior Skin-test of body and the generation of external evoked IFN-r, thereby detects the infection of Much's bacillus.
6. the described Much's bacillus of claim 1 comprises mycobacterium bovis.
7. be envelope antigen with claim 2 and the described albumen of claim 3, the mycobacterium tuberculosis antibody ELISA of preparation detects (indirect method) kit.
8. the described antibody of claim 7 comprises IgG, IgM, IgA.
9. be coated antibody with claim 2 and the described antibody of claim 3, the antigen of mycobacterium tuberculosis ELISA of preparation detects (double antibody sandwich method) kit.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02113890 CN1388378A (en) | 2002-06-17 | 2002-06-17 | Tubercle mycobaterium detecting reagent |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02113890 CN1388378A (en) | 2002-06-17 | 2002-06-17 | Tubercle mycobaterium detecting reagent |
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| CN 02113890 Pending CN1388378A (en) | 2002-06-17 | 2002-06-17 | Tubercle mycobaterium detecting reagent |
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Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1674868A1 (en) * | 2004-12-21 | 2006-06-28 | Chang Gung University (a university of Taiwan) | Method and device for detection of mycobacterium tuberculosis antigens in biological fluids |
| CN1305900C (en) * | 2004-03-16 | 2007-03-21 | 中国药品生物制品检定所 | Use of Esat-6 protein in diagnosis of tuberculosis |
| RU2296334C2 (en) * | 2004-08-16 | 2007-03-27 | Всероссийский научно-исследовательский институт бруцеллеза и туберкулеза животных (ВНИИБТЖ) | Method for intravitam prediction of tuberculosis |
| CN100368437C (en) * | 2005-01-28 | 2008-02-13 | 中国农业科学院哈尔滨兽医研究所 | A recombinant antigen protein for diagnosing bovine tuberculosis and its preparation method |
| CN1866023B (en) * | 2006-05-25 | 2010-11-03 | 上海市肺科医院 | A method for synchronously detecting multiple specific secreted antigens of Mycobacterium tuberculosis |
| CN101985474A (en) * | 2010-10-12 | 2011-03-16 | 浙江大学 | Monoclonal antibody TBCA6 resistant to mycobacterium tuberculosis CFP-10 and application |
| CN101987872A (en) * | 2010-10-12 | 2011-03-23 | 浙江大学 | Monoclonal antibody TBEF3 of tubercle bacillus-resistant ESAT-6 and application |
| CN102253204A (en) * | 2004-06-30 | 2011-11-23 | 法国巴斯德研究所 | Detection of tuberculosis and infection by mycobacterium yuberculosis using HBHA |
| CN102426232A (en) * | 2011-09-06 | 2012-04-25 | 厦门大学 | Kit for detecting tubercle bacillus protein antigen and preparation method thereof |
| CN102608333A (en) * | 2012-03-30 | 2012-07-25 | 中国科学院微生物研究所 | A kind of tuberculosis diagnostic composition and its application |
| CN102621318A (en) * | 2012-02-27 | 2012-08-01 | 浙江工业大学 | Immune chromatography test paper for detecting mycobacterium tuberculosis secretory proteins and manufacture method thereof |
| CN102702360A (en) * | 2012-07-05 | 2012-10-03 | 中国人民解放军第三〇九医院 | Novel mycobacterium tuberculosis specific fusion protein as well as preparation and application thereof |
| CN102757971A (en) * | 2012-08-07 | 2012-10-31 | 中国人民解放军第三O九医院 | Mycobacterium tuberculosis recombinant protein and preparation method thereof |
| CN102854308A (en) * | 2012-09-20 | 2013-01-02 | 陕西师范大学 | Preparation method and application of double-antibody sandwich ELISA detection kit for alicyclobacillus acidoterrestris in fruit juice |
| CN102981002A (en) * | 2012-11-29 | 2013-03-20 | 同昕生物技术（北京）有限公司 | Indirect immunoassay method adopting tag protein humanized chimeric antibody as positive contract and kit |
| CN102993283A (en) * | 2010-07-15 | 2013-03-27 | 华中农业大学 | Antigen protein for mycobacterium tuberculosis and application |
| CN103814139A (en) * | 2011-04-01 | 2014-05-21 | 澳康姆生物实验室公司 | Methods and kits for detecting cell-free pathogen-specific nucleic acids |
| CN103833849A (en) * | 2014-03-07 | 2014-06-04 | 中国人民解放军第四军医大学 | Preparation method and application of ESAT6-CFP10 (Early Secreted Antigen Target 6-Culture Filtrate Protein 10) antibody |
| CN110596382A (en) * | 2019-09-16 | 2019-12-20 | 南京拜睿生物科技有限公司 | Tuberculosis diagnostic kit and preparation method thereof |
| RU2794855C1 (en) * | 2022-01-24 | 2023-04-25 | Федеральное государственное бюджетное научное учреждение "Центральный научно-исследовательский институт туберкулеза" | Method for diagnosing tuberculosis |
-
2002
- 2002-06-17 CN CN 02113890 patent/CN1388378A/en active Pending
Cited By (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1305900C (en) * | 2004-03-16 | 2007-03-21 | 中国药品生物制品检定所 | Use of Esat-6 protein in diagnosis of tuberculosis |
| CN102253204A (en) * | 2004-06-30 | 2011-11-23 | 法国巴斯德研究所 | Detection of tuberculosis and infection by mycobacterium yuberculosis using HBHA |
| RU2296334C2 (en) * | 2004-08-16 | 2007-03-27 | Всероссийский научно-исследовательский институт бруцеллеза и туберкулеза животных (ВНИИБТЖ) | Method for intravitam prediction of tuberculosis |
| EP1674868A1 (en) * | 2004-12-21 | 2006-06-28 | Chang Gung University (a university of Taiwan) | Method and device for detection of mycobacterium tuberculosis antigens in biological fluids |
| CN100368437C (en) * | 2005-01-28 | 2008-02-13 | 中国农业科学院哈尔滨兽医研究所 | A recombinant antigen protein for diagnosing bovine tuberculosis and its preparation method |
| CN1866023B (en) * | 2006-05-25 | 2010-11-03 | 上海市肺科医院 | A method for synchronously detecting multiple specific secreted antigens of Mycobacterium tuberculosis |
| CN102993283A (en) * | 2010-07-15 | 2013-03-27 | 华中农业大学 | Antigen protein for mycobacterium tuberculosis and application |
| CN102993283B (en) * | 2010-07-15 | 2014-11-12 | 华中农业大学 | Antigen protein for mycobacterium tuberculosis and application |
| CN101985474A (en) * | 2010-10-12 | 2011-03-16 | 浙江大学 | Monoclonal antibody TBCA6 resistant to mycobacterium tuberculosis CFP-10 and application |
| CN101987872A (en) * | 2010-10-12 | 2011-03-23 | 浙江大学 | Monoclonal antibody TBEF3 of tubercle bacillus-resistant ESAT-6 and application |
| CN103814139B (en) * | 2011-04-01 | 2018-11-13 | 澳康姆生物实验室公司 | Methods and kits for the detection of cell-free pathogen-specific nucleic acids |
| CN103814139A (en) * | 2011-04-01 | 2014-05-21 | 澳康姆生物实验室公司 | Methods and kits for detecting cell-free pathogen-specific nucleic acids |
| CN102426232B (en) * | 2011-09-06 | 2014-02-26 | 厦门大学 | A kit for detecting tuberculosis protein antigen and its preparation method |
| CN102426232A (en) * | 2011-09-06 | 2012-04-25 | 厦门大学 | Kit for detecting tubercle bacillus protein antigen and preparation method thereof |
| CN102621318A (en) * | 2012-02-27 | 2012-08-01 | 浙江工业大学 | Immune chromatography test paper for detecting mycobacterium tuberculosis secretory proteins and manufacture method thereof |
| CN102608333B (en) * | 2012-03-30 | 2013-06-05 | 中国科学院微生物研究所 | Tuberculosis diagnostic composition and application thereof |
| CN102608333A (en) * | 2012-03-30 | 2012-07-25 | 中国科学院微生物研究所 | A kind of tuberculosis diagnostic composition and its application |
| CN102702360B (en) * | 2012-07-05 | 2014-02-19 | 中国人民解放军第三〇九医院 | Mycobacterium tuberculosis specific fusion protein and its preparation and application |
| CN102702360A (en) * | 2012-07-05 | 2012-10-03 | 中国人民解放军第三〇九医院 | Novel mycobacterium tuberculosis specific fusion protein as well as preparation and application thereof |
| CN102757971A (en) * | 2012-08-07 | 2012-10-31 | 中国人民解放军第三O九医院 | Mycobacterium tuberculosis recombinant protein and preparation method thereof |
| CN102854308A (en) * | 2012-09-20 | 2013-01-02 | 陕西师范大学 | Preparation method and application of double-antibody sandwich ELISA detection kit for alicyclobacillus acidoterrestris in fruit juice |
| CN102854308B (en) * | 2012-09-20 | 2015-04-08 | 陕西师范大学 | Double-antibody sandwich ELISA detection kit for alicyclobacillus acidoterrestris in fruit juice |
| CN102981002B (en) * | 2012-11-29 | 2014-08-06 | 同昕生物技术（北京）有限公司 | Indirect immunoassay method adopting tag protein humanized chimeric antibody as positive contract and kit |
| CN102981002A (en) * | 2012-11-29 | 2013-03-20 | 同昕生物技术（北京）有限公司 | Indirect immunoassay method adopting tag protein humanized chimeric antibody as positive contract and kit |
| CN103833849A (en) * | 2014-03-07 | 2014-06-04 | 中国人民解放军第四军医大学 | Preparation method and application of ESAT6-CFP10 (Early Secreted Antigen Target 6-Culture Filtrate Protein 10) antibody |
| CN110596382A (en) * | 2019-09-16 | 2019-12-20 | 南京拜睿生物科技有限公司 | Tuberculosis diagnostic kit and preparation method thereof |
| RU2794855C1 (en) * | 2022-01-24 | 2023-04-25 | Федеральное государственное бюджетное научное учреждение "Центральный научно-исследовательский институт туберкулеза" | Method for diagnosing tuberculosis |
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