CN108291190A - 用于检测微生物的化学成分确定的培养基 - Google Patents
用于检测微生物的化学成分确定的培养基 Download PDFInfo
- Publication number
- CN108291190A CN108291190A CN201680070630.3A CN201680070630A CN108291190A CN 108291190 A CN108291190 A CN 108291190A CN 201680070630 A CN201680070630 A CN 201680070630A CN 108291190 A CN108291190 A CN 108291190A
- Authority
- CN
- China
- Prior art keywords
- culture medium
- cell culture
- prokaryotes
- cell
- chemical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 71
- 239000000126 substance Substances 0.000 title claims abstract description 55
- 239000001963 growth medium Substances 0.000 title claims description 123
- 244000005700 microbiome Species 0.000 title abstract description 50
- 241000894006 Bacteria Species 0.000 claims abstract description 60
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims abstract description 46
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 241000206602 Eukaryota Species 0.000 claims abstract description 26
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims abstract description 26
- 229960003067 cystine Drugs 0.000 claims abstract description 26
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000018417 cysteine Nutrition 0.000 claims abstract description 22
- 229930024421 Adenine Natural products 0.000 claims abstract description 21
- 229960000643 adenine Drugs 0.000 claims abstract description 21
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims abstract description 19
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims abstract description 19
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims abstract description 18
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 claims abstract description 17
- 229950006238 nadide Drugs 0.000 claims abstract description 17
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960004050 aminobenzoic acid Drugs 0.000 claims abstract description 15
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims abstract description 15
- 239000006143 cell culture medium Substances 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 40
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims description 25
- 238000012360 testing method Methods 0.000 claims description 25
- 239000004615 ingredient Substances 0.000 claims description 23
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 17
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 13
- 230000001580 bacterial effect Effects 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 235000001014 amino acid Nutrition 0.000 claims description 12
- 230000008859 change Effects 0.000 claims description 12
- -1 nicotinoyl Chemical group 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 244000063299 Bacillus subtilis Species 0.000 claims description 9
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 9
- 241000588724 Escherichia coli Species 0.000 claims description 9
- 241000191967 Staphylococcus aureus Species 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 9
- 239000003349 gelling agent Substances 0.000 claims description 9
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 8
- 241000228212 Aspergillus Species 0.000 claims description 7
- 241000222122 Candida albicans Species 0.000 claims description 7
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical class [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 229940095731 candida albicans Drugs 0.000 claims description 7
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 6
- 229940088594 vitamin Drugs 0.000 claims description 6
- 229930003231 vitamin Natural products 0.000 claims description 6
- 235000013343 vitamin Nutrition 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- 238000011049 filling Methods 0.000 claims description 5
- 150000007523 nucleic acids Chemical class 0.000 claims description 5
- 108020004707 nucleic acids Proteins 0.000 claims description 5
- 102000039446 nucleic acids Human genes 0.000 claims description 5
- 150000005415 aminobenzoic acids Chemical class 0.000 claims description 4
- 241001331781 Aspergillus brasiliensis Species 0.000 claims description 3
- 150000001412 amines Chemical group 0.000 claims description 3
- 230000003139 buffering effect Effects 0.000 claims description 3
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 claims description 2
- 238000011534 incubation Methods 0.000 claims description 2
- 150000001945 cysteines Chemical class 0.000 claims 3
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 abstract 1
- 230000012010 growth Effects 0.000 description 45
- 108010080698 Peptones Proteins 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 27
- 239000001888 Peptone Substances 0.000 description 26
- 235000019319 peptone Nutrition 0.000 description 26
- 239000002609 medium Substances 0.000 description 23
- 229960002433 cysteine Drugs 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000000306 component Substances 0.000 description 13
- 239000002253 acid Substances 0.000 description 12
- 229910001868 water Inorganic materials 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 11
- 230000010261 cell growth Effects 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 230000007613 environmental effect Effects 0.000 description 10
- 239000003344 environmental pollutant Substances 0.000 description 10
- 231100000719 pollutant Toxicity 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 229920001817 Agar Polymers 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 229920001983 poloxamer Polymers 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 239000006150 trypticase soy agar Substances 0.000 description 7
- 241000193470 Clostridium sporogenes Species 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 239000008272 agar Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000011081 inoculation Methods 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 235000015097 nutrients Nutrition 0.000 description 6
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 5
- 241000589323 Methylobacterium Species 0.000 description 5
- 235000010419 agar Nutrition 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000013589 supplement Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- 241000193830 Bacillus <bacterium> Species 0.000 description 4
- 241000186427 Cutibacterium acnes Species 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000233866 Fungi Species 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 229940055019 propionibacterium acne Drugs 0.000 description 4
- 210000000717 sertoli cell Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 101100230376 Acetivibrio thermocellus (strain ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) celI gene Proteins 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000589308 Methylobacterium extorquens Species 0.000 description 3
- 241000191938 Micrococcus luteus Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
- 241000589625 Ralstonia pickettii Species 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- 241000191940 Staphylococcus Species 0.000 description 3
- 241000191963 Staphylococcus epidermidis Species 0.000 description 3
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000017858 demethylation Effects 0.000 description 3
- 238000010520 demethylation reaction Methods 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 3
- 210000004907 gland Anatomy 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000003801 milling Methods 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 241001277988 Aspergillus sydowii Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241001328122 Bacillus clausii Species 0.000 description 2
- 241000194103 Bacillus pumilus Species 0.000 description 2
- 241000606215 Bacteroides vulgatus Species 0.000 description 2
- 241000606660 Bartonella Species 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 241000588807 Bordetella Species 0.000 description 2
- 241000589562 Brucella Species 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 241000589876 Campylobacter Species 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 102000008857 Ferritin Human genes 0.000 description 2
- 108050000784 Ferritin Proteins 0.000 description 2
- 238000008416 Ferritin Methods 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000589248 Legionella Species 0.000 description 2
- 208000007764 Legionnaires' Disease Diseases 0.000 description 2
- 241000589902 Leptospira Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001542929 Methylobacterium fujisawaense Species 0.000 description 2
- 241001535042 Methylobacterium mesophilicum Species 0.000 description 2
- 241000702623 Minute virus of mice Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 241000194109 Paenibacillus lautus Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241001507677 Penicillium commune Species 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N Pyridoxal Chemical compound CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 241000607715 Serratia marcescens Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 241000736110 Sphingomonas paucimobilis Species 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000009603 aerobic growth Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000009604 anaerobic growth Effects 0.000 description 2
- 239000012062 aqueous buffer Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 229920001400 block copolymer Polymers 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical group [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229960002061 ergocalciferol Drugs 0.000 description 2
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 2
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 2
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 2
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical group CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 229910052750 molybdenum Inorganic materials 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- NHZMQXZHNVQTQA-UHFFFAOYSA-N pyridoxamine Chemical compound CC1=NC=C(CO)C(CN)=C1O NHZMQXZHNVQTQA-UHFFFAOYSA-N 0.000 description 2
- MMXZSJMASHPLLR-UHFFFAOYSA-N pyrroloquinoline quinone Chemical compound C12=C(C(O)=O)C=C(C(O)=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 MMXZSJMASHPLLR-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 235000019157 thiamine Nutrition 0.000 description 2
- 150000003544 thiamines Chemical class 0.000 description 2
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 239000011715 vitamin B12 Substances 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- 235000001892 vitamin D2 Nutrition 0.000 description 2
- 239000011653 vitamin D2 Substances 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- 239000011686 zinc sulphate Substances 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- GJJVAFUKOBZPCB-ZGRPYONQSA-N (r)-3,4-dihydro-2-methyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2h-1-benzopyran-6-ol Chemical class OC1=CC=C2OC(CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-ZGRPYONQSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 description 1
- AJTVSSFTXWNIRG-UHFFFAOYSA-N 2-[bis(2-hydroxyethyl)amino]ethanesulfonic acid Chemical compound OCC[NH+](CCO)CCS([O-])(=O)=O AJTVSSFTXWNIRG-UHFFFAOYSA-N 0.000 description 1
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- 239000007991 ACES buffer Substances 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000590020 Achromobacter Species 0.000 description 1
- 241000932047 Achromobacter sp. Species 0.000 description 1
- 241001135518 Acinetobacter lwoffii Species 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000007992 BES buffer Substances 0.000 description 1
- 241000006382 Bacillus halodurans Species 0.000 description 1
- 241000963702 Bacillus okuhidensis Species 0.000 description 1
- 241000589969 Borreliella burgdorferi Species 0.000 description 1
- 241001453380 Burkholderia Species 0.000 description 1
- 241000589513 Burkholderia cepacia Species 0.000 description 1
- 241001508395 Burkholderia sp. Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000345998 Calamus manan Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 241000370738 Chlorion Species 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241001518263 Corynebacterium tuberculostearicum Species 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- LHQIJBMDNUYRAM-AWFVSMACSA-N D-erythro-biopterin Chemical compound N1=C(N)NC(=O)C2=NC([C@H](O)[C@H](O)C)=CN=C21 LHQIJBMDNUYRAM-AWFVSMACSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 description 1
- 229930195709 D-tyrosine Natural products 0.000 description 1
- 241000235036 Debaryomyces hansenii Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241001574323 Exophiala sp. Species 0.000 description 1
- 229910016874 Fe(NO3) Inorganic materials 0.000 description 1
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 241000589602 Francisella tularensis Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 241001247311 Kocuria rhizophila Species 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- LHQIJBMDNUYRAM-UHFFFAOYSA-N L-erythro-Biopterin Natural products N1=C(N)NC(=O)C2=NC(C(O)C(O)C)=CN=C21 LHQIJBMDNUYRAM-UHFFFAOYSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- UBORTCNDUKBEOP-UHFFFAOYSA-N L-xanthosine Natural products OC1C(O)C(CO)OC1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UHFFFAOYSA-N 0.000 description 1
- 241000064289 Leifsonia sp. Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 description 1
- ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 description 1
- 241000589350 Methylobacter Species 0.000 description 1
- 241000191951 Micrococcus lylae Species 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- DBXNUXBLKRLWFA-UHFFFAOYSA-N N-(2-acetamido)-2-aminoethanesulfonic acid Chemical compound NC(=O)CNCCS(O)(=O)=O DBXNUXBLKRLWFA-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 240000002853 Nelumbo nucifera Species 0.000 description 1
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 1
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- 241000983368 Pantoea sp. Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000004695 Polyether sulfone Substances 0.000 description 1
- 229920000491 Polyphenylsulfone Polymers 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- NCYCYZXNIZJOKI-OVSJKPMPSA-N Retinaldehyde Chemical compound O=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000293025 Saksenaea vasiformis Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241001135758 Sphingomonas parapaucimobilis Species 0.000 description 1
- 241000191984 Staphylococcus haemolyticus Species 0.000 description 1
- 241000192087 Staphylococcus hominis Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000122973 Stenotrophomonas maltophilia Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000007994 TES buffer Substances 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000002070 Transferrins Human genes 0.000 description 1
- 108010015865 Transferrins Proteins 0.000 description 1
- UYXTWWCETRIEDR-UHFFFAOYSA-N Tributyrin Chemical compound CCCC(=O)OCC(OC(=O)CCC)COC(=O)CCC UYXTWWCETRIEDR-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- UBORTCNDUKBEOP-HAVMAKPUSA-N Xanthosine Natural products O[C@@H]1[C@H](O)[C@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-HAVMAKPUSA-N 0.000 description 1
- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 229950006790 adenosine phosphate Drugs 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 description 1
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000003816 axenic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000003918 blood extract Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000013590 bulk material Substances 0.000 description 1
- GHWVXCQZPNWFRO-UHFFFAOYSA-N butane-2,3-diamine Chemical compound CC(N)C(C)N GHWVXCQZPNWFRO-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- JBJSVEVEEGOEBZ-SCZZXKLOSA-K coenzyme B(3-) Chemical compound [O-]P(=O)([O-])O[C@H](C)[C@@H](C([O-])=O)NC(=O)CCCCCCS JBJSVEVEEGOEBZ-SCZZXKLOSA-K 0.000 description 1
- ZNEWHQLOPFWXOF-UHFFFAOYSA-N coenzyme M Chemical compound OS(=O)(=O)CCS ZNEWHQLOPFWXOF-UHFFFAOYSA-N 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- GEHSZWRGPHDXJO-ALELSXGZSA-N coenzyme f420 Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)CC[C@H](C(O)=O)NC(=O)[C@@H](C)O[P@@](O)(=O)OC[C@H](O)[C@@H](O)[C@H](O)CN1C2=CC(O)=CC=C2C=C2C1=NC(=O)NC2=O GEHSZWRGPHDXJO-ALELSXGZSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000009144 enzymatic modification Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000011768 flavin mononucleotide Substances 0.000 description 1
- 229940013640 flavin mononucleotide Drugs 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 1
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical group O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229940118764 francisella tularensis Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 229920000550 glycopolymer Polymers 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 210000005256 gram-negative cell Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- BTIJJDXEELBZFS-UHFFFAOYSA-K hemin Chemical compound [Cl-].[Fe+3].[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC(O)=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1 BTIJJDXEELBZFS-UHFFFAOYSA-K 0.000 description 1
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 208000010544 human prion disease Diseases 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- YOZNUFWCRFCGIH-BYFNXCQMSA-L hydroxocobalamin Chemical compound O[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O YOZNUFWCRFCGIH-BYFNXCQMSA-L 0.000 description 1
- 239000011704 hydroxocobalamin Substances 0.000 description 1
- 235000004867 hydroxocobalamin Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229910000360 iron(III) sulfate Inorganic materials 0.000 description 1
- BKWBIMSGEOYWCJ-UHFFFAOYSA-L iron;iron(2+);sulfanide Chemical compound [SH-].[SH-].[Fe].[Fe+2] BKWBIMSGEOYWCJ-UHFFFAOYSA-L 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000011177 media preparation Methods 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000009629 microbiological culture Methods 0.000 description 1
- 238000001634 microspectroscopy Methods 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 229940066779 peptones Drugs 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 1
- 235000019175 phylloquinone Nutrition 0.000 description 1
- 239000011772 phylloquinone Substances 0.000 description 1
- 229960001898 phytomenadione Drugs 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000004094 preconcentration Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229960003581 pyridoxal Drugs 0.000 description 1
- 239000011674 pyridoxal Substances 0.000 description 1
- 235000008164 pyridoxal Nutrition 0.000 description 1
- 239000011699 pyridoxamine Substances 0.000 description 1
- 235000008151 pyridoxamine Nutrition 0.000 description 1
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 235000012950 rattan cane Nutrition 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000020945 retinal Nutrition 0.000 description 1
- 239000011604 retinal Substances 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000009589 serological test Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229940037649 staphylococcus haemolyticus Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003802 tocotrienol Natural products 0.000 description 1
- 239000011731 tocotrienol Substances 0.000 description 1
- 229940068778 tocotrienols Drugs 0.000 description 1
- 235000019148 tocotrienols Nutrition 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 239000011675 vitamin B5 Substances 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 239000011735 vitamin B7 Substances 0.000 description 1
- 239000011727 vitamin B9 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000003403 water pollutant Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- UBORTCNDUKBEOP-UUOKFMHZSA-N xanthosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UUOKFMHZSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 235000009529 zinc sulphate Nutrition 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
- C12Q1/045—Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
- C12N1/16—Yeasts; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/22—Testing for sterility conditions
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/32—Amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/40—Nucleotides, nucleosides or bases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/46—Amines, e.g. putrescine
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Botany (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
本发明涉及至少包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的培养基,用于快速检测广泛范围的微生物,包括原核生物和真核生物。
Description
本发明涉及至少包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的培养基,用于检测广泛范围的微生物(包括原核生物和真核生物)。
自19世纪以来,用于细菌、酵母和霉菌的生长和培养的复杂、通用培养基已可获得。自这段时间以来,生产这些培养基的方法和所用的主要成分在其基本性质方面令人吃惊地改变极少。这些微生物培养基的主要基础是它们含有的蛋白胨。
所用的蛋白胨被设计以允许非常广泛种类的细菌、酵母和霉菌生长的组合及浓度存在。因此,这些蛋白胨的混合物是生物化学成分丰富且十分均衡的营养来源,且通常通过加入盐、缓冲剂和优化具有特殊生物化学性质的微生物的快速生长和/或选择必需的其它原材料来补充。此外,固体形式的培养基一般易溶于水。在溶解后,培养基是可灭菌的,并可在合适方便的容器中提供以在原核和/或真核细胞接种后防止污染,但同时允许氧气进入(如果这是需要的话)。随后,具有培养基和细胞的容器在合适的温度下培养并持续合适的时间,以允许细胞生长的测定(或缺乏)。
然而,只有熟悉本领域的经验丰富的个体仔细选择蛋白胨类型才产生具有足够的营养基础的培养基,其生物化学组成足够广泛且充分平衡以便能够培养很宽范围的原核生物以及真核生物。蛋白胨品质在蛋白胨类型之间变化,在相同蛋白胨的不同制造商之间变化,在来自相同制造商的不同等级之间变化和甚至在来自单一制造商的相同等级的批次之间显著变化。然而,这种变化品质的生物化学性质了解甚少,批次之间的变化水平更尤其如此。然而,生物化学变化无疑部分是由于用来产生蛋白胨的天然原材料的品质变化导致。因此,由于在这样的原材料中的营养缺乏或营养失衡,不是每一批次的蛋白胨总是适合用于特定的培养基配方,并因此对于能够使很宽泛围的原核生物和真核生物生长(即支持品种繁多的细菌、酵母和霉菌的可接受的生长)的特定培养基,每一批次必须仔细地选择。
蛋白胨的精确化学组成尚不知道。这意味着由导致细胞生长促进的这样的天然原材料提供的关键营养因素至多在一定程度上有所了解,但不是完全了解。知之甚少且同样难以控制的是培养基内这样的原材料的负面物理化学相互作用,例如这造成其沉淀。沉淀是培养基的一个不受欢迎的性质,因为它在光学上隐藏了微生物的生长,也就是说理想地,大多数培养基应该是清澈的。除了通常存在于传统培养基中的盐、缓冲剂和其它成分外,当一种蛋白胨与其它蛋白胨类型混合时,问题的复杂性增加。充分平衡的通用生长培养基的生产是一个试验、误差和长期经验的问题。加入的各蛋白胨的批次之间变化必须被充分控制,以致不适合产生测试的原核(细菌)和真核(酵母和真菌)菌株的所需细胞生长的全部范围的批次(不论是单独或是与其它蛋白胨类型组合),可从制造这样的培养基的生产过程排除。
甚至在这些测量后,对于很宽范围的细胞株的生长,这样的通用培养基不一定对所有细菌、酵母和真菌菌株的生长都是足够生物化学平衡的或营养的,所述菌株在一个通常用来确认培养基对于环境监测应用的适用性的广泛测试组中测试。在一个方面,某些细胞类型对培养基提供的生物化学品的正确平衡是非常敏感的。在另一方面,并且此外,特别是非常苛求(fastidious)的细胞需要额外的补充剂,例如新鲜血液或血液提取物以提高它们的生长性能。然而,对于某些极其高度苛求的细胞类型,甚至这些培养基不具有足够的营养组分并需要进一步加入支持生长或加速生长的补充剂,以使它们对用于通常在环境样品中发现的广泛范围的原核生物和真核生物细胞的用途是有效的。
最近,化学成分确定的细胞培养基已被开发。然而,到目前为止,用于培养微生物的化学成分确定的培养基的生产商已集中于支持原核生物(如细菌)或者真核生物(如酵母或真菌或昆虫或哺乳动物细胞)的生长,最常见地是支持特定选择的微生物的生长。
WO 2007/135385例如公开了用于细菌、特别是奈瑟氏菌属(Neisseria)物种的生长的化学成分确定的培养基。
GB 2464203公开了用于弯曲杆菌属(Campylobacter)的列举的化学成分确定的培养基。
因此,本发明的目的是提供基于化学成分确定的原材料的细胞培养基,其提供与熟知的基于蛋白胨和/或提取物的培养基相当的对于非常广泛范围的微生物(包括广泛范围的原核生物以及真核生物物种)的生长基础,例如,覆盖通常在不同的样品,例如环境样品、来自食品和饮料行业的样品、药物样品或临床样品中发现的原核和真核细胞的生长需要。
已经发现,如果某些规定的成分存在于细胞培养基中并与其它典型的培养基成分合并,可提供通用的、非-特异性的、化学成分确定的生长培养基,其能够支持通常在各种样品中发现的非常广泛范围的原核生物和真核生物生长,具有基本与传统的基于蛋白胨的培养基相同的生长潜力。培养基不仅满足大多数典型的分离株(原核生物和真核生物两者)生长的适当的生物化学平衡,而且同时满足支持苛求细胞(原核生物和真核生物两者)的生长的需要。同时,这样的培养基也通常能够比传统的基于蛋白胨的复杂培养基更加加快酵母和霉菌的生长。
因此,本发明涉及一种在化学成分确定的细胞培养基中培养原核生物和真核生物的方法,其特征在于细胞培养基包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐。
在一个优选的实施方案中,细胞培养基包含一种或多种糖成分、一种或多种氨基酸、一种或多种维生素或维生素前体、一种或多种盐、一种或多种缓冲剂成分、一种或多种辅因子和一种或多种核酸成分。
在一个优选的实施方案中,细胞培养基包含0.01-10 g/L谷氨酰胺、0.01-3 g/L半胱氨酸和/或胱氨酸、0.1-300 mg/L腺嘌呤、0.01-100 mg/L鸟嘌呤、0.01-10 g/L氨基苯甲酸和0.01-100 mg/L铁(III)盐。
在另一个优选的实施方案中,细胞培养基包含胶凝剂。
在另一个实施方案中,细胞培养基还包含至少一种发色或发荧光底物。
在一个优选的实施方案中,原核生物包含一种或多种以下菌株:金黄色葡萄球菌、枯草芽孢杆菌、大肠杆菌、酿脓链球菌、铜绿假单胞菌。
在一个优选的实施方案中,真核生物包含一种或多种以下菌株:白色念珠菌、巴西曲霉和酿酒酵母。
在一个优选的实施方案中,原核生物和真核生物包含至少一种苛求菌株。
本发明还涉及通过以下步骤在一次测定中同时检测样品中的原核生物和真核生物的方法:
a) 在包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的细胞培养基中培养样品;
b) 检测原核生物和真核生物的存在。
在一个优选的实施方案中,在步骤a)中的培养执行少于30小时。
在进一步优选的实施方案中,原核生物和真核生物的存在经由它们的生长,在光学上例如但不限于混浊度的存在和/或菌落形成和/或经由颜色变化,例如,但不限于由于原核生物和/或真核生物的存在导致的pH移动引起的颜色变化来检测。
此外,使用染色剂或染料(像色原体和/或荧光团)和/或通过使用酶促试验和/或通过鉴定微生物的存在(使用PCR或相关的遗传技术,例如,但不限于印迹技术,和/或显微镜检查和/或在生物发光试验中检测ATP和/或其衍生物和/或大规模平行测序和/或流式细胞术),可利用血清学试验和/或生物化学试验来确认微生物的存在。微生物学家已知许多其它技术。注意,可添加预浓缩步骤,例如,但不限于,离心和/或过滤,以便能够更容易和/或更快速地鉴定微生物的存在/缺乏和/或帮助鉴定。
本发明还涉及一种包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的培养基。
在一个优选的实施方案中,培养基包含0.01-10 g/L谷氨酰胺、0.01-3 g/L半胱氨酸和/或胱氨酸、0.1-300 mg/L腺嘌呤、0.01-100 mg/L鸟嘌呤、0.01-10 g/L氨基苯甲酸和0.01-100 mg/L铁(III)盐。
在一个优选的实施方案中,培养基包含胶凝剂。
本发明还涉及包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的细胞培养基用于同时培养原核生物和真核生物的用途。
优选地,化学成分确定的细胞培养基被用于生物负载、无菌性、环境或培养基填充试验。
已发现包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的细胞培养基允许生成通用的化学成分确定的和完全合成的培养基,其促进混合的或作为纯性培养物的各种原核和真核微生物的快速生长。
细胞培养是细胞在其中培养的任何设置。
细胞培养可在适合于细胞培养的任何容器,例如陪替氏培养皿、接触板、瓶、试管、孔、容器、袋、烧瓶和/或罐中执行。通常地,容器在使用前被灭菌。培养通常通过在水性培养基中,在合适的条件(例如合适的温度、渗透压、通风、搅动等)下培养细胞执行,所述条件限制来自环境的外来微生物的污染。本领域技术人员知道用于支持或维持细胞生长/培养的合适的培养条件。
依据本发明的细胞培养基(同义使用:培养基)是维持和/或支持细胞的体外生长和/或支持特定的生理学状态的任何成分混合物。它也适合于预富集培养以及用作维持培养基。
它是一种化学成分确定的培养基。所述细胞培养基可包含维持和/或支持细胞的体外生长所必需的所有成分,或用于添加与分开加入的其它成分(培养基补充剂)组合或不与所述成分组合的选择成分。优选地,细胞培养基包含维持和/或支持细胞的体外生长所必需的所有成分。
依据本发明的细胞培养基被设计为适合于原核细胞像细菌细胞以及真核细胞像酵母、真菌、藻类、植物、昆虫和/或哺乳动物细胞和任选的古生菌的生长或维持/支持它们的生长。原核生物和真核生物以及任选的古生菌在下文也称为微生物或细胞。
苛求微生物是只有在许多特殊的营养素存在于其细胞培养基中时才能生长的微生物。苛求微生物的例子是军团杆菌属(Legionella)物种、布鲁氏菌属(Brucella)物种、土拉热弗朗西斯菌(Francisella tularensis)、钩端螺旋体属(Leptospira)物种、伯氏疏螺旋体(Borrelia burgdorferi)、巴尔通氏体属(Bartonella)物种和博代特氏菌属(Bordetella)物种。
其生长将由本发明的方法和培养基维持或支持的微生物通常发现于:
- 在药物相关的环境监测期间的环境样品
- 从药物相关的原材料、中间体和/或制成品获得的样品
- 在医院检查期间的临床样品
- 兽医样品
- 用于检查饮用水和/或废水和/或游泳池水的水样品
- 用于检查微生物的污染的食品样品
- 化妆品样品。
其生长由依据本发明的培养基和方法维持/支持/检测的细胞的例子是:
- 细菌:
无色杆菌(Achromobacter sp.)野生型
鲁氏不动杆菌(Acinetobacter lwoffii) (ATCC® 17925™)
克劳氏芽孢杆菌(Bacillus clausii) (ATCC® 700160)
嗜碱芽孢杆菌(Bacillus halodurans)野生型
Bacillus okuhidensis野生型
短小芽孢杆菌(Bacillus pumilus)野生型
枯草芽孢杆菌(Bacillus subtilis) (ATCC® 6633™)
枯草芽孢杆菌(Bacillus subtilis)野生型
伯克霍尔德氏菌(Burkholderia sp.)野生型
产芽胞梭状芽胞杆菌(Clostridium sporogenes) (ATCC® 11437™)
产芽胞梭状芽胞杆菌(Clostridium sporogenes) (ATCC® 19404™)
结核硬脂酸棒状杆菌(Corynebacterium tuberculostearicum)野生型
大肠杆菌(Escherichia coli) (ATCC® 25922™)
大肠杆菌(Escherichia coli) (ATCC® 8739™)
嗜根考克氏菌(Kocuria rhizophila) (ATCC® 9341™)
雷弗森菌(Leifsonia sp.)野生型
扭脱甲基杆菌(Methylobacterium extorquens) (ATCC® 43645™)
扭脱甲基杆菌(Methylobacterium extorquens) (NBRC 15911)
藤泽氏甲基杆菌(Methylobacterium fujisawaense)野生型
嗜中温甲基杆菌(Methylobacterium mesophilicum) (ATCC® 29983™)
甲基杆菌属亚种(Methylobacterium ssp.)野生型
藤黄微球菌(Micrococcus luteus) (ATCC® 10240™)
莱拉微球菌(Micrococcus lylae)野生型
灿烂类芽胞杆菌(Paenibacillus lautus)野生型
泛菌(Pantoea sp.)野生型
痤疮丙酸杆菌(Propionibacterium acnes) (ATCC® 6919™)
铜绿假单胞菌(Pseudomonas aeruginosa) (ATCC® 9027™)
皮氏罗尔斯顿菌(Ralstonia pickettii) (ATCC® 27511™)
皮氏罗尔斯顿菌(Ralstonia pickettii)野生型
鼠伤寒沙门氏菌(Salmonella typhimurium) (ATCC® 14028™)
粘质沙雷氏菌(Serratia marcescens)野生型
少动副鞘氨醇单胞菌(Sphingomonas parapaucimobilis)野生型
少动鞘氨醇单胞菌(Sphingomonas paucimobilis) (ATCC® 29837™)
少动鞘氨醇单胞菌(Sphingomonas paucimobilis)野生型
金黄色葡萄球菌(Staphylococcus aureus) (ATCC® 25923™)
金黄色葡萄球菌(Staphylococcus aureus) (ATCC® 6538™)
表皮葡萄球菌(Staphylococcus epidermidis) (ATCC® 12228™)
表皮葡萄球菌(Staphylococcus epidermidis)野生型
溶血葡萄球菌(Staphylococcus hominis) (ATCC® 27844™)
嗜麦芽寡养单胞菌(Stenotrophomonas maltophilia) (ATCC® 13637™)
酿脓链球菌(Streptococcus pyogenes) (ATCC® 12344™)
酿脓链球菌(Streptococcus pyogenes) (ATCC® 21059™)
- 酵母:
白色念珠菌(Candida albicans) (ATCC® 10231™)
汉逊德巴利酵母(Debaryomyces hansenii) (DSM 3428)
外瓶霉(Exophiala sp.)野生型
- 霉菌:
巴西曲霉(Aspergillus brasiliensis) (ATCC® 16404™)
巴西曲霉(Aspergillus brasiliensis)野生型
聚多曲霉(Aspergillus sydowii) (DSM 63373)
普通青霉菌(Penicillium commune) (ATCC® 10428™)
例如,依据本发明的化学成分确定的培养基可支持真核生物和原核生物像革兰氏阳性微生物和革兰氏阴性微生物的生长,例如人皮肤污染物、水污染物、酵母和霉菌,如枯草芽孢杆菌(Bacillus subtilis)、普通拟杆菌(Bacteroides vulgatus)、产芽胞梭状芽胞杆菌(Clostridium sporogenes)、痤疮丙酸杆菌(Propionibacterium acnes)、金黄色葡萄球菌、巴西曲霉(Apergillus brasiliensis)、白色念珠菌(Candida albicans)、大肠杆菌(Escherichia coli)、扭脱甲基杆菌(Methylobacterium extorquens)、藤泽氏甲基杆菌(Methylobacterium fujisawaense)、嗜中温甲基杆菌(Methylobacterium mesophilicum)、铜绿假单胞菌(Pseudomonas aeruginosa)、灿烂类芽胞杆菌(Paenibacillus lautus)、皮氏罗尔斯顿菌(Ralstonia pickettii)、表皮葡萄球菌(Staphylococcus epidermidis)。
化学成分确定的细胞培养基是包含化学上充分表征的“确定的”原材料的细胞培养基。这意味着用于培养基的所有化学品的化学组成是已知的。化学成分确定的培养基不包含化学上不充分确定的物质如化学上不充分确定的酵母、动物或植物组织;它们不包含蛋白胨、饲养细胞、血清、不充分确定的提取物或消化物或可向培养基提供化学上不好确定的蛋白和/或肽和/或水解产物的其它成分。化学未限定的、不充分确定的或不好确定的化学成分是化学组成和结构不是熟知的那些,存在于不好确定的和变化的组合物中或只能用巨大的科学实验努力来确定。在一些情况下,化学成分确定的培养基可包含化学成分确定的蛋白或肽 - 一个例子是胰岛素(见下文的其它实例)。
粉末状细胞培养基或干粉培养基或脱水培养基是通常由粉碎过程或冻干过程产生的细胞培养基。那意味着粉末状细胞培养基通常是一种精细微粒、颗粒状培养基 – 不是一种液体培养基。术语"干粉"可与术语"粉末"互换使用;然而,如本文所用的"干粉"仅仅指的是粒状材料的大体外观,并不打算指材料完全不含复合或凝聚的溶剂,除非另外指明。粉末状细胞培养基也可以是颗粒状细胞培养基,如通过碾压进行干法制粒或通过流化床喷雾粒化进行湿法制粒。这样的培养基也可通过喷雾干燥来制备。
用于支持原核生物和真核生物的一般生长的本发明的培养基显示出与用于这个目的的标准培养基可比较的(明显的)生长特征。因此它们通常
a. 含有促进大多数细胞的细胞生长的生物化学品的平衡,所述细胞易于被检测
i) 含有足够的特殊的生物化学品以补充非常宽范围的原核生物和真核生物的需要,但同时
ii) 不含可高至显著地抑制某些敏感细胞株生长的浓度的特殊生物化学品
b. 含有适合于桥接存在于许多原核和真核物种中的营养缺陷型差距的丰富营养基础
c. 含有能够喂给细胞的某些复杂的生物化学品,以使生长不被广泛重新酶合成不必要地延迟。这样的不合需要的广泛重新酶合成可导致
i) 显著延长的停滞期或
ii) 细胞的死亡,因为它们不能够恢复足够的代谢活性以克服至关重要的细胞损害和/或抵消过度的细胞合成代谢活性。
包含维持和/或支持细胞体外生长所必需的所有成分的细胞培养基通常至少包含一种或多种糖成分、一种或多种氨基酸、一种或多种维生素或维生素前体、一种或多种盐、一种或多种缓冲剂成分、一种或多种辅因子和一种或多种核酸成分(含氮碱基)或它们的衍生物。它也可包含化学成分确定的生物化学品例如重组蛋白,如r胰岛素、rBSA、r转铁蛋白、r细胞因子等(见上文)。
培养基也可包含丙酮酸钠、高度纯化并因而化学上明确限定的提取物、脂肪酸和/或脂肪酸衍生物和/或在特定泊洛沙姆188 (有时称为普流罗尼克F 68或Kolliphor P 188或Lutrol F 68)中的普流罗尼克产品成分(基于环氧乙烷和环氧丙烷的嵌段共聚物),和/或表面活性成分例如化学制备的非-离子表面活性剂。合适的非-离子表面活性剂的一个例子是以伯羟基端接的双官能的嵌段共聚物表面活性剂,也称为泊洛沙姆,如从德国BASF以商品名pluronic ®购得。这样的普流罗尼克产品成分在下文简称为普流罗尼克。螯合剂、激素和/或生长因子也可被加入。
可包含的其它成分是以下化合物的纯化合物、盐、轭合物和/或衍生物:乳酸、硫代乙醇酸、硫代硫酸盐、连四硫酸盐、二氨基丁烷、肌醇、磷脂酰胆碱(卵磷脂)、鞘磷脂、含铁化合物(包括具有铁硫簇的化合物)、尿酸、氨甲酰磷酸酯、琥珀酸、硫氧还蛋白、乳清酸、磷脂酸、聚胺(例如腐胺、亚精胺、精胺和/或尸胺)、甘油三酯、类固醇(包括但不限于胆固醇)、金属硫蛋白(metallothionine)、氧、甘油、脲、α-酮戊二酸、氨、甘油磷酸酯、淀粉、糖原、乙醛酸盐、类异戊二烯、甲醇、乙醇、丙醇、丁醇、丙酮、脂质(包括但不限于在胶束中的那些)、三丁酸甘油酯、酪脂、胆酸、脱氧胆酸、多磷酸盐、乙酸盐、酒石酸盐、苹果酸盐和/或草酸盐。
糖成分全部是单糖或二糖,像葡萄糖、半乳糖、核糖或果糖(单糖的例子)或蔗糖、乳糖或麦芽糖(二糖的例子)或其衍生物像糖醇。糖成分也可以是寡糖或多糖。
特别地,依据本发明的氨基酸的例子是蛋白质性氨基酸,特别是必需氨基酸,亮氨酸、异亮氨酸、赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、色氨酸和缬氨酸,以及非蛋白质性氨基酸,例如D-氨基酸。
酪氨酸意指L-或D-酪氨酸,优选L-酪氨酸。
半胱氨酸意指L-或D-半胱氨酸,优选L-半胱氨酸。
氨基酸前体和类似物也包括在内。
维生素的例子有维生素A (视黄醇、视黄醛、各种类维生素A和四种类胡萝卜素)、维生素B1 (硫胺)、维生素B2 (核黄素)、维生素B3 (烟酸、烟酰胺)、维生素B5 (泛酸)、维生素B6(吡哆醇、吡哆胺、吡哆醛)、维生素B7 (生物素)、维生素B9 (叶酸、亚叶酸)、维生素B12 (氰钴胺素、羟钴胺素、甲基钴胺素)、维生素C (抗坏血酸) (包括抗坏血酸的磷酸酯)、维生素D(麦角钙化醇、胆钙化醇)、维生素E (生育酚、生育三烯酚)和维生素K (叶绿醌、甲基萘醌)。维生素前体和类似物也包括在内。
盐的例子是包含无机离子例如碳酸氢根、钙、氯离子、镁、磷酸根、钾和钠或微量元素例如Co、Cu、F、Fe、Mn、Mo、Ni、Se、Si、Ni、Bi、V和Zn的成分。例子是五水硫酸铜(II)(CuSO4 .5 H2O)、氯化钠(NaCl)、氯化钙(CaCl2 .2 H2O)、氯化钾(KCl)、硫酸亚铁(II)、无水磷酸二氢钠(NaH2PO4)、无水硫酸镁(MgSO4)、无水磷酸氢二钠(Na2HPO4)、六水氯化镁(MgCl2 .6H2O)、七水硫酸锌(ZnSO4 .7 H2O)。
缓冲剂的例子是碳酸盐、柠檬酸盐、磷酸盐、HEPES、PIPES、ACES、BES、TES、MOPS和TRIS。
辅因子的例子是以下的化合物、盐、复合物和/或衍生物:硫胺、生物素、维生素C、钙化醇、胆碱、NAD/NADP (还原的和/或氧化的)、钴胺素、维生素B12、黄素单核苷酸和衍生物、黄素腺嘌呤二核苷酸和衍生物、谷胱甘肽(还原的和/或氧化的和/或作为二聚体)、血红素(haeme)、氯化血红素(haemin)、血红蛋白、铁蛋白、磷酸核苷酸和/或衍生物(如磷酸腺苷)、辅酶F420、s-腺苷基甲硫氨酸、辅酶B、辅酶M、辅酶Q、乙酰Co-A、钼蝶呤、吡咯喹啉醌、四氢生物喋呤。
依据本发明的核酸成分是核碱基,像胞嘧啶、鸟嘌呤、腺嘌呤、胸腺嘧啶、尿嘧啶、黄嘌呤和/或次黄嘌呤,核苷像胞苷、尿苷、腺苷、黄苷、肌苷、鸟苷和胸苷,和核苷酸例如一磷酸腺苷或二磷酸腺苷或三磷酸腺苷,包括但不限于其脱氧和/或磷酸衍生物和/或二聚体、三聚体和/或多聚体,像RNA和/或DNA。
可加入改善培养基的理化性质的化合物,如但不限于,增加培养基和/或其一种或多种成分的透明度和/或溶解度,而不显著地负面影响在所用浓度下的细胞生长性质。这样的化合物包括但不限于螯合剂(如EDTA)、抗氧化剂、去垢剂、表面活性剂、乳化剂(像聚山梨醇酯80)、中和剂(像聚山梨醇酯80)、胶束形成剂、胶束抑制剂和/或聚丙二醇、聚乙烯醇和/或羧甲基纤维素。
培养基通常含有碳水化合物例如糖和/或糖混合物和/或糖二聚体和/或糖聚合物和/或它们的衍生物。通常,葡萄糖和/或乳糖和/或半乳糖可以是主要碳水化合物糖成分。葡萄糖通常以在水性介质溶液中0.001 mM-250 mM,更优选1 mM-100 mM,甚至更优选5 mM-50 mM的浓度被包括在培养基中。
通常,培养基包含范围从10 mg-3g每升,优选范围从40 mg-1 g每升的每种氨基酸。
培养基通常包含维生素。培养基中的维生素的典型量是在5 µg-10 mg每升的范围内,优选地在50 µg-6 mg每升的范围内。
通常,培养基包含盐。一种类型的盐的量通常是在2 µg-5 mg每升的范围内,优选地在10 µg-1.5 mg每升的范围内。特殊的盐也可以更高得多的量存在;NaCl的浓度可例如是至多5 g每升。
包含在培养基中的核酸的典型量是在0.5-10 mg每升的范围内,优选地在1-5 mg每升的范围内。
培养基通常含有全部蛋白质性氨基酸(和/或它们的衍生物和/或它们的轭合物和/或其二聚体(纯的和/或混合的))。应该注意到,在固体培养基中的成分的浓度可显著地不同于溶解后实际测量的那些。这是因为,例如,某些氨基酸可在水性介质中与其它成分反应,形成然后间接地含有氨基酸的产物,由此在溶液中的纯氨基酸从而被耗尽。这个过程也可发生于其它容易反应的成分,例如,但不限于维生素C,和/或事实上氨基酸可互相或与它们自身反应。这个过程可以是依赖于氧浓度和微量和/或超微量元素(特别是过渡金属离子像作为成分直接加入和/或作为污染物存在的铜和/或铁的那些)存在的氧化过程。
其它限定的成分像指示剂也可加入以帮助检测或鉴定微生物。
依据本发明的化学成分确定的培养基还可包含至少一种发色或发荧光底物。发荧光底物是复杂的分子,其在与由微生物合成的酶接触时,被裂解且成为发荧光的。发射的荧光可在视觉上和/或用分析仪器像光谱仪,通过使用UV或可见光谱辐射,照亮生长培养基而被检测到。发荧光底物的例子是荧光素衍生物(CFA、CFDA)、甲基伞形酮衍生物或AldolsTM(由Biosynth公司开发)。
发色底物是当它们例如通过微生物的特殊的酶修饰时,改变其颜色的底物。发色底物的例子是ONPG (邻-硝基苯基-β-D-吡喃半乳糖苷)或X-Gal (5-溴-4-氯-3-吲哚基-β-D-吡喃半乳糖苷)。在这种情况下,在感兴趣的某些微生物的生长后,培养基颜色将会变色,并指示这样的微生物。
通常合适的液体细胞培养基具有2-50 g/L、更优选5-30 g/L的典型组合物。具有胶凝剂的培养基通常由于在1和50 g/L之间,更优选在2和30 g/L之间的胶凝剂而具有额外的重量。
培养基的渗透压通常是在50 mOsm和1000 mOsm之间,更优选在150 mOsm和500mOsm之间。
因为合适的细胞培养基不含源自动物和植物的蛋白胨,它们在其例如在药物应用或环境测试中使用的观点上,代表了作为外源因子污染来源的可能性高度减少。在其存在中将非常显著地减少的这样的感染性污染物包括,但不限于:
- 蛋白质性污染物,像牛海绵状脑病(BSE),
- 病毒污染物,像小鼠微小病毒(MVM),
- 耐热芽孢形成原核生物,
- 真核污染物,
- 已知在某些条件下由于它们的非常小的尺寸在无菌过滤期间能够渗透膜孔的细胞,例如支原体,像洋葱伯克霍尔德氏菌(Burkholderia cepacia)。
除了典型的化学成分确定的细胞培养基(例如用于CHO细胞培养)之外,依据本发明的化学成分确定的细胞培养基还包含以下成分和/或它们的盐和/或它们的衍生物和/或轭合物和/或二聚体(纯的或混合的)。
成分 | 典型 | 优选 | 更优选 | 甚至更优选 |
谷氨酰胺 | 0,001-50 g/L | 0,01-10 g/L | 0,02-2 g/L | 0,1 g/L |
半胱氨酸和/或胱氨酸 | 0,001-10 g/L | 0,01-3 g/L | 0,05-1 g/L | 0,5 g/l |
腺嘌呤 | 0,01-1000 mg/L | 0,1-300 mg/L | 2-50 mg/L | 10 mg/L |
鸟嘌呤 | 0,001-500 mg/L | 0,01-100 mg/L | 0,05-5 mg/L | 0,5 mg/L |
氨基苯甲酸 | 0,001-100 g/L | 0,01-10 g/L | 0,02-2 g/L | 0,1 g/L |
烟酰胺腺嘌呤二核苷酸 | 0,001-500 mg/L | 0,1-100 mg/L | 0,5-25 mg/L | 2,5 mg/L |
Fe浓度,例如来自柠檬酸Fe(III) | 0,001-500 mg/L | 0,01-100 mg/L | 0,05-5 mg/L | 0,5 mg/L |
表1
合适的铁盐的例子是六水合硫酸铁(II)铵、七水合硫酸铁(II)或九水合硝酸铁(III)。铁的螯合物和/或含铁蛋白或肽也可使用。
半胱氨酸和/或胱氨酸可作为L-半胱氨酸、L-半胱氨酸盐酸盐、L-胱氨酸、N-乙酰基-半胱氨酸加入。
谷氨酰胺可例如作为纯化合物和/或l-丙氨酰(analyl)-l-谷氨酰胺或盐酸盐加入。
腺嘌呤和鸟嘌呤可例如作为纯化合物或作为盐酸盐加入。
氨基苯甲酸可作为纯化学品或作为盐例如钠盐加入。
烟酰胺腺嘌呤二核苷酸可作为氧化或还原形式和/或作为磷酸衍生物和/或作为本领域技术人员已知的其它衍生物加入。
细胞培养基可以是干粉培养基、液体培养基或半-固体培养基。在半-固体培养基的情况下,除了化学成分确定的成分外,培养基还包含胶凝剂。合适的胶凝剂的例子是琼脂(agar-agar)和/或琼脂糖。
粉末状细胞培养基优选地通过混合所有成分并碾磨它们制备。所述成分的混合是通过碾磨生产干燥粉末状细胞培养基的领域的技术人员已知的。优选地,所有成分被充分混合,以致混合物的所有部分均具有几乎相同的组成。组合物的均匀度越高,生成的培养基关于同质性的品质就越好。
碾磨可用适合于生产粉末状细胞培养基的任何类型的碾磨机执行。典型的例子是球磨机、针磨机、菲兹微粉碎机(fitz mill)或喷磨机。优选的是针磨机、菲兹微粉碎机或喷磨机,非常优选的是针磨机。甚至更优选的是其中碾磨室用氮冷却的针磨机。
优选地,经历碾磨的混合物的所有成分是干燥的。这意味着如果它们包含水,它们仅包含结晶水,但不超过10%,优选不超过5%,最优选不超过2%重量的未结合的或未配位的水分子。它们也可在培养基内含有结合的液体,以致粉末性质没有受到显著影响。
干粉细胞培养基也可作为压实物(compactates)使用以有利于处理。通常压实的培养基有良好的溶解性质且由于减少粉尘的形成而易于处理。
粉末培养基优选以辊压机压实。
对于干燥粉末状培养基的使用,溶剂,优选水(最特别是蒸馏水和/或去离子水或纯化水和注射用水)或水性缓冲剂被加入到培养基中并混合成分,直至培养基完全溶解于溶剂中。
溶剂也可包含盐水、提供合适的pH范围(通常在pH 1和pH 10之间的范围内)的可溶性酸或碱离子、稳定剂、表面活性剂、防腐剂和醇或其它极性有机溶剂以及用于生产半-固体培养基的胶凝剂。
培养基优选经处理以在使用前显著地减少生物负载荷量至这样一种水平,即,在使用前生物污染物极其罕有地存在于最终的处理的培养基中。这种处理可优选通过过滤和/或通过热处理(如121℃ 15分钟)和/或通过UV处理以液态执行。
溶解的培养基在加入细胞之前的pH通常是在pH 2和12之间,更优选在pH 4和10之间,甚至更优选在pH 6和8之间且最优选在pH 6.5-7.5之间且理想地在pH 7.0-7.5之间。
依据本发明的培养基可在有氧和厌氧生长条件下使用。本领域技术人员熟悉对于有氧或厌氧生长所采取的各自的措施。通常,对于厌氧培养条件,氧被除去,例如通过减少或优选地消除水性培养基中的氧的添加剂和/或在真空下通过物理方式和/或通过沸腾排出氧气。如果使用添加剂,则优选地,添加剂与培养基中溶解的氧反应以化学除去氧,因而创造一个厌氧环境。无论通过何种方式,包含氧耗尽的培养基的容器应该防止新鲜氧气侵入培养基中。添加剂可包含还原剂,或也可以是氧吸收剂或清除剂如钯催化剂,或酶,如单-和/或双-加氧酶,和/或琥珀酸盐。
已经发现,包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的细胞培养基支持原核生物和真核生物二者的生长。培养基在其组成上可有广泛变化,只要它们包含所述成分。因此,为广泛范围的原核生物和真核生物二者生长的目的,谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐可被加入和/或掺入广泛种类的化学成分确定的细胞培养基中,以改进那些培养基的适用性。
本发明因此还涉及一种包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的细胞培养基补充剂。合适的和优选的量在表1中提供。
在一个实施方案中,细胞培养基补充剂含有0.01-10 g/L谷氨酰胺、0.01-3 g/L半胱氨酸和/或胱氨酸、0.1-300 mg/L腺嘌呤、0.01-100 mg/L鸟嘌呤、0.01-10 g/L氨基苯甲酸和0.01-100 mg/L铁(III)盐。
本发明的培养基补充剂通常以与本发明的细胞培养基相同的方式生产并使用。补充剂可被加入到干粉培养基中并在溶解和使用之前与这种培养基充分混合。它可能也溶于水或水性缓冲液如细胞培养基本身中并与溶解的细胞培养基混合,此后在处理之后或之前例如通过过滤除去生物污染物。
可用本发明的培养基补充剂补充的化学成分确定的培养基的实例是用于哺乳动物和/或昆虫细胞生长目的的那些。
用本发明的补充剂补充的特别合适的培养基是用于CHO细胞的细胞培养基制剂。那些培养基在文献里有充分记载,并且几种是可市售获得的,例如从Merck KGaA(Darmstadt,德国)获得。
用于培养CHO细胞培养物的典型的限定培养基基质(无任何蛋白胨或碳酸氢钠加入)可在下面发现:
- 用于F-12K培养基的制剂,ATCC® 30-2004
- 无血清培养基CHO-T1-SF的组合物
(来自:Journal of Biotechnology, 2004, 108, p 279–292, Schröder et al.,“Serum- and protein-free media formulations for the Chinese hamster ovarycell line DUKXB11”)。
- 授予Gorfien等的美国专利申请号US 2006/0148074 A1, 申请日06.07.2006,“Serum-free mammalian cell culture medium, and uses thereof”。
本发明因此还涉及一种通过添加细胞培养基补充剂至化学成分确定的哺乳动物和/或昆虫细胞培养基中,制备支持原核生物和真核生物的培养/生长的化学成分确定的细胞培养基的方法,所述细胞培养基补充剂包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐。
本发明的主旨是提供一种化学成分确定的并支持非常广泛范围的原核生物和真核生物快速培养/生长的细胞培养基。因为培养基具有精确的化学配方,批次间生产表现出最小的变化且可保证再现性。因为培养基基本上不含动物和植物来源的蛋白胨,它们在其例如在药物应用或环境测试中使用的观点上,代表了作为外源因子污染来源的可能性高度减少。
本发明还涉及在如上定义的培养基中培养微生物的方法,以及依据本发明的细胞培养基用于培养微生物的用途。在一个优选的实施方案中,所述微生物选自细菌、酵母和真菌。
通常,培养基被置于合适的容器中并用微生物或潜在地包含所述微生物的样品接种。合适的容器如上所定义。样品可以是可与细胞培养基接触的任何液体、气体或固体实体。样品可以是例如与包含细胞培养基的接触板接触的表面。它可例如是与细胞培养基接触的拭子(swap)或放在培养基中或培养基上的任何液体或固体。
允许细胞生长的培养基的培养温度通常是在0℃和100℃之间,更通常是在15℃和50℃之间,还更通常是在20和45℃之间。样品可例如于室温下(约20℃),如在22.5℃或在32.5℃培养。
一般地,在接种后,将培养基培养一段时间以使微生物有些生长,以致它们可容易地被检测到。对于传统方法,这样的时间可在从最少数小时至数周的范围内。一般地,培养时间是在约1和14天之间。用本方法生产的培养基能够在不到24小时后检测某些微生物,甚至传统上花费2天来生长的微生物。特别是,酵母和霉菌显示出与用蛋白胨生产的传统培养基相比显著快的生长速率。
本发明还涉及通过以下步骤在一次测定中同时检测样品中的原核生物和真核生物的方法:
a) 使样品与包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的细胞培养基接触;
b) 培养步骤a)中的接种的细胞培养基;
c) 检测原核生物和真核生物在所述细胞培养基中的存在。
如上所述执行步骤a)和b)以培养微生物。步骤c)中的检测可通过任何已知的方法进行。例子是视觉检测在半-固体培养基上形成的菌落或在液体培养基中的混浊度,检测从存在于培养基中的发色或发荧光底物生成的颜色变化或荧光。生长可使用由产生有机酸的微生物酶促活性(例如,或,导致pH显著升高的铵产生)造成的生物化学转换导致的pH改变来识别。用于检测的其它方法包括PCR分析。本领域的熟练技术人员能够鉴别可与这样的培养基组合使用的许多其它方法,其能够直接或间接检测微生物的存在(即使没有明显的生长)。
依据本发明的化学成分确定的培养基可在各种应用中,如在生物药物或环境领域,在食品和饮料行业或在诊断学中替代传统的复杂培养基。示例性应用在下文列出:
无菌性和生物负载测试:
依据本发明的培养基可用于无菌性和生物负载测试。过程中材料和成品的无菌性测试必须在药物和医疗器械的生产期间得到证明。饮料或饮用水的常规微生物控制也非常重要。
测试样品的生物负载水平或无菌性的典型方法是在膜滤器上过滤液体样品,所述膜滤器保留样品的可能的污染物,并在培养基中培养滤器。如果样品不能过滤,可将样品直接接种到培养基中。在存在一种或多种污染物的情况下,透明的培养基由于细胞的生长而变得浑浊。
在这方面,使用依据本发明的化学成分确定的培养基是有利的,因为清澈的培养基是优选的,其中甚至低的混浊度可容易地被检测到。一个优点是培养基颜色可更容易转变以有助于视觉检测。
用于这种应用的滤器具有小到足以捕捉样品中的任何微生物的孔径。这样的滤器通常具有从约0.1 µm至最多1.2 µm的孔径。优选地,孔径具有0.45 µm或更小。滤器可由通常用于这样的应用的任何合适材料形成,例如再生纤维素、混合纤维素酯、醋酸纤维素、聚醚砜、聚芳砜和聚苯砜。
用于滤器的支撑物可能只是不锈钢设备例如漏斗。或者,可以使用包含一次性、预消毒的和透明的过滤器的设备,例如Steritest TM EZ设备(Merck Millipore),其是允许进行整个试验(采样、过滤、培养基加入和培养)的封闭设备。
环境测试:
测试设施中的环境微生物水平的典型方法是通过设备过滤空气样品,使微生物保留在滤器上。然后滤器可在如上讨论的依据本发明的培养基中培养。
另一种典型的方法是使用在接触板中的这样的培养基。特别是在这里,培养基中原材料的高纯度和化学成分确定的性质意味着所述培养基显著更少可能含有外来因子。接触板的表面包含呈半-固体形式的培养基。将培养基表面压在例如设备表面,以确定设备是否污染有微生物。根据定义,然后少量的培养基留在这种设备表面上。这意味着测试后留在这种关键表面(如在药物环境)上的培养基的指纹被培养基略有污染。对于传统培养基,则表面随后被不确定的蛋白胨和其它不确定的原材料污染。这样的原材料带有随它们携带外来因子例如BSE/TSE因子和病毒的高得多的风险。对此,化学成分确定的合成培养基是一个低风险的选项,其携带这样的外来因子的可能性低得多。
培养基填充试验:
培养基填充试验定期执行,以验证无菌生产过程不受微生物的污染,例如腐败细菌、酵母或霉菌的影响,例如在制药或食品和饮料行业中。通常,在培养基填充试验中,产品生产的整个过程用无菌培养基代替各自的产品模拟。培养基然后装入独立的设备中,其经受如上定义的无菌性测试。同样,如在上面的情况下,当使用不含不确定的蛋白胨/提取物(其源自过程且具有基于动物组织和/或农场的来源)的培养基时,外来因子的疏忽污染的风险减少是低得多的。
在特定鉴定之前预富集:
在进一步的方面,依据本发明的培养基可用于在鉴定前微生物的预富集。为了这个目的,将样品接种于培养基中,使微生物生长一段足够的时间。一旦达到所需的浓度,样品就经受进一步的处理,例如特定的微生物鉴定。
因此,本发明的进一步的方面是一种检测样品中的微生物的方法(试图确定样品是否被活微生物污染),其特征在于它包括将样品接种于如上定义的培养基中的步骤和观察微生物生长的步骤。
本发明还涉及依据本发明的细胞培养基用于生物负载、无菌性、环境或培养基填充试验的用途。
本发明可以显示,化学成分确定的细胞培养基还适合于同时检测真核生物和原核生物,如果所述培养基除了细胞培养基的典型的成分外,还包含某些添加剂(谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐)的组合的话。已知包含一种或多种所述添加剂的细胞培养基,但到目前为止尚未认识到包含所述成分的化学成分确定的培养基特别适合于支持宽泛围的微生物的生长。本发明的培养基和方法因此提供生长和任选还检测这样的微生物的可能性,无需被迫使用包含已知带有外来因子的化学上不确定的蛋白胨和/或提取物的细胞培养基。本发明的培养基和方法是与包括使用蛋白胨的已知培养基和方法同样敏感和快速的。
本发明通过以下实施例进一步说明,然而,并不局限于此。
以上和以下引用的所有申请、专利和出版物以及对应的EP 15197739.4 (2015年12月3日提交)的全部公开内容通过引用结合到本文中。
实施例
所有菌株的试验程序:
- 滤器除菌的液体培养基被临时制备或在使用前在冰箱中贮存于125mL玻璃瓶中。
-于-80℃贮存于HEPES/甘油中的菌株溶液的系列稀释在0.9%氯化钠溶液中执行。
- 每个培养基瓶用20-50 CFU/mL接种。
- 将接种的瓶于22.5℃±2.5和32.5℃±2.5培养最多14天(取决于菌株)。
- 无菌瓶被平行培养作为对照。
- 在各瓶中视觉观察微生物生长。
实施例1
选择通常用于测试胰蛋白酶大豆琼脂(TSA)的生长潜力的8个细胞株以供筛选补充有琼脂的、化学成分确定的合成培养基CHO培养基(得自Merck-Millipore, Darmstadt, 德国的Cellvento™ CHO-100,产品项目编号1.00899)作为所述TSA的替代品的适宜性。与购自Merck-Millipore, Darmstadt, 德国的项目编号1.05458.0500的TSA相比,测量CHO-S的生长参数。预-培养物在购自Merck-Millipore, Darmstadt, 德国的项目编号1.05459.0500的胰蛋白酶大豆肉汤(TSB)中准备,其中它们于37℃有氧生长24小时,除了曲霉(Aspergillus spp.)外,其通过直接从琼脂板洗掉并再悬浮真菌孢子来准备。预-培养物在氯化钠蛋白胨肉汤中稀释并使用螺旋铺板仪(spiral plater)铺板。CHO-S培养基从使用碳酸钠调整pH至7.3的双倍浓缩的CHO-100培养基制备,溶液在加入水性补充浓缩液后经无菌过滤。单独地,使琼脂以双倍浓度(26 g/L)悬浮于水中并于121℃高压灭菌处理20分钟。然后使琼脂溶液冷却至约46℃并在相同的温度下与双倍浓缩的CHO-S培养基混合。琼脂板在温和但充分混合两种溶液后制备,同时避免外来微生物的污染。在表面接种后,将板于32℃+/- 2.5℃有氧培养并在24小时后评分。
结果示于表2中。
按在32.5 +/- 2.5℃培养后24小时的读数,生长以菌落的相对直径给出,范围为0(无生长)至5 (对于各细胞株,生长旺盛)。
概述
由24小时后的菌落大小表示的生长速度,和回收百分率,都与TSA有很好的比较,但仅仅在加入补充成分谷氨酰胺、半胱氨酸/胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐至CHO培养基之后。对于几乎所有测试的细菌包括革兰氏阳性微生物(两个酿脓链球菌细胞株、金黄色葡萄球菌和枯草芽孢杆菌)以及革兰氏阴性细胞株铜绿假单胞菌,都是这种情况。事实上,这种积极的效果对于测试的真核细胞也可看到:包括巴西曲霉的百分回收率的提高以及测试的念珠菌属菌株的菌落大小的稍微增加。因此,测试的原核生物和真核生物二者显示出显著的生长改善和/或使所述培养基与胰蛋白酶大豆琼脂相当的菌落大小。
实施例2
以下49个原核生物和真核生物菌株被选择以供测试,因为它们可能是环境相关的或从真实的环境样品分离。
阳性生长的结果,如在给定温度下培养14天内视觉鉴定的,显示在表3中。
接种物是指接种到TSB或CHO S培养基中的细胞数量。CHO-S培养基的制备描述于实施例1中。
结果显示,所有测试的原核生物和真核生物在TSA和在依据本发明的化学成分确定的细胞培养基中生长良好。
Claims (15)
1.一种在化学成分确定的细胞培养基中培养原核生物和真核生物的方法,其特征在于细胞在包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的细胞培养基中培养。
2.依据权利要求1的方法,其特征在于细胞培养基包含一种或多种糖成分、一种或多种氨基酸、一种或多种维生素或维生素前体、一种或多种盐、一种或多种缓冲剂成分、一种或多种辅因子和一种或多种核酸成分。
3. 依据权利要求1或2的方法,其特征在于细胞培养基包含0.01-10 g/L谷氨酰胺、0.01-3 g/L半胱氨酸和/或胱氨酸、0.1-300 mg/L腺嘌呤、0.01-100 mg/L鸟嘌呤、0.01-10g/L氨基苯甲酸和0.01-100 mg/L铁(III)盐。
4.依据权利要求1-3的一或多项的方法,其特征在于细胞培养基包含胶凝剂。
5. 依据权利要求1-4的一或多项的方法,其特征在于培养的原核生物包含一种或多种以下菌株:金黄色葡萄球菌(Staphylococcus aureus)、枯草芽孢杆菌(Bacillussubtilis)、大肠杆菌(Escherichia coli)、酿脓链球菌(Streptococcus pyogenes)、铜绿假单胞菌(Pseudomonas aeruginosa)。
6. 依据权利要求1-5的一或多项的方法,其特征在于培养的真核生物包含一种或多种以下菌株:白色念珠菌(Candida albicans)、巴西曲霉(Aspergillus brasiliensis)和/或酿酒酵母(Saccharomyces cerevisiae)。
7.依据权利要求1-6的一或多项的方法,其特征在于原核生物和真核生物包含至少一种苛求菌株。
8.通过以下步骤检测样品中的原核生物和真核生物的方法:
a) 使样品与包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐的化学成分确定的细胞培养基接触;
b) 培养步骤a)的细胞培养基;
c) 检测原核生物和真核生物在细胞培养基中的存在。
9.依据权利要求8的方法,其特征在于在步骤a)中的培养执行少于30小时。
10.依据权利要求8或9的方法,其特征在于原核生物和真核生物的存在经由它们的生长或经由由原核生物和真核生物导致的颜色或pH的改变来检测。
11. 依据权利要求8-10的一或多项的方法,其特征在于培养基包含0.01-10 g/L谷氨酰胺、0.01-3 g/L半胱氨酸和/或胱氨酸、0.1-300 mg/L腺嘌呤、0.01-100 mg/L鸟嘌呤、0.01-10 g/L氨基苯甲酸和0.01-100 mg/L铁(III)盐。
12.依据权利要求8-11的一或多项的方法,其特征在于培养基包含胶凝剂。
13.化学成分确定的细胞培养基在培养原核生物和真核生物用于生物负载、无菌性、环境或培养基填充试验中的用途,所述化学成分确定的细胞培养基包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐。
14.细胞培养基补充剂,其包含谷氨酰胺、半胱氨酸和/或胱氨酸、腺嘌呤、鸟嘌呤、氨基苯甲酸、烟酰胺腺嘌呤二核苷酸和铁盐。
15. 依据权利要求14的细胞培养基补充剂,其特征在于它含有0.01-10 g/L谷氨酰胺、0.01-3 g/L半胱氨酸和/或胱氨酸、0.1-300 mg/L腺嘌呤、0.01-100 mg/L鸟嘌呤、0.01-10g/L氨基苯甲酸和0.01-100 mg/L铁(III)盐。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15197739.4 | 2015-12-03 | ||
EP15197739 | 2015-12-03 | ||
PCT/EP2016/001848 WO2017092842A1 (en) | 2015-12-03 | 2016-11-09 | Chemically defined media for the detection of microorganisms |
Publications (1)
Publication Number | Publication Date |
---|---|
CN108291190A true CN108291190A (zh) | 2018-07-17 |
Family
ID=54838177
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201680070630.3A Pending CN108291190A (zh) | 2015-12-03 | 2016-11-09 | 用于检测微生物的化学成分确定的培养基 |
Country Status (9)
Country | Link |
---|---|
US (1) | US20180355306A1 (zh) |
EP (1) | EP3384001B1 (zh) |
JP (1) | JP6923523B2 (zh) |
CN (1) | CN108291190A (zh) |
ES (1) | ES2781373T3 (zh) |
HU (1) | HUE048986T2 (zh) |
PL (1) | PL3384001T3 (zh) |
SI (1) | SI3384001T1 (zh) |
WO (1) | WO2017092842A1 (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110241171B (zh) * | 2019-07-24 | 2023-06-02 | 山西省食品药品检验所(山西省药品包装材料监测中心) | 一种不含动植物源性的伊红美蓝纯化学成分琼脂培养基及配制方法 |
WO2021170606A1 (en) | 2020-02-26 | 2021-09-02 | Merck Patent Gmbh | Device and method for testing differential growth of microorganisms |
CN111635925B (zh) * | 2020-06-15 | 2023-08-25 | 深圳市瑞赛生物技术有限公司 | 一种即用型生物素检测载体及其制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101918582A (zh) * | 2007-11-06 | 2010-12-15 | 克拉罗科学有限责任公司 | 利用血液中的物理变化和化学变化检测血液中的微生物 |
WO2014019696A1 (en) * | 2012-08-02 | 2014-02-06 | Università degli Studi "G. D'Annunzio" Chieti-Pescara | Transport medium for isolation and identification of helicobacter pylori. |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4443546A (en) * | 1980-07-07 | 1984-04-17 | The Beth Israel Hospital Association | Process and composition for propagating mammalian cells |
GB9929923D0 (en) * | 1999-12-17 | 2000-02-09 | Baldwin Thomas J | Antigen preparations |
US20110281817A1 (en) * | 2007-08-31 | 2011-11-17 | Sugar Industry Innovation Pty. Ltd. | Production of hyaluronic acid |
-
2016
- 2016-11-09 HU HUE16794211A patent/HUE048986T2/hu unknown
- 2016-11-09 ES ES16794211T patent/ES2781373T3/es active Active
- 2016-11-09 EP EP16794211.9A patent/EP3384001B1/en active Active
- 2016-11-09 WO PCT/EP2016/001848 patent/WO2017092842A1/en active Application Filing
- 2016-11-09 JP JP2018528796A patent/JP6923523B2/ja active Active
- 2016-11-09 CN CN201680070630.3A patent/CN108291190A/zh active Pending
- 2016-11-09 US US15/780,872 patent/US20180355306A1/en active Pending
- 2016-11-09 PL PL16794211T patent/PL3384001T3/pl unknown
- 2016-11-09 SI SI201630681T patent/SI3384001T1/sl unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101918582A (zh) * | 2007-11-06 | 2010-12-15 | 克拉罗科学有限责任公司 | 利用血液中的物理变化和化学变化检测血液中的微生物 |
WO2014019696A1 (en) * | 2012-08-02 | 2014-02-06 | Università degli Studi "G. D'Annunzio" Chieti-Pescara | Transport medium for isolation and identification of helicobacter pylori. |
Non-Patent Citations (1)
Title |
---|
I VAN DE RIJN等: "Growth characteristics of group A streptococci in a new chemically defined medium.", 《INFECTION AND IMMUNITY》 * |
Also Published As
Publication number | Publication date |
---|---|
WO2017092842A1 (en) | 2017-06-08 |
EP3384001B1 (en) | 2019-12-25 |
EP3384001A1 (en) | 2018-10-10 |
JP6923523B2 (ja) | 2021-08-18 |
SI3384001T1 (sl) | 2020-04-30 |
HUE048986T2 (hu) | 2020-09-28 |
PL3384001T3 (pl) | 2020-06-29 |
ES2781373T3 (es) | 2020-09-01 |
JP2018535687A (ja) | 2018-12-06 |
US20180355306A1 (en) | 2018-12-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Atlas | Handbook of microbiological media | |
US6046021A (en) | Comparative phenotype analysis of two or more microorganisms using a plurality of substrates within a multiwell testing device | |
US6387651B1 (en) | Comparative phenotype analysis of two or more microorganisms using a plurality of substrates within a microwell device | |
CN108291190A (zh) | 用于检测微生物的化学成分确定的培养基 | |
US20100003740A1 (en) | Chemically defined culture medium for neisseria | |
Hyeon et al. | Roseomonas aerofrigidensis sp. nov., isolated from an air conditioner | |
Ellinghausen Jr | Growth temperatures, virulence, survival, and nutrition of leptospires | |
US8313938B1 (en) | Culture medium for cultivation of microorganisms | |
Margolles et al. | Methods for isolation and recovery of bifidobacteria | |
JP5818787B2 (ja) | マイコバクテリウムの増強された検出のための方法および培地 | |
CN101469340B (zh) | 革兰阳性需氧菌鉴定板及其制备方法 | |
WO2023273019A1 (zh) | 培养基及其制备方法、用其培养脆弱拟杆菌的方法 | |
CN106086159B (zh) | 一种能够同时检测两种粪便污染指示菌的酶底物培养基及其应用 | |
CN102827795B (zh) | 用于沙门氏菌、志贺氏菌和金黄色葡萄球菌复合增菌的培养基及制备方法 | |
JP7030695B2 (ja) | 微生物の増殖または検出のための化学的に明らかな培地 | |
JP5879261B2 (ja) | マイコバクテリウムの増強された検出のための方法および培地 | |
Aydogan et al. | Proposal of Mucilaginibacter galii sp. nov. isolated from leaves of Galium album | |
Chaudhary et al. | Experimental setup for a diffusion bioreactor to isolate unculturable soil bacteria | |
Atmanto et al. | Culture media | |
Cluss et al. | Interaction of albumin and phospholipid: cholesterol liposomes in growth of Mycoplasma spp | |
CN114369557A (zh) | 一种纯化学成分合成rv沙门氏菌增菌液体培养基及配制方法 | |
Kassab | Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt | |
CN107400643A (zh) | 一种巴氏杆菌培养基及其制备鉴别方法 | |
CN117801964A (zh) | 一种快速富集培养真菌的培养基、培养方法及应用 | |
Shigidi | This work was carried out at the Department of Microbiology, Faculty of Veterinary Medicine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180717 |