Izindaba - Ukuqapha Amazinga Omoya Oyincibilikisiwe Kunqubo Ye-Bio Pharmaceutical Fermentation

Yini I-Oxygen Echithiwe?

I-Oxygen Encibilikisiwe (DO) ibhekisela kumoya-mpilo wamangqamuzana (O_₂) encibilika emanzini. Ihlukile kuma-athomu omoya-mpilo akhona kuma-molecule amanzi (H_₂O), njengoba ukhona emanzini ngendlela yama-molecule omoya-mpilo azimele, avela emkhathini noma akhiqizwe yi-photosynthesis izitshalo zasemanzini. Ukugxila kwe-DO kuthonywa izici ezihlukahlukene, okuhlanganisa izinga lokushisa, usawoti, ukugeleza kwamanzi, nemisebenzi yebhayoloji. Ngakho-ke, isebenza njengenkomba ebalulekile yokuhlola isimo sezempilo nokungcoliswa kwezindawo zasemanzini.

I-oxygen encibilikisiwe idlala indima ebalulekile ekuthuthukiseni i-microbial metabolism, ibe nomthelela ekuphefumuleni kwamangqamuzana, ukukhula, kanye ne-biosynthesis yemikhiqizo ye-metabolic. Nokho, amazinga aphezulu omoya-mpilo oncibilikile awazuzi ngaso sonke isikhathi. I-oxygen eyengeziwe ingase iholele ekuqhubekeleni phambili kwemetabolism yemikhiqizo enqwabelene futhi kubangele ukusabela okunobuthi. Amazinga e-DO alungile ayahluka phakathi kwezinhlobo zamabhaktheriya ahlukene. Isibonelo, ngesikhathi se-biosynthesis ye-penicillin, i-DO ivamise ukugcinwa ekugcwalisweni komoya okungaba ngu-30%. Uma i-DO yehlela kuqanda futhi ihlala kulelo zinga imizuzu emihlanu, ukwakheka komkhiqizo kungakhinyabezeka kakhulu. Uma lesi simo siqhubeka imizuzu engu-20, kungase kwenzeke umonakalo ongenakulungiseka.

Njengamanje, izinzwa ze-DO ezisetshenziswa kakhulu zingakala kuphela ukugcwala komoya okuhlobene, kunokuhlanganisa okuphelele komoyampilo oncibilikisiwe. Ngemuva kokufakwa inzalo kwe-culture medium, i-aeration kanye nokunyakazisa kwenziwa kuze kube yilapho ukufundwa kwezinzwa kuzinza, lapho inani libekwe ku-100% saturation emoyeni. Izilinganiso ezilandelayo phakathi nenqubo yokuvutshelwa zisekelwe kulesi sithenjwa. Amanani e-DO aphelele awakwazi ukunqunywa kusetshenziswa izinzwa ezijwayelekile futhi adinga amasu athuthuke kakhulu, njenge-polarography. Nokho, izilinganiso zokugcwala komoya ngokuvamile zanele ukuqapha nokulawula izinqubo zokuvutshelwa.

Ngaphakathi kwe-fermenter, amazinga e-DO angahluka ezifundeni ezahlukene. Ngisho noma ukufunda okuzinzile kutholakala ngesikhathi esisodwa, ukushintshashintsha kungase kwenzeke emithonjeni ethile yezamasiko. Ama-fermenters amakhulu avame ukukhombisa ukuhluka okukhulu kwendawo kumazinga e-DO, okungaba nomthelela omkhulu ekukhuleni kwe-microbial kanye nokukhiqiza. Ubufakazi bokuhlola bubonise ukuthi, nakuba izinga elijwayelekile le-DO lingase libe ngu-30%, ukusebenza kokuvutshelwa ngaphansi kwezimo ezishintshayo kuphansi ngokuphawulekayo kunangaphansi kwezimo ezinzile. Ngakho-ke, ekukhushulweni kwe-fermenters-ngaphezu kokucatshangelwa kwejometri nokufana kwamandla-ukunciphisa ukuhluka kwe-DO yendawo kuhlala kuyinhloso yocwaningo ebalulekile.

Kungani I-Dissolved Oxygen Monitoring Ibalulekile ku-Biopharmaceutical Fermentation?

1. Ukugcina Imvelo Ekahle Yokukhula Kwezinto Ezincane Ezincane noma Amaseli
Ukuvutshelwa kwemboni kuvame ukubandakanya ama-microorganisms e-aerobic, afana ne-Escherichia coli ne-yeast, noma amaseli ezilwane ezincelisayo, njengamaseli e-Chinese Hamster Ovary (CHO). Lawa maseli asebenza "njengezisebenzi" ngaphakathi kwesistimu yokuvutshelwa, edinga umoya-mpilo wokuphefumula kanye nomsebenzi wokugaya ukudla. Umoya-mpilo usebenza njengesamukeli se-electron esibulalayo ekuphefumuleni kwe-aerobic, okwenza ukukhiqizwa kwamandla ngendlela ye-ATP. Ukungatholakali komoyampilo okwanele kungaholela ekucindezelekeni kwamaselula, ekuboshweni kokukhula, noma ngisho nokufa kwamangqamuzana, ekugcineni kubangele ukwehluleka ukuvutshelwa. Ukuqapha amazinga e-DO kuqinisekisa ukuthi ukugxila komoyampilo kuhlala ngaphakathi kwebanga elifanele lokukhula kwamaseli okuqhubekayo nokusebenza.

2. Ukuqinisekisa Ukuhlanganiswa Okuphumelelayo Kwemikhiqizo Eqondiwe
Inhloso yokuvutshelwa kwe-biopharmaceutical akukhona nje ukukhuthaza ukwanda kwamangqamuzana kodwa ukusiza ukuhlanganiswa okuphumelelayo kwemikhiqizo eqondiwe efiselekayo, njenge-insulin, amasosha omzimba e-monoclonal, imigomo, nama-enzyme. Lezi zindlela ze-biosynthetic ngokuvamile zidinga ukufaka amandla amakhulu, ngokuyinhloko atholakala ekuphefumuleni kwe-aerobic. Ukwengeza, izinhlelo eziningi ze-enzymatic ezihilelekile ekuhlanganiseni komkhiqizo zincike ngokuqondile kumoya-mpilo. Ukuntuleka komoyampilo kungase kuphazamise noma kunciphise ukusebenza kahle kwalezi zindlela.

Ngaphezu kwalokho, amazinga e-DO asebenza njengesignali yokulawula. Kokubili ukugxila kwe-DO okuphezulu kakhulu nokuphansi kunga:
- Shintsha izindlela ze-metabolic metabolism, isibonelo, ukusuka ekuphefumuleni kwe-aerobic kuye ekuvubeleni okunganele kwe-anaerobic.
- Qalisa izimpendulo zengcindezi yeselula, okuholela ekukhiqizweni kwemikhiqizo engathandeki.
- Ithonya amazinga enkulumo yamaprotheni angaphandle.

Ngokulawula ngokunembile amazinga e-DO ezigabeni ezihlukene zokuvutshelwa, kungenzeka ukuqondisa umzimba weselula ekuhlanganiseni okuphezulu komkhiqizo oqondiwe, ngaleyo ndlela kuzuzwe ukuvutshelwa kokuminyana okuphezulu kanye nesivuno esikhulu.

Isingeniso Seshadi Lokugeleza Kwamanzi le-Bio Pharmaceuticals

3. Ukuvimbela Ukuntuleka Kweoksijini Noma Ukweqisa
Ukuntuleka komoyampilo (hypoxia) kungaba nemiphumela emibi kakhulu:
- Ukukhula kwamaseli nokuhlanganiswa komkhiqizo kuyayeka.
- I-Metabolism ishintshela ezindleleni ze-anaerobic, okuholela ekuqongeleleni ama-acids ephilayo njenge-lactic acid ne-acetic acid, ehlisa i-pH yendawo yesiko futhi engase ibe nobuthi kumaseli.
- I-hypoxia ende ingabangela umonakalo ongalungiseki, nokululama kungaphelele ngisho nangemva kokubuyiselwa komoyampilo.

I-oxygen eyengeziwe (i-supersaturation) nayo ibeka izingozi:
- Ingabangela ukucindezeleka kwe-oxidative kanye nokwakheka kwezinhlobo ze-oxygen esebenzayo (ROS), ezilimaza ulwelwesi lwamangqamuzana nama-biomolecules.
- Ukungena komoya okweqile kanye nokuyaluza kwandisa ukusetshenziswa kwamandla kanye nezindleko zokusebenza, okuholela ekumoshweni kwezinsiza ngokungadingekile.

4. Njengepharamitha Ebalulekile Yokuqapha Kwesikhathi Sangempela Nokulawula Kwempendulo

I-DO ipharamitha yesikhathi sangempela, eqhubekayo, nephelele ebonisa izimo zangaphakathi zesistimu yokuvutshelwa. Izinguquko kumazinga e-DO zingakhombisa ngokuzwela izimo ezihlukahlukene zomzimba nezokusebenza:
- Ukukhula kwamangqamuzana okusheshayo kukhulisa ukusetshenziswa komoyampilo, okwenza amazinga e-DO ehle.
- Ukuncipha kwe-substrate noma ukuvimbela kubambezela umzimba, kunciphisa ukusetshenziswa komoyampilo futhi kubangela amazinga e-DO akhuphuke.
- Ukungcoliswa ama-microorganisms angaphandle kushintsha iphethini yokusetshenziswa komoyampilo, okuholela ekuguquguqukeni okungavamile kwe-DO futhi isebenze njengesignali yesixwayiso sangaphambi kwesikhathi.
- Ukungasebenzi kahle kwezisetshenziswa, njengokuhluleka kwe-stirrer, ukuvaleka kwamapayipi okungenisa umoya, noma ukonakala kwesihlungi, nakho kungaholela ekuziphatheni kwe-DO okungavamile.

Ngokuhlanganisa ukuqapha kwe-DO kwesikhathi sangempela ohlelweni oluzenzakalelayo lokulawula impendulo, ukulawulwa okunembile kwamazinga e-DO kungafinyelelwa ngokulungiswa okuguquguqukayo kwamapharamitha alandelayo:
- Isivinini esinyakazayo: Ukwenyusa isivinini kuthuthukisa ukuthintana koketshezi lwegesi ngokuhlephula amabhamuza, ngaleyo ndlela kuthuthukiswe ukusebenza kahle kokudlulisa umoya-mpilo. Lena indlela evame ukusetshenziswa futhi ephumelelayo.
- Izinga lokungenisa umoya: Ukulungisa izinga lokugeleza noma ukwakheka kwegesi engenisa umoya (isb, ukukhulisa ingxenye yomoya noma umoya-mpilo omsulwa).
- Ukucindezela kwethangi: Ukucindezela okuphakamisayo kwandisa ukucindezela kwengxenye ye-oksijini, ngaleyo ndlela kuthuthukise ukuncibilika.
- Izinga lokushisa: Ukwehlisa izinga lokushisa kwandisa ukuncibilika komoyampilo endaweni yesiko.

Izincomo zomkhiqizo we-BOQU zokuqapha ku-inthanethi ukuvutshelwa kwebhayoloji: