Iindaba - Ukubeka iliso kwiNqanaba le-Oxygen eNyibilikileyo kwi-Bio Pharmaceutical Fermentation Process

Yintoni i-Oxygen eNyityisiweyo?

I-Oxygen eNyibilikileyo (DO) ibhekisela kwi-oksijini yemolekyuli (O_₂) enyibilikiswa emanzini. Yahlukile kwiiathom zeoksijini ezikhoyo kwiimolekyuli zamanzi (H_₂O), njengoko ikhona emanzini ngendlela yeemolekyuli zeoksijini ezizimeleyo, nokuba zisuka emoyeni okanye ziveliswe ngephotosynthesis zizityalo zasemanzini. Uxinzelelo lwe-DO luphenjelelwa zizinto ezahlukeneyo, kubandakanya ubushushu, ubutyuwa, ukuhamba kwamanzi, kunye nemisebenzi yebhayoloji. Ngaloo ndlela, isebenza njengesalathisi esibalulekileyo sokuvavanya impilo kunye nesimo songcoliseko lweendawo ezihlala emanzini.

Ioksijini echithiweyo idlala indima ebalulekileyo ekukhuthazeni i-microbial metabolism, ifuthe ukuphefumla kweselula, ukukhula, kunye ne-biosynthesis yeemveliso ze-metabolic. Nangona kunjalo, amanqanaba aphezulu e-oksijini enyibilikileyo ayisoloko inenzuzo. Ioksijini egqithisileyo inokukhokelela kwimetabolism eyongezelelekileyo yeemveliso eziqokelelweyo kwaye inokubangela ukusabela okuyityhefu. Amanqanaba e-DO afanelekileyo ayahluka phakathi kweentlobo zebhaktiriya ezahlukeneyo. Umzekelo, ngexesha le-biosynthesis ye-penicillin, i-DO igcinwa malunga ne-30% yokugcwala komoya. Ukuba i-DO yehla iye kwi-zero kwaye ihlala kwelo nqanaba imizuzu emihlanu, ukubunjwa kwemveliso kunokonakala kakhulu. Ukuba le meko iyaqhubeka kangangemizuzu engama-20, umonakalo ongenakulungiseka unokwenzeka.

Okwangoku, ezona zinzwa ze-DO ziqhele ukusetyenziswa zinokulinganisa kuphela ukuzala komoya, endaweni yoxinaniso olupheleleyo lweoksijini enyibilikileyo. Emva kwe-sterilization ye-culture medium, i-aeration kunye nokuvuselela kwenziwa kuze kube yilapho ukufundwa kwenzwa kuzinzile, apho ixabiso libekwe kwi-100% yokugcwala komoya. Imilinganiselo elandelayo ngexesha lenkqubo yokuvutshelwa isekelwe kwesi salathisi. Amaxabiso e-DO apheleleyo akanakumiselwa kusetyenziswa abenzi boluvo abaqhelekileyo kwaye bafuna ubuchule obuphezulu, obufana nepolarography. Nangona kunjalo, imilinganiselo yokugcwalisa umoya yanele ngokubanzi ukubeka iliso kunye nokulawula iinkqubo zokuvutshelwa.

Kwi-fermenter, amanqanaba e-DO anokwahluka kwimimandla eyahlukeneyo. Kwanaxa ufundo oluzinzileyo lufunyenwe ngaxeshanye, ukuguquguquka kusenokubakho kumajelo athile enkcubeko. Izivundisi ezinkulu zidla ngokubonisa umahluko omkhulu wendawo kumanqanaba e-DO, anokuchaphazela kakhulu ukukhula kwentsholongwane kunye nemveliso. Ubungqina bovavanyo bubonise ukuba, nangona i-avareji inqanaba le-DO linokuba yi-30%, ukusebenza kokuvundiswa phantsi kweemeko eziguquguqukayo kuphantsi kakhulu kuneemeko ezizinzileyo. Ke ngoko, kwi-scale-up of fermenters-ngaphaya kokuqwalaselwa kwejometri kunye nokufana kwamandla-ukunciphisa ukuhluka kwe-DO yendawo kuhlala kuyinjongo ephambili yophando.

Kutheni i-Dissolved Oxygen Monitoring ibalulekile kwi-Biopharmaceutical Fermentation?

1. Ukugcina iNdawo yokuKhula ngokuLungileyo kwiiMicroorganisms okanye iiSeli
Ukuvutshelwa kweshishini ngokuqhelekileyo kubandakanya ii-microorganisms ze-aerobic, ezifana ne-Escherichia coli kunye negwele, okanye iiseli ezincancisayo, ezifana neeseli ze-Chinese Hamster Ovary (CHO). Ezi seli zisebenza "njengabasebenzi" ngaphakathi kwenkqubo yokuvubela, zifuna ioksijini yokuphefumla kunye nomsebenzi we-metabolic. Ioksijini isebenza njengomamkeli we-electron we-terminal kwi-aerobic respiration, eyenza ukuveliswa kwamandla ngendlela ye-ATP. Ukungonelanga kweoksijini kunokukhokelela ekufuthaniseleni kweeseli, ukubanjwa kokukhula, okanye ukufa kweeseli, ekugqibeleni kubangele ukusilela kokuvuthela. Ukubeka iliso kumanqanaba e-DO kuqinisekisa ukuba ugxininiso lwe-oksijini luhlala luphakathi koluhlu olufanelekileyo lokukhula kweeseli okuqhubekayo kunye nokusebenza.

2. Ukuqinisekisa uHlanganiso oluLungileyo lweeMveliso ekujoliswe kuzo
Injongo ye-biopharmaceutical fermentation ayikuko nje ukukhuthaza ukwanda kweeseli kodwa kukwenza kube lula ukudityaniswa okusebenzayo kweemveliso ezinqwenelekayo, ezifana ne-insulin, izilwa-buhlungu ze-monoclonal, izitofu, kunye nee-enzymes. Ezi ndlela ze-biosynthetic zihlala zifuna igalelo lamandla amakhulu, ngokuyintloko asuka kukuphefumula kwe-aerobic. Ukongezelela, ezininzi iinkqubo ze-enzymatic ezibandakanyekayo kwimveliso yemveliso zixhomekeke ngokuthe ngqo kwi-oksijini. Ukunqongophala kweoksijini kunokuphazamisa okanye kunciphise ukusebenza kakuhle kwezi ndlela.

Ngaphezu koko, amanqanaba e-DO asebenza njengophawu lolawulo. Zombini ugxininiso lwe-DO oluphezulu kakhulu kunye nolusezantsi lunokuthi:
- Ukutshintsha iindlela zemetabolism zeselula, umzekelo, ukusuka kwi-aerobic respiration ukuya kwi-anaerobic fermentation engasebenzi kakuhle.
- Qalisa iimpendulo zoxinzelelo lweselula, ezikhokelela ekuvelisweni kweemveliso ezingafunekiyo.
- Ukuphembelela amanqanaba okubonakaliswa kweeproteni zangaphandle.

Ngokulawula ngokuchanekileyo amanqanaba e-DO kumanqanaba ahlukeneyo okuvundiswa, kunokwenzeka ukukhokela i-metabolism yeselula ukuya ekudibaneni kwemveliso ekujoliswe kuyo, ngaloo ndlela kuzuzwe ukuxinana okuphezulu kunye nemveliso ephezulu yokuvubela.

Intshayelelo yeTshati yokuHamba kwamanzi kwiBio Pharmaceuticals

3. Ukuthintela ukunqongophala kweoksijini okanye uKugqithisela
Ukunqongophala kweoksijini (hypoxia) kunokuba neziphumo ezibi:
- Ukukhula kweeseli kunye nokuhlanganiswa kwemveliso kuyeka.
- I-Metabolism itshintshela kwiindlela ze-anaerobic, ezikhokelela ekuqokeleleni kwee-asidi eziphilayo ezifana ne-lactic acid kunye ne-acetic acid, ethoba i-pH ye-culture medium kwaye inokutyhefa iiseli.
- I-hypoxia ende inokubangela umonakalo ongenakuguqulwa, kunye nokubuyiswa kungagqibekanga nangemva kokuba ukunikezelwa kwe-oksijini kubuyiselwe.

Ioksijini egqithisileyo (i-supersaturation) nayo ibeka umngcipheko:
- Inokubangela uxinzelelo lwe-oxidative kunye nokwakhiwa kweentlobo ze-oksijini esebenzayo (ROS), ezonakalisa i-membrane zeseli kunye ne-biomolecules.
- Ukungena komoya okugqithisileyo kunye nokuphazamiseka kwandisa ukusetyenziswa kwamandla kunye neendleko zokusebenza, okukhokelela kwinkcitho yobutyebi obungeyomfuneko.

4. NjengeParameter eBalulekileyo yokuJonga i-Real-Time Monitoring kunye noLawulo lweeMpendulo

I-DO yiparamitha yexesha langempela, eqhubekayo, kunye nebanzi ebonisa iimeko zangaphakathi zenkqubo yokuvutshelwa. Utshintsho kumanqanaba e-DO lunokubonakalisa ngovakalelo iimeko ezahlukeneyo zomzimba kunye nokusebenza:
- Ukukhula ngokukhawuleza kweeseli kwandisa ukusetyenziswa kwe-oksijini, kubangela ukuba amanqanaba e-DO ehle.
- Ukutshatyalaliswa kwe-substrate okanye inhibition kunciphisa imetabolism, ukunciphisa ukusetyenziswa kwe-oksijini kunye nokubangela ukuba amanqanaba e-DO anyuke.
- Ungcoliseko ngama microorganisms angaphandle kuguqula ipateni yokusetyenziswa kweoksijini, okukhokelela ekuguquguqukeni okungaqhelekanga kwe-DO kunye nokusebenza njengophawu lwesilumkiso kwangoko.
- Ukungasebenzi kakuhle kwezixhobo, ezinjengokusilela kwe-stirrer, ukuvaleka kombhobho wokungenisa umoya, okanye ukungcola kwesihluzi, nako kunokukhokelela ekuziphatheni okungaqhelekanga kwe-DO.

Ngokudibanisa uhlolo lwe-DO lwexesha lokwenyani kwinkqubo yolawulo lwengxelo ezenzekelayo, ulawulo oluchanekileyo lwamanqanaba e-DO lunokufezekiswa ngohlengahlengiso oluguqukayo lwezi parameters zilandelayo:
- Isantya esishukumisayo: Ukunyusa isantya sonyusa unxibelelwano lwerhasi-elulwelo ngokuqhekeza amaqamza, ngaloo ndlela kuphuculwe ukusebenza kakuhle kokuhanjiswa kweoksijini. Le yeyona ndlela isetyenziswa ngokuqhelekileyo nesebenzayo.
- Izinga lomoya: Ukulungelelanisa izinga lokuhamba okanye ukwakheka kwerhasi yokungena (umzekelo, ukunyusa umlinganiselo womoya okanye ioksijini esulungekileyo).
- Uxinzelelo lwetanki: Ukunyusa uxinzelelo lonyusa uxinzelelo lweoksijini, ngaloo ndlela kuphucula ukunyibilika.
- Ubushushu: Ukwehlisa ubushushu kwandisa ukunyibilika kweoksijini kwindawo yenkcubeko.

Iingcebiso zemveliso ye-BOQU yokubeka iliso kwi-intanethi ye-biological fermentation: