Amakuru - Gukurikirana urwego pH murwego rwa Bio Pharmaceutical Fermentation

PH electrode igira uruhare runini mugikorwa cya fermentation, cyane cyane ikora mugukurikirana no kugenzura acide na alkaline yumunyu wa fermentation. Mugukomeza gupima agaciro ka pH, electrode ituma igenzura neza ibidukikije bya fermentation. Ubusanzwe pH electrode igizwe na electrode yunvikana hamwe na electrode yerekana, ikora ku ihame ryikigereranyo cya Nernst, igenga ihinduka ryingufu za chimique mubimenyetso byamashanyarazi. Ubushobozi bwa electrode bufitanye isano itaziguye nigikorwa cya hydrogène ion mugisubizo. Agaciro pH kagenwa no kugereranya itandukaniro rya voltage yapimwe nigisubizo gisanzwe cya buffer, cyemerera kalibrasi yukuri kandi yizewe. Ubu buryo bwo gupima butuma amabwiriza ya pH ahamye mugikorwa cya fermentation, bityo agashyigikira ibikorwa byiza bya mikorobe cyangwa selile kandi akanatanga ubuziranenge bwibicuruzwa.

Gukoresha neza electrode ya pH bisaba intambwe nyinshi zo kwitegura, harimo no gukora electrode - mubisanzwe bigerwaho no kwibiza electrode mumazi yatoboye cyangwa igisubizo cya pH 4 - kugirango harebwe neza kandi bipime neza. Kugirango uhuze ibyifuzo byinganda zikoreshwa na fermentation ya biofarmaceutical, pH electrode igomba kwerekana ibihe byihuse byihuse, bisobanutse neza, hamwe nubukomezi mubihe bikomeye byo kuboneza urubyaro nkubushyuhe bwo hejuru (SIP). Ibiranga bituma imikorere yizewe mubidukikije. Kurugero, mugukora aside glutamic, kugenzura neza pH ningirakamaro mugucunga ibipimo byingenzi nkubushyuhe, umwuka wa ogisijeni ushonga, umuvuduko ukabije, na pH ubwayo. Kugenzura neza ibyo bihinduka bigira ingaruka ku musaruro nubwiza bwibicuruzwa byanyuma. Electrode zimwe na zimwe zateye imbere, zirimo ibirahuri byihanganira ubushyuhe bukabije hamwe na sisitemu ya polymer gel yerekanwe mbere, byerekana ihindagurika ridasanzwe mugihe cy'ubushyuhe bukabije hamwe n’umuvuduko ukabije, bigatuma bikenerwa cyane na SIP ikoreshwa muburyo bwo gusembura ibinyabuzima n'ibiribwa. Ikigeretse kuri ibyo, ubushobozi bwabo bwo kurwanya ububi butuma imikorere ihoraho mumyanya itandukanye ya fermentation. Shanghai Boqu Instrument Co., Ltd itanga amahitamo atandukanye ya electrode ihuza, ikongerera abakoresha uburyo bworoshye no guhuza sisitemu.

Kuki gukurikirana pH bikenewe mugihe cya fermentation ya biofarmaceuticals?

Muri fermentation ya biopharmaceutical, kugenzura no kugenzura igihe nyacyo ni ngombwa kugirango umusaruro ugerweho neza no kongera umusaruro nubwiza bwibicuruzwa bigamije nka antibiotike, inkingo, antibodiyite za monoclonal, na enzymes. Muri rusange, igenzura rya pH ritera ibidukikije byiza bya mikorobe cyangwa inyamaswa z’inyamabere - zikora nk "inganda nzima" - gukura no guhuza imiti ivura, bisa nuburyo abahinzi bahindura ubutaka pH bakurikije ibihingwa.

1. Komeza ibikorwa byiza bya selile
Fermentation ishingiye ku ngirabuzimafatizo (urugero, selile CHO) kugirango itange biomolecules igoye. Metabolism ya selile yunvikana cyane kubidukikije pH. Enzymes, itera ibinyabuzima byose byimikorere ya biohimiki, bifite pH optima; gutandukana kururu rwego birashobora kugabanya cyane ibikorwa byimisemburo cyangwa bigatera gutandukana, kubangamira imikorere ya metabolike. Byongeye kandi, gufata intungamubiri zinyuze mu ngirabuzimafatizo - nka glucose, aside amine, hamwe n'umunyu ngenga-biterwa na pH. Urwego rwa pH rwinshi rushobora kubuza intungamubiri kwinjiza, biganisha ku gukura kwa suboptimal cyangwa kutagira metabolike. Byongeye kandi, indangagaciro zikabije za pH zirashobora guhungabanya ubusugire bwa membrane, bikavamo cytoplasmeque yamenetse cyangwa lysis selile.

2. Kugabanya ibicuruzwa biva mu mahanga hamwe no gukuramo imyanda
Mugihe cya fermentation, metabolism selile itanga aside aside cyangwa metabolite yibanze. Kurugero, mikorobe nyinshi zitanga acide kama (urugero, acide lactique, acide acetike) mugihe glucose catabolism, bigatuma igabanuka rya pH. Niba bidakosowe, pH nkeya ibuza gukura kwingirabuzimafatizo kandi irashobora guhindura imitekerereze ya metabolike yerekeza kumihanda idatanga umusaruro, byiyongera kubicuruzwa. Ibicuruzwa byongera umusaruro wa karubone ningufu zingirakamaro ubundi byashyigikira synthesis yibicuruzwa, bityo bikagabanya umusaruro muri rusange. Igenzura ryiza rya pH rifasha gukomeza inzira za metabolike zifuzwa no kunoza imikorere.

3. Menya neza ibicuruzwa bihamye kandi wirinde kwangirika
Ibicuruzwa byinshi bikomoka ku binyabuzima, cyane cyane poroteyine nka antibodiyite za monoclonal na hormone peptide, birashobora guhinduka bitewe n’imiterere ya pH. Hanze ya pH ihagaze neza, izo molekile zirashobora gutandukana, kwegeranya, cyangwa kudakora, bishobora guteza imvura yangiza. Byongeye kandi, ibicuruzwa bimwe na bimwe bikunze kwibasirwa na hydrolysis ya chimique cyangwa kwangirika kwa enzymatique mugihe cya acide cyangwa alkaline. Kugumana pH ikwiye bigabanya kwangirika kwibicuruzwa mugihe cyo gukora, kubungabunga imbaraga numutekano.

4. Hindura uburyo bunoze bwo gukora kandi urebe neza ko buri cyiciro gihoraho
Urebye mu nganda, kugenzura pH bigira ingaruka ku musaruro no mu bukungu. Ubushakashatsi bwimbitse burakorwa kugirango hamenyekane icyerekezo cyiza cya pH kubice bitandukanye bya fermentation - nko gukura kwingirabuzimafatizo no kwerekana ibicuruzwa - bishobora gutandukana cyane. Igenzura rya pH ryemerera gukora icyiciro cyihariye cyo gutezimbere, kugwiza biomass hamwe na titre yibicuruzwa. Byongeye kandi, ibigo bishinzwe kugenzura nka FDA na EMA bisaba kubahiriza byimazeyo imyitozo ngororamubiri myiza (GMP), aho ibipimo bihoraho ari itegeko. pH izwi nka Parameter Critical Process Parameter (CPP), kandi igenzura ryayo rihoraho ryororoka mubyiciro, byemeza umutekano, imikorere, nubwiza bwibicuruzwa bya farumasi.

5. Gukora nk'ikimenyetso cyubuzima bwa fermentation
Inzira ya pH ihinduka itanga ubumenyi bwingenzi kumiterere yumuco. Impinduka zitunguranye cyangwa zitunguranye muri pH zirashobora kwerekana ibimenyetso byanduye, imikorere mibi ya sensor, kugabanuka kwintungamubiri, cyangwa metabolike idasanzwe. Kumenya hakiri kare bishingiye kuri pH bigenda bifasha abakoresha mugihe gikwiye, koroshya gukemura no gukumira gutsindwa kwinshi.

Nigute sensor ya pH igomba guhitamo inzira ya fermentation muri biofarmaceuticals?

Guhitamo icyerekezo cya pH gikwiye kuri fermentation ya biofarmaceutical nicyemezo gikomeye cyubwubatsi kigira ingaruka kubikorwa byokwizerwa, ubuziranenge bwamakuru, ubwiza bwibicuruzwa, no kubahiriza amabwiriza. Ihitamo rigomba kwegerwa kuri gahunda, urebye imikorere ya sensor gusa ariko nanone igahuzwa nibikorwa byose bioprocessing.

1. Ubushyuhe bwo hejuru hamwe no kurwanya umuvuduko
Uburyo bwa biofarmaceutique bukoreshwa muburyo bwo guhinduranya amavuta (SIP), mubisanzwe kuri 121 ° C hamwe na 1-22 yumuvuduko wiminota 20-60. Kubwibyo, sensor ya pH yose igomba kwihanganira guhura nibibazo nkibi nta kunanirwa. Byaba byiza, sensor igomba gupimwa byibuze 130 ° C na 3-4 bar kugirango itange umutekano. Gufunga bikomeye ni ngombwa kugirango wirinde kwinjiza amazi, kumeneka kwa electrolyte, cyangwa kwangirika kwa mashini mugihe cyamagare yubushyuhe.

2. Ubwoko bwa Sensor na sisitemu yerekana
Iki nicyo kintu cyibanze cya tekiniki kigira ingaruka kumutekano muremure, gukenera kubungabunga, no kurwanya nabi.
Ibikoresho bya electrode: Gukomatanya electrode, ihuza ibipimo byombi byo gupima no kwerekana umubiri umwe, byemewe cyane kubera koroshya kwishyiriraho no gukora.
Sisitemu yerekana:
• Amazi yuzuye yuzuye (urugero, igisubizo cya KCl): Itanga igisubizo cyihuse kandi cyukuri ariko gisaba kuzuzwa buri gihe. Mugihe cya SIP, igihombo cya electrolyte gishobora kubaho, kandi amasangano manini (urugero, ceramic frits) akunda gufungwa na poroteyine cyangwa uduce, biganisha ku gusoma no kwizerwa.
• Polymer gel cyangwa ikomeye-yerekana: Kwiyongera cyane muri bioreactors zigezweho. Izi sisitemu zikuraho ibikenerwa byuzuzwa na electrolyte, kugabanya kubungabunga, no kwerekana imiyoboro yagutse (urugero, impeta ya PTFE) irwanya ikosa. Zitanga ituze ryiza hamwe nigihe kirekire cyumurimo mubitangazamakuru bigoye, viscous fermentation media.

3. Urwego rwo gupima no kumenya ukuri
Rukuruzi igomba gukwirakwiza ibikorwa byinshi, mubisanzwe pH 2–12, kugirango ihuze ibyiciro bitandukanye. Urebye ibyiyumvo bya sisitemu y'ibinyabuzima, ibipimo nyabyo bigomba kuba muri ± 0.01 kugeza ± 0.02 pH ibice, bigashyigikirwa nibisohoka cyane.

4. Igihe cyo gusubiza
Igihe cyo gusubiza gikunze gusobanurwa nka t90 - igihe gisabwa kugirango ugere kuri 90% yo gusoma kwa nyuma nyuma yintambwe ihinduka muri pH. Mugihe gel-electrode yo mu bwoko bwa gel irashobora kwerekana gahoro gahoro kuruta iyuzuyemo amazi, mubisanzwe byujuje ibyangombwa bisabwa kugirango fermentation igenzurwe, ikora kumasaha aho kuba amasegonda.

5. Biocompatibilité
Ibikoresho byose bifitanye isano numuco bigomba kuba bidafite uburozi, kutarekura, hamwe nubusembwa kugirango birinde ingaruka mbi kubuzima bwimikorere cyangwa ubwiza bwibicuruzwa. Ibirahuri byabugenewe byabugenewe bikoreshwa mu gutunganya bioprocessing birasabwa kwemeza imiti irwanya imiti hamwe na biocompatibilité.

6. Ibimenyetso bisohoka hamwe ninteruro
• Ibisohoka bisa (mV / pH): Uburyo bwa gakondo ukoresheje uburyo bwo kugereranya kuri sisitemu yo kugenzura. Ikiguzi-cyiza ariko cyoroshye kubangamira amashanyarazi hamwe no kwerekana ibimenyetso kure.
• Ibisohoka muburyo bwa digitale (urugero, MEMS ishingiye cyangwa sensor yubwenge): Yinjiza mikorobe ya elegitoronike kugirango yohereze ibimenyetso bya digitale (urugero, binyuze kuri RS485). Itanga ubudahangarwa bw’urusaku, ishyigikira itumanaho rirerire, kandi igufasha kubika amateka ya kalibrasi, nimero zikurikirana, hamwe n’ibiti byakoreshejwe. Yubahiriza amahame ngenderwaho nka FDA 21 CFR Igice cya 11 kijyanye nibyuma bya elegitoroniki n'umukono, bigatuma irushaho gutoneshwa mubidukikije bya GMP.

7. Imigaragarire yububiko hamwe nuburaro bukingira
Rukuruzi igomba guhuzwa nicyambu cyabigenewe kuri bioreactor (urugero, tri-clamp, isuku ikwiye). Amaboko arinda cyangwa abarinzi birasabwa gukumira ibyangiritse mugihe cyo gukora cyangwa gukora no korohereza gusimburwa byoroshye bitabangamiye ubugumba.