Nkhani - Kuyang'anira Ma Level pH mu Bio Pharmaceutical Fermentation Process

Ma elekitirodi a pH amagwira ntchito yofunika kwambiri pakuwotchera, makamaka kuyang'anira ndi kuwongolera acidity ndi alkalinity ya msuzi wowotchera. Poyesa mosalekeza kuchuluka kwa pH, ma elekitirodi amatha kuwongolera bwino malo omwe nayonso mphamvu. Ma elekitirodi wanthawi zonse a pH amakhala ndi ma elekitirodi ozindikira komanso ma elekitirodi, omwe amagwira ntchito motsatira ndondomeko ya Nernst equation, yomwe imayang'anira kusandutsidwa kwamphamvu kwamankhwala kukhala ma siginecha amagetsi. Mphamvu ya elekitirodi imagwirizana mwachindunji ndi ntchito ya ayoni ya haidrojeni mu yankho. Phindu la pH limatsimikiziridwa poyerekeza kusiyana kwa voteji yoyezedwa ndi njira yokhazikika ya bafa, kulola kuwongolera kolondola komanso kodalirika. Njira yoyezera iyi imatsimikizira kukhazikika kwa pH mu nthawi yonse yowotchera, potero kumathandizira kuti ma microbial kapena ma cell awonetsetse kuti zinthu zili bwino.

Kugwiritsa ntchito bwino ma electrode a pH kumafuna njira zingapo zokonzekera, kuphatikiza kuyambitsa ma elekitirodi - komwe kumachitika mwa kumiza ma elekitirodi m'madzi osungunuka kapena njira ya pH 4 buffer - kuti muwonetsetse kuyankha koyenera komanso kuyeza kwake. Kuti akwaniritse zofuna zamakampani opangira mphamvu ya biopharmaceutical fermentation, ma elekitirodi a pH amayenera kuwonetsa nthawi yoyankhira mwachangu, kulondola kwambiri, komanso kulimba pansi pamikhalidwe yovuta kwambiri yoletsa kubereka monga kutentha kwamphamvu kwa nthunzi (SIP). Makhalidwewa amathandizira kugwira ntchito modalirika m'malo osabala. Mwachitsanzo, popanga glutamic acid, kuwunika kwa pH molondola ndikofunikira pakuwongolera magawo ofunikira monga kutentha, mpweya wosungunuka, kuthamanga kwa chipwirikiti, ndi pH yokha. Kuwongolera kolondola kwa zosinthazi kumakhudza mwachindunji zokolola komanso mtundu wa chinthu chomaliza. Maelekitirodi ena apamwamba a pH, okhala ndi nembanemba yagalasi yosagwira kutentha kwambiri komanso makina owonetsera gel opumira a polima, amawonetsa kukhazikika kwapadera pakutentha kwambiri komanso kupanikizika, zomwe zimawapangitsa kukhala oyenera kugwiritsa ntchito SIP pazachilengedwe komanso zowotchera chakudya. Kuonjezera apo, mphamvu zawo zotsutsana ndi zowonongeka zimawathandiza kuti azigwira ntchito mosasinthasintha pakati pa mitundu yosiyanasiyana ya fermentation broths. Shanghai Boqu Instrument Co., Ltd. imapereka zosankha zingapo zolumikizira ma elekitirodi, kumathandizira kusavuta kwa ogwiritsa ntchito komanso kusinthasintha kwa kaphatikizidwe kazinthu.

Chifukwa chiyani kuwunika kwa pH kuli kofunikira panthawi ya fermentation ya biopharmaceuticals?

Mu biopharmaceutical fermentation, kuyang'anira nthawi yeniyeni ndi kuwongolera pH ndikofunikira kuti apange bwino komanso kuti achulukitse zokolola komanso mtundu wazinthu zomwe mukufuna monga maantibayotiki, katemera, ma antibodies monoclonal, ndi ma enzyme. M'malo mwake, kuwongolera kwa pH kumapangitsa kuti pakhale malo abwino kwambiri achilengedwe a ma cell aang'ono kapena ma mammalian - omwe amagwira ntchito ngati "mafakitale amoyo" - kuti akule ndi kupanga mankhwala ochizira, ofanana ndi momwe alimi amasinthira nthaka pH malinga ndi zomwe mbewu zimafunikira.

1. Pitirizani kuchita bwino kwambiri ma cell
Fermentation imadalira maselo amoyo (mwachitsanzo, ma cell O) kuti apange ma biomolecules ovuta. Ma cell metabolism amakhudzidwa kwambiri ndi pH ya chilengedwe. Ma enzymes, omwe amathandizira zonse zomwe zimachitika m'magazi am'magazi, amakhala ndi pH yocheperako; kupatuka kuchokera pamtunduwu kumatha kuchepetsa kwambiri ntchito ya enzymatic kapena kuyambitsa kusokoneza, kusokoneza kagayidwe kachakudya. Kuphatikiza apo, kutengeka kwa michere kudzera mu nembanemba ya cell - monga shuga, ma amino acid, ndi mchere wachilengedwe - kumadalira pH. Mulingo wocheperako wa pH ukhoza kulepheretsa kuyamwa kwa michere, zomwe zimabweretsa kukula kosakwanira kapena kusalinganika kwa metabolic. Kuphatikiza apo, ma pH apamwamba amatha kusokoneza kukhulupirika kwa membrane, zomwe zimapangitsa kutayikira kwa cytoplasmic kapena cell lysis.

2. Chepetsani mapangidwe azinthu ndi zinyalala zapansi
Pakuwola, ma cell metabolism amapanga acidic kapena Basic metabolites. Mwachitsanzo, tinthu tating'onoting'ono tambiri timatulutsa ma organic acid (mwachitsanzo, lactic acid, acetic acid) panthawi ya glucose catabolism, zomwe zimapangitsa kutsika kwa pH. Ngati sichinasinthidwe, pH yotsika imalepheretsa kukula kwa maselo ndipo imatha kusintha kusintha kwa kagayidwe kachakudya kupita ku njira zopanda phindu, ndikuwonjezera kudzikundikira kwazinthu. Zogulitsazi zimawononga zinthu zamtengo wapatali za carbon ndi mphamvu zomwe zikanathandizira kaphatikizidwe kazinthu zomwe zikufuna, motero zimachepetsa zokolola zonse. Kuwongolera bwino kwa pH kumathandizira kuti njira za metabolic zisungidwe ndikuwongolera magwiridwe antchito.

3. Onetsetsani kukhazikika kwazinthu ndikupewa kuwonongeka
Mankhwala ambiri a biopharmaceutical, makamaka mapuloteni monga monoclonal antibodies ndi mahomoni a peptide, amatha kusintha kusintha kwa pH. Kunja kwa pH yamitundu yokhazikika, mamolekyuwa amatha kusinthika, kuphatikizika, kapena kusagwira ntchito, zomwe zimatha kupanga mafunde owopsa. Kuphatikiza apo, zinthu zina zimatha kukhala ndi hydrolysis yamankhwala kapena kuwonongeka kwa enzymatic pansi pa acidic kapena zamchere. Kusunga pH yoyenera kumachepetsa kuwonongeka kwa zinthu panthawi yopanga, kusunga potency ndi chitetezo.

Malingaliro a kampani Bio Pharmaceuticals

4. Konzani bwino ntchito ndikuwonetsetsa kuti batch-to-batch sagwirizana
Kuchokera kumakampani, kuwongolera kwa pH kumakhudza kwambiri zokolola komanso kuthekera kwachuma. Kafukufuku wozama amachitidwa kuti azindikire malo abwino a pH a magawo osiyanasiyana a fermentation-monga kukula kwa maselo motsutsana ndi kafotokozedwe kazinthu-zomwe zingasiyane kwambiri. Kuwongolera kwamphamvu kwa pH kumalola kukhathamiritsa mwachindunji, kukulitsa kudzikundikira kwa biomass ndi titers zazinthu. Kuphatikiza apo, mabungwe olamulira monga FDA ndi EMA amafunikira kutsatira mosamalitsa Njira Zabwino Zopangira Zinthu (GMP), pomwe magawo osasinthika amafunikira. PH imadziwika kuti Critical Process Parameter (CPP), ndipo kuwunika kwake kosalekeza kumatsimikizira kuberekana m'magulu onse, kutsimikizira chitetezo, mphamvu, komanso mtundu wazinthu zamankhwala.

5. Kutumikira monga chizindikiro cha nayonso mphamvu thanzi
Kusintha kwa pH kumapereka chidziwitso chofunikira pa chikhalidwe cha chikhalidwe. Kusintha kwadzidzidzi kapena kosayembekezereka kwa pH kumatha kuwonetsa kuipitsidwa, kusagwira ntchito kwa sensor, kuchepa kwa michere, kapena kusokonezeka kwa metabolic. Kuzindikira koyambirira kutengera kusintha kwa pH kumathandizira kulowererapo kwanthawi yake, kumathandizira kuthana ndi mavuto komanso kupewa kulephera kwamagulu okwera mtengo.

Kodi masensa a pH ayenera kusankhidwa bwanji panjira yowotchera mu biopharmaceuticals?

Kusankha sensa yoyenera ya pH ya kuwira kwa biopharmaceutical ndi lingaliro lofunikira laukadaulo lomwe limakhudza kudalirika kwa ndondomeko, kukhulupirika kwa data, mtundu wazinthu, komanso kutsata malamulo. Kusankhidwa kuyenera kuyanjidwa mwadongosolo, osaganizira magwiridwe antchito a sensor komanso kuyanjana ndi kayendedwe ka bioprocessing.

1. Kutentha kwakukulu ndi kukana kupanikizika
Njira za biopharmaceutical nthawi zambiri zimagwiritsa ntchito in-situ steam sterilization (SIP), nthawi zambiri pa 121 ° C ndi 1-2 bar pressure kwa mphindi 20-60. Chifukwa chake, sensor iliyonse ya pH iyenera kupirira kuwonetsedwa mobwerezabwereza kuzinthu zotere popanda kulephera. Moyenera, sensa iyenera kuvoteredwa osachepera 130 ° C ndi 3-4 bar kuti ipereke malire achitetezo. Kusindikiza mwamphamvu ndikofunikira kuti muteteze kulowetsedwa kwa chinyezi, kutayikira kwa electrolyte, kapena kuwonongeka kwamakina panthawi yanjinga yotentha.

2. Mtundu wa sensa ndi dongosolo lolozera
Uku ndiye kuwunika kwaukadaulo komwe kumakhudza kukhazikika kwanthawi yayitali, zosowa zosamalira, komanso kukana kusokoneza.
Kukonzekera kwa Electrode: Maelekitirodi ophatikizika, kuphatikiza zinthu zonse zoyezera ndi zofotokozera m'thupi limodzi, amavomerezedwa kwambiri chifukwa chosavuta kukhazikitsa ndi kusamalira.
Reference System:
• Maumboni odzaza madzi (monga, yankho la KCl): Amapereka mayankho ofulumira komanso olondola kwambiri koma amafuna kuwonjezeredwa nthawi ndi nthawi. Panthawi ya SIP, kutayika kwa electrolyte kumatha kuchitika, ndipo ma porous junctions (mwachitsanzo, ma ceramic frits) amatha kutsekeka ndi mapuloteni kapena tinthu tating'onoting'ono, zomwe zimatsogolera ku kuwerenga kosadalirika.
• Gelisi ya polima kapena mafotokozedwe olimba: Amakondedwa kwambiri ndi ma bioreactor amakono. Machitidwewa amachotsa kufunika kwa electrolyte replenishment, kuchepetsa kukonza, ndi mawonekedwe amadzimadzi ambiri (monga PTFE mphete) amene amakana kuipitsa. Amapereka kukhazikika kwapamwamba komanso moyo wautali wautumiki m'ma media ovuta, a viscous fermentation.

3. Muyeso wosiyanasiyana ndi kulondola
Kachipangizo kameneka kamayenera kuphimba ntchito zambiri, nthawi zambiri pH 2-12, kuti igwirizane ndi magawo osiyanasiyana. Chifukwa cha kukhudzika kwa machitidwe achilengedwe, kulondola kwa kuyeza kuyenera kukhala mkati mwa ± 0.01 mpaka ± 0.02 pH mayunitsi, mothandizidwa ndi kutulutsa kwamphamvu kwamphamvu.

4. Nthawi yoyankhira
Nthawi yoyankhira nthawi zambiri imatanthauzidwa kuti t90-nthawi yofunikira kuti ifike 90% ya kuwerenga komaliza pambuyo pa kusintha kwa pH. Ngakhale ma elekitirodi amtundu wa gel amatha kuyankha pang'onopang'ono kusiyana ndi omwe amadzazidwa ndi madzi, nthawi zambiri amakwaniritsa zofunikira za malupu oletsa kuwira, omwe amagwira ntchito pa ola limodzi osati masekondi.

5. Biocompatibility
Zipangizo zonse zomwe zimakhudzana ndi chikhalidwe cha chikhalidwe ziyenera kukhala zopanda poizoni, zopanda leaching, komanso zopanda mphamvu kuti zipewe zotsatira zoyipa zama cell kapena mtundu wazinthu. Magalasi apadera opangidwa kuti agwiritse ntchito bioprocessing akulimbikitsidwa kuti atsimikizire kukana kwa mankhwala komanso kuyanjana kwachilengedwe.

6. Kutulutsa kwa chizindikiro ndi mawonekedwe
• Kutulutsa kwaanalogi (mV / pH): Njira yachikale yogwiritsira ntchito kutumiza kwa analogi ku dongosolo lolamulira. Zotsika mtengo koma zosatetezeka kusokonezedwa ndi ma electromagnetic komanso kutsika kwa ma sign pamtunda wautali.
• Kutulutsa kwa digito (monga, masensa opangidwa ndi MEMS kapena anzeru): Zimaphatikiza ma microelectronics omwe ali pamtunda kuti atumize ma siginecha a digito (mwachitsanzo, kudzera pa RS485). Amapereka chitetezo chokwanira chaphokoso, amathandizira kulumikizana kwakutali, ndikusunga mbiri yoyeserera, manambala amtundu, ndi zolemba zogwiritsira ntchito. Imatsata miyezo yoyendetsera monga FDA 21 CFR Gawo 11 lokhudza ma rekodi apakompyuta ndi siginecha, ndikupangitsa kuti ikhale yokondedwa kwambiri m'malo a GMP.

7. Kuyika mawonekedwe ndi nyumba zoteteza
Sensa iyenera kukhala yogwirizana ndi doko lokhazikitsidwa pa bioreactor (mwachitsanzo, tri-clamp, sanitary fittting). Manja odzitchinjiriza kapena alonda amalangizidwa kuti apewe kuwonongeka kwamakina panthawi yogwira kapena pogwira ntchito ndikuthandizira kusintha kosavuta popanda kuwononga sterility.