Nhau - Kuongororwa kwemazinga epH muBio Pharmaceutical Fermentation Process

Electrode yepH inoita basa rakakosha mukuita kwekuvirisa, ichinyanya kushanda pakutarisa nekudzora acidity uye alkalinity yemuto wekuvirisa. Nekuramba uchiyera kukosha kwepH, electrode iyi inoita kuti pave nekudzora kwakanyatsojeka nharaunda yekuvirisa. Electrode yepH yakajairika ine electrode inonzwa uye electrode inotarisa, inoshanda pasi peNernst equation, iyo inodzora kushandurwa kwesimba remakemikari kuita masaini emagetsi. Electrode potential ine chekuita zvakananga nebasa rehydrogen ions mumushonga. PH value inoonekwa nekuenzanisa musiyano wevoltage yakayerwa neiyo ye standard buffer solution, zvichibvumira calibration chaiyo uye yakavimbika. Iyi nzira yekuyera inoita kuti pH irambe yakagadzikana mukati mekuita kwekuvirisa, nokudaro ichitsigira hutachiona hwakanaka kana masero uye ichivimbisa mhando yechigadzirwa.

Kushandiswa kwemaelectrode epH nemazvo kunoda matanho akati wandei ekugadzirira, kusanganisira electrode activation—inowanzoitwa nekunyudza electrode mumvura yakasanganiswa kana pH 4 buffer solution—kuti ive nechokwadi chekuti mhinduro yakakwana uye kuyera kwakarurama. Kuti isangane nezvinodiwa zvakasimba zveindasitiri yekuvirisa biopharmaceutical, maelectrode epH anofanira kuratidza nguva yekupindura nekukurumidza, kunyatsojeka, uye kusimba pasi pemamiriro akaomarara akadai se high-temperature steam sterilization (SIP). Hunhu uhu hunogonesa kushanda kwakavimbika munzvimbo dzakachena. Semuenzaniso, mukugadzirwa kweglutamic acid, kutarisa pH kwakanyatsojeka kwakakosha pakudzora maparamendi akakosha akadai setembiricha, oxygen yakanyungudutswa, kumhanya kwekunyepedzera, uye pH pachayo. Kudzora kwakarurama kwezvimiro izvi kunokanganisa zvakananga goho uye mhando yechigadzirwa chekupedzisira. Mamwe maelectrode epH epamusoro, ane magirazi anodzivirira kupisa kwakanyanya uye masystem epolymer gel reference akagadzirwa kare, anoratidza kugadzikana kwakanyanya pasi pemamiriro ekupisa kwakanyanya uye kumanikidzwa, zvichiita kuti anyatsokodzera kushandiswa kweSIP mumaitiro ehupenyu nekudya. Uyezve, kugona kwawo kwakasimba kwekudzivirira kusvibiswa kunobvumira kushanda kwakafanana mumisungo yakasiyana-siyana yekuvirisa. Shanghai Boqu Instrument Co., Ltd. inopa nzira dzakasiyana-siyana dzekubatanidza ma electrode, zvichiita kuti zvive nyore kushandisa uye kubatanidzwa kwemasisitimu kuve nyore.

Sei kuongorora pH kuchikosha panguva yekuvirisa mishonga yemishonga ye biopharmaceuticals?

Mukuvirisa mishonga yemishonga, kutarisa nekudzora pH panguva chaiyo kwakakosha kuti kugadzirwa kubudirire uye kuti goho riwedzere uye kunaka kwezvigadzirwa zvakatarwa zvakaita semishonga inorwisa mabhakitiriya, majekiseni, maantibayotiki emonoclonal, uye maenzyme. Muchidimbu, kudzora pH kunogadzira nzvimbo yakakwana yemuviri yemasero ehutachiona kana emhuka dzinoyamwisa—anoshanda se "mafekitori mupenyu"—kukura nekugadzira mishonga yekurapa, zvakafanana nekushanda kunoita varimi kugadzirisa pH yevhu zvichienderana nezvinodiwa nezvirimwa.

1. Chengetedza mashandiro akanaka emasero
Kuvirisa kunoenderana nemasero mapenyu (semuenzaniso, masero eCHO) kuti agadzire mamorekuru akaomarara. Kugayiwa kwemasero kunonyanya kukanganiswa nepH yezvakatipoteredza. MaEnzayimu, ayo anokonzera maitiro ese emukati memasero, ane pH yakamanikana; kutsauka kubva padanho iri kunogona kuderedza zvakanyanya mashandiro eenzymatic kana kukonzera denaturation, zvichikanganisa mashandiro emetabolism. Pamusoro pezvo, kutorwa kwezvinovaka muviri kuburikidza nemembrane yesero—senge glucose, amino acids, uye inorganic salts—kunoenderana nepH. Mazinga epH asina kunaka anogona kukanganisa kunyudzwa kwezvinovaka muviri, zvichikonzera kukura kusina kunaka kana kusawirirana kwemetabolism. Uyezve, pH yakawandisa inogona kukanganisa kusimba kwemembrane, zvichikonzera kubuda kwe cytoplasmic kana lysis yesero.

2. Deredza kuumbwa kwezvinobva muzvigadzirwa uye marara epasi pevhu
Munguva yekuvirisa, metabolism yemasero inogadzira acidic kana basic metabolites. Semuenzaniso, tupukanana twakawanda tunogadzira organic acids (semuenzaniso, lactic acid, acetic acid) panguva yeglucose catabolism, zvichikonzera kudzikira kwepH. Kana ikasagadziriswa, pH yakaderera inodzivirira kukura kwemasero uye inogona kushandura metabolic flux kuenda kunzira dzisina zvibereko, zvichiwedzera kuunganidzwa kwezvibereko. Izvi zvigadzirwa zvinoshandisa kabhoni nesimba rakakosha izvo zvaizotsigira kugadzirwa kwechigadzirwa, nokudaro zvichideredza goho rose. Kudzora pH kunoshanda kunobatsira kuchengetedza nzira dzinodiwa dzemetabolism uye kunovandudza kushanda zvakanaka kwemaitiro.

3. Iva nechokwadi chekuti chigadzirwa chakasimba uye kudzivirira kuora
Zvigadzirwa zvakawanda zvemishonga, kunyanya mapuroteni akadai sema antibodies e monoclonal uye ma peptide hormones, zvinogona kuchinja chimiro che pH. Kunze kwehuwandu hwazvo hwe pH hwakagadzikana, mamorekuru aya anogona kuchinja, kuungana, kana kusashanda, zvichikonzera kukuvadza. Pamusoro pezvo, zvimwe zvigadzirwa zvinogona kukanganiswa ne chemical hydrolysis kana enzyme degradation pasi pemamiriro e acidic kana alkaline. Kuchengetedza pH yakakodzera kunoderedza kuora kwechigadzirwa panguva yekugadzira, kuchengetedza simba uye kuchengetedzeka.

4. Gadzirisa mashandiro ebasa uye ita shuwa kuti zvese zvinoenderana nezvinodiwa
Kubva pamaonero emaindasitiri, kudzora pH kunokanganisa zvakananga kugadzirwa uye kugara zvakanaka kwehupfumi. Tsvagiridzo yakakura inoitwa kuti paonekwe nzvimbo dzakakodzera dze pH dzezvikamu zvakasiyana zvekuvirisa—zvakadai sekukura kwemasero kana kugadzirwa kwechigadzirwa—izvo zvinogona kusiyana zvakanyanya. Kudzora pH kunochinja kunobvumira kugadziriswa kwezvikamu zvakasiyana, zvichiwedzera kuunganidzwa kwebiomass uye titers dzechigadzirwa. Uyezve, masangano ekutonga akadai seFDA neEMA anoda kutevedzera zvakanyanya Good Manufacturing Practices (GMP), uko parameters dzemaitiro akafanana dzinodikanwa. pH inozivikanwa seCritical Process Parameter (CPP), uye kutarisa kwayo nguva dzose kunovimbisa kudzokororwa kwemhando dzakasiyana, zvichivimbisa kuchengetedzeka, kushanda zvakanaka, uye mhando yezvigadzirwa zvemishonga.

5. Inoshanda sechiratidzo chehutano hwekuvirisa
Kuchinja kwepH kunopa ruzivo rwakakosha pamusoro pemamiriro emuviri wemhuka. Kuchinja kamwe kamwe kana kusingatarisirwi kwepH kunogona kuratidza kusvibiswa, kusashanda zvakanaka kwe sensor, kupera kwezvinovaka muviri, kana kusagadzikana kwe metabolic. Kuonekwa kwekutanga kwakavakirwa pamaitiro epH kunogonesa kupindira kwemushandi panguva, zvichiita kuti zvigadziriswe uye kudzivirira kukundikana kwe batch kunodhura.

Masensa epH anofanira kusarudzwa sei pakuita kwekuvirisa mumishonga yemishonga?

Kusarudza pH sensor yakakodzera yekuvirisa biopharmaceutical chisarudzo chakakosha cheinjiniya chinokanganisa kuvimbika kwemaitiro, kuvimbika kwedata, mhando yechigadzirwa, uye kutevedzera mitemo. Sarudzo yacho inofanira kuitwa nenzira yakarongeka, tichifunga kwete chete nezvekushanda kwesensor asiwo kuenderana nekushanda kwese kwebioprocessing.

1. Kudzivirira kupisa kwakanyanya uye kumanikidzwa
Maitiro emishonga yekurapa anowanzo shandisa in-situ steam sterilization (SIP), kazhinji pa121°C uye 1–2 bar pressure kwemaminitsi 20–60. Saka, chero pH sensor inofanira kutsungirira kusangana nemamiriro ezvinhu akadaro kakawanda pasina kukanganisa. Zvakanaka, sensor inofanira kuverengerwa kweinenge 130°C uye 3–4 bar kuti ipe mukana wekuchengetedza. Kuvhara kwakasimba kwakakosha kudzivirira kupinda kwehunyoro, kubuda kwe electrolyte, kana kukuvara kwemuchina panguva yekupisa.

2. Rudzi rwesensor uye sisitimu yekutarisa
Iyi inyaya huru yekufunga nezvehunyanzvi inokanganisa kugadzikana kwenguva refu, zvinodiwa pakugadzirisa, uye kuramba kusvibiswa.
Kugadzika kwema electrode: Ma electrode akabatanidzwa, anobatanidza zvinhu zvekuyera uye zvekutarisa muchikamu chimwe chete, anoshandiswa zvakanyanya nekuda kwekureruka kwekuiswa uye kubata.
Sisitimu yekutarisa:
• Mhinduro yakazadzwa nemvura (semuenzaniso, mhinduro yeKCl): Inopa mhinduro nekukurumidza uye kunyatsoita zvinhu asi inoda kuzadzazve nguva nenguva. Munguva yeSIP, kurasikirwa kwe electrolyte kunogona kuitika, uye maburi emvura (semuenzaniso, ceramic frits) anogona kuvharika nemapuroteni kana zvidimbu, zvichikonzera kudonha uye kuverenga kusina kuvimbika.
• Polymer gel kana solid-state reference: Zviri kunyanya kufarirwa mu bioreactors dzemazuva ano. Masisitimu aya anobvisa kudiwa kwekudzoreredzwa kwema electrolyte, anoderedza kugadziriswa, uye ane ma liquid junctions akafara (semuenzaniso, PTFE rings) anodzivirira kusvibiswa. Anopa kugadzikana kwakanyanya uye hupenyu hwebasa hurefu mumidziyo yakaoma, ine viscous fermentation.

3. Kuyera uye kururama
Sensor inofanira kushanda munzvimbo dzakasiyana-siyana, kazhinji pH 2–12, kuti ikwane matanho akasiyana-siyana ekuita. Zvichienderana nekunzwa kwemasystem ehupenyu, kurongeka kwekuyera kunofanirwa kunge kuri mukati me ±0.01 kusvika ±0.02 pH units, zvichitsigirwa ne high-resolution signal output.

4. Nguva yekupindura
Nguva yekupindura inowanzotsanangurwa se t90—nguva inodiwa kuti isvike 90% yekuverengwa kwekupedzisira mushure mekuchinja kwenhanho mu pH. Kunyange zvazvo ma electrodes erudzi rwe gel anogona kuratidza kupindura kunononoka zvishoma pane akazadzwa nemvura, anowanzo sangana nezvinodiwa zve fermentation control loops, izvo zvinoshanda paawa imwe neimwe pane masekondi.

5. Kuenderana kwezvinhu zvipenyu
Zvinhu zvese zvinosangana nechinhu chinokura zvinofanira kunge zvisina chepfu, zvisingaburitse mvura, uye zvisina simba kudzivirira migumisiro yakaipa pakugara zvakanaka kwemasero kana kunaka kwechigadzirwa. Magirazi akagadzirwa nenzira dzakasiyana anokurudzirwa kuti ave nechokwadi chekuti makemikari haapindi uye kuti zvinhu zvienderane nezvinodiwa.

6. Kubuda kwechiratidzo uye interface
• Kubuda kweanalog (mV/pH): Nzira yechinyakare inoshandisa analog transmission kuenda ku control system. Inodhura zvishoma asi inogona kukanganiswa ne electromagnetic interference uye signal attenuation padaro refu.
• Zvinobuda mudhijitari (semuenzaniso, masensa akavakirwa paMEMS kana akangwara): Zvinoshandisa ma microelectronics ari mubhodhi kutumira masaini edhijitari (semuenzaniso, kuburikidza neRS485). Zvinopa dziviriro yakanaka yeruzha, zvinotsigira kutaurirana kure, uye zvinogonesa kuchengetwa kwenhoroondo yekuongorora, nhamba dzeserial, uye magwaro ekushandiswa. Zvinoenderana nemitemo yakadai seFDA 21 CFR Chikamu 11 maererano nemarekodhi emagetsi nemasaini, zvichiita kuti zvinyanye kufarirwa munzvimbo dzeGMP.

7. Kuiswa kwenzvimbo uye dzimba dzekudzivirira
Sensor inofanira kunge ichishanda pamwe chete nepaburi rayo pa bioreactor (semuenzaniso, tri-clamp, sanitary fitting). Zvishongo zvekudzivirira kana maguard zvinokurudzirwa kudzivirira kukuvara kwemuchina panguva yekubata kana kushanda uye kuti zvive nyore kutsiva pasina kukanganisa kusabereka.