Xov Xwm - Kev Saib Xyuas Cov Qib pH hauv Cov Txheej Txheem Fermentation Bio Pharmaceutical

Lub pH electrode ua lub luag haujlwm tseem ceeb hauv cov txheej txheem fermentation, feem ntau yog saib xyuas thiab tswj cov acidity thiab alkalinity ntawm cov kua fermentation. Los ntawm kev ntsuas tus nqi pH tas li, lub electrode ua rau muaj kev tswj hwm qhov chaw fermentation kom meej. Ib qho pH electrode ib txwm muaj ib lub sensing electrode thiab ib lub reference electrode, ua haujlwm raws li lub hauv paus ntsiab lus ntawm Nernst equation, uas tswj kev hloov pauv ntawm lub zog tshuaj mus rau hauv cov teeb liab hluav taws xob. Lub peev xwm electrode yog ncaj qha cuam tshuam rau kev ua haujlwm ntawm hydrogen ions hauv cov tshuaj. Tus nqi pH yog txiav txim siab los ntawm kev sib piv qhov sib txawv ntawm qhov ntsuas voltage nrog rau ntawm cov tshuaj buffer txheem, uas tso cai rau kev ntsuas kom raug thiab txhim khu kev qha. Txoj kev ntsuas no ua kom muaj kev tswj hwm pH ruaj khov thoob plaws hauv cov txheej txheem fermentation, yog li txhawb nqa cov kab mob lossis cov haujlwm ntawm tes zoo tshaj plaws thiab ua kom cov khoom zoo.

Kev siv cov electrodes pH kom raug yuav tsum muaj ntau kauj ruam npaj, suav nrog kev ua kom electrode ua haujlwm - feem ntau ua tiav los ntawm kev muab lub electrode tso rau hauv dej distilled lossis pH 4 buffer solution - kom ntseeg tau tias muaj kev teb zoo tshaj plaws thiab kev ntsuas qhov tseeb. Txhawm rau kom tau raws li qhov xav tau ntawm kev lag luam biopharmaceutical fermentation, pH electrodes yuav tsum ua kom pom lub sijhawm teb sai, qhov tseeb siab, thiab kev ruaj khov nyob rau hauv cov xwm txheej sterilization nruj xws li kub siab steam sterilization (SIP). Cov yam ntxwv no ua rau muaj kev ua tau zoo hauv cov chaw sterilization. Piv txwv li, hauv kev tsim glutamic acid, kev saib xyuas pH kom raug yog qhov tseem ceeb rau kev tswj cov yam ntxwv tseem ceeb xws li kub, cov pa oxygen yaj, qhov ceev ntawm kev sib xyaw, thiab pH nws tus kheej. Kev tswj hwm qhov tseeb ntawm cov hloov pauv no cuam tshuam ncaj qha rau ob qho tib si qhov tshwm sim thiab qhov zoo ntawm cov khoom kawg. Qee cov electrodes pH siab heev, uas muaj cov iav tiv taus kub siab thiab cov txheej txheem polymer gel ua ntej, qhia txog kev ruaj khov tshwj xeeb nyob rau hauv qhov kub thiab txias heev, ua rau lawv tsim nyog rau kev siv SIP hauv cov txheej txheem biological thiab zaub mov fermentation. Ntxiv mus, lawv cov peev xwm tiv thaiv kev ua qias tuaj yeem ua rau muaj kev ua tau zoo sib xws thoob plaws ntau yam fermentation broths. Shanghai Boqu Instrument Co., Ltd. muaj ntau yam kev xaiv electrode connector, txhim kho kev yooj yim rau tus neeg siv thiab kev sib koom ua ke ntawm lub cev.

Vim li cas kev soj ntsuam pH thiaj li tsim nyog thaum lub sijhawm fermentation ntawm biopharmaceuticals?

Hauv kev ua tshuaj biopharmaceutical fermentation, kev saib xyuas thiab tswj pH tiag tiag yog qhov tseem ceeb rau kev tsim khoom zoo thiab rau kev ua kom muaj txiaj ntsig zoo tshaj plaws thiab zoo ntawm cov khoom lag luam xws li tshuaj tua kab mob, tshuaj tiv thaiv kab mob, monoclonal antibodies, thiab enzymes. Hauv paus ntsiab lus, kev tswj pH tsim ib puag ncig zoo tshaj plaws rau cov kab mob me me lossis cov tsiaj txhu - ua haujlwm ua "cov chaw tsim khoom muaj sia" - kom loj hlob thiab tsim cov tshuaj kho mob, zoo ib yam li cov neeg ua liaj ua teb kho pH av raws li cov qoob loo xav tau.

1. Tswj kev ua haujlwm ntawm tes zoo tshaj plaws
Kev ua kom cov cell muaj sia nyob (piv txwv li, CHO cell) los tsim cov biomolecules nyuaj. Kev ua haujlwm ntawm cov cell yog qhov rhiab heev rau pH ib puag ncig. Cov enzymes, uas ua rau txhua yam kev cuam tshuam biochemical hauv cell, muaj pH nqaim; qhov sib txawv ntawm qhov ntau no tuaj yeem txo qhov kev ua haujlwm enzymatic lossis ua rau denaturation, ua rau kev ua haujlwm metabolic tsis zoo. Tsis tas li ntawd, kev nqus cov khoom noj khoom haus los ntawm lub cell membrane - xws li glucose, amino acids, thiab inorganic salts - yog pH-nyob ntawm. Cov pH qis dua tuaj yeem cuam tshuam kev nqus cov khoom noj khoom haus, ua rau kev loj hlob qis dua lossis kev tsis sib npaug ntawm cov metabolism. Ntxiv mus, cov nqi pH siab dhau tuaj yeem ua rau lub membrane integrity, ua rau cytoplasmic leakage lossis cell lysis.

2. Txo cov khoom tsim tawm thiab cov khib nyiab hauv cov substrate
Thaum lub sijhawm fermentation, cov metabolism hauv cellular tsim cov acidic lossis cov metabolites yooj yim. Piv txwv li, ntau cov kab mob me me tsim cov organic acids (piv txwv li, lactic acid, acetic acid) thaum lub sijhawm glucose catabolism, ua rau pH poob qis. Yog tias tsis kho, pH qis yuav txwv tsis pub cov cell loj hlob thiab tej zaum yuav hloov cov metabolism flux mus rau txoj kev tsis tsim khoom, ua rau cov khoom seem ntau ntxiv. Cov khoom seem no siv cov pa roj carbon thiab cov peev txheej zog uas yuav txhawb nqa cov khoom tsim tawm, yog li txo cov txiaj ntsig tag nrho. Kev tswj pH zoo pab tswj cov kev metabolic xav tau thiab txhim kho cov txheej txheem ua haujlwm zoo.

3. Xyuas kom cov khoom ruaj khov thiab tiv thaiv kev puas tsuaj
Ntau yam khoom siv biopharmaceutical, tshwj xeeb tshaj yog cov protein xws li monoclonal antibodies thiab peptide hormones, yooj yim rau pH-induced kev hloov pauv ntawm cov qauv. Sab nraum lawv qhov pH ruaj khov, cov molecules no yuav dhau los ua denaturation, aggregation, lossis inactivation, uas ua rau muaj kev phom sij precipitates. Tsis tas li ntawd, qee cov khoom yooj yim rau tshuaj hydrolysis lossis enzymatic degradation nyob rau hauv acidic lossis alkaline mob. Kev tswj hwm pH kom tsim nyog txo qhov kev puas tsuaj ntawm cov khoom thaum lub sijhawm tsim khoom, khaws cia lub zog thiab kev nyab xeeb.

4. Txhim kho cov txheej txheem kom zoo dua thiab xyuas kom meej tias muaj kev sib xws ntawm ib pawg mus rau ib pawg
Los ntawm kev lag luam, kev tswj pH ncaj qha cuam tshuam rau kev tsim khoom thiab kev lag luam muaj txiaj ntsig. Kev tshawb fawb dav dav tau ua los txheeb xyuas cov pH teeb tsa zoo tagnrho rau ntau theem fermentation - xws li kev loj hlob ntawm tes piv rau kev qhia tawm khoom - uas yuav txawv ntau heev. Kev tswj pH dynamic tso cai rau kev ua kom zoo tshaj plaws rau theem, ua kom muaj kev sib sau ua ke ntawm biomass thiab cov khoom lag luam siab tshaj plaws. Ntxiv mus, cov koom haum tswj hwm xws li FDA thiab EMA xav tau kev ua raws li Kev Ua Haujlwm Zoo (GMP), qhov twg cov txheej txheem txheej txheem sib xws yog qhov yuav tsum tau ua. pH raug lees paub tias yog Critical Process Parameter (CPP), thiab nws txoj kev saib xyuas tas mus li ua kom muaj kev rov ua dua thoob plaws cov pawg, lav qhov kev nyab xeeb, kev ua haujlwm zoo, thiab qhov zoo ntawm cov khoom lag luam tshuaj.

5. Ua ib qho cim qhia txog kev noj qab haus huv ntawm kev fermentation
Qhov kev hloov pauv ntawm pH muab cov kev nkag siab zoo rau qhov xwm txheej ntawm lub cev. Kev hloov pauv sai lossis tsis tau xav txog hauv pH tej zaum yuav ua rau muaj kev ua qias tuaj, kev ua haujlwm tsis zoo ntawm lub sensor, kev noj zaub mov tsis txaus, lossis kev ua haujlwm tsis zoo ntawm lub cev. Kev kuaj pom thaum ntxov raws li qhov sib txawv ntawm pH ua rau tus neeg teb xov tooj cuam tshuam raws sijhawm, pab daws teeb meem thiab tiv thaiv kev ua tsis tiav ntawm cov khoom kim heev.

Yuav tsum xaiv cov pH sensors li cas rau cov txheej txheem fermentation hauv biopharmaceuticals?

Kev xaiv lub ntsuas pH uas tsim nyog rau kev ua kom cov tshuaj biopharmaceutical fermentation yog qhov kev txiav txim siab tseem ceeb hauv kev tsim kho uas cuam tshuam rau kev ntseeg tau ntawm cov txheej txheem, kev ncaj ncees ntawm cov ntaub ntawv, qhov zoo ntawm cov khoom, thiab kev ua raws li txoj cai. Kev xaiv yuav tsum tau ua tib zoo xav txog, tsis yog xav txog kev ua haujlwm ntawm lub ntsuas xwb tab sis kuj xav txog kev sib raug zoo nrog tag nrho cov txheej txheem bioprocessing.

1. Kev kub thiab siab tsis kam
Cov txheej txheem biopharmaceutical feem ntau siv cov pa dej ua kom tsis muaj kab mob hauv qhov chaw (SIP), feem ntau ntawm 121 ° C thiab 1-2 bar siab rau 20-60 feeb. Yog li ntawd, txhua lub pH sensor yuav tsum tiv taus kev raug rau cov xwm txheej zoo li no yam tsis muaj kev puas tsuaj. Qhov zoo tshaj plaws, lub sensor yuav tsum tau ntsuas rau tsawg kawg 130 ° C thiab 3-4 bar kom muab qhov kev nyab xeeb. Kev kaw ruaj khov yog qhov tseem ceeb kom tiv thaiv cov dej noo nkag, electrolyte xau, lossis kev puas tsuaj thaum lub sijhawm thermal cycling.

2. Hom sensor thiab qhov system siv los ntsuas
Qhov no yog qhov kev txiav txim siab tseem ceeb ntawm kev siv tshuab uas cuam tshuam rau kev ruaj khov mus sij hawm ntev, kev xav tau kev saib xyuas, thiab kev tiv thaiv kev ua qias tuaj.
Kev teeb tsa electrode: Cov electrodes sib xyaw ua ke, kev sib xyaw ua ke ob qho tib si ntsuas thiab cov ntsiab lus siv rau hauv ib lub cev, tau txais kev pom zoo dav dav vim yooj yim ntawm kev teeb tsa thiab kev tuav.
Kev siv lub tshuab:
• Cov ntaub ntawv siv dej uas muaj kua (piv txwv li, KCl kua): Muaj cov lus teb sai thiab raug siab tab sis yuav tsum tau rov ua dua tsis tu ncua. Thaum lub sijhawm SIP, kev poob electrolyte yuav tshwm sim, thiab cov qhov sib txuas (piv txwv li, ceramic frits) yuav raug txhaws los ntawm cov protein lossis cov khoom me me, ua rau kev nyeem ntawv tsis ruaj khov thiab tsis ntseeg tau.
• Polymer gel lossis solid-state reference: Nce qib nyiam siv rau hauv cov bioreactors niaj hnub no. Cov kab ke no tshem tawm qhov xav tau electrolyte replenishment, txo kev txij nkawm, thiab muaj cov kua sib txuas dav dua (piv txwv li, PTFE rings) uas tiv taus fouling. Lawv muab kev ruaj khov zoo dua thiab lub neej ntev dua hauv cov khoom siv fermentation nyuaj, viscous.

3. Kev ntsuas ntau yam thiab qhov tseeb
Lub sensor yuav tsum npog ntau yam kev ua haujlwm, feem ntau yog pH 2–12, kom haum rau ntau theem txheej txheem. Vim tias qhov rhiab heev ntawm cov kab ke hauv lub cev, qhov tseeb ntawm kev ntsuas yuav tsum nyob hauv ± 0.01 txog ± 0.02 pH units, txhawb nqa los ntawm cov teeb liab tso zis siab.

4. Lub sijhawm teb
Lub sijhawm teb feem ntau txhais tias yog t90—lub sijhawm uas yuav tsum tau mus txog 90% ntawm qhov nyeem kawg tom qab hloov pauv pH ib kauj ruam. Txawm hais tias cov electrodes hom gel yuav teb qeeb dua li cov uas muaj kua, feem ntau lawv ua tau raws li qhov yuav tsum tau ua ntawm cov voj voog tswj kev fermentation, uas ua haujlwm rau txhua teev sijhawm es tsis yog vib nas this.

5. Kev sib haum xeeb ntawm lub cev
Txhua yam khoom siv uas kov tau cov khoom siv cog qoob loo yuav tsum tsis muaj tshuaj lom, tsis leaching, thiab inert kom tsis txhob muaj kev cuam tshuam tsis zoo rau kev muaj sia nyob ntawm cov cell lossis qhov zoo ntawm cov khoom. Cov qauv iav tshwj xeeb uas tsim los rau kev siv bioprocessing raug pom zoo kom ntseeg tau tias tiv taus tshuaj lom neeg thiab biocompatibility.

6. Cov zis teeb liab thiab interface
• Cov zis analog (mV/pH): Txoj kev ib txwm siv kev xa mus rau lub kaw lus tswj hwm. Tsim nyog tus nqi tab sis muaj kev cuam tshuam los ntawm kev cuam tshuam hluav taws xob thiab kev txo qis ntawm cov teeb liab hauv qhov deb.
• Cov zis digital (piv txwv li, MEMS-based lossis smart sensors): Muaj cov microelectronics hauv onboard los xa cov teeb liab digital (piv txwv li, ntawm RS485). Muab kev tiv thaiv suab nrov zoo heev, txhawb kev sib txuas lus ntev, thiab ua rau khaws cia keeb kwm calibration, cov lej serial, thiab cov cav siv. Ua raws li cov qauv kev cai lij choj xws li FDA 21 CFR Part 11 txog cov ntaub ntawv hluav taws xob thiab cov kos npe, ua rau nws nyiam dua hauv GMP ib puag ncig.

7. Kev teeb tsa interface thiab tsev tiv thaiv
Lub sensor yuav tsum sib xws nrog lub qhov chaw uas tau teev tseg rau ntawm lub bioreactor (piv txwv li, tri-clamp, sanitary fitting). Cov tes tsho tiv thaiv lossis cov neeg tiv thaiv yog qhov zoo kom tiv thaiv kev puas tsuaj thaum lub sijhawm tuav lossis ua haujlwm thiab kom yooj yim hloov pauv yam tsis muaj kev cuam tshuam rau kev huv.