Xov Xwm - Saib xyuas cov qib pH hauv Bio Pharmaceutical Fermentation Process

Lub pH electrode plays lub luag haujlwm tseem ceeb hauv cov txheej txheem fermentation, feem ntau ua haujlwm los saib xyuas thiab tswj cov acidity thiab alkalinity ntawm fermentation broth. Los ntawm kev ntsuas pH tsis tu ncua, lub electrode ua kom muaj kev tswj xyuas meej ntawm qhov chaw fermentation. Ib tug raug pH electrode muaj ib tug sensing electrode thiab ib tug siv electrode, kev khiav hauj lwm nyob rau hauv lub hauv paus ntsiab lus ntawm lub Nernst kab zauv, uas tswj kev hloov dua siab tshiab ntawm chemical zog rau hauv hluav taws xob signals. Lub peev xwm electrode yog ncaj qha ntsig txog kev ua haujlwm ntawm hydrogen ions hauv cov tshuaj. Tus nqi pH yog txiav txim siab los ntawm kev sib piv qhov ntsuas qhov sib txawv ntawm qhov sib txawv ntawm cov txheej txheem kev daws teeb meem, tso cai rau kev ntsuas kom raug thiab txhim khu kev qha. Qhov kev ntsuas no ua kom ruaj khov pH kev cai thoob plaws hauv cov txheej txheem fermentation, yog li txhawb kev pom cov microbial lossis cellular kev ua haujlwm thiab ua kom cov khoom zoo.

Kev siv cov pH electrodes kom raug yuav tsum tau ua ntau yam kev npaj, suav nrog kev ua kom electrode - feem ntau ua tiav los ntawm kev tso cov electrode hauv dej distilled los yog pH 4 tsis haum tshuaj - kom ntseeg tau tias qhov ua tau zoo thiab ntsuas qhov tseeb. Txhawm rau ua kom tau raws li qhov xav tau nruj ntawm kev lag luam biopharmaceutical fermentation, pH electrodes yuav tsum muaj sijhawm teb sai, siab precision, thiab robustness nyob rau hauv nruj sterilization tej yam kev mob xws li high-temperature steam sterilization (SIP). Cov yam ntxwv no pab txhim kho kev ua tau zoo hauv qhov chaw tsis muaj menyuam. Piv txwv li, hauv glutamic acid ntau lawm, kev saib xyuas pH meej yog qhov tseem ceeb rau kev tswj hwm qhov tseem ceeb xws li kub, yaj oxygen, agitation ceev, thiab pH nws tus kheej. Cov kev cai raug cai ntawm cov kev hloov pauv no ncaj qha cuam tshuam rau ob qho tib si tawm los thiab qhov zoo ntawm cov khoom kawg. Qee cov pH electrodes siab heev, muaj cov iav uas muaj qhov kub-resistant iav thiab pre-pressurized polymer gel siv tshuab, ua kom pom kev ruaj ntseg tshwj xeeb nyob rau hauv qhov kub thiab txias, ua rau lawv tshwj xeeb tshaj yog haum rau SIP daim ntaub ntawv hauv cov txheej txheem lom neeg thiab zaub mov fermentation. Tsis tas li ntawd, lawv lub peev xwm tiv thaiv fouling muaj zog tso cai rau kev ua haujlwm zoo ib yam ntawm ntau hom fermentation broths. Shanghai Boqu Instrument Co., Ltd. muaj ntau yam kev xaiv electrode connector, txhim kho cov neeg siv khoom yooj yim thiab kev sib koom ua ke yooj yim.

Vim li cas kev soj ntsuam pH tsim nyog thaum lub sij hawm fermentation ntawm biopharmaceuticals?

Hauv biopharmaceutical fermentation, kev saib xyuas thiab tswj lub sijhawm ntawm pH yog qhov tseem ceeb rau kev tsim cov khoom lag luam zoo thiab ua kom cov txiaj ntsig zoo thiab cov khoom lag luam zoo xws li tshuaj tua kab mob, tshuaj tiv thaiv, monoclonal antibodies, thiab enzymes. Nyob rau hauv qhov tseeb, pH tswj tsim ib qho chaw zoo rau lub cev zoo rau cov kab mob microbial lossis mammalian hlwb - ua haujlwm li "cov chaw ua neej nyob" - kom loj hlob thiab sib txuas cov tshuaj kho mob, zoo ib yam li cov neeg ua liaj ua teb kho cov av pH raws li cov qoob loo xav tau.

1. Ua kom pom kev ua haujlwm ntawm tes
Fermentation cia siab rau cov hlwb nyob (xws li, CHO hlwb) los tsim cov biomolecules complex. Cellular metabolism yog rhiab heev rau ib puag ncig pH. Enzymes, uas catalyze tag nrho intracellular biochemical cov tshuaj tiv thaiv, muaj nqaim pH optima; Kev sib txawv ntawm qhov ntau no tuaj yeem txo qis kev ua haujlwm enzymatic lossis ua rau muaj qhov tsis zoo, cuam tshuam kev ua haujlwm metabolic. Tsis tas li ntawd, kev noj zaub mov zoo los ntawm cov cell membrane-xws li qabzib, amino acids, thiab inorganic ntsev-yog pH-nyob ntawm seb. Cov qib pH zoo tshaj plaws tuaj yeem cuam tshuam kev nqus cov as-ham, ua rau kev loj hlob tsis zoo lossis metabolic tsis txaus. Tsis tas li ntawd, pH qhov tseem ceeb tshaj plaws tuaj yeem cuam tshuam qhov kev ncaj ncees ntawm daim nyias nyias, ua rau cytoplasmic to lossis cell lysis.

2. Txo qhov tsim los ntawm cov khoom lag luam thiab cov khoom pov tseg substrate
Thaum lub sij hawm fermentation, cellular metabolism generates acidic los yog yooj yim metabolites. Piv txwv li, ntau cov kab mob tsim cov organic acids (xws li, lactic acid, acetic acid) thaum lub sij hawm qabzib catabolism, ua rau poob pH. Yog tias tsis kho, pH qis inhibits cell loj hlob thiab tuaj yeem hloov pauv metabolic flux mus rau txoj hauv kev uas tsis tsim khoom, ua rau cov khoom sib xyaw ua ke. Cov khoom siv los ntawm cov khoom siv no siv cov khoom muaj txiaj ntsig zoo thiab cov khoom siv hluav taws xob uas yuav txhawb nqa cov khoom sib txuas, yog li txo cov txiaj ntsig tag nrho. Kev tswj pH zoo pab tswj cov txheej txheem metabolic uas xav tau thiab txhim kho cov txheej txheem ua haujlwm.

3. Ua kom cov khoom ruaj khov thiab tiv thaiv kev degradation
Ntau cov khoom lag luam biopharmaceutical, tshwj xeeb tshaj yog cov proteins xws li cov tshuaj tiv thaiv monoclonal thiab peptide cov tshuaj hormones, muaj kev cuam tshuam rau cov kev hloov pauv ntawm pH. Sab nraum lawv cov pH ruaj khov, cov molecules no tuaj yeem raug denaturation, sib sau ua ke, lossis inactivation, uas tuaj yeem tsim teeb meem nag lossis daus. Tsis tas li ntawd, qee cov khoom lag luam muaj cov tshuaj hydrolysis los yog enzymatic degradation nyob rau hauv acidic los yog alkaline tej yam kev mob. Kev tswj kom zoo pH txo cov khoom degradation thaum lub sij hawm tsim khoom, khaws cia potency thiab kev nyab xeeb.

4. optimize cov txheej txheem efficiency thiab xyuas kom meej batch-to-batch sib xws
Los ntawm kev pom kev lag luam, pH tswj ncaj qha cuam tshuam kev tsim khoom thiab kev lag luam muaj txiaj ntsig. Kev tshawb fawb ntau yog ua los txheeb xyuas qhov zoo tshaj pH setpoints rau txawv fermentation theem-xws li cell loj hlob piv rau cov khoom qhia-uas yuav txawv heev. Dynamic pH tswj tso cai rau theem tshwj xeeb optimization, maximizing biomass tsub zuj zuj thiab cov khoom titers. Tsis tas li ntawd, cov koom haum tswj hwm xws li FDA thiab EMA yuav tsum tau ua raws li Kev Tswj Xyuas Zoo (GMP), qhov uas cov txheej txheem tsis tu ncua yog qhov yuav tsum tau ua. pH tau lees paub tias yog Cov Txheej Txheem Txheej Txheem Tseem Ceeb (CPP), thiab nws cov kev soj ntsuam tas li ua kom muaj kev rov ua dua tshiab ntawm cov khoom siv, lav kev nyab xeeb, ua tau zoo, thiab cov khoom siv tshuaj zoo.

5. Ua ib qho qhia txog kev noj qab haus huv fermentation
Kev hloov pauv ntawm pH muab kev nkag siab zoo rau hauv lub cev lub cev ntawm kab lis kev cai. Kev hloov pauv sai sai hauv pH tuaj yeem ua rau muaj kev sib kis, kev ua haujlwm tsis zoo, kev noj zaub mov tsis txaus, lossis metabolic anomalies. Kev tshawb pom ntxov raws li cov qauv pH ua rau muaj kev cuam tshuam rau tus neeg teb xov tooj raws sijhawm, pab daws teeb meem thiab tiv thaiv kev ua haujlwm tsis zoo ntawm cov nqi.

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

Xaiv qhov tsim nyog pH sensor rau biopharmaceutical fermentation yog qhov kev txiav txim siab engineering tseem ceeb uas cuam tshuam rau cov txheej txheem kev ntseeg siab, cov ntaub ntawv ncaj ncees, cov khoom lag luam zoo, thiab kev tswj hwm kev tswj hwm. Kev xaiv yuav tsum tau mus kom ze rau qhov systematically, txiav txim siab tsis yog tsuas yog kev ua haujlwm ntawm lub sensor tab sis kuj sib raug zoo nrog tag nrho bioprocessing workflow.

1. High-temperature thiab siab tsis kam
Cov txheej txheem biopharmaceutical feem ntau siv rau hauv-situ steam sterilization (SIP), feem ntau ntawm 121 ° C thiab 1-2 bar siab rau 20-60 feeb. Yog li ntawd, txhua tus pH sensor yuav tsum tiv thaiv rov qab raug rau cov xwm txheej zoo li no yam tsis muaj kev ua haujlwm. Qhov zoo tshaj plaws, lub sensor yuav tsum tau ntsuas tsawg kawg yog 130 ° C thiab 3-4 bar kom muaj kev nyab xeeb. Kev sib khi ruaj khov yog qhov tseem ceeb los tiv thaiv kom tsis txhob ya raws, electrolyte to, lossis kev puas tsuaj thaum lub sij hawm thermal cycling.

2. Sensor hom thiab siv qhov system
Qhov no yog ib qho tseem ceeb rau kev txiav txim siab txog kev ruaj ntseg mus ntev, kev xav tau kev saib xyuas, thiab fouling kuj.
Electrode configuration: Composite electrodes, integrating ob qho tib si ntsuas thiab siv cov ntsiab lus nyob rau hauv ib lub cev, yog dav saws vim yooj yim ntawm installation thiab tuav.
Reference system:
• Cov ntaub ntawv ua kua (piv txwv li, KCl tov): Muab cov lus teb sai thiab raug siab tab sis yuav tsum tau ua kom rov qab ua ntu zus. Thaum lub sij hawm SIP, electrolyte poob yuav tshwm sim, thiab ntxeem tau junctions (xws li, ceramic frits) yog nquag mus clogging los ntawm cov proteins los yog particulates, ua rau drift thiab unreliable nyeem ntawv.
• Polymer gel lossis solid-state reference: Ntau dua nyiam nyob rau niaj hnub bioreactors. Cov tshuab no tshem tawm qhov xav tau ntawm cov khoom siv electrolyte ntxiv, txo cov txij nkawm, thiab ua kom muaj cov kua dej dav dua (piv txwv li, PTFE rings) uas tiv thaiv fouling. Lawv muab kev ruaj ntseg zoo dua thiab kev pab cuam lub neej ntev dua hauv cov xov xwm nyuaj, fermentation viscous.

3. Kev ntsuas ntau thiab qhov tseeb
Lub sensor yuav tsum npog ntau yam kev ua haujlwm, feem ntau pH 2-12, kom haum rau cov txheej txheem sib txawv. Muab qhov rhiab heev ntawm cov kab mob lom, kev ntsuas qhov tseeb yuav tsum nyob rau hauv ± 0.01 txog ± 0.02 pH units, txhawb los ntawm cov teeb liab daws teeb meem siab.

4. Lub sijhawm teb
Lub sij hawm teb feem ntau txhais tau tias yog t90-lub sij hawm xav tau kom ncav cuag 90% ntawm qhov kev nyeem ntawv kawg tom qab hloov pauv hauv pH. Thaum cov gel-hom electrodes tuaj yeem pom cov lus teb qeeb me ntsis dua li cov kua dej puv, lawv feem ntau ua tau raws li cov kev xav tau ntawm fermentation tswj loops, uas ua haujlwm ntawm cov sijhawm teev sijhawm ntau dua li vib nas this.

5. Biocompatibility
Tag nrho cov ntaub ntawv nyob rau hauv kev sib cuag nrog kab lis kev cai nruab nrab yuav tsum tsis muaj tshuaj lom, tsis yog-leaching, thiab inert kom tsis txhob muaj kev phiv los ntawm cell viability los yog cov khoom zoo. Tshwj xeeb iav formulations tsim rau bioprocessing daim ntaub ntawv raug pom zoo los xyuas kom meej cov tshuaj tiv thaiv thiab biocompatibility.

6. Teeb liab tso zis thiab interface
• Analog tso zis (mV/pH): Ib txwm siv txoj kev siv analog kis mus rau qhov system tswj. Nqi-zoo tab sis yooj yim rau electromagnetic cuam tshuam thiab teeb liab attenuation nyob ntev.
• Cov zis digital (piv txwv li, MEMS-raws li lossis ntse sensors): suav nrog onboard microelectronics kom xa cov cim digital (xws li ntawm RS485). Muab lub suab nrov tiv thaiv zoo, txhawb kev sib txuas lus mus ntev, thiab ua kom muaj kev cia siab ntawm cov ntaub ntawv keeb kwm, cov lej xov tooj, thiab cov ntaub ntawv siv. Ua raws li cov qauv kev cai xws li FDA 21 CFR Part 11 hais txog cov ntaub ntawv hluav taws xob thiab kos npe, ua rau nws nyiam nyob hauv GMP ib puag ncig.

7. Installation interface thiab tiv thaiv vaj tse
Lub sensor yuav tsum sib haum nrog rau qhov chaw nres nkoj ntawm bioreactor (xws li, tri-clamp, huv si haum). Lub tes tsho tiv thaiv los yog cov neeg tiv thaiv raug pom zoo los tiv thaiv kev puas tsuaj thaum tuav lossis ua haujlwm thiab ua kom yooj yim hloov pauv yam tsis muaj kev cuam tshuam tsis muaj menyuam.