Nhau - Kutariswa kweMatanho epH muBio Pharmaceutical Fermentation process

Iyo pH electrode inoita basa rakakosha mukuvirisa, kunyanya kushanda kutarisa nekugadzirisa acidity uye alkalinity yemuto wekuvirisa. Nekuramba uchiyera pH kukosha, iyo electrode inogonesa kudzora chaiko pamusoro penzvimbo yekuvirisa. Yakajairika pH electrode ine sensing electrode uye referensi electrode, inoshanda pamusimboti weNernst equation, inotonga kushandurwa kwesimba remakemikari kuita masaini emagetsi. Iyo electrode inogona kuenderana zvakananga nebasa rehydrogen ions mune mhinduro. Iyo pH kukosha inotarwa nekuenzanisa yakayerwa voltage musiyano neiyo yeyakajairwa buffer mhinduro, ichibvumira iyo chaiyo uye yakavimbika calibration. Iyi yekuyera nzira inovimbisa kugadzikana pH kurongeka mukati mekuvirisa, nekudaro ichitsigira yakakwana microbial kana cellular chiitiko uye kuve nechokwadi chemhando yechigadzirwa.

Kushandiswa kwakakodzera kwepH electrode kunoda matanho ekugadzirira akati wandei, anosanganisira electrode activation-inowanzoitwa nekunyudza electrode mumvura yakadirwa kana pH 4 buffer solution-kuti ive nechokwadi chekudavirwa kwakakwana uye kuyerwa kwechiyero. Kuti isangane nezvinoda kuomesesa zveindasitiri yekuvirisa yebiopharmaceutical, pH maelectrode anofanirwa kuratidza nguva dzekupindura nekukurumidza, kunyatsojeka, uye kusimba pasi pemamiriro ekuomarara akadai seyepamusoro-temperature steam sterilization (SIP). Aya maitiro anogonesa kuita kwakavimbika munzvimbo dzisina hutachiona. Semuenzaniso, mukugadzirwa kwe glutamic acid, kunyatso tarisa pH kwakakosha pakudzora akakosha paramita senge tembiricha, yakanyungudika okisijeni, kumhanya kweagitation, uye pH pachayo. Kudzora kwakaringana kwezvichinjika izvi kunokanganisa zvakananga zvese goho uye kunaka kwechigadzirwa chekupedzisira. Mamwe epamusoro pH electrode, ane yakakwirira-tembiricha-inodzivirira girazi membranes uye pre-yakadzvanywa polymer gel referefeta masisitimu, anoratidza kugadzikana kwakasarudzika pasi pekupisa kwakanyanya uye kudzvanywa kwemamiriro ezvinhu, zvichiita kuti anyanya kukodzera kushandiswa kweSIP mubiological uye chikafu kuvirisa maitiro. Uyezve, masimba avo akasimba e-anti-fouling anobvumira kuita kwakafanana mumhando dzakasiyana dzekuvirisa. Shanghai Boqu Instrument Co., Ltd inopa akasiyana emagetsi ekubatanidza sarudzo, inosimudzira mushandisi nyore uye sisitimu yekubatanidza inoshanduka.

Sei pH yekutarisa ichidikanwa panguva yekuvirisa maitiro ebiopharmaceuticals?

Mu biopharmaceutical fermentation, chaiyo-nguva yekutarisa uye kutonga kwepH kwakakosha pakubudirira kugadzirwa uye nekuwedzera goho uye mhando yezvakanangwa zvigadzirwa senge mishonga inorwisa mabhakitiriya, vaccin, monoclonal antibodies, uye ma enzymes. Muchidimbu, kudzora kwepH kunogadzira nharaunda yakaringana yemuviri yemasero emicrobial kana mammalian - anoshanda se "mafekitori ehupenyu" - kukura nekugadzira mishonga yekurapa, inofananidzwa nemagadzirirwo evarimi ivhu pH zvinoenderana nechirimwa chinodiwa.

1. Chengetedza optimal cellular activity
Kuvirisa kunoenderana nemasero mapenyu (semuenzaniso, CHO masero) kugadzira biomolecules yakaoma. Sero metabolism inotarisisa zvakanyanya kune zvakatipoteredza pH. Enzymes, iyo inokonzeresa ese intracellular biochemical reactions, ine nhete pH optima; kutsauka kubva mumhando iyi kunogona kuderedza zvakanyanya enzymatic chiitiko kana kukonzera denaturation, kukanganisa metabolic basa. Pamusoro pezvo, kutora chikafu kuburikidza nesero membrane-senge glucose, amino acids, uye inorganic munyu-inoenderana nepH. Suboptimal pH mazinga anogona kutadzisa kunyura kwekudya, zvichikonzera kukura kwakanyanya kana kusaenzana kwemetabolism. Uyezve, yakanyanyisa pH kukosha inogona kukanganisa kutendeseka kwe membrane, zvichikonzera kudonha kwe cytoplasmic kana sero lysis.

2. Kuderedza ne-chigadzirwa kuumbwa uye substrate tsvina
Panguva yekuvirisa, cellular metabolism inogadzira acidic kana basic metabolites. Semuenzaniso, ma microorganisms mazhinji anogadzira organic acids (semuenzaniso, lactic acid, acetic acid) panguva yeglucose catabolism, zvichikonzera kudonha kwepH. Kana isina kurongeka, yakaderera pH inhibits kukura kwesero uye inogona kushandura metabolic flux kuenda kune isiri-kugadzira nzira, ichiwedzera ne-chigadzirwa kuunganidza. Izvi zvigadzirwa zvinoshandisa kabhoni yakakosha uye zviwanikwa zvesimba izvo zvaizotsigira chinangwa chechigadzirwa synthesis, nekudaro kuderedza goho rose. Kushanda pH kutonga kunobatsira kuchengetedza inodiwa metabolic nzira uye inovandudza maitiro ekuita.

3. Iva nechokwadi chekugadzikana kwechigadzirwa uye kudzivirira kuora
Zvigadzirwa zvakawanda zvebiopharmaceutical, kunyanya mapuroteni akadai semonoclonal antibodies uye mahomoni epeptide, anotapukirwa nepH-induced structural shanduko. Kunze kwavo kwakagadzikana pH renji, mamorekuru aya anogona kuita denaturation, aggregation, kana kusashanda, zvichigona kuumba mvura inokuvadza. Pamusoro pezvo, zvimwe zvigadzirwa zvinotarirwa kumakemikari hydrolysis kana enzymatic degradation pasi pe acidic kana alkaline mamiriro. Kuchengetedza pH yakakodzera kunoderedza kuparara kwechigadzirwa panguva yekugadzira, kuchengetedza potency uye kuchengeteka.

4. Gadzirisa maitiro ekushanda uye chengetedza batch-to-batch kuenderana
Kubva pakuona kwemaindasitiri, pH kutonga inokanganisa zvakananga kubereka uye kugona kwehupfumi. Tsvagiridzo yakadzama inoitwa kuona yakanakira pH seti yezvikamu zvakasiyana zvekuvirisa-sekukura kwesero maringe nekutaura kwechigadzirwa-izvo zvingasiyana zvakanyanya. Dynamic pH kutonga inobvumira nhanho-chaiyo optimization, kuwedzera biomass kuunganidza uye zvigadzirwa titers. Zvakare, masangano anodzora akadai seFDA neEMA anoda kuteedzera kwakasimba kune Yakanaka Kugadzira Maitiro (GMP), uko kunoenderana maitiro maparamita anosungirwa. pH inozivikanwa seCritical process Parameter (CPP), uye kuenderera kwayo kutarisisa kunovimbisa kuberekana mumabatch ese, kuvimbisa kuchengetedzwa, kushanda, uye mhando yezvigadzirwa zvemishonga.

5. Shandira sechiratidzo chehutano hwekuvirisa
Maitiro ekushanduka kwepH anopa ruzivo rwakakosha muchimiro chechimiro chetsika. Kamwe kamwe kana zvisingatarisirwi shanduko mupH inogona kuratidza kusvibiswa, kusashanda zvakanaka kwesensor, kupera kwemuviri, kana metabolic anomalies. Kuonekwa kwekutanga kwakavakirwa pamaitiro epH kunogonesa kupindira kwemushandisi panguva, kufambisa matambudziko uye kudzivirira kutadza kwebatch kunodhura.

Ko pH sensors inofanira kusarudzwa sei yekuvirisa maitiro mubiopharmaceuticals?

Kusarudza yakakodzera pH sensor ye biopharmaceutical fermentation isarudzo yakakosha yeinjiniya iyo inokanganisa kuvimbika kwemaitiro, kutendeseka kwedata, mhando yechigadzirwa, uye kutevedzera mutemo. Sarudzo yacho inofanirwa kusvikirwa zvakarongeka, tichifunga kwete chete sensor performance asiwo kuenderana neyese bioprocessing workflow.

1. High-temperature uye pressure resistance
Biopharmaceutical process inowanzo shandisa in-situ steam sterilization (SIP), kazhinji pa121°C uye 1–2 bar pressure kwemaminitsi 20–60. Naizvozvo, chero pH sensor inofanirwa kumira yakadzokororwa kuratidzwa kune akadaro mamiriro pasina kukundikana. Nenzira yakanaka, iyo sensor inofanirwa kuverengerwa kweinenge 130 ° C uye 3-4 bar kuti ipe muganho wekuchengetedza. Kuiswa chisimbiso kwakasimba kwakakosha kudzivirira hunyoro huchipinda, kubuda kwe electrolyte, kana kukuvara kwemuchina panguva yekupisa bhasikoro.

2. Sensor type uye reference system
Iyi ndiyo yepakati tekinoroji yekutarisisa inokanganisa kugadzikana kwenguva refu, zvinodiwa zvekugadzirisa, uye kutadza kuramba.
Electrode configuration: Composite electrodes, kubatanidza zvose kuyera uye mareferensi zvinhu mumuviri mumwe, anogamuchirwa zvakanyanya nekuda kwekureruka kwekugadzika uye kubata.
Reference system:
• Liquid-filled reference (eg, KCl solution): Inopa mhinduro yekukurumidza uye nekururama kwepamusoro asi inoda kuzadzazve nguva nenguva. Munguva yeSIP, kurasikirwa kweelectrolyte kunogona kuitika, uye majunctions ane porous (semuenzaniso, ceramic frits) anowanzovharika nemapuroteni kana zvikamu, zvinotungamirira kukukurwa uye kusavimbika kuverenga.
• Polymer gel kana solid-state reference: Inowedzera inosarudzwa mune zvemazuva ano bioreactors. Aya masisitimu anobvisa kudiwa kwekudzoreredzwa kwe electrolyte, kuderedza kugadzirisa, uye kuratidza mijenya yakafararira yemvura (semuenzaniso, mhete dzePTFE) dzinoramba kusvibiswa. Vanopa kugadzikana kwepamusoro uye hupenyu hurefu hwesevhisi mune yakaoma, viscous fermentation media.

3. Chiyero chekuyera uye kururama
Iyo sensor inofanirwa kuvhara yakafara yekushanda renji, kazhinji pH 2-12, kugarisa akasiyana-siyana maitiro. Zvichipa kunzwisiswa kwemaitiro ezvipenyu, kuyerwa kwechiyero kunofanirwa kunge kuri mukati me ± 0.01 kusvika ± 0.02 pH mayuniti, anotsigirwa ne-high-resolution signal yakabuda.

4. Nguva yekupindura
Nguva yekupindura inowanzotsanangurwa se t90-nguva inodiwa kuti isvike 90% yekuverenga kwekupedzisira mushure mekuchinja nhanho mupH. Nepo maelectrode emhando yegel achigona kuratidza kunonoka zvishoma pane akazara-mvura, anowanzo kusangana nezvinodavirwa zvekuvirisa zvishwe zvekudzora zvishwe, zvinoshanda neawa imwe neimwe kwete masekonzi.

5. Biocompatibility
Zvese zvinhu zvinosangana netsika svikiro zvinofanirwa kunge zvisiri-chepfu, zvisiri-leaching, uye inert kudzivirira kukanganisa kwakashata pakuita kwesero kana kunaka kwechigadzirwa. Yakasarudzika girazi magadzirirwo akagadzirirwa bioprocessing application anokurudzirwa kuve nechokwadi chemakemikari kuramba uye biocompatibility.

6. Chiratidzo chekubuda uye chimiro
• Analog output (mV / pH): Nzira yemazuva ano inoshandisa analog transmission kune control system. Mutengo-unoshanda asi uri panjodzi yekukanganiswa kwemagetsi uye chiratidzo chekumisikidza pamusoro pemadaro marefu.
• Digital output (eg, MEMS-based or smart sensors): Inobatanidza onboard microelectronics kutumira zviratidzo zvedhijitari (semuenzaniso, kuburikidza neRS485). Inopa yakanakisa ruzha kusadzivirirwa, inotsigira kutaurirana kureba, uye inogonesa kuchengetedza nhoroondo yecalibration, serial nhamba, uye matanda ekushandisa. Inoenderana nezviyero zvekutonga senge FDA 21 CFR Chikamu 11 zvine chekuita nemagetsi marekodhi uye siginicha, zvichiita kuti iwedzere kufarirwa munzvimbo dzeGMP.

7. Kuisa interface uye dzimba dzekudzivirira
Iyo sensor inofanirwa kuenderana neyakatemerwa chiteshi pane bioreactor (semuenzaniso, tri-clamp, sanitary fitting). Mawoko ekudzivirira kana magadhi anokurudzirwa kudzivirira kukuvadzwa kwemuchina panguva yekubata kana kushanda uye kuita kuti kutsiva kuri nyore pasina kukanganisa sterility.