Litaba - Tlhokomelo ea Maemo a pH ho Ts'ebetso ea Bio Pharmaceutical Fermentation

Eleketrode ea pH e bapala karolo ea bohlokoa ts'ebetsong ea ho belisoa, haholo-holo e sebeletsa ho beha leihlo le ho laola acidity le alkalinity ea moro oa belisoa. Ka ho tsoela pele ho lekanya boleng ba pH, eleketrode e etsa hore ho be le taolo e nepahetseng holim'a tikoloho ea ho belisoa. Electrode e tloaelehileng ea pH e na le electrode e utloang le eleketrode ea referense, e sebetsang ho latela molao-motheo oa Nernst equation, e laolang phetoho ea matla a lik'hemik'hale hore e be mats'oao a motlakase. Monyetla oa elektrode o amana ka kotloloho le ts'ebetso ea li-ion tsa hydrogen tharollong. Boleng ba pH bo khethoa ka ho bapisa phapang ea motlakase e lekantsoeng le ea tharollo e tloaelehileng ea buffer, e lumellang hore ho be le tekanyo e nepahetseng le e tšepahalang. Mokhoa ona oa ho lekanya o netefatsa taolo e tsitsitseng ea pH nakong eohle ea ho belisoa, ka hona e tšehetsa tšebetso e nepahetseng ea likokoana-hloko kapa lisele le ho netefatsa boleng ba sehlahisoa.

Tšebeliso e nepahetseng ea li-electrode tsa pH e hloka mehato e 'maloa ea boitokisetso, ho kenyelletsa ts'ebetso ea li-electrode-hangata e finyelloang ka ho qoelisa eleketrode metsing a hloekisitsoeng kapa tharollo ea pH 4 buffer-ho netefatsa karabelo e nepahetseng le ho nepahala ha tekanyo. Ho fihlela litlhoko tse thata tsa indasteri ea ho belisa ea biopharmaceutical, li-electrode tsa pH li tlameha ho bonts'a linako tsa karabelo tse potlakileng, ho nepahala ho holimo, le ho tiea tlas'a maemo a thata a ho thibela likokoana-hloko joalo ka high-themperature steam sterilization (SIP). Litšobotsi tsena li nolofalletsa ts'ebetso e tšepahalang libakeng tse nyopa. Mohlala, tlhahisong ea glutamic acid, tlhahlobo e nepahetseng ea pH e bohlokoa bakeng sa ho laola maemo a bohlokoa joalo ka mocheso, oksijene e qhibilihisitsoeng, lebelo la ho sisinyeha, le pH ka boeona. Taolo e nepahetseng ea mefuta ena e ama ka kotloloho chai le boleng ba sehlahisoa sa ho qetela. Li-electrode tse ling tse tsoetseng pele tsa pH, tse nang le li-membrane tsa khalase tse sa keneleng mocheso o phahameng le litsamaiso tsa litšupiso tsa li-polymer tse hatelletsoeng pele, li bonts'a botsitso bo ikhethang tlas'a maemo a mocheso a feteletseng le khatello, e leng se etsang hore li tšoanelehe haholo bakeng sa ts'ebeliso ea SIP lits'ebetsong tsa baeloji le ho belisoa ha lijo. Ho feta moo, matla a bona a matla a ho thibela litšila a lumella hore ho be le ts'ebetso e tsitsitseng ho pholletsa le mefuta e sa tšoaneng ea ho belisoa. Shanghai Boqu Instrument Co., Ltd. e fana ka likhetho tse fapaneng tsa sehokelo sa li-electrode, ho ntlafatsa boiketlo ba basebelisi le ho feto-fetoha ha tsamaiso ea tsamaiso.

Hobaneng ho lekola pH ho hlokahala nakong ea ho belisoa ha biopharmaceuticals?

Ho fermentation ea biopharmaceutical, tlhahlobo ea nako ea 'nete le taolo ea pH li bohlokoa bakeng sa tlhahiso e atlehileng le bakeng sa ho eketsa chai le boleng ba lihlahisoa tse shebiloeng joalo ka lithibela-mafu, liente, li-anti-monoclonal, le li-enzyme. Ha e le hantle, taolo ea pH e theha tikoloho e nepahetseng ea 'mele bakeng sa lisele tsa likokoana-hloko kapa tsa mammalian-tse sebetsang e le "lifeme tse phelang"-ho hōla le ho kopanya metsoako ea phekolo, e tšoanang le kamoo lihoai li fetolang pH ea mobu ho latela litlhoko tsa lijalo.

1. Boloka tšebetso e nepahetseng ea cellular
Ho belisoa ho itšetlehile ka lisele tse phelang (mohlala, lisele tsa CHO) ho hlahisa li-biomolecules tse rarahaneng. Metabolism ea cellular e ameha haholo ho pH ea tikoloho. Li-enzyme, tse susumetsang karabelo eohle ea biochemical ea intracellular, li na le pH optima e nyane; Ho kheloha ho tloha mofuteng ona ho ka fokotsa haholo ts'ebetso ea enzymatic kapa ho baka denaturation, ho sitisa ts'ebetso ea metabolic. Ho feta moo, ho kenngoa ha limatlafatsi ka lera la sele-joalo ka tsoekere, li-amino acid le matsoai a sa tloaelehang-ho itšetlehile ka pH. Maemo a ka tlase a pH a ka sitisa ho monya limatlafatsi, a lebisa kholong e tlase kapa ho se leka-lekane ha metabolism. Ho feta moo, litekanyetso tsa pH tse feteletseng li ka senya botšepehi ba membrane, e leng se bakang ho lutla ha cytoplasmic kapa lysis ea lisele.

2. Fokotsa sebopeho sa sehlahisoa le litšila tsa substrate
Nakong ea ho belisoa, metabolism ea cellular e hlahisa acidic kapa metabolites ea motheo. Ka mohlala, likokoana-hloko tse ngata li hlahisa organic acid (mohlala, lactic acid, acetic acid) nakong ea "glucose" catabolism, e bakang ho theoha ha pH. Haeba e sa lokisoe, pH e tlase e thibela kholo ea lisele mme e ka fetola phallo ea metabolism ho ea litseleng tse sa hlahiseng, ho eketsa pokello ea lihlahisoa. Lihlahisoa tsena li sebelisa lisebelisoa tsa bohlokoa tsa khabone le matla tse neng li ka tšehetsa tlhahiso ea lihlahisoa tse lebisitsoeng, kahoo li fokotsa chai ka kakaretso. Taolo e sebetsang ea pH e thusa ho boloka litsela tse lakatsehang tsa metabolic le ho ntlafatsa ts'ebetso ea ts'ebetso.

3. Etsa bonnete ba botsitso ba sehlahisoa le ho thibela ho senyeha
Lihlahisoa tse ngata tsa biopharmaceutical, haholo-holo liprotheine tse kang monoclonal antibodies le li-hormone tsa peptide, li kotsing ea liphetoho tsa sebopeho sa pH. Ka ntle ho maemo a bona a tsitsitseng a pH, limolek'hule tsena li ka 'na tsa fetoha denaturation, aggregation, kapa inctivation, tse ka' nang tsa theha pula e kotsi. Ho feta moo, lihlahisoa tse ling li na le tšekamelo ea ho ba le hydrolysis ea lik'hemik'hale kapa ho senyeha ha enzymatic tlasa maemo a asiti kapa a alkaline. Ho boloka pH e nepahetseng ho fokotsa ho senyeha ha sehlahisoa nakong ea tlhahiso, ho boloka potency le polokeho.

4. Ntlafatsa ts'ebetso e sebetsang hantle 'me u netefatse hore batch-to-batch e lumellana
Ho ea ka pono ea indasteri, taolo ea pH e ama ka kotloloho tlhahiso le katleho ea moruo. Patlisiso e batsi e etsoa ho fumana libaka tse nepahetseng tsa pH bakeng sa mekhahlelo e fapaneng ea ho belisoa - joalo ka kholo ea lisele khahlano le polelo ea sehlahisoa - e ka fapana haholo. Taolo e matla ea pH e lumella ho ntlafatsa ho ea ka sethala, ho eketsa pokello ea biomass le li-titers tsa sehlahisoa. Ntle le moo, mekhatlo ea taolo e joalo ka FDA le EMA e hloka ho ts'oaroa ka tieo ho Mekhoa e Metle ea Tlhahiso (GMP), moo litsamaiso tse sa fetoheng tsa ts'ebetso li tlamang. PH e amoheloa e le Critical Process Parameter (CPP), 'me tlhokomelo ea eona e tsoelang pele e netefatsa ho ikatisa ho pholletsa le lihlopha, ho netefatsa polokeho, katleho le boleng ba lihlahisoa tsa meriana.

5. Sebeletsa e le sesupo sa bophelo bo botle ba ho belisoa
Phetoho ea pH e fana ka leseli la bohlokoa mabapi le boemo ba fisioloji ea setso. Phetoho ea tšohanyetso kapa e sa lebelloang ea pH e ka supa tšilafalo, ho se sebetse hantle ha sensor, ho felloa ke limatlafatsi, kapa mathata a metabolism. Ho lemoha pele ho nako ho ipapisitse le litloaelo tsa pH ho thusa ho kenella ka nako, ho thusa ho rarolla mathata le ho thibela ho hloleha ho theko e boima.

Li-sensor tsa pH li lokela ho khethoa joang bakeng sa ts'ebetso ea ho belisoa ho biopharmaceuticals?

Ho khetha sensor e nepahetseng ea pH bakeng sa fermentation ea biopharmaceutical ke qeto ea bohlokoa ea boenjiniere e amang ts'episo ea ts'ebetso, ts'epo ea data, boleng ba sehlahisoa, le ho latela melao. Khetho e lokela ho atameloa ka mokhoa o hlophisitsoeng, o sa nahane feela ka ts'ebetso ea sensor empa hape e lumellana le ts'ebetso eohle ea bioprocessing.

1. Mocheso o phahameng le ho hanyetsa khatello
Mekhoa ea biopharmaceutical hangata e sebelisa in-situ steam sterilization (SIP), hangata ka 121°C le khatello ea 1-2 bar bakeng sa metsotso e 20-60. Ka hona, sensor efe kapa efe ea pH e tlameha ho mamella ho pepesetsoa khafetsa maemo a joalo ntle le ho hloleha. Ha e le hantle, sensor e lokela ho lekanyetsoa bonyane 130 ° C le 3-4 bar ho fana ka moeli oa tšireletso. Ho tiisa ka matla ho bohlokoa ho thibela ho kenella ha mongobo, ho lutla ha electrolyte, kapa tšenyo ea mochini nakong ea libaesekele tse futhumetseng.

2. Mofuta oa kutlo le tsamaiso ea litšupiso
Ena ke taba ea mantlha ea tekheniki e amang botsitso ba nako e telele, litlhoko tsa tlhokomelo, le ho hanyetsa ho se sebetse hantle.
Tlhophiso ea Electrode: Li-electrode tse kopantsoeng, tse kopanyang likarolo tsa ho lekanya le litšupiso 'meleng o le mong, li amoheloa ka bongata ka lebaka la boiketlo ba ho kenya le ho sebetsana le tsona.
Sistimi ea litšupiso:
• Referense e tletseng metsi (mohlala, tharollo ea KCl): E fana ka karabelo e potlakileng le ho nepahala ho phahameng empa e hloka ho tlatsoa nako le nako. Nakong ea SIP, tahlehelo ea electrolyte e ka 'na ea etsahala,' me li-junctions tsa porous (mohlala, li-ceramic frits) li atisa ho koaloa ke liprotheine kapa li-particulate, tse lebisang ho hole le ho bala ho sa tšepahaleng.
• Polymer gel kapa solid-state reference: E ntse e ratoa haholo ho li-bioreactors tsa sejoale-joale. Litsamaiso tsena li felisa tlhoko ea ho tlatsa li-electrolyte, li fokotsa tlhokomelo, 'me li na le li-junctions tse pharalletseng tsa mokelikeli (mohlala, mehele ea PTFE) e hanelang ho silafatsoa. Li fana ka botsitso bo phahameng le bophelo bo bolelele ba ts'ebeletso mecheng ea litaba e rarahaneng, ea viscous fermentation.

3. Lethathamo la tekanyo le ho nepahala
Sensor e lokela ho koahela mefuta e mengata ea ts'ebetso, hangata pH 2-12, ho amohela mekhahlelo e fapaneng ea ts'ebetso. Ka lebaka la kutloisiso ea litsamaiso tsa likokoana-hloko, ho nepahala ha tekanyo ho lokela ho ba ka har'a ± 0.01 ho ± 0.02 li-pH units, tse tšehetsoeng ke tlhahiso ea matšoao a phahameng.

4. Nako ea ho arabela
Nako ea ho arabela hangata e hlalosoa e le t90-nako e hlokahalang ho fihla 90% ea 'malo oa ho qetela ka mor'a phetoho ea mohato pH. Le hoja li-electrode tsa mofuta oa gel li ka 'na tsa bontša karabelo e liehang ho feta tse tletseng metsi, ka kakaretso li finyella litlhoko tse matla tsa li-loops tsa ho laola, tse sebetsang ka nako ea hora ho e-na le metsotsoana.

5. Biocompatibility
Lisebelisoa tsohle tse amanang le mokhoa oa setso li tlameha ho ba tse se nang chefo, tse se nang chefo, le tse sa tsitsang ho qoba liphello tse mpe ho sebetsa ha sele kapa boleng ba sehlahisoa. Lisebelisoa tse khethehileng tsa khalase tse etselitsoeng lits'ebetso tsa bioprocessing li khothaletsoa ho netefatsa khanyetso ea lik'hemik'hale le biocompatibility.

6. Phallo ea pontšo le sebopeho
• Sehlahisoa sa Analog (mV/pH): Mokhoa oa setso o sebelisang phetiso ea analoge ho sistimi ea taolo. E boloka litšenyehelo empa e le kotsing ea ho sitisoa ke motlakase le ho fokotsa matšoao libakeng tse telele.
• Digital output (mohlala, disensara tse thehilweng ho MEMS kapa tse bohlale): E kenyelletsa di-microelectronics tsa onboard ho fetisa matshwao a dijithale (mohlala, ka RS485). E fana ka tšireletso e ntle ea lerata, e ts'ehetsa puisano ea sebaka se selelele, 'me e nolofalletsa ho boloka nalane ea calibration, linomoro tsa serial, le lits'ebetso tsa ts'ebeliso. E lumellana le litekanyetso tsa taolo tse joalo ka FDA 21 CFR Karolo ea 11 mabapi le lirekoto tsa elektroniki le mesaeno, e etsa hore e ratehe haholoanyane tikolohong ea GMP.

7. Sebopeho sa ho kenya le matlo a sireletsang
Sensor e tlameha ho lumellana le boema-kepe bo khethiloeng ho bioreactor (mohlala, tri-clamp, sanitary fitting). Matsoho a ts'ireletso kapa balebeli ba eletsoa ho thibela tšenyo ea mochini nakong ea ts'ebetso kapa ts'ebetso le ho thusa ho nkela sebaka habonolo ntle le ho senya sterility.