Kev tswj qhov viscosity ntawm cov protein solutions yog qhov tseem ceeb rau kev ua kom zoo dua cov txheej txheem ultrafiltration concentration hauv biopharmaceutical manufacturing. Qhov viscosity siab hauv cov protein solutions—tshwj xeeb tshaj yog ntawm cov protein concentration siab—cuam tshuam ncaj qha rau kev ua haujlwm ntawm daim nyias nyias, kev ua haujlwm zoo, thiab kev lag luam hauv kev siv ultrafiltration protein concentration. Qhov viscosity ntawm cov kua nce nrog cov protein vim yog kev sib sau ua ke ntawm lub cev thiab kev sib cuam tshuam electrostatic, uas ua rau muaj kev tiv thaiv rau kev ntws thiab kev poob siab hla daim nyias nyias ultrafiltration. Qhov no ua rau cov permeate fluxes qis dua thiab lub sijhawm ua haujlwm ntev dua, tshwj xeeb tshaj yog hauv cov txheej txheem transverse flow filtration (TFF).
Lub zog siab transmembrane (TMP), lub zog tsav tsheb tom qab ultrafiltration, yog txuas nrog viscosity. Kev ua haujlwm sab nraum qhov ntau ntawm lub zog siab transmembrane ib txwm ua rau cov membrane fouling sai dua thiab ua rau cov concentration polarization hnyav dua - qhov kev sib sau ua ke ntawm cov protein ze ntawm daim nyias nyias uas ua rau cov viscosity hauv zos nce ntxiv. Ob qho tib si concentration polarization thiab membrane fouling ua rau kev ua haujlwm ntawm daim nyias nyias ultrafiltration txo qis thiab tuaj yeem ua rau lub neej ntawm daim nyias nyias luv dua yog tias tsis kuaj xyuas. Cov haujlwm sim qhia tau hais tias membrane fouling thiab concentration polarization hauv ultrafiltration pom tseeb dua ntawm cov nqi TMP siab dua thiab nrog cov khoom noj ntau dua, ua rau kev tswj hwm TMP tiag tiag tseem ceeb kom ua tiav qhov siab tshaj plaws thiab txo qhov zaus ntxuav.
Kev ua kom zoo dua ntawm kev siv ultrafiltration concentration yuav tsum muaj cov tswv yim sib koom ua ke:
- Kev ntsuas viscosity ntawm cov kua proteinKev ntsuam xyuas viscosity tsis tu ncua—sivcov viscometers hauv kab—pab kwv yees cov nqi lim dej thiab kwv yees cov teeb meem ntawm cov txheej txheem, txhawb kev hloov pauv sai.
- Kev kho kom zoo rau kev pub misKev kho pH, lub zog ionic, thiab qhov kub tuaj yeem txo qhov viscosity thiab txo qhov fouling. Piv txwv li, kev ntxiv sodium ions ua rau kom muaj kev sib zog ntawm cov protein, txo qhov kev sib sau ua ke thiab fouling, thaum calcium ions feem ntau txhawb kev sib txuas protein thiab fouling.
- Kev siv cov khoom xyawKev sib xyaw ua ke ntawm cov tshuaj uas txo qhov viscosity rau hauv cov tshuaj protein uas muaj zog heev ua rau cov membrane permeability zoo dua thiab txo cov siab transmembrane hauv ultrafiltration, ua rau muaj kev ua haujlwm zoo dua.
- Cov txheej txheem ntws siab heevKev ua kom cov dej ntws nrawm dua, siv cov dej ntws sib hloov, lossis siv cov tshuab txhaj tshuaj cua yuav cuam tshuam cov txheej av uas muaj av qias. Cov txheej txheem no pab txhawb nqa cov dej ntws thiab txo qhov zaus hloov pauv ntawm daim nyias nyias los ntawm kev txo qis cov av tsim.
- Kev xaiv thiab kev ntxuav membraneKev xaiv cov daim nyias nyias uas muaj zog tshuaj lom neeg (piv txwv li, SiC lossis thermosalient hybrids) thiab kev ua kom zoo dua qhov zaus ntxuav daim nyias nyias nrog cov txheej txheem tsim nyog (piv txwv li, kev ntxuav sodium hypochlorite) yog qhov tseem ceeb rau kev ua kom lub neej ntawm daim nyias nyias ntev dua thiab txo cov nqi ua haujlwm.
Zuag qhia tag nrho, kev tswj hwm viscosity zoo thiab kev tswj hwm TMP yog lub hauv paus ntawm kev ua tau zoo ntawm theem ultrafiltration concentration, uas cuam tshuam ncaj qha rau cov khoom tsim tawm, zaus ntxuav membrane, thiab lub neej ntev ntawm cov khoom kim heev membrane.
Nkag Siab Txog Cov Protein Solution Viscosity Hauv Ultrafiltration
1.1. Qhov Viscosity ntawm Cov Tshuaj Protein yog dab tsi?
Qhov viscosity piav qhia txog cov kua dej tsis kam rau kev ntws; hauv cov tshuaj protein, nws cim tias muaj pes tsawg qhov kev sib txhuam molecular cuam tshuam kev txav mus los. Lub chav SI rau viscosity yog Pascal-second (Pa·s), tab sis centipoise (cP) feem ntau siv rau cov kua dej biological. Viscosity cuam tshuam ncaj qha rau qhov yooj yim ntawm cov tshuaj protein tuaj yeem pumped lossis lim thaum lub sijhawm tsim khoom thiab cuam tshuam rau kev xa tshuaj, tshwj xeeb tshaj yog rau cov tshuaj biotherapy uas muaj concentration siab.
Qhov kev sib sau ua ke ntawm cov protein yog qhov tseem ceeb uas cuam tshuam rau qhov viscosity. Thaum cov protein ntau ntxiv, kev sib cuam tshuam ntawm cov protein thiab kev sib sau ua ke nce ntxiv, ua rau qhov viscosity nce ntxiv, feem ntau tsis yog linearly. Saum toj no qee qhov threshold, kev sib cuam tshuam ntawm cov protein-protein ntxiv tiv thaiv kev sib kis hauv cov tshuaj. Piv txwv li, cov tshuaj monoclonal antibody uas muaj concentrated siv hauv cov tshuaj feem ntau ncav cuag cov viscosity uas ua rau cov tshuaj txhaj rau hauv qab lossis txwv cov nqi ua haujlwm.
Cov qauv kwv yees qhov viscosity hauv cov protein concentrated tam sim no suav nrog molecular geometry thiab aggregation tendencies. Protein morphology—txawm tias nws yog elongated, globular, lossis prone rau aggregation—cuam tshuam rau viscosity ntawm high concentrations. Cov kev nce qib tsis ntev los no hauv kev ntsuam xyuas microfluidic ua rau muaj kev ntsuas viscosity meej los ntawm cov qauv tsawg kawg nkaus, pab txhawb kev tshuaj xyuas sai ntawm cov protein formulations tshiab.
1.2. Viscosity Hloov Pauv Li Cas Thaum Lub Sijhawm Ultrafiltration
Thaum lub sijhawm ultrafiltration, qhov kev sib xyaw ua ke ntawm cov protein sai sai sib sau ua ke ntawm qhov sib txuas ntawm daim nyias nyias thiab cov kua. Qhov no tsim cov kev hloov pauv hauv zos thiab ua rau cov viscosity nce ze ntawm daim nyias nyias. Cov viscosity siab hauv thaj chaw no cuam tshuam kev hloov pauv ntawm cov pawg thiab txo cov dej ntws.
Kev sib xyaw ua ke ntawm cov dej tsis huv (concentration polarization) txawv ntawm kev ua qias ntawm daim nyias nyias (membrane fouling). Kev sib xyaw ua ke ntawm cov dej tsis huv (polarization) yog qhov hloov pauv tau thiab rov qab tau, tshwm sim hauv ob peb feeb thaum kev lim dej mus ntxiv. Piv txwv li, kev ua qias ntawm cov dej tsis huv no tshwm sim raws sijhawm thiab feem ntau cuam tshuam nrog kev tso dej tsis huv lossis kev hloov pauv tshuaj lom neeg ntawm qhov chaw ntawm daim nyias nyias. Kev kuaj mob kom raug tso cai rau kev taug qab lub sijhawm tiag tiag ntawm cov txheej sib xyaw ua ke ntawm cov dej tsis huv, qhia txog nws qhov kev nkag siab rau qhov ceev ntawm cov dej ntws thiab qhov siab ntawm daim nyias nyias. Piv txwv li, kev nce qhov ceev lossis txo qhov siab ntawm daim nyias nyias (TMP) pab cuam tshuam cov txheej ciam teb viscous, rov qab ua kom cov dej ntws rov qab.
Cov kev ua haujlwm tsis ncaj qha cuam tshuam rau tus cwj pwm viscosity:
- Lub siab ntawm daim nyias nyias (TMP)TMP siab dua ua rau polarization ntau ntxiv, ua rau cov viscosity hauv zos nce ntxiv thiab txo cov flux.
- Qhov ceev ntawm kev ntws hla: Kev nrawm dua txwv tsis pub muaj kev sib sau ua ke, ua kom cov viscosity nyob ze ntawm daim nyias nyias tsis hloov pauv.
- Kev ntxuav membrane zausKev ntxuav ntau zaus txo qhov kev sib sau ua ke mus sij hawm ntev thiab txo qhov kev poob ntawm kev ua haujlwm uas tshwm sim los ntawm viscosity.
Cov theem concentration ultrafiltration yuav tsum ua kom zoo dua cov kev ntsuas no kom txo cov teebmeem viscosity tsis zoo thiab tswj tau qhov throughput.
1.3. Cov Khoom Siv Protein Uas Cuam Tshuam Rau Qhov Viscosity
Qhov hnyav ntawm cov moleculethiabkev sau ua kefeem ntau txiav txim siab qhov viscosity. Cov protein loj dua, nyuaj dua lossis cov aggregates ua rau muaj viscosity ntau dua vim muaj kev txav mus los tsis zoo thiab muaj zog ntau dua ntawm cov intermolecular. Cov duab ntawm cov protein ntxiv hloov pauv qhov ntws - cov saw hlau ntev lossis cov saw hlau sib sau ua ke ua rau muaj kev tiv thaiv ntau dua li cov protein globular compact.
pHMuaj feem cuam tshuam loj heev rau cov protein charge thiab solubility. Kev kho cov pH ntawm cov kua dej ze ntawm cov protein isoelectric point yuav txo qhov net charge, txo cov protein-protein repulsion, thiab txo qhov viscosity ib ntus, ua rau kev lim dej yooj yim dua. Piv txwv li, kev siv ultrafiltration ze ntawm qhov isoelectric point ntawm BSA lossis IgG tuaj yeem ua rau cov permeate flux thiab kev xaiv sib cais zoo dua.
Lub zog ioniccuam tshuam rau qhov viscosity los ntawm kev hloov cov txheej hluav taws xob ob txheej nyob ib puag ncig cov protein. Kev nce ntxiv ntawm lub zog ionic tshuaj ntsuam xyuas kev sib cuam tshuam electrostatic, txhawb kev sib kis protein los ntawm cov membranes tab sis kuj ua rau muaj kev pheej hmoo ntawm kev sib sau ua ke thiab cov viscosity spikes sib xws. Qhov kev pauv pauv ntawm kev ua haujlwm ntawm kev sib kis thiab kev xaiv feem ntau nyob ntawm kev kho kom zoo ntawm cov ntsev concentration thiab cov khoom sib xyaw buffer.
Cov tshuaj ntxiv me me—xws li arginine hydrochloride lossis guanidine—siv tau los txo qhov viscosity. Cov neeg sawv cev no cuam tshuam kev nyiam hydrophobic lossis electrostatic, txo kev sib sau ua ke, thiab txhim kho cov yam ntxwv ntawm kev ntws ntawm cov kua. Qhov kub ua haujlwm ua lwm yam kev hloov pauv tswj; qhov kub qis dua ua rau viscosity nce, thaum qhov kub ntxiv feem ntau ua rau nws txo qis.
Kev ntsuas qhov viscosity ntawm cov kua protein yuav tsum xav txog:
- Kev faib tawm ntawm qhov hnyav molecular
- Cov tshuaj sib xyaw (ntsev, cov khoom siv, cov khoom ntxiv)
- Kev xaiv pH thiab buffer system
- Kev teeb tsa lub zog ionic
Cov yam no yog qhov tseem ceeb rau kev ua kom zoo dua ntawm kev ua haujlwm ntawm ultrafiltration membrane thiab ua kom muaj kev sib xws thoob plaws cov theem concentration thiab cov txheej txheem TFF.
Cov Ntsiab Lus Tseem Ceeb ntawm Ultrafiltration Protein Concentration
Cov Ntsiab Cai ntawm Ultrafiltration Concentration Theem
Kev siv lub zog ntawm cov protein ultrafiltration los ntawm kev siv lub zog siab transmembrane (TMP) hla lub membrane semi-permeable, tsav cov kuab tshuaj thiab cov kuab me me hla thaum khaws cov protein thiab cov molecule loj dua. Cov txheej txheem no siv kev xaiv permeation raws li qhov loj ntawm molecular, nrog rau qhov hnyav molecular ntawm daim nyias nyias (MWCO) txhais qhov loj tshaj plaws ntawm cov molecule uas hla dhau. Cov protein uas tshaj MWCO sib sau ua ke ntawm sab retentate, ua rau lawv cov concentration nce ntxiv thaum permeate raug rho tawm.
Lub sijhawm ultrafiltration concentration tsom mus rau qhov ntim txo thiab kev nplua nuj ntawm cov protein kua. Thaum kev lim dej nce qib, qhov viscosity ntawm cov protein kua feem ntau nce siab, cuam tshuam rau qhov flux thiab TMP xav tau. Cov protein khaws cia yuav cuam tshuam nrog ib leeg thiab nrog daim nyias nyias, ua rau cov txheej txheem tiag tiag nyuaj dua li kev tshem tawm qhov loj me yooj yim. Kev sib cuam tshuam electrostatic, kev sib sau ua ke ntawm cov protein, thiab cov yam ntxwv ntawm cov kua xws li pH thiab ionic lub zog cuam tshuam rau kev khaws cia thiab kev sib cais. Hauv qee kis, kev thauj mus los advective dominates hla diffusion, tshwj xeeb tshaj yog nyob rau hauv daim nyias nyias nrog cov qhov loj dua, ua rau kev cia siab nyuaj raws li kev xaiv MWCO xwb [saib kev tshawb fawb luv luv].
Kev Piav Qhia Txog Transverse Flow Filtration (TFF)
Kev lim dej transverse flow, tseem hu ua tangential flow filtration (TFF), xa cov protein kua tangentially hla lub ntsej muag membrane. Txoj hauv kev no sib txawv nrog kev lim dej tuag, qhov twg cov dej ntws yog perpendicular rau lub membrane, thawb cov khoom me me ncaj qha mus rau hauv thiab nkag mus rau hauv lub lim.
Qhov sib txawv tseem ceeb thiab cov kev cuam tshuam:
- Kev Tswj Xyuas Qhov Phem:TFF txo cov protein thiab cov txheej particulate, hu ua cake formation, los ntawm kev ntxuav cov foulants tawm ntawm daim nyias nyias. Qhov no ua rau cov permeate flux ruaj khov dua thiab yooj yim dua rau kev saib xyuas.
- Kev Khaws Cov Protein:TFF txhawb kev tswj hwm zoo dua ntawm kev sib xyaw ua ke ntawm cov tshuaj - ib txheej ntawm cov tshuaj uas nyob ze ntawm daim nyias nyias - uas, yog tias tsis tswj tau, tuaj yeem txo qhov kev xaiv sib cais thiab ua rau muaj kev puas tsuaj ntau ntxiv. Cov dej ntws hauv TFF txo qhov cuam tshuam no, pab tswj kom muaj cov protein khaws cia thiab ua haujlwm sib cais tau zoo.
- Kev Ruaj Ntseg Flux:TFF ua rau lub sijhawm ua haujlwm ntev dua ntawm cov dej ntws sib xws, ua kom muaj txiaj ntsig zoo hauv cov txheej txheem nrog cov khoom noj muaj protein ntau lossis cov khoom noj muaj ntau. Los ntawm qhov sib piv, kev lim dej tuag-kawg raug cuam tshuam sai sai los ntawm kev ua qias tuaj, txo qis kev ua haujlwm thiab xav tau kev ntxuav ntau zaus.
Cov TFF uas hloov pauv siab heev, xws li kev hloov pauv ntawm cov dej ntws tangential (ATF), cuam tshuam ntxiv rau qhov ua kom cov av qias thiab cov khoom qab zib los ntawm kev hloov pauv lossis hloov pauv cov tangential velocities, ua kom lub lim dej siv tau ntev dua thiab txhim kho cov protein throughput [saib cov ntsiab lus tshawb fawb]. Hauv ob qho tib si classic thiab advanced TFF teeb tsa, cov chaw ua haujlwm—xws li TMP, crossflow velocity, thiab kev ntxuav zaus—yuav tsum tau kho kom haum rau cov protein system tshwj xeeb, hom membrane, thiab lub hom phiaj concentration kom ua tau zoo tshaj plaws thiab txo qhov ua kom cov av qias.
Transmembrane Pressure (TMP) hauv Ultrafiltration
3.1. Lub Siab Transmembrane Yog Dab Tsi?
Lub siab ntawm daim nyias nyias (TMP) yog qhov sib txawv ntawm lub siab hla daim nyias nyias lim dej, tsav cov kuab tshuaj los ntawm sab pub mus rau sab permeate. TMP yog lub zog tseem ceeb tom qab cov txheej txheem sib cais hauv ultrafiltration, uas tso cai rau cov kuab tshuaj hla dhau daim nyias nyias thaum khaws cov protein thiab lwm yam macromolecules.
TMP cov qauv:
- Qhov txawv yooj yim: TMP = P_feed − P_permeate
- Txoj kev tsim kho: TMP = [(P_feed + P_retentate)/2] − P_permeate
Ntawm no, P_feed yog lub siab nkag, P_retentate yog lub siab tawm ntawm sab retentate, thiab P_permeate yog lub siab sab permeate. Kev suav nrog lub siab retentate (lossis concentrate) muab tus nqi tseeb dua ntawm qhov chaw membrane, suav nrog cov gradients siab los ntawm kev tiv thaiv dej ntws thiab fouling. - Lub zog pub thiab tus nqi ntws
- Kev nias kom ruaj khov (yog tias siv tau)
- Lub zog nkag mus (feem ntau yog atmospheric)
- Kev tiv thaiv ntawm daim nyias nyias
TMP sib txawv raws li hom membrane, tsim qauv, thiab cov xwm txheej ntawm cov txheej txheem.
Kev Tswj Cov Hloov Pauv:
3.2. TMP thiab Cov Txheej Txheem Ultrafiltration
TMP ua lub luag haujlwm tseem ceeb hauv kev sib sau ua ke ntawm cov protein hauv ultrafiltration, tsav cov protein solutions hla lub membrane. Lub siab yuav tsum siab txaus kom kov yeej qhov kev tiv thaiv los ntawm lub membrane thiab cov khoom sib sau ua ke tab sis tsis txhob siab dhau uas nws ua rau cov av qias sai dua.
Kev Cuam Tshuam ntawm Viscosity thiab Protein Concentration ntawm Cov Tshuaj
- Viscosity ntawm cov kua protein:Qhov viscosity siab dua ua rau cov dej ntws tsis kam, xav tau TMP siab dua kom tswj tau tib qhov permeate flux. Piv txwv li, ntxiv glycerol rau hauv cov pub lossis siv cov protein concentrated ua rau cov viscosity nce thiab yog li qhov TMP ua haujlwm xav tau.
- Kev sib sau ua ke ntawm cov protein:Thaum qhov concentration nce ntxiv thaum lub sijhawm ultrafiltration concentration, qhov viscosity ntawm cov kua dej nce ntxiv, TMP nce ntxiv, thiab qhov kev pheej hmoo ntawm membrane fouling lossis concentration polarization nce ntxiv.
- Txoj Cai Darcy:TMP, permeate flux (J), thiab viscosity (μ) muaj feem cuam tshuam los ntawm TMP = J × μ × R_m (membrane resistance). Rau cov protein solutions uas muaj viscosity siab, kev kho TMP kom zoo yog qhov tseem ceeb rau kev ua haujlwm ultrafiltration zoo.
Piv txwv li:
- Kev lim dej ntawm cov tshuaj antibody ntom ntom yuav tsum tau tswj hwm TMP kom zoo kom tiv thaiv tau qhov nce viscosity.
- PEGylation lossis lwm yam kev hloov pauv protein hloov pauv kev sib cuam tshuam nrog daim nyias nyias, cuam tshuam rau TMP uas xav tau rau cov dej ntws xav tau.
3.3. Kev Saib Xyuas thiab Kev Txhim Kho TMP
Kev tswj hwm TMP hauvqhov ntau ntawm cov siab transmembrane ib txwm muajyog qhov tseem ceeb rau kev ua haujlwm ruaj khov ntawm daim nyias nyias ultrafiltration thiab cov khoom zoo. Raws li lub sijhawm dhau mus, thaum ultrafiltration nce mus, kev sib xyaw ua ke ntawm cov concentration thiab fouling tuaj yeem ua rau TMP nce siab, qee zaum sai.
Kev Ua Haujlwm Saib Xyuas:
- Kev saib xyuas tiag tiag:TMP raug taug qab los ntawm kev nkag, rov qab, thiab nkag muscov khoom xa tawm siab.
- Raman Spectroscopy:Siv rau kev saib xyuas tsis muaj kev cuam tshuam ntawm cov protein thiab cov khoom siv ntxiv, pab txhawb kev tswj hwm TMP thaum lub sijhawm ultrafiltration thiab diafiltration.
- Kev tswj hwm siab heev:Cov Lim Kalman Ntev (EKF) tuaj yeem ua cov ntaub ntawv sensor, kho TMP kom tsis txhob muaj kev qias neeg ntau dhau.
- Teem thawj TMP hauv qhov ntau thiab tsawg ib txwm:Tsis txhob qis dhau los txo cov dej ntws, tsis txhob siab dhau los tiv thaiv kev ua qias sai.
- Kho TMP thaum viscosity nce ntxiv:Thaum lub sijhawm ultrafiltration concentration, maj mam nce TMP tsuas yog thaum xav tau.
- Tswj cov dej ntws thiab pH ntawm cov khoom noj:Kev nce cov dej pub mis lossis txo qis TMP txo qhov concentration polarization thiab fouling.
- Kev ntxuav thiab hloov daim nyias nyias:TMPs siab dua cuam tshuam nrog kev ntxuav ntau zaus thiab txo lub neej ntawm daim nyias nyias.
Kev Txhim Kho Cov Tswv Yim:
Piv txwv li:
- Kev xeb hauv cov kab ua cov protein ua rau muaj TMP ntau ntxiv thiab txo cov dej ntws, xav tau kev ntxuav lossis hloov daim nyias nyias kom rov ua haujlwm li qub.
- Kev kho ua ntej enzymatic (piv txwv li, pectinase ntxiv) tuaj yeem txo qis TMP thiab ntev lub neej ntawm daim nyias nyias thaum lub sijhawm ua cov protein rapeseed uas muaj viscosity siab.
3.4. TMP hauv TFF Systems
Tangential (transverse) flow filtration (TFF) ua haujlwm los ntawm kev xa cov kua dej pub hla lub membrane es tsis yog ncaj qha los ntawm nws, cuam tshuam rau TMP dynamics.
Kev Tswj thiab Kev Sib Npaug ntawm TMP
- TFF transmembrane siab (TFF TMP):Nws raug tswj los ntawm kev tswj ob qho tib si qhov nrawm ntawm kev pub dej thiab lub zog ntawm lub twj tso kua mis kom tsis txhob muaj TMP ntau dhau thaum ua kom cov dej ntws mus rau hauv lub cev ntau tshaj plaws.
- Optimizing parameters:Kev nce ntxiv ntawm cov khoom noj pub rau hauv plab yuav txo cov protein uas tso rau hauv plab, ua kom TMP ruaj khov, thiab txo cov membrane fouling.
- Kev suav lej ua qauv:Cov qauv CFD kwv yees thiab ua kom zoo dua TFF TMP rau qhov siab tshaj plaws rov qab tau cov khoom, kev ntshiab, thiab cov txiaj ntsig - tshwj xeeb tshaj yog qhov tseem ceeb rau cov txheej txheem xws li mRNA lossis kev cais cov vesicle sab nraud.
Piv txwv li:
- Hauv kev ua bioprocessing, qhov zoo tshaj plaws TFF TMP ua rau ntau dua 70% mRNA rov qab los yam tsis muaj kev puas tsuaj, ua tau zoo dua li cov txheej txheem ultracentrifugation.
- Kev tswj hwm TMP uas hloov tau yooj yim, uas tau txais kev qhia los ntawm cov qauv lej thiab cov lus teb ntawm lub sensor, txo qhov zaus hloov daim nyias nyias thiab ua kom daim nyias nyias siv tau ntev dua los ntawm kev txo qhov fouling.
Cov ntsiab lus tseem ceeb:
- TMP transmembrane pressure yuav tsum tau tswj hwm kom zoo hauv TFF kom tswj tau cov txheej txheem ua haujlwm tau zoo, flux, thiab kev noj qab haus huv ntawm daim nyias nyias.
- Kev ua kom zoo dua TMP tsis tu ncua txo cov nqi ua haujlwm, txhawb kev rov qab tau cov khoom muaj txiaj ntsig zoo, thiab ua kom lub membrane siv tau ntev dua hauv cov protein ultrafiltration thiab cov txheej txheem cuam tshuam.
Cov Txheej Txheem Fouling thiab Lawv Txoj Kev Sib Raug Zoo rau Viscosity
Cov Kev Ua Phem Tseem Ceeb hauv Protein Ultrafiltration
Protein ultrafiltration yog cuam tshuam los ntawm ntau txoj kev fouling sib txawv:
Kev puas tsuaj los ntawm corrosion:Tshwm sim thaum cov khoom xeb—feem ntau yog cov hlau oxides—sib sau ua ke rau ntawm cov nplaim ntawm daim nyias nyias. Cov no txo cov dej ntws thiab nyuaj rau tshem tawm nrog cov tshuaj ntxuav tshuaj ib txwm muaj. Kev xeb ua rau lub ntsej muag puas tsuaj ua rau lub ntsej muag poob qis thiab ua rau lub ntsej muag hloov pauv ntau zaus dhau sijhawm. Nws qhov cuam tshuam loj heev nrog PVDF thiab PES daim nyias nyias siv rau hauv kev kho dej thiab kev siv protein.
Kev ua qias tuaj ntawm cov organic:Feem ntau yog cov protein xws li bovine serum albumin (BSA) ua rau muaj kev phom sij, thiab tej zaum yuav ua rau muaj zog dua yog tias muaj lwm yam organic xws li polysaccharides (piv txwv li, sodium alginate). Cov txheej txheem suav nrog kev nqus mus rau ntawm cov qhov hws ntawm daim nyias nyias, qhov hws txhaws, thiab kev tsim cov txheej ncuav mog qab zib. Cov teebmeem synergistic tshwm sim thaum muaj ntau yam khoom xyaw organic, nrog rau cov kab ke sib xyaw ua rau muaj kev phom sij ntau dua li cov khoom noj protein ib leeg.
Kev sib xyaw ua ke ntawm kev sib xyaw ua ke:Thaum ultrafiltration nce qib, cov protein uas khaws cia yuav sib sau ua ke ze ntawm qhov chaw ntawm daim nyias nyias, ua rau cov concentration thiab viscosity hauv zos nce ntxiv. Qhov no tsim ib txheej polarization uas ua rau cov av qias neeg thiab txo cov dej ntws. Cov txheej txheem no ua kom nrawm dua thaum theem ultrafiltration concentration nce qib, cuam tshuam ncaj qha los ntawm lub siab transmembrane thiab cov dej ntws.
Colloidal thiab Mixed-Foulant Fouling:Cov khoom Colloidal (piv txwv li, silica, cov zaub mov inorganic) yuav cuam tshuam nrog cov protein, tsim cov txheej sib xyaw ua ke uas ua rau cov membrane fouling ntxiv. Piv txwv li, qhov muaj colloidal silica ua rau cov nqi flux qis dua, tshwj xeeb tshaj yog thaum ua ke nrog cov organic lossis nyob rau hauv cov xwm txheej pH tsis zoo.
Kev cuam tshuam ntawm Viscosity ntawm Cov Tshuaj rau Kev Loj Hlob Fouling
Qhov viscosity ntawm cov protein solutions muaj feem cuam tshuam rau fouling kinetics thiab membrane compaction:
Kev Ua Kom Ceev Ceev:Qhov viscosity ntawm cov kua protein ntau dua ua rau muaj kev tiv thaiv rau kev thauj rov qab ntawm cov solutes uas khaws cia, ua rau cov txheej ncuav mog qab zib sai dua. Qhov no ua rau lub siab transmembrane (TMP) loj zuj zus, ua rau cov membrane compaction thiab fouling sai dua.
Cov teebmeem ntawm cov tshuaj sib xyaw:Hom protein hloov viscosity; cov protein globular (piv txwv li, BSA) thiab cov protein txuas ntxiv ua txawv txog kev ntws thiab polarization. Ntxiv cov tshuaj xws li polysaccharides lossis glycerol ua rau viscosity nce siab, ua rau fouling. Cov khoom ntxiv thiab cov protein sib sau ua ke ntawm cov concentration siab ntxiv ua rau qhov ceev uas cov membranes clog, ncaj qha txo cov flux thiab membrane lub neej.
Cov txiaj ntsig ntawm kev ua haujlwm:Qhov viscosity siab dua yuav tsum tau nce TMP kom tswj tau qhov kev lim dej hauv cov txheej txheem lim dej transverse flow. Kev raug TMP siab ntev ua rau muaj qhov tsis zoo uas tsis tuaj yeem rov qab tau, feem ntau yuav tsum tau ntxuav daim nyias nyias ntau zaus lossis hloov daim nyias nyias ua ntej.
Lub Luag Haujlwm ntawm Cov Yam Ntxwv ntawm Pub Noj
Cov yam ntxwv ntawm cov khoom noj - xws li cov khoom ntawm cov protein thiab cov tshuaj lom neeg ntawm cov dej - txiav txim siab qhov hnyav ntawm qhov ua qias tuaj:
Qhov Loj thiab Kev Faib Tawm ntawm Cov Protein:Cov protein loj dua lossis sib sau ua ke muaj feem ntau dua los ua rau lub qhov hws thaiv thiab ua rau lub ncuav mog qab zib loj hlob, ua rau cov viscosity thiab compaction nce ntxiv thaum lub sijhawm ultrafiltration protein concentration.
pH:Qhov pH siab dua ua rau electrostatic repulsion ntau ntxiv, tiv thaiv cov protein kom tsis txhob sib sau ua ke ze ntawm daim nyias nyias, yog li ntawd txo qhov fouling. Qhov sib txawv, cov xwm txheej acidic txo qhov repulsion, tshwj xeeb tshaj yog rau colloidal silica, ua rau daim nyias nyias fouling ntau ntxiv thiab txo cov nqi flux.
Kub:Feem ntau qhov kub ntawm cov txheej txheem qis dua yuav txo qhov zog kinetic, uas tuaj yeem ua rau qeeb qeeb ntawm kev ua qias tuaj tab sis kuj ua rau cov kua nplaum viscosity nce ntxiv. Qhov kub siab ua rau kev ua qias tuaj sai dua tab sis kuj tseem yuav ua rau kev ntxuav zoo dua.
Cov Khoom Colloidal / Inorganic:Qhov muaj cov colloidal silica lossis cov hlau ua rau muaj kev qias neeg ntau ntxiv, tshwj xeeb tshaj yog nyob rau hauv cov xwm txheej acidic. Cov khoom me me ntawm silica ua rau tag nrho cov kua viscosity thiab ua rau cov qhov hws tsis ua haujlwm zoo, ua rau kev siv ultrafiltration tsawg dua thiab txo qis lub neej thiab kev ua haujlwm ntawm daim nyias nyias.
Cov khoom sib xyaw ntawm Ionic:Ntxiv qee cov hom ionic (Na⁺, Zn²⁺, K⁺) yuav txo qhov fouling los ntawm kev hloov kho electrostatic thiab hydration forces ntawm cov protein thiab membranes. Txawm li cas los xij, cov ions zoo li Ca²⁺ feem ntau txhawb kev sib sau ua ke thiab ua rau muaj peev xwm fouling ntau dua.
Piv txwv li:
- Thaum lub sijhawm lim dej transverse flow, cov khoom noj uas muaj cov protein ntau thiab viscosity siab yuav poob qis sai, ua rau kev ntxuav thiab hloov pauv sai dua.
- Thaum cov dej pub muaj cov colloidal silica thiab raug acidified, silica aggregation thiab deposition yuav ua rau muaj zog, ua rau cov nqi fouling nce ntxiv thiab txo qis kev ua haujlwm ntawm daim nyias nyias.
Hauv kev xaus lus, kev nkag siab txog kev sib cuam tshuam ntawm cov kua viscosity, cov hom fouling, thiab cov yam ntxwv pub yog qhov tseem ceeb rau kev ua kom zoo dua ultrafiltration concentration, txo cov membrane fouling, thiab ua kom lub neej membrane ntev tshaj plaws.
Kev Sib Cais Polarization thiab Nws Txoj Kev Tswj Xyuas
Kev sib xyaw ua ke ntawm kev sib xyaw ua ke yog dab tsi?
Kev sib xyaw ua ke ntawm cov tshuaj yaj uas khaws cia - xws li cov protein - ntawm qhov sib txuas ntawm daim nyias nyias / cov kua dej thaum lub sijhawm ultrafiltration. Hauv cov ntsiab lus ntawm cov kua protein, thaum cov kua ntws tawm tsam daim nyias nyias semi-permeable, cov protein uas daim nyias nyias tsis lees txais feem ntau yuav sib sau ua ke hauv ib txheej ciam teb nyias uas nyob ib sab ntawm qhov chaw. Qhov kev sib sau ua ke no ua rau muaj qhov sib txawv ntawm cov concentration: cov protein concentration siab ntawm daim nyias nyias, qis dua hauv cov kua dej ntau. Qhov xwm txheej no yog qhov rov qab tau thiab tswj hwm los ntawm cov zog hydrodynamic. Nws sawv cev rau qhov sib txawv ntawm daim nyias nyias fouling, uas cuam tshuam nrog kev tso dej mus tas li lossis kev nqus mus rau hauv lossis rau ntawm daim nyias nyias.
Yuav ua li cas Concentration Polarization Exacerbates Viscosity thiab Fouling
Ntawm qhov chaw ntawm daim nyias nyias, cov protein sib sau ua ke tas li tsim ib txheej ciam teb uas ua rau cov tshuaj yaj hauv zos ntau ntxiv. Qhov no muaj ob qho teeb meem tseem ceeb:
Kev Nce Qib Hauv Viscosity:Thaum qhov concentration ntawm cov protein nce siab ze ntawm daim nyias nyias, qhov viscosity ntawm cov protein solution hauv qhov microregion no kuj nce ntxiv. Qhov viscosity siab dua ua rau cov solute rov qab los ntawm daim nyias nyias, ua rau qhov concentration gradient steeping ntxiv thiab tsim kom muaj lub voj voog rov qab los ntawm kev tiv thaiv kev ntws. Qhov no ua rau cov permeate flux txo qis thiab xav tau lub zog ntau dua rau kev lim dej txuas ntxiv.
Kev pab txhawb rau Membrane Fouling:Qhov muaj protein ntau nyob ze ntawm daim nyias nyias ua rau muaj feem ntau ntawm cov protein sib sau ua ke thiab, hauv qee lub tshuab, tsim cov txheej gel. Cov txheej no thaiv cov qhov hws ntawm daim nyias nyias thiab ua rau qhov tsis kam ntws ntau ntxiv. Cov xwm txheej zoo li no yog lub sijhawm rau qhov pib ntawm qhov tsis rov qab los, qhov twg cov protein sib sau ua ke thiab cov khoom tsis huv khi rau lub cev lossis tshuaj lom neeg lub cev.
Kev kuaj duab sim (piv txwv li, electron microscopy) lees paub qhov sib sau ua ke sai ntawm cov protein pawg nanosized ntawm daim nyias nyias, uas tuaj yeem loj hlob mus rau hauv cov chaw tso nyiaj loj yog tias qhov chaw ua haujlwm tsis raug tswj hwm kom zoo.
Cov Tswv Yim Los Txo Qhov Kev Sib Cais ntawm Kev Sib Cais
Kev tswj hwm qhov kev sib xyaw ua ke ntawm cov protein hauv ultrafiltration lossis transverse flow filtration xav tau ob txoj hauv kev: kho cov hydrodynamics thiab kho cov kev ua haujlwm.
Kev Txhim Kho Qhov Ceev Ntawm Cov Dej Ntws:
Kev nce qhov ceev ntawm kev ntws hla daim nyias nyias ua rau cov dej ntws tangential hla daim nyias nyias, txhawb kev txiav thiab ua rau cov txheej txheem concentration boundary nyias nyias. Kev txiav uas muaj zog dua yuav tshem cov protein uas tau sib sau ua ke tawm ntawm daim nyias nyias, txo ob qho tib si polarization thiab kev pheej hmoo ntawm kev fouling. Piv txwv li, kev siv cov khoom sib xyaw static lossis kev qhia cov roj sparging cuam tshuam cov txheej solute, tshwj xeeb tshaj yog txhim kho permeate flux thiab kev ua haujlwm zoo hauv cov txheej txheem lim dej transverse.
Kev Hloov Kho Cov Kev Cai Ua Haujlwm:
Siab hla daim nyias nyias (TMP):TMP yog qhov sib txawv ntawm lub siab hla lub membrane thiab lub zog tsav rau ultrafiltration. Txawm li cas los xij, thawb TMP siab dua kom ua kom lub lim dej nrawm dua tuaj yeem rov qab los ntawm kev ua kom lub polarization ntawm cov concentration nce ntxiv. Kev ua raws li qhov ntau ntawm lub siab transmembrane ib txwm muaj - tsis pub dhau qhov txwv uas tau teeb tsa rau protein ultrafiltration - pab tiv thaiv kom tsis txhob muaj cov solute ntau dhau thiab qhov nce ntxiv ntawm cov viscosity hauv zos.
Tus Nqi Txiav:Qhov nrawm ntawm kev txiav, ib qho haujlwm ntawm qhov nrawm ntawm kev ntws hla thiab kev tsim cov channel, ua lub luag haujlwm tseem ceeb hauv kev thauj cov kuab tshuaj. Qhov nrawm siab ua rau cov txheej polarization nyias thiab txav tau, ua rau thaj chaw uas cov kuab tshuaj tsis muaj zog nyob ze ntawm daim nyias nyias rov ua dua tshiab. Qhov nrawm ntawm kev txiav nce ntxiv yuav txo lub sijhawm uas cov protein yuav tsum sib sau ua ke thiab txo qhov viscosity nce ntawm qhov interface.
Cov Khoom Noj Khoom Haus:Kev kho cov yam ntxwv ntawm cov kua protein uas nkag los—xws li txo qhov viscosity ntawm cov kua protein, txo cov ntsiab lus sib sau ua ke, lossis tswj pH thiab lub zog ionic—tuaj yeem pab txo qhov dav thiab qhov cuam tshuam ntawm kev sib xyaw ua ke. Kev kho ua ntej pub mis thiab kev hloov pauv ntawm cov mis yuav ua rau kev ua haujlwm ntawm daim nyias nyias ultrafiltration zoo dua thiab ntev lub neej ntawm daim nyias nyias los ntawm kev txo qhov zaus ntawm kev ntxuav daim nyias nyias.
Piv txwv daim ntawv thov:
Ib lub Hoobkas siv tangential flow filtration (TFF) los ua kom cov monoclonal antibodies sib sau ua ke siv cov cross-flow velocities zoo tshaj plaws thiab tswj TMP hauv lub sijhawm nruj. Los ntawm kev ua li ntawd, cov neeg ua haujlwm txo qis qhov kev sib xyaw ua ke thiab cov membrane fouling, txo ob qho tib si zaus hloov membrane thiab cov voj voog ntxuav - ncaj qha txo cov nqi ua haujlwm thiab txhim kho cov khoom tsim tau.
Kev kho kom zoo thiab kev saib xyuas cov kev hloov pauv no—xws li kev ntsuas viscosity ntawm cov kua protein tiag tiag—yog qhov tseem ceeb rau kev ua kom zoo dua qhov kev ua haujlwm ntawm ultrafiltration concentration thiab txo cov teebmeem tsis zoo uas cuam tshuam nrog kev sib xyaw ua ke hauv kev ua cov protein.
Kev Txhim Kho Ultrafiltration rau Cov Tshuaj Protein High-Vicosity
6.1. Cov Kev Xyaum Ua Haujlwm Zoo Tshaj Plaws
Kev tswj hwm qhov ua tau zoo tshaj plaws ntawm ultrafiltration nrog cov protein uas muaj viscosity siab yuav tsum muaj qhov sib npaug zoo ntawm transmembrane pressure (TMP), protein concentration, thiab cov kua viscosity. TMP—qhov sib txawv ntawm qhov siab hla lub membrane—muaj feem cuam tshuam ncaj qha rau qhov ultrafiltration protein concentration rate thiab qib ntawm membrane fouling. Thaum ua cov kua viscous xws li monoclonal antibodies lossis cov protein serum uas muaj concentration siab, txhua qhov kev nce ntxiv ntawm TMP yuav ua rau muaj flux ntau ntxiv, tab sis nws kuj ua rau muaj fouling thiab protein sib sau ua ke sai sai ntawm qhov chaw ntawm lub membrane. Qhov no ua rau muaj kev cuam tshuam thiab tsis ruaj khov ntawm cov txheej txheem lim dej, lees paub los ntawm kev tshawb fawb duab qhia txog cov protein tuab uas tsim ntawm TMP siab thiab cov protein concentration siab dua 200 mg/mL.
Txoj kev zoo tshaj plaws yog khiav lub kaw lus ze, tab sis tsis pub tshaj qhov TMP tseem ceeb. Thaum lub sijhawm no, kev tsim khoom tau siab tshaj plaws tab sis qhov kev pheej hmoo ntawm kev ua qias tuaj yeem tsis rov qab tau tseem tsawg heev. Rau cov viscosities siab heev, cov kev tshawb pom tsis ntev los no qhia tias txo TMP thiab tib lub sijhawm nce cov dej ntws pub (transverse flow filtration) los pab txo qhov concentration polarization thiab protein deposition. Piv txwv li, kev tshawb fawb hauv Fc-fusion protein concentration qhia tau tias qhov chaw TMP qis dua pab tswj cov dej ntws ruaj khov thaum txo cov khoom poob.
Qhov kev nce ntxiv ntawm cov protein concentration thaum lub sijhawm ultrafiltration yog qhov tseem ceeb heev. Cov kauj ruam concentration sai sai tuaj yeem yuam cov tshuaj mus rau hauv qhov kev tswj hwm high-viscosity sai dhau, ua rau muaj kev pheej hmoo ntawm kev sib sau ua ke thiab qhov hnyav ntawm fouling. Hloov chaw, kev nce qib protein maj mam tso cai rau cov txheej txheem parallel xws li TMP, cross-flow velocity, thiab pH kom raug kho ua ke, pab tswj kev ruaj khov ntawm lub cev. Cov kev tshawb fawb txog enzyme ultrafiltration lees paub tias kev tswj hwm qis dua kev ua haujlwm thaum lub sijhawm no ua kom ntseeg tau tias muaj kev tswj hwm kev nce ntxiv ntawm concentration, txo qis kev poob qis thaum tiv thaiv kev ncaj ncees ntawm cov khoom.
6.2. Kev Hloov Paug Thiab Kev Txij Nkawm
Qhov zaus ntawm kev hloov daim nyias nyias hauv ultrafiltration yog txuas nrog cov cim qhia ntawm fouling thiab cov dej ntws poob qis. Es tsis txhob cia siab rau qhov poob qis ntawm cov dej ntws ua qhov qhia txog qhov kawg ntawm lub neej, kev saib xyuas qhov kev tiv thaiv fouling tshwj xeeb - qhov kev ntsuas ntau yam uas sawv cev rau qhov kev tiv thaiv los ntawm cov khoom siv sib sau ua ke - tau ua pov thawj ntau dua, tshwj xeeb tshaj yog nyob rau hauv cov protein sib xyaw lossis protein-polysaccharide pub, qhov twg fouling tuaj yeem tshwm sim sai dua thiab hnyav dua.
Kev saib xyuas cov cim qhia txog kev ua qias tuaj ntxiv kuj tseem ceeb heev. Cov cim qhia pom tseeb ntawm qhov chaw tso dej, cov dej ntws tsis sib npaug, lossis TMP nce ntxiv tas li (txawm tias ntxuav tas li) yog cov cim ceeb toom ntawm kev ua qias tuaj ua ntej ua rau daim nyias nyias puas tsuaj. Cov txheej txheem xws li taug qab cov ntsuas kev ua qias tuaj hloov kho (MFI-UF) thiab sib txuas nrog kev ua haujlwm ntawm daim nyias nyias ua rau muaj peev xwm kwv yees lub sijhawm hloov pauv es tsis yog kev hloov pauv, yog li txo qis lub sijhawm tsis ua haujlwm thiab tswj cov nqi kho.
Kev ua kom lub membrane ruaj khov tsis yog tsuas yog los ntawm cov organic foulant xwb tab sis kuj los ntawm kev xeb, tshwj xeeb tshaj yog nyob rau hauv cov txheej txheem khiav ntawm pH siab lossis nrog cov ntsev ntau. Yuav tsum tau kuaj xyuas tsis tu ncua thiab kev ntxuav tshuaj kom tswj tau ob qho tib si xeb thiab foulant deposition. Thaum pom muaj kev xeb, yuav tsum tau kho qhov zaus ntxuav membrane thiab lub sijhawm hloov pauv kom ntseeg tau tias lub neej membrane ntev thiab kev ua haujlwm ntawm ultrafiltration membrane. Kev saib xyuas kom zoo thiab teem sijhawm yog qhov tseem ceeb rau kev txo qhov cuam tshuam ntawm cov teeb meem no thiab ua kom ntev kev ua haujlwm zoo.
6.3. Kev Tswj Xyuas Txheej Txheem thiab Kev Ntsuas Viscosity Inline
Kev ntsuas qhov tseeb thiab lub sijhawm tiag tiag ntawm qhov viscosity ntawm cov kua protein yog qhov tseem ceeb rau kev tswj cov txheej txheem hauv ultrafiltration, tshwj xeeb tshaj yog thaum cov concentration thiab viscosities nce ntxiv. Cov txheej txheem ntsuas viscosity inline muab kev saib xyuas tas mus li, tso cai rau kev tawm tswv yim tam sim ntawd thiab ua kom muaj kev hloov kho dynamic rau cov txheej txheem.
Cov thev naus laus zis tshiab tau hloov pauv qhov kev ntsuas viscosity ntawm cov kua protein:
Raman Spectroscopy nrog Kalman FilteringKev tshuaj xyuas Raman tiag tiag, txhawb nqa los ntawm cov lim Kalman txuas ntxiv, ua rau muaj kev taug qab zoo ntawm cov protein concentration thiab cov buffer composition. Txoj hauv kev no ua rau muaj kev nkag siab thiab raug, txhawb nqa cov txheej txheem automation rau ultrafiltration concentration thiab diafiltration.
Kev Ntsuas Kinematic Capillary Viscometry Tsis Siv NeegSiv lub computer vision, cov thev naus laus zis no ntsuas qhov viscosity ntawm cov kua, kov yeej qhov yuam kev ntawm tes thiab muab kev saib xyuas ntau zaus, ntau txoj kev sib txuas ntawm ntau txoj kev ua haujlwm. Nws tau lees paub rau ob qho tib si cov qauv protein thiab cov qauv protein nyuaj thiab txo cov kev cuam tshuam thaum lub sijhawm ultrafiltration concentration.
Cov Khoom Siv Microfluidic RheologyCov txheej txheem microfluidic xa cov ntaub ntawv rheological ntxaws ntxaws, txuas ntxiv mus, txawm tias rau cov tshuaj protein uas tsis yog Newtonian, cov kua protein viscosity siab. Cov no muaj txiaj ntsig zoo hauv kev tsim tshuaj, txhawb nqa cov txheej txheem analytical technology (PAT) cov tswv yim thiab kev koom ua ke nrog cov voj voog tawm tswv yim.
Kev tswj cov txheej txheem siv cov cuab yeej no ua rau muaj kev siv cov voj voog tawm tswv yim rau kev hloov kho lub sijhawm tiag tiag ntawm TMP, tus nqi pub, lossis qhov ceev ntawm kev ntws hla teb rau kev hloov pauv viscosity. Piv txwv li, yog tias inline sensing pom tias muaj kev nce siab sai sai hauv viscosity (vim muaj kev nce ntxiv lossis kev sib sau ua ke), TMP tuaj yeem txo qis lossis qhov ceev ntawm kev ntws hla kom txwv qhov pib ntawm kev sib xyaw polarization hauv ultrafiltration. Txoj hauv kev no tsis yog tsuas yog ua kom lub neej ntawm daim nyias nyias ntev xwb tab sis kuj txhawb nqa cov khoom zoo sib xws los ntawm kev tswj hwm cov yam ntxwv cuam tshuam rau viscosity ntawm cov kua protein dynamically.
Kev xaiv cov thev naus laus zis saib xyuas viscosity zoo tshaj plaws nyob ntawm qhov xav tau tshwj xeeb ntawm daim ntawv thov ultrafiltration, suav nrog qhov ntau ntawm viscosity xav tau, qhov nyuaj ntawm cov protein formulation, kev xav tau kev koom ua ke, thiab tus nqi. Cov kev nce qib no hauv kev saib xyuas lub sijhawm tiag tiag thiab kev tswj hwm cov txheej txheem dynamic tau txhim kho lub peev xwm los ua kom zoo dua ultrafiltration rau cov tshuaj protein viscosity siab, ua kom ntseeg tau tias ob qho tib si kev ua haujlwm ruaj khov thiab cov khoom lag luam siab.
Kev daws teeb meem thiab cov teeb meem feem ntau hauv Protein Ultrafiltration
7.1. Cov tsos mob, ua rau, thiab cov kev kho
Kev Nce Siab Transmembrane
Qhov nce ntawm lub siab transmembrane (TMP) thaum lub sijhawm ultrafiltration qhia tau tias muaj kev tiv thaiv ntau ntxiv thoob plaws lub membrane. Cov teebmeem ntawm lub siab transmembrane rau ultrafiltration yog ncaj qha: qhov ntau ntawm lub siab transmembrane ib txwm yog nyob ntawm cov txheej txheem, tab sis kev nce ntxiv mus tas li tsim nyog tshawb nrhiav. Ob qho laj thawj tseem ceeb sawv cev:
- Cov viscosity siab dua ntawm cov kua protein:Thaum qhov viscosity ntawm cov protein solutions nce ntxiv—feem ntau ntawm cov protein concentration ultrafiltration siab—lub siab xav tau rau kev ntws nce ntxiv. Qhov no yog qhov pom tseeb hauv cov kauj ruam concentration kawg thiab diafiltration qhov twg cov kua nplaum yog viscous tshaj plaws.
- Kev puas tsuaj ntawm daim nyias nyias:Cov khoom tsis zoo xws li cov protein aggregates lossis polysaccharide-protein sib xyaws tuaj yeem lo rau lossis thaiv cov qhov hws ntawm daim nyias nyias, ua rau TMP nce siab sai.
Cov Kev Kho Mob:
- Txo TMP thiab nce cov khoom noj khoom hausTxo TMP thaum ua kom qhov ceev ntawm kev pub mov txo qhov kev sib xyaw ua ke thiab kev tsim cov txheej gel, txhawb kev ruaj khov ntawm cov dej ntws.
- Kev ntxuav daim nyias nyias tas liTsim kom muaj zaus ntxuav daim nyias nyias kom zoo tshaj plaws kom tshem tawm cov av qias uas tau sib sau ua ke. Saib xyuas qhov ua tau zoo los ntawm kev ntsuas qhov viscosity ntawm cov kua protein tom qab ntxuav.
- Hloov cov membranes laus: Tej zaum yuav tsum tau hloov daim nyias nyias ntau zaus yog tias kev ntxuav tsis txaus lossis daim nyias nyias lub neej ntev.
Tus Nqi Flux Uas Poob Qis: Tsob Ntoo Kuaj Mob
Qhov kev txo qis ntawm cov dej ntws thaum lub sijhawm ultrafiltration concentration qhia txog kev txhawj xeeb txog kev tsim khoom. Ua raws li txoj hauv kev kuaj mob no:
- Saib xyuas TMP thiab viscosity:Yog tias ob qho tib si tau nce ntxiv, xyuas seb puas muaj cov av qias lossis cov txheej gel.
- Tshawb xyuas cov khoom noj thiab pH:Kev hloov pauv ntawm no tuaj yeem hloov pauv qhov viscosity ntawm cov protein solutions thiab txhawb kev fouling.
- Soj ntsuam kev ua haujlwm ntawm daim nyias nyias:Txo qhov permeate flux txawm tias ntxuav los xij qhia tau tias tej zaum yuav muaj kev puas tsuaj rau daim nyias nyias lossis qhov tsis zoo uas tsis rov qab tau.
Cov Kev Daws Teeb Meem:
- Txhim kho qhov kub thiab txias, pH, thiab lub zog ionic hauv cov khoom noj kom txo tau qhov fouling thiab concentration polarization hauv ultrafiltration.
- Siv cov modules membrane uas tau hloov kho saum npoo av lossis tig los cuam tshuam cov txheej gel thiab rov qab kho cov flux.
- Ua qhov kev ntsuas viscosity ntawm cov kua protein kom paub txog kev hloov pauv uas cuam tshuam rau kev ntws.
Kev Ua Phem Sai lossis Kev Tsim Txheej Gel
Cov txheej gel sai sai yog los ntawm kev sib xyaw ua ke ntau dhau ntawm qhov chaw ntawm daim nyias nyias. Transverse flow filtration (TFF) transmembrane pressure yog qhov tshwj xeeb tshaj yog nyob rau hauv cov xwm txheej pub mis uas muaj viscosity siab lossis muaj protein ntau.
Cov Tswv Yim Txo Kev Txo:
- Siv cov nplaim membrane uas muaj hydrophilic, negatively charged (piv txwv li, Polyvinylidene fluoride [PVDF] membranes) kom txo qhov kev khi thiab kev sib txuas ntawm cov protein.
- Ua ntej siv cov tshuaj coagulation lossis electrocoagulation los kho cov khoom noj kom tshem tawm cov tshuaj uas muaj kuab lom ntau ua ntej ultrafiltration.
- Siv cov khoom siv kho tshuab xws li cov modules tig rau hauv cov txheej txheem lim dej transverse kom txo cov tuab ntawm cov txheej ncuav mog qab zib thiab ncua cov txheej gel.
7.2. Kho kom haum rau qhov hloov pauv ntawm cov khoom noj
Cov txheej txheem lim dej protein yuav tsum hloov kho rau qhov sib txawv ntawm cov khoom lossis cov khoom sib xyaw ntawm cov protein pub. Cov yam ntxwv uas cuam tshuam rau qhov viscosity ntawm cov kua protein - xws li cov khoom sib xyaw ntawm buffer, protein concentration, thiab aggregation propensity - tuaj yeem hloov pauv tus cwj pwm ntawm lub cev.
Cov Tswv Yim Teb
- Kev soj ntsuam viscosity thiab cov khoom sib xyaw ua ke tiag tiag:Siv cov cuab yeej ntsuas kev ntsuas hauv kab (Raman spectroscopy + Kalman filtering) rau kev ntes tau sai ntawm kev hloov pauv ntawm cov khoom noj, ua tau zoo dua li cov txheej txheem UV lossis IR qub.
- Kev tswj cov txheej txheem hloov kho tau:Kho cov kev teeb tsa parameter (tus nqi ntws, TMP, xaiv daim nyias nyias) teb rau cov kev hloov pauv uas pom. Piv txwv li, qhov viscosity ntawm cov kua protein ntau ntxiv yuav xav tau TMP qis dua thiab cov nqi shear siab.
- Kev xaiv daim nyias nyias:Siv cov membranes uas muaj qhov loj me thiab cov tshuaj lom neeg ntawm qhov chaw uas tau ua kom zoo rau cov khoom noj tam sim no, ua kom cov protein khaws cia thiab cov dej ntws sib npaug.
- Kev kho ua ntej pub mis:Yog tias kev hloov pauv sai sai ntawm qhov xwm txheej pub mis ua rau muaj kev qias neeg, ua rau muaj cov kauj ruam coagulation lossis filtration upstream ntawm ultrafiltration.
Piv txwv li:
- Hauv kev ua bioprocessing, cov buffer switches lossis kev hloov pauv hauv cov antibody aggregates yuav tsum ua rau TMP thiab kev hloov pauv ntws los ntawm lub kaw lus tswj.
- Rau chromatography-linked ultrafiltration, adaptive mixing-integer optimization algorithms tuaj yeem txo qhov sib txawv thiab txo cov nqi ua haujlwm thaum tswj hwm kev ua haujlwm ntawm ultrafiltration membrane.
Kev taug qab tsis tu ncua ntawm kev ntsuas viscosity ntawm cov kua protein thiab kev hloov kho tam sim ntawd rau cov txheej txheem pab ua kom zoo dua qhov kev sib xyaw ua ke ntawm ultrafiltration, tswj kev ua haujlwm, thiab txo qis qhov membrane fouling thiab concentration polarization.
Cov Lus Nug Feem Ntau
8.1. Qhov ntau thiab tsawg ib txwm rau lub siab transmembrane hauv ultrafiltration ntawm cov protein solutions yog dab tsi?
Qhov siab transmembrane (TMP) ib txwm muaj nyob rau hauv cov txheej txheem ultrafiltration protein concentration nyob ntawm hom membrane, tsim module, thiab cov yam ntxwv pub. Rau feem ntau cov txheej txheem protein ultrafiltration, TMP feem ntau tswj hwm ntawm 1 txog 3 bar (15–45 psi). Cov nqi TMP siab dua 0.2 MPa (kwv yees li 29 psi) tuaj yeem ua rau daim nyias nyias puas tsuaj, fouling sai, thiab lub neej ntawm daim nyias nyias luv dua. Hauv cov ntawv thov biomedical thiab bioprocessing, TMP pom zoo feem ntau yuav tsum tsis pub tshaj 0.8 bar (~ 12 psi) kom tsis txhob muaj daim nyias nyias tawg. Rau cov txheej txheem zoo li transverse flow filtration, nyob hauv qhov TMP no tiv thaiv ob qho tib si yield thiab protein integrity.
8.2. Qhov viscosity ntawm cov protein solutions cuam tshuam li cas rau kev ua haujlwm ultrafiltration?
Qhov viscosity ntawm cov protein kua ncaj qha cuam tshuam rau kev ua haujlwm ntawm ultrafiltration concentration. Viscosity siab ua rau cov dej ntws tsis kam thiab nce TMP, ua rau cov permeate flux txo qis thiab cov membrane fouling sai. Cov nyhuv no yog pronounced nrog monoclonal antibodies lossis Fc-fusion proteins ntawm qhov concentration siab, qhov twg viscosity nce vim yog protein-protein sib cuam tshuam thiab cov teebmeem them. Kev tswj hwm thiab kev ua kom zoo dua viscosity nrog cov tshuaj excipients lossis enzymatic kev kho mob txhim kho flux, txo cov fouling, thiab tso cai rau cov concentration siab dua thaum lub sijhawm ultrafiltration concentration. Kev saib xyuas cov protein kua viscosity ntsuas yog qhov tseem ceeb rau kev tswj hwm kev ua haujlwm zoo.
8.3. Kev sib cais ntawm qhov concentration yog dab tsi thiab vim li cas nws thiaj tseem ceeb hauv TFF?
Kev sib xyaw ua ke ntawm cov protein hauv ultrafiltration yog kev sib sau ua ke ntawm cov protein ntawm qhov chaw ntawm daim nyias nyias, ua rau muaj kev hloov pauv ntawm cov kua dej loj thiab qhov sib txuas ntawm daim nyias nyias. Hauv kev lim dej transverse flow, qhov no ua rau muaj kev nce ntxiv ntawm cov viscosity hauv zos thiab qhov ua rau cov dej ntws rov qab tau poob qis. Yog tias tsis tswj hwm, nws yuav ua rau daim nyias nyias fouling thiab txo qhov ua haujlwm ntawm lub cev. Kev daws teeb meem ntawm kev sib xyaw ua ke ntawm cov concentration hauv ultrafiltration suav nrog kev ua kom zoo dua ntawm cov nqi ntws hla, TMP, thiab kev xaiv daim nyias nyias kom tswj tau cov txheej nyias nyias. Kev tswj hwm kom raug ua rau cov khoom siv siab thiab kev pheej hmoo fouling qis.
8.4. Kuv yuav txiav txim siab li cas thaum twg yuav hloov kuv daim ntaub lim dej ultrafiltration?
Thaum koj pom tias muaj kev txo qis ntawm cov dej ntws (flux), TMP nce ntxiv tas li uas kev ntxuav ib txwm tsis tuaj yeem daws tau, lossis pom cov av qias uas tseem nyob tom qab ntxuav. Cov cim qhia ntxiv suav nrog kev poob ntawm kev xaiv (ua tsis tau txais cov protein raws li xav tau) thiab tsis muaj peev xwm ua tiav cov lus qhia kev ua tau zoo. Kev saib xyuas zaus hloov daim nyias nyias nrog kev sim flux thiab kev xaiv tsis tu ncua yog lub hauv paus rau kev ua kom daim nyias nyias muaj sia nyob hauv cov txheej txheem kev sib xyaw ua ke ntawm cov kua protein ultrafiltration.
8.5. Kuv tuaj yeem hloov kho cov kev ua haujlwm twg kom txo qis cov protein fouling hauv TFF?
Cov kev ua haujlwm tseem ceeb kom txo tau cov protein fouling hauv transverse flow filtration suav nrog:
- Tswj kom muaj qhov ceev ntawm kev ntws hla kom txaus kom txo tau cov protein hauv zos thiab tswj kev sib cais ntawm cov concentration.
- Ua haujlwm hauv qhov ntau ntawm TMP uas pom zoo, feem ntau yog 3–5 psi (0.2–0.35 bar), kom tiv thaiv cov khoom xau ntau dhau thiab ua rau daim nyias nyias puas tsuaj.
- Siv cov txheej txheem ntxuav daim nyias nyias kom tsis txhob muaj qhov qias neeg uas tsis rov qab los tau.
- Saib xyuas thiab, yog tias tsim nyog, ua ntej kho cov kua pub kom tswj tau qhov viscosity (piv txwv li, siv cov kev kho mob enzymatic xws li pectinase).
- Xaiv cov ntaub ntawv membrane thiab qhov loj ntawm qhov pore (MWCO) uas haum rau qhov loj ntawm cov protein thiab cov hom phiaj txheej txheem.
Kev siv hydrocyclone prefiltration los yog enzymatic pretreatment tuaj yeem txhim kho kev ua haujlwm ntawm lub cev, tshwj xeeb tshaj yog rau cov khoom noj uas muaj viscosity siab. Saib xyuas cov khoom noj kom zoo thiab kho qhov chaw kom tsis txhob muaj membrane fouling thiab ua kom zoo dua qhov ultrafiltration concentration.
Lub sijhawm tshaj tawm: Kaum Ib Hlis-03-2025
