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Diafilter
Anthony Holmes
Will MacMillanBen Thorek
Andrea Weeks
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Presentation outline
• Overview of diafiltration• Continuous diafiltration
theory• Design• Cost analysis
• Design alternatives
www en wiki!edia org
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Overview of diafiltration
• "ur!ose# $ %emoval of small molecular
com!onents &!rimarily salts'from !rotein(containingmi)tures
• *ses ultrafiltrationmem+ranes
• Mem+ranes allow forse!aration +ased on# $ molecular si,es $ densities
htt!#--www !all com
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Overview (2)
• .m!ortant terminology# $ /iltrate# material that !asses
through the mem+rane $ %etenate# material that
remains on the filter
• Diafilter considerations# $ Molecular si,e of !articles
• 0elect filter with MWCO $ Mem+rane flu) rate
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Overview (3)
• Advantages of diafiltration# $ 1uick2 efficient !rocess
$ "roduct loss is minimi,ed $ Traditional filters would re3uire e)tra ste!s 4 and
costs5 $ Material filtering a +uffer e)change occur all done
within the unit• Common techni3ues#
$ Discontinuous &volume reduction or se3uential dilution' $ Continuous &less harsh and allows for +etter sta+ility'
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Continuous filtration (2)
• "ermea+ility measured +y re7ectioncoefficient &%C' $ C! i# concentration in filtrate $ Cc i# concentration in retenate
• To determine fraction of solute in retenate#
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Design
• 0tart with defining !rocess goals $ /inal !roduct concentration $ /eed volume reduction $ 8)tent of +uffer e)change $ Contaminant removal s!ecification
• Will the desired !roduct +e in the retentateor the filrate9
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Design (2)
• Desired !roduct in the retentate $ 0elect MWCO :(;) smaller than !roduct
• Calculate /lu) $ < = 1-&At'
• /ilter Area Calculations $ /iltrate >olume - &< ) "rocess Time' $ ?@ 0afety factor
AQ J -=
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Design (3)
• Calculate Diavolume washes $ Based on !roduct loss in filter
"roduct oss = 6@@e&%(6' ln>C/DEF $ Where % is the re7ection coefficient of the mem+rane
$ E is the num+er of num+er of diavolume washes $ >C/ is the concentration ratio
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Design (4)
6@(G@@@?@Working >olume
@ (6I ;m?:m ?J/ilter Area
6 kD MWCOK6 IL kDMWCO
Omega O0 filter MWCO
0elected/ilter 0!ecifications
%e3uired"arameter
Com!onent
J0u!er"ro calculated @ Lm ? for the filter area
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Cost analysis: mem rane
• N?@@-m? &0u!er"ro'• "olysul!hone %L6 ultrafiltration mem+rane on a
!oly!ro!ylene su!!ort material with MWCO of?@2@@@ Dalton &retains 6@@ of !rotein'
• ? stage diafilter is a!!ro)imately P6:I-m ? or N6LL*0D-m ? & i!ni,ki and Boelsmand2 ?@@?'
• N?@@-m? will +e used• !rocess only demands an area of @ Lm ? • cost N6 ? to re!lace the mem+rane every ?@@@ hrs
• N LI-year
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Cost analysis: !ower "onsum!tion
• ?@@W-m? of mem+rane&0u!er"ro'
• 6? kW-;6 Lm? or?;@W-m ? & i!ni,ki andBoelsmand2 ?@@?' &thisvalue was used'
• *tilities Qingston&.ndustrial %ating'#N@ ; -kWh NL G;-kWN6 ; GI-month'
• "ower costs# NLII ;CAE-mem+rane lifes!an
or N? ;G ?I CAE-year www dri++leglass com
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Cost analysis: a!!aratus
• Diafiltration a!!aratus with a mem+rane area of;@m? costs N6;6 ?I? *0D &>ankova et al 2 ?@@;'
• Correlates to N? @G *0D for a+ove designJ
www scilog com
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Possi le #etu!s $ Alternatives
• Eormal vs tangential flow filtration#
$ Microfiltration
$ %everse osmosis
• *ltrafiltration
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%angential flow filtration
• Designed for concentrating and !urifying !rotein
• .ncreases economic life of mem+rane
Milli!ore2 ?@@L
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&i"rofiltration
• Commonly used to !urifywater
$ /ilters out ma7or !athogens $ !orous mem+rane &@ 6(6@Rm'
• Why not9 Because micro( !orous mem+rane would noteffectively remove salts
• 8ither flow ty!e would !roduce the same result
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'everse osmosis
• 0imilar to nanofiltration• >ery tight mem+ranes used to se!arate salts
and small molecules from water • Would not work for insulin
$ 0alts would not +e se!arated from insulin
• Could +e used with either flow ty!e
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ltrafiltration
• Alternative to diafiltration• Designed for desalting and se!arating !roteins from a
+uffer solution• Mem+rane !ore si,e ranges from 6kDalton to 6@@@kDalton
&Dalton is a molecular weight measurement thatcorres!onds to the MWCO of the filter'
• Does not include addition of +uffer +uffer solution&limitation'
• Additional tank and water source would +e re3uired
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'eferen"es
• i!,inski / and Boelsmand < ?@@? Conce!ts of industrial scale diafiltrationsystems Desalination ssue 6GG# 6 (6IG
• Milli!ore ?@@L "rotein concentration and diafiltration +y tangential flowfiltration $ an overview We+site# htt!#--www milli!ore com-!u+lications nsf-docs-t+@:?
• >ankova Q 2 Antosova M 2 and Qola!ovic M ?@@; Design and economics ofindustrial !roduction of /ructosyltransferase C*emi"al Pa!er ; &La'# GG6(GGI
• Milli!ore &?@@:' Protein Con"entration and Diafiltration y %angential +low +iltration htt!#--www milli!ore com-!u+lications nsf-IL 6Ge+Ic6@dcecGI;?;L+:c@@;aI+d -a+:
+a:a d@LccLf6I;?;L+d6@@LI+@de-N/. 8-TB@:? !df
• 0evick2 0 H &?@@;'Com!ata ility of ,arious P*arma"euti"al Agents wit* Pall &edi"al#u!or- &em rane +ilter Devi"es "all Medical2 M.
http://www.millipore.com/publications.nsf/docs/tb032http://www.millipore.com/publications.nsf/86714eb8c10dcec485256b3c005a8bd7/ab3ba3a9d06cc6f185256bd10068b0de/$FILE/TB032.pdfhttp://www.millipore.com/publications.nsf/86714eb8c10dcec485256b3c005a8bd7/ab3ba3a9d06cc6f185256bd10068b0de/$FILE/TB032.pdfhttp://www.millipore.com/publications.nsf/86714eb8c10dcec485256b3c005a8bd7/ab3ba3a9d06cc6f185256bd10068b0de/$FILE/TB032.pdfhttp://www.millipore.com/publications.nsf/86714eb8c10dcec485256b3c005a8bd7/ab3ba3a9d06cc6f185256bd10068b0de/$FILE/TB032.pdfhttp://www.millipore.com/publications.nsf/docs/tb032