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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.

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