IFPACConference-Feb14,2018ChemCal,asurfacecleaningvalida?ontoolfordeposi?ngpre-determined

chemicalconcentra?ons,usedinthecalibra?onofsurfacecleaningvalida?ontools.

Authors:MichaelReidWilliamHugRayReid

•  SurfaceChemicalDeposi?on:•  Featuresize,resolu?onofthedepositsandnega?vespace.•  Chemistryofdeposi?onandringforma?on.•  Solventmorphologies:alcohols,water,acetonitrile,acetates•  Solventviscosi?es.•  Interleave/overlayofmul?plechemicals.•  DryingpaNerns.•  Unusualsubstrates:i.e.EPDM,TEFLON,screens,meshandcurvedsurfaces.

WewillbediscussingtheChemCal–asurfacechemicalprinter.

Areyouattherighttalk???

Why?Rapidsurfacecleaningvalida?on(RCV)holdsthepromiseofreducedrelianceonswabbingandHPLC,yieldingimmediatecleaningfeedback.Ascompaniesuseon-surfacechemicaldetectorsforquan?fyingresiduestheneedtocalibratethesedeviceswithhomogenouschemicaldeposi?ontechniquesbecomesparamount.Applica?ons:Calibra?on/valida?onofnewrapidcleaningvalida?ontoolsi.eTraC.Crea?onofnewswabbingprotocols.Trainingnewswabbingpersonnel.Prin?ngknownamountsofthinlayerAPIfordrugdelivery.In-Situhotspotdetec?ontraining.ResearchonthinlayerAPIchemistrysuchassublima?on,oxida?vedamage,photo-stabilityetc.

ChemCal–asurfacechemicaldepositor.

InkjetPrin?ng

ManualDeposi?on

ChemCalPrinter

UltrasonicPiezoPrin?ngSprayCoa?ng

Speed Uniformity

KnownQuan4ty

SpinCoa?ng

ChemCal: Status Of Deposi3on Methods

ChemCal: Overview

TraCsensor

Opera?onalScenario:1.  LoadAPIsinMicro-centrifugerack.2.  Loadcouponsontotray.3.  PressStart.4.  Thesystemoutputsafullcalibra?oncurvein

under4hours.(Printandscan16coupons.)

Howdoesitwork?ANISTtraceablesyringeacquiressample.Then,thesyringedispensesknownmassperunitareaontoasinglecouponinanarrayformat...Repeatforeachcoupon. ChemPrinthead

Createscouponswithanaprioriknownconcentra?onsofmanydifferentchemicals,includingAPIs,detergents,excipients,etc.onPharma-typesurfacesforthepurposeofperformingcalibra?onofhand-heldTraCsensorsforrapidcleaningvalida?on.

22xVialHolder16xCouponPlaAer

Surface Deposi3on Vocabulary

Drop–asessileliquidonasurfaceDeposit–adrysampleaaeradrophasdesiccated.Beam–theareaofalightsourcemappedontoasurface.Iwilltrynottousethewordsspotormarkorsample(ambiguity).Arealconcentra?on(microgram/cm2).Volumetricconcentra?on(microgram/microliter).

Coffee Ring Drying PaCern

ThreeRequirementsforCoffeeRingForma4on:1.  Solventmeetsthesurfaceatanonzerocontactangle(OrangeArrow).2.  Contactlineispinnedatit’sini?alposi?on(GreenArrow).3.  Thesolventevaporates(slowly).

DarkerPerimeter

LighterCenter

Detailsofhowacoffeeringstainforms.

Deegan,RobertD.;Bakajin,Olgica;Dupont,ToddF.;Huber,Greb;Nagel,SidneyR.;IwiNen,ThomasA.(1997)."Capillaryflowasthecauseofringstainsfromdriedliquiddrops".Nature.389(6653):827–829.

Assumeanevenevapora?onasafunc?onofsurfacearea:Tomaintainthegeometry(i.e.pinnedouterborder)thedropletinteriormustflow(bluearrow)fromthethickcenterareatotheouterthinareatoreplenishthesolventlosttoevapora?on(green).Thisresultsinanetcompensa?ngflowofsolventfromthecentertotheperiphery,thenetoutwardsolventflowcarrieswithitsoluteand/orsuspendedpar?cles.Thisresultsinasolutesringmassthatisdispropor?onatelylargeinaerialdistribu?on.

OtherFactorsinfluencingdryingmorphologies.

IrregularSoluteAccumula?on:Gravita?onalBuoyancyForce.Circula?ngsurfacetensiongradientdrivenflow.

RoughMorphologyCauses:

Evapora?vegradients.Shapeofsolute.Solventdryingrate.AppliedVoltage.

Images:Thermocapillaryconvec?oninliquiddroplets.NASASTIProgram.J.C.Duh,SverdrupTechnology,Inc,NASALewisResearchCenter.

Circula?ngsurfacetensiongradientdrivenflow.

Gravita?onalBuoyancyForce.

Whydowerequiredepositswithsmallradiitoincreasehomogeneity?Varia?onofsolutesmassdistribu?onacrossanindividualdepositislarge.Generallythisiscounteredbyintra-depositinconsistenciesasvolumedecreases(Difficul?esinkeepingsmalldropsconsistent).

Issueswithlargedeposits:Op?calpenetra?onofdetectors.Swabbingremovalissues.Chemicalmodelingissuesofreac?ons:sublima?on,photo-oxida?on,autoxida?on,orstainlesssteelmediatedcatalysis.

Homogenous Non-Homogenous

MicrographCrosssec4on

Quan?tyofdropletsinDetectorpath

ActualPrint

Polka-Do

tFish-Scale

FishScale: PolkaDot:Pinnedcontactline. De-wenngRapiddryrate. SlowdryrateLowcontactangle HighcontactangleHighsurfaceadhesion Lowsurfaceadhesion

Wewillconsiderthreeareasofsurfacechemicaldeposi?on:1.Printquality

NISTtraceability,intra/intersamplereproducibilityaprioriknowledgeofdepositedarealconcentra?on.

2.Chemistrylimita?ons:solventcompa?bility,solventviscositylimita?ons,interleave/overlayofmul?plechemicalsanddryingpaNerns.

3.Substratecompa?bility.

Unusualsubstrates:i.e.StainlessSteel,EPDM,TEFLON,screens,meshandcurvedsurfaces.

PrintqualityNISTtraceability.Intra&intersamplereproducibility.Aprioriknowledgeofdepositedconcentra?on.

y=31296x-282152R²=0.9846

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

5,000

40 60 80 100 120 140 160

Photod

iode

Signa

l(Co

unts*1000)

PercentageofTargetAPI

API-1Calibra4onCurveRange=50%to150%

100%Targetis8.48µg/cm2

Concentra?onOrdersofMagnitude(30ng/cm2to10micrograms/cm2),

y=25369x2+2E+06x+146124R²=0.99991

100000

5100000

10100000

15100000

20100000

25100000

0 1 2 3 4 5 6 7 8 9 10

Signal(C

ounts)

Concentra?on(microgramspercm2)

Calibra?onCurve(API#072TraC_C-CH3)

20 40 80 160 320 640 1,2802,5605,12010,240

Solventcompa?bility•  DryingpaNerns.•  Emptyring•  Homogenousring•  SmallSpot

Acetonitrile Ethanol EthanolWaterMix

MixedAlcohol EthylAcetate Methanol

2.Chemistrylimita?ons•  Solventviscosi?es

GlycerolStockSolu?onwithRedInk. Water 0.00089Pa*sEthanol 0.00109Pa*sGlycerol 0.95 Pa*s

3.Substratecompa?bility

Considera?ons:Interplaybetweenthesurfacetensionofthedepositandadhesiontothesubstrate.Cleanlinessdeterminespinnedperimeterforsolventsthathaverecedingperimeter.SuccessfulPrintedMaterials:StainlessSteel(304,316,[#8,#7,#4])TeflonAluminumEPDMPaperQuartzPolycarbonatePVCAcrylicManymore..

Stainless316#8 TeflonAluminum EPDM

2.Chemistrylimita?onsSecond,thechemicalinterac?onsdealwith:•  Interleave/overlayofmul?ple

chemicalsSomechemicalsinteractlikesodiumhydroxideandAPIs.Yetuserswanttocombinethemwithouttouching.Presstheinterleaveop?onandenterthewellnumbers.

Screens&mesh.(50%Stainlesssteelmeshshownhere)

Wholecoupon

Frac4onalcoupon

100% 46%

Depositaknownamountandtestyourfacili?esSwabbers!OrifyouareaNemp?ngtospincoat,tryascreen/mesh.

Substratecompa?bilitydealswithtopographicallychallengedsubstrates:i.eCurvedsurfaces.

Conclusion:Inconclusion,wehavegivenyouthechemicalgroundworktodebugyourdeposi?onproblemsand/orenhanceyourcurrentsurfacedeposi?onmethodologies.Ihopewehavemadeacompellingcasethatifyouarefumblingwithspincoa?ng,spraycoa?ng,ormanualdeposi?oncontactusandwecangivesomehelpwithyourdeposi?oninstrumenta?onorrapidcleaningtoolsneeds.

Micrographs