Calibration Requirements for Determining Particle Size Distribution Using Light Interaction Methods

CalibrationRequirementsforDetermining
ParticleSizeDistributionUsingLightInteraction
Methods
SponsoredbyBeckmanCoulterLifeSciences Nov112014

TopicsCovered
IntroductiontoISO21501
CalibrationofLiquidParticleCountersandAirParticleCounters
ExistingStandardstoWhichISO21501OffersanAlternative
CountingEfficiency
SignificanceoftheISO21501Standard
Conclusion
AboutBeckmanCoulter,Inc.ParticleCharacterization

IntroductiontoISO21501
TheISO21501standardoutlinestheinstrumentsandcalibrationprerequisitesfor
determinationofparticlesizedistributionbymeansoflightinteractiontechniques.The
standardisvaluabletothelifescienceindustrywherecleanroomsaremonitoredinreal
timeforairparticlecontaminationwiththehelpoflightscatteringairparticlecounters.

Moreover,theimpactofairborneparticlesonthequalityoffinalproductshasbeen
establishedinharddiskstorage,flatpaneldisplay,andthesemiconductormanufacturing
industry.

CalibrationofLiquidParticleCountersandAirParticle
Counters
TheISO21501standarddescribesthecalibrationproceduresforliquidparticlecountersto
achieveaccurateandreproducibleperformanceinthedeterminationofparticle
contaminationininjectionsandinfusions,thusprovidinganalternativetotheIST
calibrationmethodsthatwerepreviouslydescribedinUSP<788>.

Thecalibrationofairparticlecountersismoredifficultthanthatofliquidparticlecounters
becauseofthenecessitytoproduceairsamplesconsistingofhomogenouslysizedand
distributedsubmicroscopicparticles.Thecalibrationofanytwoairparticlecountersin
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Calibration Requirements for Determining Particle Size Distribution Using Light Interaction Methods

distributedsubmicroscopicparticles.Thecalibrationofanytwoairparticlecountersin
ordertogeneratethesameresultsusingthesameairsampleisatedioustask.The
calibrationmethoddescribedbytheISO21501standardhelpsoptimizingthe
reproducibilityandrepeatabilityofairparticlecounters.

Therearemanydifferenttechniquesavailabletodeterminetheparticlecountandsize
basedonthesizeoftheparticlestobeanalyzed(Figure1).

Figure1.Particlesizerangeandcountingtechniques

ExistingStandardstoWhichISO21501Offersan
Alternative
TheISO14644standardiscommonlyappliedfortheclassificationofcleanroomsby
meansofopticalparticlecounters(OPCs).InspiteoftheavailabilityofISO14644,before
theapprovalandlaunchofISO21501atthestartof2007,noISOstandardswere
availabletodescribethecalibrationandperformanceofOPCsemployedincleanroom
classificationasoutlinedbyISO14644.However,severalmajorparticlecounter
manufacturershaveusedthefollowingcomprehensivenonISOstandardsandcalibration
methods:

ASTMF32898(2003)StandardPracticeforCalibrationofanAirborneParticle
CounterUsingMonodisperseSphericalParticles(withdrawnMay2007).
IESTRPCC014.1CalibrationandCharacterizationofOpticalAirborneParticle
Counters(describingactualmethodstoperformthecalibration).
JISB9921:1997Lightscatteringautomaticparticlecounter,aJapanesestandard
describingtheperformanceofOPCdesign,especiallyintheareaofcounting
efficiency.

Thecountingefficiencyparameteristhekeyfactorpertainingtotheactualcountaccuracy

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Calibration Requirements for Determining Particle Size Distribution Using Light Interaction Methods

ofOPCs,mostnotablyairparticlecounters.

CountingEfficiency
ThecalibrationofthesizechannelsofOPCsisperformedtocountparticleslargerthana
givenparticlesize.Thetypicalunitforparticlesizeismicrometers(m).Theabilityofan
OPCinstrumentforcountingparticlesofaspecifiedsizeisdefinedasitscounting
efficiency.

ThecalibrationprocedureinvolvesexposingtheOPCssensortoacontinuousstreamof
standard,monosizedparticles,yieldingastreamofelectricalpulsesthatvaryinproportion
tothesizeofeachindividualparticle.

Themedianofadistributionofpulseheightsgeneratedbythemonosizedstandard
particlesisconsideredastheappropriatechannelcalibrationthresholdforthatparticular
size.Hence,theprobabilityofcountingaparticlethathasasizesameasagivenchannel
is50%(Figure2a).Therefore,thecountingefficiencyofOPCsthatarecalibratedinthis
fashionis50%.However,itdoesnotmeanthatonly50%oftheparticleswillbepractically
countedbyOPCs.

TheISO21501standardtakesadvantageofthespecificationforcountingefficiency
describedintheJISB9921standard,accordingtowhichthecountingefficiencymustbe
50%20%inthefirstchannel(Figure2a).Inaddition,particlesofbetween1.5Xto2.0X
thesizeofchannel1particlesmustbecountedwithacountingefficiencyof100%10%
inthefirstchannel(Figure2b).

Figure2.a)The50%calibrationpoint.b)Verifying100%efficiencyatahighersize

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Calibration Requirements for Determining Particle Size Distribution Using Light Interaction Methods

SignificanceoftheISO21501Standard
BeforetheISO21501standard,thecountingefficiencywasnotexaminedateach
calibrationinterval.ThecountingefficiencyofanOPChasbeenaffectedbyanumberof
factors,includingtheslightoptomechanicalmisalignmentoftheilluminationsource.

Asaresult,theOPCmaymisscountingsomeoftheparticles.ThenewISO21501
standardensuresthecheckingofallcriticalcountingefficiencyelementduringcalibration.

ThecountingefficiencyofanOPCischeckedbyrunningtheOPCfollowingitscalibration
forsizingcharacteristicswiththehelpoftraceablesizestandardsandcomparingitwith
eitherahighersensitivityOPCinstrumentoranElectrostaticClassifier.

ThisOPCisrecognizedasasecondarystandardwith100%countingefficiencyforthe
sizeofinterest.Besidesthebasicsizecalibration,theISO21501standardrequiresthe
followingelementstobetested:

Samplingvolume
Samplingflowrate
Samplingtime
Concentrationlimit
Falsecountrate
Sizingresolution
Countingefficiency

TheabilityofOPCinstrumentstoappropriatelysizeandcountparticleswillbeensuredby
theISO21501standardwiththehelpofatraceablereferenceinstrument.Asaresult,
therewillbeaclosecorrelationbetweendifferentOPCmodelsfromvariousmanufacturers
intermsofactualparticlecountsmeasured.This,inturn,yieldstraceable,accurateOPC
instrumentsforcleanroomclassificationandvalidationaccordingtoISO14644.

Conclusion
Besidesairparticlecounters,theISO21501familyofstandardsalsocoversextinctionand
scatteringtypeliquidparticlecounters.HachUltraoffersarangeofparticlecounters
complyingwiththeISO21501standard,andispresentlyworkingonthedeploymentofan
ISO21501fieldservicecapabilitytocalibrateavailableproducts.

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Calibration Requirements for Determining Particle Size Distribution Using Light Interaction Methods

AboutBeckmanCoulter,Inc.ParticleCharacterization
Introducedinthemid1950s,theCoulterPrinciplebecamethefoundationofanindustry
respondingtotheneedforautomatedcellcountinginstruments.Theindustrydevelopedin
threeacts,asWallaceH.CoulterandhisbrotherJosephR.Coulter,Jr.,developedthe
simpleideaofpassingcellsthroughasensingaperture.

InActI,Wallacesdesiretoautomatetheroutineerythrocytecountledtoasimpleidea,
thedefinitionoftheCoulterPrinciple,itspatenting,itsacceptancebytheNational
InstitutesofHealth,anditsdescriptionatanationalconference.

InActII,theCoulterbrothersaddressedthepracticalitiesofacommercialinstrumentand
ofabusinessorganizationtosupportitsmanufactureandsale.

InActIII,abroadresearcheffortdevelopedregardingvolumetricerrorsoriginatingin
functionalcharacteristicsofthesensingaperture,andthebrothersgrowingorganization
foundsolutionspermittingintroductionofincreasinglyautomatedhematologyanalyzers.
Todaytheindustrythrives,withseveralparticipants.

BeckmanCoulteroffersarangeofparticlecharacterizationtoolsincluding:

Laserdiffractionparticlesizeanalyzers
MultisizerCOULTERCOUNTER
Zetapotentialandsubmicronparticlesizeanalyzer
Surfaceareaandporesizeanalyzer

Thisinformationhasbeensourced,reviewedandadaptedfrommaterialsprovidedby
BeckmanCoulter,Inc.ParticleCharacterization.

Formoreinformationonthissource,pleasevisitBeckmanCoulter,Inc.Particle
Characterization.

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Calibration Requirements for Determining Particle Size Distribution Using Light Interaction Methods

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anddevelopment.Aleaderincentrifugationandflowcytometry,BeckmanCoulterhaslong
beenaninnovatorinparticlecharacterizationandlaboratoryautomation,anditsproductsare
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