cohesivehaole10.com

FEATUREARTICLEThemetamorphosisofanalyticalchemistryFreddyAdams1&MiekeAdriaens2Received:14October2019/Revised:20November2019/Accepted:29November2019/Publishedonline:17December2019AbstractDefininganalyticalchemistryasthemeasurementofisolatedcompositionalfeaturesinaselectedstudyobjectignorestheuniqueperspectivethatanalyticalchemistsbringtotwenty-firstcenturyscienceandsociety.
Inthisfeaturearticle,wewilldiscusssomeoftheexistingpreconceptionsandmisinterpretationsofanalyticalchemistrythatoccuratpresentandwilltacklethemfromthemoreup-to-dateperspectiveofscienceintheBigDataEra.
Thiswillplacetheirinfluenceincontextwhilesimultaneouslyenlargingthescopeofthedisciplineanalyticalchemistrytoitswell-deservedprevalentpositioninpresent-dayscienceandtechnology.
KeywordsAnalyticalchemistry.
Chemicalanalysis.
Scope.
Evolution.
Review.
BigDataEra.
MeasurementscienceIntroductionOverthelast20yearsorso,analyticalchemistrybecameincreasinglyintertwinedandembeddedasanimportantcom-ponentofscienceintheBigDataEra.
BigData,coupledwithnewdataanalytics,challengeswell-establishedconceptsinanalyticalchemistry,engenderingparadigmshiftsacrossthediscipline.
Thisarticleexaminestheconsequencesofthistransformationprocessinvariousaspects.
Thedisciplinemustrethinkitsfundamentals,itspositioninscienceatlarge,itseducationalaspectsanditspractices,rules,anddefinitions.
Withinchemistry,analyticalchemistryisthedisciplinethatscrutinisesthedetailsofthecompositionandstructureofbothnaturalandman-madeobjects.
Itdrawsupontechnologicaldevelopmentsandscientificknowledge—bothfromwithinchemistryitselfandfromotherscientificdisciplinessuchasphysicsandbiology—toperformitsbasictasks,solvingpar-ticularscientificortechnologicalproblemsforscienceandsociety.
Asacentralscientificdiscipline,providingmanyoth-erscienceswithinformation,itdeliversspectacularlyinthescientificworldoftoday,forexample,inthematerialssci-encesandnanotechnologyandparticularlyinthebiologicalandbiomedicalsciencesandbiotechnology.
Analyticalchemistryhasundergoneareal"metamorpho-sis"duringthelasttwodecades.
Incontrasttotheword"change",whichimpliesthatsomethingschangebutthattheessence,thebasicprinciples,remainwhattheywere,"metamorphosis"impliesamuchmoreradicaltransforma-tion,aparadigmshift,inwhichtheoldcertaintiesfallawayandsomethingquitenewemerges.
Metamorphosiscanbeconsideredasasituationwherenormalevolutionisnolongerthecase.
Undersuchgame-changingconditions,itisneces-sarytoredefinetheoreticalandconceptualframeworks.
Itis,atpresent,notfullyclearhowanalyticalchemistryandchemicalanalysisshouldbedefinedandrelatedtoothersci-ences,particularlytochemistryandmetrology.
Thepresentsituationiscompoundedbythecirculationofdistorted,oftenincompleteandminimalistic,historicallyinfluencedviewsontheessentialfeaturesofthedisciplineandonitsetymology.
Itsrules,principlesanddefinitionsneedtobeconceptualisedbeyondaworldofsimplifiedconceptsofthepast,definingchemicalanalysisasasinglemeasurementofagiven,well-definedchemicalsubstance.
Definitionsandrules,methods,proceduresandprotocolsarecreationsoftheirtime.
Weneedtoexplorehowtheyevolvedfromroughlythe1960stotheneedsoftoday.
Inthispaper,wewilldiscusssomeoftheexistingpreconceptionsandmisinterpretationsofanalyticalchemistrythat,despitefundamentalchanges,stillapplyatpresentandtacklethemPublishedinthetopicalcollectionEuroanalysisXXwithguesteditorSibelA.
Ozkan.
*FreddyAdamsfreddy.
adams@uantwerpen.
beMiekeAdriaensmieke.
adriaens@ugent.
be1DepartmentofChemistry,UniversityofAntwerp,DrieEikenCampus,Universiteitsplein1,2610Antwerp,Belgium2DepartmentofChemistry,GhentUniversity,Krijgslaan281-S12,9000Ghent,BelgiumAnalyticalandBioanalyticalChemistry(2020)412:3525–3537https://doi.
org/10.
1007/s00216-019-02313-z#TheAuthor(s)2019fromanup-to-dateperspective.
Thiswillplacetheirinfluenceincontextwhilesimultaneouslyenlargingthescopeofthedisciplineanalyticalchemistrytoitsprevalentpositioninpresent-dayscienceandtechnology.
Abrief"analysis"ofanalyticalchemistryWemustrevisitthebasicconceptsbeforewecanmoveontoadiscussiononwhatanalyticalchemistrymeansnowandhowweshouldproperlyinterpretitsoperationalcharacteristicsandtheirmeaningintoday'sscienceandtechnology.
Thisisbe-causeanalyticalchemistryconcernsdifferent,quitedistinctactivitiesthatarenotalwaysproperlydiscernedfromeachother.
Inordertobeabletomakereliableconclusions,itisnecessarytomovebacktothebasicfeaturesofthediscipline,butthiswithoutcommentingorcriticisingtheachievementsofthepast.
TheanatomyofanalyticalchemistryJustlikefactoriesproducingeverythingfromscratch,fromnutsandboltstocompletemachineries,includingbigair-planes(withpotentiallydefectivesoftware),analyticalchem-istrynotonlyencompassesthesimpledeterminationofasin-gleconstituent.
Italsoencounterssituationsthatrequireafullydetaileddescriptionofthechemicalconstitutionofcomplexandoftenhighlyheterogeneousobjectsorsituationsinvolvingmultiplerelatedbutnon-identicalobjects.
Defininganalyticalchemistryastheapplicationofcompo-sitionalchemicalknowledge,therefore,ignorestheuniqueperspectivethatanalyticalchemistsbringtothestudyofchemistry.
Thecraftofanalyticalchemistryisnotinperformingaroutineanalysisonaroutinesample,whichmoreappropriatelyiscalledchemicalanalysis,butinimprovingestablishedanalyticalmethods,inextendingexistinganalyti-calphenomena[1].
Therealmofanalyticalchemistryincludesproducersofscienceanditsusers:ithasmakersandtakers.
ItcanbesubdividedintothreedistinctworkingareasthataresummarisedinFig.
1.
Wediscernontheleftanalyticalchem-istryasthefundamentaldiscipline(1)withinchemistrycon-cernedwiththescienceofmeasurementofchemicalcompo-sition.
Itisthefundamentalscienceofinventingandapplyingconcepts,principlesandstrategiesformeasuringthecharac-teristicsofchemicalsystems.
Itincludesthemeasurementofconcentrationsbutalsoanythingthatisimportanttodistin-guishanobject[2].
Ontheotherhand,thereischemicalanal-ysisinthemiddleofFig.
1(2),whichinvolvesmethodsandprocedures,ideas,toolsandinstrumentationdevelopedforapplicationnotonlyinvariousscientificfieldsinchemistrybutalsoinothernaturalsciencesandintechnologicalandsocietalapplications.
Theseactivitiescanbefundamental(creatingnewknowledge)orappliedscience,helpingtoun-derstandthecomplexityofnatureorthesophisticationoftheworldoftoday.
Fundamentalanalyticalchemistryandchem-icalanalysisarecloselyrelatedandsometimesindistinguish-ablefromeachother.
Furthermore,pureandappliedchemicalanalysismustbeclearlydistinguishedfromathirdtypeofchemicalanalysis-relatedactivity,i.
e.
analyticalservices(3):aformalistic,routinelyappliedtechnologyplatforminindus-try,societyandtheenvironment.
Withanalyticalservices,qualitycontrolreliesheavilyontheuseofformalassessmentmetrics,whiletheothertwoitemsofthetriadfollowtherulesofscientificdecision-makingprocesses.
Thereisaprocessofsupplyanddemand:activitiesinchemicalanalysisandanalyticalservicefieldsstimulatethedevelopmentprocessesactivitiesin(1).
Withoutsuchinput,developmentofnewmethodologiesmightbecomeartificial.
Nexttothat,activities(1)and(2)arediscoverydrivenwhileactivity(3)consistsofapplicationsforindustryandsociety.
Analyticalchemistry:howitevolvedDescribingtherevolutioninthelifesciences,SydneyBrennerremarkedthat"studentsdividehistoryintotwoepochs:thepast2yearsandeverythingelsebeforethat"[3].
Inasimilarway,seenfromamoredistantvantagepointintime,wecanmarkanalyticalchemistry'srapiddevelopmentwiththechangesoccurringaroundthe1960softhepreviouscentury.
Beforethatwasthepre-historyofthediscipline,whichwasdominatedbyanalyticalmethodsbasedonthedestructionofthesample,chemicalseparations,equilibriumchemistryandsimpleinstrumentalspectrometrictoolsorelectrochemistry.
Theformerdealtmostlyinandaroundthevisiblepartoftheelectromagneticspectrum.
Nevertheless,manybasicconceptsdevelopedinthatperiodarestillvalidtodayandremainthesolidbasisofthediscipline.
Sincetheearly1960s,thedisciplinehasbeentransferredintoanewera,oftenreferredtoastheBigScienceEra,withalargeinherentcomplexitybothinthenatureandinthenumberofmethodologicalapproaches.
Theearlyphaseoftheexplo-siveexpansionofthedisciplineis,forinstance,wellillustratedbythemonthlyeditorialsofHerbertLaitineninAnalyticalChemistry,thejournal.
Thefieldexpandedandincreasedphe-nomenallythroughtheintroductionofinstrumentaltech-niquesbasedontheinteractionofradiationandmatter,rang-ingovertheelectromagneticspectrumfromtheterahertzre-giontohardX-raysandbeyond.
Theuseofspectroscopyisubiquitousasacharacterisationtoolinmanyscientificandindustrialdisciplines.
Itbecamepossibletorelatesubtleinter-actionsofradiationwithmattertotheinsituchemicalcom-positionofincreasinglysmallerobjectsofstudy.
Variousformsofspectroscopyandmassspectrometry(MS)providedmajoradvancesinsensitivity,specificity,spatial3526AdamsF.
,AdriaensM.
discrimination(samplesize)andspeedofanalysiswithanimpressiverangeofnowfullyautomatedanalyticalinstruments.
Theresultingfullrangeofanalyticalmethodsconstitutesapowerhouseofscientificprogress.
Atpresent,itneedstoad-dressproblemsofgrowingcomplexitywithmethodologiesthatincreasinglyneedfastrepetitivemeasurementsofawid-eningrangeofelementalandincreasinglycomplex,oftenla-bile,molecularspeciesandstructuralarrangementsandstruc-turaldefects.
Thephenomenaldevelopmentofanalyticalchemistryoverthelast50yearswasdrivenbothbytoolsandbyideas[4].
Drivingforcescametop-downbychangessuchasmicroelec-tronicsandinformationtechnology,analyticalinstrumentationcompanies,micro-andnanotechnology,andbottom-upbygen-eralscientificprogressinchemistry,biologyandphysics(Fig.
2).
ThemetamorphosisofanalyticalchemistryThephenomenaldevelopmentsseeninanalyticalchemistryarenotuncommoninscience.
Infact,theyareinlinewiththegradualevolutionaryprocessdrivenbyideasandtoolsinmanyotherareasofscience[4].
However,whatconstitutesarealmetamorphosisforanalyticalchemistryisthemassiveandcombineduseofanalyticalinstrumentation.
Ithasopeneduppossibilitiestounderstandcomplex(naturalandtechnolog-ical)heterogeneousmaterials.
Italsoprovidesspatialtemporalrelationsbetweenchemicalcomposition,structureandmor-phologyontheonehandandthepropertiesandperformanceofmaterialsontheother.
ThisrelationisshowninFig.
3bandiscomparedwiththeconventionalapproachofanalyticalchemistryinFig.
3a.
Itisclearthat,inFig.
3a,thequalityofthemeasurement(metrol-ogy,qualityassurance)isthemostimportantitemofconcern,whileinFig.
3bthecollecteddataneedtobeconvertedintoinformationtoultimatelyprovideknowledge,andthisisdriv-enbyinformationscience.
WhythischangeInordertounderstandthelinkbetweencompositionandstructureatthenano/microscopicspatiallev-elandthefunctionalbehaviouratthemacroscopicscale,itbecamenecessarytovastlyincreasetheinformationacquiredfromtheanalyticalprocess.
Nanotechnologybroughtnewim-agingtoolssuchasscanningtunnellingmicroscopy,atomicforcemicroscopyandvariousderivedtechniques.
Theseareincreasinglyusedasobservationaltoolsincombinationwithspectroscopicchemicalimaginganalysisandrevealdetailsdowntothesub-microscopiclevelandeventothatofindivid-ualatomsandmolecules.
Thefocusofmanyapplicationsinanalyticalchemistrythereforechangedfromthesingularlevelinwhicheachanal-ysisconcernsauniquecompositionalentity(Fig.
3a)totheplural,comprehensivelevelinwhichanalysisconcernstheentiredetailedcompositionincludingstructuraldetailandtheinterrelationofdifferentcomponents(Fig.
3b).
Overall,themetamorphosisinvolvedthefollowingchanges:&Fromsimplemeasurementstocombinationsoftoolsandtechniques(multispectral,hyperspectral,multiplexingofinstrumentalapproaches,compositionalrelationsbetweenmanysamples,etc.
)&Fromproblem-driventodiscovery-drivenapplications(hypothesisgenerating)Fig.
2Thedevelopmentofanalyticalchemistry,toolsandideas,top-downandbottom-upFig.
1Theanatomyofanalyticalchemistry:(1)analyticalchemis-try,(2)chemicalanalysisand(3)analyticalservicesThemetamorphosisofanalyticalchemistry3527&Increasinglycomplexissuesforstudyingnatureandmaterials&Theuseofasystemic(holistic)approachratherthanonebasedonunitoperations,basedonindividualmeasurementsThesedevelopmentshavemovedanalyticalchemistryoutofthebox,outsideoforbeyondwhatisconsideredusual,traditionalandconventionalfortheevaluationofanalyticalresults.
Hence,theyhaveintroducedanalyticalchemistrytoinformationscienceandintotheBigDataEra.
Ofparticularsignificancehereistheuseofthedisciplineinthecharacterisationandanalysisofmicro-andnanostructuredheterogeneoustechnologicalmaterialsandinvariousdomainsofbiologyincludingthestudyofnaturalobjectssuchasthosethatevolvedfromevolutionaryprocesses.
Thenewconceptsinanalyticalchemistryreverberatetheconceptof"thegaleofcreativedestruction"coinedbyJosephSchumpeter,NobelPrizeineconomicsfor1993,inwhichnewproductsandprocessinnovationmechanismsreplaceoutdatedones[5].
However,inourparticularcase,theydonotreplaceanyofthewell-establishedapproachesdevelopedinthepast.
Instead,theyaddanewdimensionandconsider-ablyenlargethescope,thefootprintofanalyticalchemistryinscience.
AnalyticalchemistryandchemicalimagingFormanysamples,itisdesirabletoobtaininformationaboutthethree-dimensionalstructureandcompositionofaparticu-larobject,includinganalyticalinformationasafunctionofdepth,beyondmeasurementofa2Dsurfaceoraplanewithinthesample.
Thiscanbedonebyimaginganalysis,whichisbasedonthesystematicextensionfromsingleobservations(point,0-D)toaline(1-D),thento2-Dimagesonasurface,finallytoobtain3-Dinformation[6].
Chemicalimagingis,hence,asignificantbroadeningofspectroscopicanalysis.
TheoverallneedsforafullmultispectralandmultimodalchemicalimaginganalysisaresummarisedinFig.
4.
Inaddi-tiontothechemicalimagingmethodsforelementalinforma-tion,thereareothersthatprovidemolecular(thespatialrepar-titionofmoleculesorfunctionalgroupsofmolecules),struc-tural(thespatialrepartitionofcrystallinity,crystalorientationorphase)ormorphologicalmappinginformation.
Variousmo-lecularimagingmethodsbasedonIR-VIS-UVobservationexistforsurfaceandin-depthmolecularcharacterisationandimaging[7].
Othersarebasedonparticleorlaserbeaminter-actionwiththesamplemeasuringvariousspectroscopicinter-actionmechanisms.
Chemicalimagingleadstocomplexdatagatheringandinterpretation.
Figure5illustratesschematicallythedatastruc-tureofmultispectral/hyperspectralimaginganalysis.
Everydistinctelementofa3Dor4D(forrepeatedmeasurements)imagecanbeconsideredaspartofnumericalinformationrepresentativeofcompositionalfeaturesinaheterogeneousobject.
Itcanalsobeconsiderablymorecomplicatedwhenmultispectral/hyperspectraldatasetsresultfromthecombineduseofdistinctandsometimesorthogonal,observationaltools,includingdensityvariations(evenvoids),structuralfeatures,changesinmorphologyorphysicalproperties.
Inthiscase,theresultisadatacubeforeverymeasurementpoint,witharangeofstructuredinformation(numberswiththeirspecificsignif-icancelevels),structuredinformationsuchasdiffractionpat-ternsorhigh-resolutionmassspectra,includingsetsofcollision-inducedfragments,morphologicalinformation,eventextualdata,etc.
[6].
Allthisleadstoextensivemultidimensionaldatasets,whichrequiredeconstructionusingvariouscomputermanip-ulationandstatistical(chemometrics)toolsforobtaining2Dor3Dimagesforimprovingtheinterpretationefficiency.
Suchchemicaldatasetsareusuallyquitelarge.
Forinstance,astate-of-the-artimagingMSdatasetcaneasilyconsistofapixelsetofmassspectrarepresentingtherelativeabundancesofionisedmoleculeswithupto50,000m/zvaluesformediumabFig.
3Conventionalapproachforchemicalanalysis(a)andap-proachusedinnewapproaches(b)3528AdamsF.
,AdriaensM.
massresolutionwhileanalysersbasedontimeofflightareabletoaccessm/zvaluesupto100,000andm/zratiosuptoamillionormorecanbereachedwithanalyserssuchasFourier-transformioncyclotronresonanceMSorOrbitrapinstruments[8].
Theinterpretationoftheentiresetofdataandtheirmutualrelationtoeachotherisasimportantasthemetrologicalqualityoftheindividualmeasurements.
ManyfieldsofsciencehaveundergoneaBigDatarevolu-tion,includinganalyticalchemistry[9].
Theanalyticalchem-istryillustratedinFigs.
3b,4and5exemplifiesitssolidincor-porationintheBigDataEraandthedigitalrevolution.
Largequantitiesofreliabledataoriginatingfromnaturalorman-madeobjectsmustbeexploitedthroughtrustablehigh-performancecomputingcapabilitiesandartificialintelligencetechniques.
Thedataconsistinacohesiveandconsistentconglomerationofinterrelatedandinterdependentmeasure-mentsofindividualconstituentsthataredelineatedbyitsspa-tialandtemporalboundaries.
Inaddition,withtheriseinthenumberofinstrumentalimagingmethodscurrentlyavailable,differentanalyticalmethodsareincreasinglybeingcombinedforexploringthesameobjectofanalysis.
Suchacombinationalapproachisperformedeitherinasinglemultifunctionalinstrumentalsetuporbycombiningseveraldiscreteinstruments.
Combinedim-agingmethodologiesaimatprovidingtheextractionofasmuchinformationaspossiblefromaparticularsample:ele-mental,molecular,orotherkindsofchemicalorphysicalin-formation,evensupramolecularstructureswithcomplexar-chitecture.
Inatargetedapproach,onemustdecidewhatneedstobemeasuredandthemethodshouldbeselectedandvali-datedbeforeperformingtheanalysis.
Inanon-targetedap-proach,theaimistoextracteverythingfeasiblefromthecol-lecteddata[6].
Fusionofimagesconsistsinmergingimagestogetherthatoriginatefromdifferentmodalitiesinordertocreateanewhybridimage.
Doingthisisnecessarytokeepcontrolofallexperimentalparametersforreliableandconsistentdatainter-pretation.
Fusinginformationacrossdifferentimagingtech-nologiesenablesdeeperinsightsandimprovesinterpretation.
TheadventofbioanalyticalchemistryTheleadingareaofdevelopmentinthe"NewAge"analyticalchemistryisinbioanalysis(molecularbiology,biotechnology,pharmacy,medicine).
Overthepastdecade,theadventofmicroarraytechnologyandroboticshasenabledaparadigmshiftinmolecularbiology:achangeofemphasisfromreduc-tionistapproachesand"single-protein"studiesforcoordinat-edinvestigationsofincreasinglymorecomplexsystemsofmoleculesandtheirinteractionsandinterrelationsinspaceandtime.
These"systemsapproaches"(seefurther)areusedFig.
4The"chemicalanalyticalmicroscope":differentcharacteristicsthatdeterminechemicalimaginganalysisFig.
5Datastructureinmultispectral/hyperspectralchemicalimaging.
FromAdamsandBarbante[6];producedwithpermissionThemetamorphosisofanalyticalchemistry3529toinvestigateprocessesasawholeandenablemodelstobebuilttopredictthebehaviourofasysteminresponsetovar-iousexternalcues,disturbancesormodificationsofitscom-position[10].
Infact,theimportanceofbiologyandbiotechnologyinanalyticalchemistryisexemplifiedbythechangeofthenameofthisjournalaroundtheturnofthecentury,from(inGerman)ZeitschriftfürAnalytischeChemietoAnalyticalandBioanalyticalChemistry.
Massspectrometry(MS)isakeycontributorinanalyticalchemistry,particularlyforbiologicalapplications.
Anexten-siverangeofMStechniquesprovidesunprecedentedcapabil-itytoidentifyandspecificallydeterminehighlycomplexcom-poundswithextremesensitivityathighsamplethroughputfromminuteamountsofsample.
ThedevelopmentofMShasbenefittedfromtheabilitytounderstandandmodelionmotioninelectricandmagneticfields,andnumerousmethodsforhardandsoftionisationofcompoundsfromcomplexsam-ples[11].
High-resolutionMSalsohasauniquepotentialofbeingabletomakeuseofisotopedilution,amethodthatistraceabletothefundamentalmeasurementunits.
Itisessentialformanykey-omicsmeasurements,suchasproteomics,metabolomics,lipidomicsandglycomics.
Amongallthese-omicplatforms,metabolomicsisusedtodetecttheperturbationsthatdisease,drugsortoxinsmightcauseonconcentrationsandfluxesofmetabolitesinvolvedinkeybio-chemicalpathways.
Traditionally,MS-basedmetabolomicsstudiescanbeclassifiedintotwoprimarystrategies—adiscovery-drivenuntargetedprofilingapproachusinghigh-resolution,accurateMStoidentifymolecularentities,follow-edbyahypothesis-driventargetedapproachtoquantifyanumberofthem.
Thediscoverystagedetectsandidentifiespotentialmetabolitesthatarebiologicallysignificantonthelevelofsinglecells,whilethetargetedvalidationstagecanconfirmtheidentityonthebasisoffragmentationpatternsandquantifythesemetabolitesacrosslargesamplepopulationstoenablefunctionalunderstanding.
Whiletheuntargetedap-proachispurelyqualitative,targetedanalysiscanbeper-formedwiththehighestmetrologicalorthodoxyusingisotopedilutionMS,amethoddirectlytraceabletotheSIunitofmass(sincethe2019redefinitionoftheSIunitofmasswiththenumericalvalueofPlanck'sconstant).
Majorobstaclesintranslatingomicdataintotangibleben-efitsforpracticalapplicationsresultfromthemassivehigh-dimensionalnatureofthe"pan"-omicdata.
Measuringmolec-ularpropertiesathundredsofthousands,ifnotamillionormore,featuresmeansthatassociationswithoutcomesofin-terestcanarisepurelyoutofrandomchance.
Inaddition,omicdataisoftenplaguedbypoorlyunderstoodsourcesofdata[12].
Advancesincomputervision,machinelearningandsta-tisticalbioinformaticsareneededtotacklechallenges[13].
Theemergingfieldofsingle-cellcharacterisationmethodsaddressesfundamentalbiologicalquestionsandallowsonetoobservemetabolicphenomenainheterogeneouspopulationsofsinglecells.
Single-cellmetabolomicsisanemergingfieldthataddressesfundamentalbiologicalquestionsandallowsonetoobservemetabolicphenomenainheterogeneouspopu-lationsofsinglecells.
TheentirearrangementisschematicallyrepresentedinFig.
6.
Selectedsinglecellsaresortedbycyto-metrictechniquesandaresubjectedtomultiplexedandmultitechniqueanalysis.
Thepan-omicsstudiesincorporatevariousomicsmethodswithmetabolomicsanalysis.
Itincor-poratesgenomics(targetingDNA),epigenomics(forDNAmethylationandnon-codingRNA),transcriptomics(messen-gerRNA)andproteomics(proteinexpression)withuntargetedmetabolomicsMSanalysisforthedetectionofsmallmolecules[14].
Thesestudiesalsotendtoincorporateimagingtechniquesthatarecapableoftrackingthemovementofsingleproteinsandmolecularcomplexesinsub-cellularentitiesvisualisingthedynamicsofalargenumberofmacro-molecularassemblies.
TheprecedingexampleillustratesthemaincharacteristicsoftheanalyticalchemistryofFig.
3b.
First,suchexperimentsproduceextremelylargemultidimensionaldatacollectionswithmanythousandsofindividualsampleseachofwhichgivingrisetoahighlycomplexdataset.
Second,thecompo-sitionalanalyticaldataareintegratedandmustbeinterpretedtogetherwiththoseresultingfromtheomicsplatform.
Third,theentirestudyishypothesisgeneratingratherthanhypothe-sisdriven.
Techniquesformultidimensionalscalingareusedtovisu-aliseobjectsaspointsinlow-dimensionalmetricmaps,forincreasedunderstandingandvisualisingsimilaritiesinalargenumberofdistinctobjectssuchascells.
Thesemethodsareadaptationsofprincipalcomponentanalysis,andbasedone.
g.
aquitepopularapplicationofstochasticneighbourembeddinginamethodcalledt-SNE[15],amethodologyparticularlywellsuitedforthevisualisationofhigh-dimensionaldatasets.
Chemicalimagingandbioanalysisare,therefore,majorareasofdevelopmentinBigDatascience.
Theyproduceenor-mousamountsofdata.
WeshouldnowrelatethemtotheFig.
6Single-cellpan-omicscombininggenomics,epigenomics,tran-scriptomicsandproteomicswithmetabolomicsanalysis3530AdamsF.
,AdriaensM.
traditionalconceptsofanalyticalchemistry,emphasisedastheywere,andstillare,onmetrology.
AnalyticalchemistryandphysicsManyofthenewapplicationsofchemicalanalysisdependontheapplicationofphysics.
Themostspectacularsuccessesofanalyticalchemistryconcernthedirectobservationofatoms(e.
g.
withtheelectronmicroscope)andmoleculararrange-ments(e.
g.
withfluorescencemassspectrometryorvibration-almicroscopies).
Thehighestspatialresolutionmeasurementonecanmakeisatthesingleatomormoleculelevel.
Todeterminetheconcentrationofamolecule,thebestwayistocountthenumberofmoleculesinagivenvolume.
AslongasthevolumecontainsastatisticallylargeenoughnumberofmoleculesandisabovethePoissonnoiselimit,countingatomsormoleculesispotentiallythemostaccurate(andalsothemostdirect)waytomakeameasurement[16].
Suchana-lyticalchemistryisasgoodasitcaneverget.
Oneparticularexampleoftheinfluenceofphysicsonan-alyticalchemistry'sdevelopmentisvibrationalspectroscopy.
Onthemacroscopiclevel,infrared,Ramanandfluorescencespectroscopyarequiteinsensitivemethodologies.
Thisistheresultoftheconsiderablemismatchbetweenthemoleculardimensionsandthewavelengthoftheradiationinvolved.
In1974,Fleischmannetal.
[17]reportedstronglyenhancedRamansignalsfrompyridineadsorbedonasilverelectrode,aneffectcalledsurface-enhancedRamanspectroscopy(SERS).
SERSremainedanalyticallynon-exploitableformanyyearsbecauseofitserraticnatureandthisuntilthedetailedmechanismsinvolvedinlocalisedsurfaceplasmonresonance(LSPR)asafunctionofmorphologicaldetailswereclarified.
Currently,amethodbeingusedistip-enhancedRamanspectrometry(TERS),asensitivemoleculardetectionandimagingtoolwithadetectionlimitdowntothesingle-moleculelevel[18,19].
Metallicnanoparticlescanalsobeusedtoincreasethesensitivityoffluorescentdetectionbe-causetheygenerateaphenomenonknownasmetal-enhancedfluorescence,thusincreasingfluorescencelifetimeandquantumyields.
Weidentifythisrevolutionarytransfor-mationprocess,fromascientificcuriosityintoanultrasensi-tiveanalyticaltool,asametamorphosis.
Therearemanyothersuchmetamorphosesinanalyticalchemistry.
RichardFeynmanaccuratelyforesawmanyoftheminhisfamousCaltechlectureatthattimein1959:theadventofnanotechnology,theextrememiniaturisation,thedirectmanipulationofindividualatomsandtheinfinitesimalmachinery[20].
Onthesubjectoftheelectronmicroscope,heclaimedthatitwouldeventuallybecomepowerfulenoughtolocaliseandidentifyatomswithaprecisionlevelofafewpicometres(1012m).
Healsocommentedonchemicalanal-ysisanditsfuturedevelopmentinthefollowingpropheticstance:"…physicssuppliesthefoundationsofchemistry.
Butchemistryalsohasanalysis.
Ifyouhaveastrangesub-stanceandyouwanttoknowwhatitis,yougothroughalongandcomplicatedprocessofchemicalanalysis.
Youcanana-lyzealmostanythingtoday,soIamabitlatewithmyidea.
Butifthephysicistswantedto,theycouldalsodigunderthechemistsintheproblemofchemicalanalysis.
Itwouldbeveryeasytomakeananalysisofanycomplicatedchemicalsub-stance,allonewouldhavetodowouldbetolookatitandseewheretheatomsare.
"Overrecentyears,steadyadvancesintransmissionandscanningtransmissionelectronmicroscopyprovidedtheultra-precisedeterminationoftheatomicarrangementofnon-periodicstructuresinmaterialsandthecontrolofnano-structures[21].
Thisallowsfortheexplanationofvariousmaterialproperties,forexample,thatstraininducedbythelatticemismatchbetweenasubstrateandasuperconductinglayergrownontopcanchangetheinteratomicdistancesbytheorderofafewpicometresandcaninthismannerturnaninsulatorintoaconductor[22].
Also,asanticipatedbyFeynman,wemaysoonhavedetailedimagesoflife'scom-plexmachinerieswithatomicresolution.
TheNobelPrizeinChemistryfor2017wasawardedforthedevelopmentofcryo-electronmicroscopy,whichbothsimplifiesandimprovesdi-rectimagingoftheformanddetailedstructureofindividualbiomoleculesinsitu.
Thedetailedstructuralarrangementofsingleproteinmoleculessituatedatparticularlocationsofacellmembranecanbemeasured,whileevenfollowingtheirstructuralchanges.
Thisnewmethodstandsinstarkcontrasttoconventionalproteincrystallographywhereitisnecessarytocrystallisethemoleculeforthemeasurementofthecollectivestructure.
WouldthismethodeventuallybeabletoreplaceX-raydiffractionofcrystallisedmaterialforstructuralcharacterisationButwasFeynmanrightwithhismethodologicallyreduc-tionistandcreativelydisruptivepredictiononanalyticalchem-istryOfcoursenot,asheexplainedhimselfinhisreminis-cencesinhisbookSurelyyou'rejoking,MrFeynman[23].
Theapproachbasedonthedirectobservationofatomicar-rangementswiththeelectronmicroscopetosolveproblemsinanalyticalchemistryremains—andwillundoubtedlyremaininthefuture—theexceptionratherthantherule.
Thisisbe-causeFeynmanreasonedasaphysicistwhileanalyticalchem-istryrespondstothefundamentalapproachofchemistry:an-alyticalchemistryincorporatesphysicsandisnotincorporatedinphysics.
AnalyticalchemistryandchemistryBothphysicsandchemistryareconcernedwithmatteranditsinteractionwithenergy,butthetwodisciplinesdifferinap-proachastheyobservethescientificworldfromdifferentper-spectives,fromadifferentviewingangle.
Inphysics,itistypicaltoabstractfromthespecifictypeofmatterandtofocusThemetamorphosisofanalyticalchemistry3531onthecommonpropertiesofmanydifferentmaterials,whilechemistrystudiesthepropertiesofmatterwithconsiderablymoredetail.
BernadetteBensaude-Vincent,philosopherofchemistryandtheauthorofChemistry—theimpurescience[24],abookconcernedwiththephilosophicalandhistoricbasicsofchem-istry,expressesthisdifferenceasfollows[25]:"Inoptics,forexample,materialsarecharacterisedbytheirindexofrefrac-tion,andmaterialswiththesameindexofrefractionwillhaveidenticalproperties.
Chemistry,ontheotherhand,focusesonwhatcompoundsarepresentinasample,andexploreshowchangingthestructureofmoleculeswillchangetheirreactiv-ityandtheirphysicalproperties.
"Thisbringsustotheconclusionthatanalyticalchemistryischemistry,andthisnotonlybecausechemistryshapeditsidentity.
Itisaparticulardisciplineinchemistry;infact,to-getherwithsynthesis,itremainsoneofthebasicpillarsonwhichthedisciplinerests.
Itscrutinisesthedetailsofthecom-positionofnaturalandman-madeobjects.
Itborrowsscientificknowledgeandtechnologicaldevelopments—fromwithinchemistryitself,butalsofromothersciencessuchasphysics,biology,etc.
andfromtechnologicaldevelopments—toper-formitsbasictaskofsolvingaparticularscientificortechnicalquestionbyusingaplethoraofdifferentapproaches.
Thatiswhy"analyticalchemistry"isnowoftenreferredtoas"ana-lyticalsciences".
Assuch,itreadilyincorporatesinitsrealmandembraces,thenabsorbs,thepossibilitiesofferedbynano-technologyandalsotheelectronmicroscope'spotentialofdirectobservationofatomsratherthanbeingreplacedbythesedevelopments.
Whatisanalyticalchemistryanno2020Whilstchemistryisthesciencethatlooksfortheassemblyofcollectionsofelementaryparticlesandtheplusvalueitcreateswithmolecularandsupramolecularentities,analyticalchem-istryisthedisciplinewithinchemistrythatkeepstrackofthesearrangements.
Thiscanbedoneonseverallevelsofcomplex-ity,theprimarylevelofcompositionaldetailsandtheirquan-titativeaspectsor,inmoredetail,wherearetheylocated,howaretheyrelatedtoeachother.
Thisviewassumesthatanalyt-icalchemistryinvolvesscrutinyofeverythingdistinguishinganobject,naturalorman-made,hardorsoft,livingornot,onthebasisofappearance,structureorproperties.
Insuchcon-ditions,thecentralconceptofanalyticalchemistryanditsrelationtostandardmetrologicalconcepts(uncertainty,vali-dationand/ortraceabilitytofundamentalstandards)seemtolosetheircentralguidingrole.
Withsuchanenlargedfootprintinscience,wecansimplysummariseanalyticalchemistryasquotedbyVirginiaWoolf(ofcourseinanentirelydifferentcontext):"Iamnotoneandsimple,butcomplexandmany.
"DiscussionWithallthis,wecannowmovetoadiscussiononhowtoevaluateanalyticalchemistryasithasevolvedoverthelasttwodecades.
Wewillfocusonscientificaspects(1)and(2)ofFig.
1whilewellrealisingtheimportanceofthetechnologicroleofthedisciplinein(3).
Thenewapplicationareasofthedisciplinediscussedinthepreviousparagraphsbelongtosys-temstheory,theinterdisciplinarystudyofsystems,tosystemsthinkinginsteadofanalyticalthinking.
Itmightbestrangetoconsideranalyticalchemistrytransferring,atleastpartly,tosyntheticthinkingmodus,butweneedtoconsideritsutilityinthelightofrecentdevelopments.
AnalyticalchemistryandmetrologyWhenconsideringFig.
2aandtheprominentplacethatthemeasurementisgivenintheanalyticalprocess,itistemptingtoconsiderthat(1)analyticalchemistrydealswithmeasure-ments,and(2)sincemetrologyisthescienceofmeasure-ments,(3)analyticalchemistryispartofmetrology.
This(ap-parentlyfalse)applicationofdeductiveinferencelogicleadstopropositionstore-baptiseanalyticalchemistryasmeasure-mentscience,chemicalmetrologyorchemicalmeasurementscience[26,27].
Thatisalsowhydefinitionscirculateinmanytextbooks(andissupportedbyEuropeanlearnedsocieties)suchas"Analyticalchemistryisametrologicaldisciplinefordeveloping,optimisingandapplyingmeasurementpro-cessesinordertoobtainquality(bio)chemicalinforma-tionfromnaturalandartificialsystems.
"ThesituationbecomesconsiderablymorecomplicatedfortheBigDatasituationasinFigs.
2band3.
Thequalityofthemeasurementsremainsimportant,buttheproperinterpretationofthedataiscompoundedbymanyothersourcesoferror.
Inaworldofincreasinglyautonomouscomputersystems,soft-warebugsareabiggerthreatthaneverbefore.
Whileitcannotbedeniedthatmetrologyformalisesthepracticeofmakingareliablemeasurement,inanalyticalchemistryandinotherscientificfields,suchstatementsconstitute—toexpressitinpsychologicalterms—acognitivedissonancetous,authorsofthisreview,andprobablyalsotomanyotheranalyticalchemists.
Justlikeanyotherscientificdiscipline,analyticalchemistrymustbeafaithfuluserofmetrologicalprinciples,butnotmorethanthat.
Allthisiscompoundedbythefactthat,historically,metrologyarosefromandisstilllargelydominatedbythedefinitionofmeasurementunits.
Inpractice,requirementsforaccuracyandprecisionmayvarydependinguponthepur-posesandaimsofanalysisandthecharacterofthesample[28].
Analyticalchemistryandchemicalanalysisare3532AdamsF.
,AdriaensM.
informationrelatedanddependontherulesofscientificre-searchandontherulesandpracticeofscientificobjectivity[29].
Thisleadstotheconceptof"consensusvalues",withwhichitispossibletoarriveatcomplianceoragreementbe-tweenanalyticalresults[30].
Thisidea,whichisalsosignifi-cantbeyondtheanalyticalcommunity,pointsbacktothebasicphilosophicalideasconcerningscientifictruthsuchasexpressedinscience-philosophicaltreatiesbye.
g.
KarlPopper[31]andscience-philosophicalconceptssuchascom-mensurabilityintroducedbyThomasKuhnandPaulFeyerabend.
Inshort,theessentialsofsciencemustbebroughtbackinthediscipline.
Inthissense,JonathanSweedleradvisedrepro-ducibilityandreplicabilityasbasicqualityconceptsforana-lyticalchemistry,thefield,andAnalyticalChemistry,thejour-nal[32].
Afewyearsago,theworldofpsychologicalresearchbasedonfunctionalmedicalresonanceimagingwasrockedwhenanattempttoreplicatestudiesresultedinunsuccessfulreplica-tionsforasignificantpartofthemasaresultoftheuseofdefectivesoftwarefordatainterpretation[33].
Suchadiscov-eryisnotuniquetopsychology.
Failuretoreplicateinfluentialresultshasalsobeendocumentedinpreclinicalcancerre-search,behaviouralsocialscienceandexperimentaleconom-ics,amongotherfields[34].
ItisexampleslikethesethatleadtoideasthatmetrologymustadapttothedecisionprocessesintheBigDataEraandtransformitselfintosmartmetrology,frommetrologyofinstrumentationtothemetrologyofdeci-sion[35].
AnalyticalchemistryintheBigDataEra:chemicalanalysisinthetwenty-firstcenturyWiththestartofthetwenty-firstcentury,wehaveseenthebirthofanewindustrialrevolution,thedigitalrevolution:theabilitytostoredatafromvarioussources(inparticularthroughrelateditems)inunprecedentedbigquantitiesandtoexploitthemthroughincreasinglyhighcomputingcapabilitiesusingartificialintelligence(AI)techniquesandmachinelearn-ing.
Inthisnewscenariocalled"BigData",datareliabilitybecomesanindispensableproperty:thelargeamountofdatacollectedandtheiranalysisarecompletelyuselessifuntrustedinformationisstoredthatcannothelptounderstandacomplexreality.
Inanentirelydifferentcontext,RobKitchindetailsthatBigDataishugeinvolume(consistingofterabytes,evenpetabytesofdata),highinvelocity(beingcreatedinornearrealtime),diverseinvariety(beingstructuredandunstruc-turedinnature)andexhaustiveinscope(strivingtocaptureentirepopulationsorsystems)[36].
Insuch"data-driven"re-search,analyticalmeasurementsareperformedtogenerateandconfirmnewhypothesesratherthantoconfirmexistingonesanduseanon-targetedapproach.
Insuchconditions,thecentralconceptofconventionalanalyticalchemistry,theanalyteanditsrelationtostandardmetrologicalconcepts(un-certainty,validationand/ortraceabilitytofundamentalcon-stants)seemtolosetheircentralguidingrole.
Analyticalinstrumentationingeneralandchemicalimag-ingtoolsinparticularfollowtheconceptsofthefourthindus-trialrevolutioninintegratingdifferenttechnologies.
Atitsheart,thefourthindustrialrevolutionrepresentsanunprece-dentedfusionbetweenandacrossdigital,physicalandbiolog-icaltechnologies,andaresultinganticipatedtransformationinhowproductsaremadeandused[37].
Asaparticipatingactor,analyticalchemistrybecomesapartnerinalargerscientificandtechnologicalaggregatethanchemistry.
Weneedtoexaminetheseparticularcircumstancesandseehowtheyaffectthefundamentalsofanalyticalchemistryasascientificdiscipline.
SystemsthinkingversusanalyticthinkingInsystemsthinking,asinglemeasurementbecomespartofaconglomeratedinterrelatedentitywhosemeaningislargerthanthesumofitsparts.
Table1summarisessomeofthemostimportantdifferencesbetweenboththoughtprocesses.
Inbrief,analyticthinkingisadiscriminatingprocess,wherebyindividualdimensions,conceptsandideasaredifferentiatedfromsimilarones.
Incontrast,systemic(orsynthetic)thinkingistheintegrativeprocessofbringingtogetherconceptualdi-mensions[38].
Systemstypeanalyticalchemistryactsonthemetaleveloftheentireexperimentinsteadofconcentratingonthedetails.
Itistheapproachtounderstandingthelargerpictureofcompo-sitionandstructureoftheobjectofanalysis,ratherthantheindividualmeasurements,byputtingitspiecestogether.
Thisisincontrastwithdecadesofreductionistviews,whichin-volvetakingthepiecesapart,concentratingontheindividualmeasurements[39].
WesummarisethemajordifferencesofthetwoapproachesforanalyticalchemistryinTable2.
Surprisingly,thenewanalyticalchemistryconceptsrespondtosyntheticratherthananalyticthinkingandforproblem-solvingconcepts.
Ispresent-dayanalyticalchemistrystillpartofchemistryScienceisnotsubdividedinseparatedisciplinesbyanynatu-rallaw,butforpracticalreasons,andchemistryisoneofthosedisciplines.
ButisanalyticalchemistrystillchemistryinitspresentstateofdevelopmentThisquestionhasimportantrepercussionsandcaveatsthatwillbediscussedinthefollow-ingthreesectionsofthispaper.
Weneedtoaddressacentralitemofconcern:whatisthecorebusinessofanalyticalchemistrytodayShouldanalyticalchemistryresearchandanalyticalchemistryeducationbeorganisedfromwithinthechemistrydepartmentsintheThemetamorphosisofanalyticalchemistry3533universitiesorresearchcentresThereisnostraightforwardanswertoallthesequestions,buttheyareworthathoroughdebate.
TheetymologyandsemioticsofanalyticalchemistryWealreadydiscussedthatanalyticalchemistrycannotbeiden-tifiedwithmetrologyorwithphysics.
Itisoftenarguedthatthename"analyticalchemistry"doesnotcoverthesubjectofthedisciplineanymoreandthatitisanamethatdatesfromtheperiodwhenanalyticalchemistrywasnotmuchmorethanacollectionofwet-chemicalmethodsofanalysis.
Suchanamemaybeconsideredasahistoricartefact,inthesamewayaspaintingschoolssuchas"FlemishPrimitives"or"Pre-Raphaelites"arehistoricnamesthatdonotdescribetheirrealcontentasanaccuratedescriptionofaspecificartform.
TheFlemishPrimitiveswerenotprimitivepaintersinthefifteenthcentury;onthecontrary,theywereattheforefrontofartisticandtechnicaldevelopmentatthattime.
ThePre-Raphaelites,equally,didnotoriginateandworkbeforeRaphael;instead,theywereagroupofBritishpaintersthatbroughtaninnovativetwisttoartisticexpressioninthesecondhalfofthenineteenthcentury.
Atpresent,nobodyreallymindstheseapparentlycompletelyfalsedenominations.
Wecanarguealongsimilarargumentsforanalyticalchemistry,wecanjustwaitawhileandbepatientuntilanalyticalchemistryasaterminologywillgetameaningfarbeyonditspresent,literalconnotation.
Infact,thissituationisalreadythecase.
Thelinguisticsbehindanameintersectswithphilosophicalconsiderations.
Apropernameshouldrefertoaspecificob-ject,butspecificnamesmayalsorefertoamorecollectivewhole.
Thishappenswiththesemanticsofanalyticalchemis-try.
Thedisciplineis,atpresent,abroadaggregateofmethod-ologiesthatderivenotonlyfromchemistrybutalsofromphysicsandbiology.
Ofparticularsignificanceisthestudyoftheevolutionaryprocessesthat,overthepast2billionyears,producedmanypotentiallyimportantmaterials.
But,increasingly,ithasalsoderivedfromtechnologicalareasandhowtheywillfulfiltheneedsandexpectationsofthecomplexsocietyoftomorrowinasustainableway[40].
Re-baptisingthedisciplineinto"analyticalscience"or"an-alyticalscienceandtechnology"mighthavesomeadvantageasthisterminologyencompassestheessentialactivity—itconcernsanalysisandthedevelopmentandapplicationofan-alyticalscience—andputsitinabroaderscientificcontext.
Butwhat'sinanameArosebyanyothernamewillsmellassweet…Wekeepbelieving,however,thatanalyticalchemistryre-mainstherightnameasitlinksthedisciplinewhereitbelongs:chemistry.
ThehighestquotedjournalinthedisciplineisandremainslabelledandidentifiedasAnalyticalChemistry;itcoversalotmorethanchemicalresearchandnobodyseemstomind.
TheofficialIUPACdefinitionofanalyticalchemistrystartsasfollows:ascientificdisciplinethatdevelopsandap-pliesmethods,instrumentsandstrategiestoobtaininforma-tiononthecompositionandnatureofmatter.
Thisdefinitionpassedthoughcountlesscommitteemeetings,andnobodyseemstoobjecttoit.
Table2Syntheticthinkingin"newstyle"analyticalchemistryAnalyticthinkingSyntheticthinkingMeasurementscienceFocusesonmeasurementuncertaintyMetrologyisdominantfactorInformationscienceFocusesonscientificconsensusbuildingAcceptscertainlevelsofuncertaintyScientifictruth,falsifiabilityFavourshomogeneityHeterogeneityisasourceofanalyticalerrorFocusesonheterogeneityItisastudyobjectofnaturalandtechnologicalobjectsLeadstodiscipline-orientededucationandmethod-basedorganisationLeadstomultidisciplinaryeducationandproblem-orientedorganisationTable1DifferencesbetweenanalyticalthinkingapproachandsystemicthinkingAnalyticalapproachSystemicapproachReductionistapproachEmphasisondetailsIsolatesthenconcentratesononeormoredetailsoftheobjectofinterestHolistic(comprehensive)approachUnifiesandconcentratesontheinteractionbetweenitemsofstudyEmphasisesglobalperceptionLeadstoactionprogrammedindetailLeadstoactionthroughobjectivesPossessesknowledgeofdetails,poorlydefinedgoalsPossessesknowledgeofgoals,fuzzydetails3534AdamsF.
,AdriaensM.
Maybe,allthingsdulyconsidered,thebestistoavoidanydefinitionofanalyticalchemistry,adheringtotheage-oldad-agethatsayssimply:"Analyticalchemistryiswhatanalyticalchemistsdo".
AnalyticalchemistryineducationTwoofthecoreprinciplesofgeneralscientificpracticearequantificationandsystematisation.
Inthatrespect,studentsaretaughtalreadyearlyonintheircurriculumabouttheim-portanceofmeasurementuncertaintyandreproducibilityofresults.
Itisthereforesurprisingthat,invariousdisciplines,particularlywithinthenaturalsciences,relativelysimpleoroutdatedmethodologiesarebeingusedforquantifyingdataandfortestingphysicaltheories.
Thesameapplieswiththechemistrycurriculum.
Systematicsareintroducedwiththeapparentsimplicityoftheperiodicsystemandthenfurtherdevelopedwiththeintrin-siccomplexityoforganicchemistryanditsnomenclatureandsynthesis.
Quantitativeaspectsofthedisciplineareintroducedwithelementaryaspects:equilibriumchemistryconceptsin-troducequantificationinthediscipline.
Importantasthesedeep-rootedprinciplesmaybeintheeducationofachemist,theyalsoprovideanoutdatedviewofthediscipline.
Wheninmosttextbooksthisissupplementedwithinstrumentalchem-icalanalysis,treatmentisfragmentalwithadeepdivisionbetweenorganicandinorganicanalysisandastrictseparationbetweenthedifferentmethodologies.
Overall,themeasure-mentanditsaccuracydominatethepicture.
Largelymissingintheaveragetextbookisthenewholisticsyntheticap-proachesforproblemsolvingdescribedinthepreviouspara-graphsofthispaper.
Atpresent,numerouseducationalinitiativesaretakenforre-enforcingtheanalyticalchemistrycurriculum,andthisbothontheconventionalchemistryandmeasurementsciencelevelofFig.
3a,asonthemultidisciplinary,informationsciencelevelofFig.
3b.
TheErasmusMundusMasterprogrammeEACH(ExcellenceinAnalyticalCHemistry),forinstance,remainslargelyonthemonodisciplinary(chemistry)levelandonmeasurementandmetrology[41].
TheSALSA(theGraduateSchoolofAnalyticalSciencesAdlershof)GraduateSchoolinitiative,ontheotherhand,offersstructuredmultidisciplinaryresearchcombinedwithanintegratedcurric-uluminanalyticalsciences[42].
TheinitiativeiscarriedoutattheHumboldtUniversityinBerlinandfollowstheopen-mindintegrativeconceptsofAlexandervonHumboldt[43].
Bothoftheseapproacheshavetheirprosandconsforeducatingtheyounganalyticalchemistsforthecomplextasksaheadofthem.
Ingeneral,webelievethateducationaleffortsinanalyticalchemistryshouldfocusontheparticipation,aschemists,incross-disciplinaryandinterdisciplinaryteamsratherthanonbreakingdownthedisciplinaryborderandleavingchemistry.
TheprominentplaceofanalyticalchemistryinscienceAccordingtoMiguelValcárcel,analyticalchemistryisnotoptimallyperceived,andeventreatedasasecond-classdisci-pline.
Heattributesthistolong-lastingprejudicesblaminganalyticalchemists,chemistsfromotherdisciplinesandevenprofessionalsfromotherfields[44].
Webelievethatsuchneg-ativeviews,iftheyreallyexistsomewhere,residewithintheanalyticalchemistrycommunityitselfandaretheresultofalackofself-esteem.
ThedisciplineisnotaCinderellasufferingfromundeservedneglectbutascientificpowerhouse,amightysourceofinfluenceandinspiration.
Theprofessionalsuccessofanalyticalchemistrygraduatesisobvious.
Ithasbeendemonstratedthatthereisashortageofwell-educatedanalyticalchemistsinEurope[45].
Aconsider-ablefractionoftheEuropeanResearchCouncilgrantsofthelastyearshighlightsinnovativeresearchprojectslinkedwithchemicalanalysisoranalyticalmethodsdevelopment.
Table3showsabriefselectionofrecentNobelPrizesandtheplaceofchemicalanalysisinthem.
Strikingistheplaceofbioanalysisandthenano-sizelevelinallthis.
Theparticularplaceofanalyticalchemistryinthe2018PhysicsPrizeisdocumentedbyAsplundetal.
,inarecentarticleinthisjournal[46].
Theimportanceoflasersandtoolsformanipulatingnano-sizesamplesisobvious.
Thattheothertwoexamplesbelongtothefieldofanalyticalchemistrymightbeamatterofdebate,butwestronglybelievetheydo.
The2014ChemistryPrizedealswithdetectingandtracinginspaceofsinglebiomole-culesinordertostudytheirinteractionprocesses,whilethe2018ChemistryPrizeinvolvesthemeasurementoftheTable3RecentNobelPrizesconnectedwithanalyticalchemistryYearDisciplineAwardedtoMotivation2014ChemistryEricBetzig,StefanHell,WilliamMoernerSuperresolvedfluorescencemicroscopy2017ChemistryJacquesDubochet,JoachimFrank,RichardHendersonCryo-electronmicroscopyforhigh-resolutionstructuredeterminationofbiomoleculesinsolution2018Physics(joint)ArthurAshkinOpticaltweezersandtheirapplicationtobiologicalsystemsPhysics(joint)GérardMourou,DonnaStricklandMethodforgeneratinghigh-intensityultrashortlaserpulsesThemetamorphosisofanalyticalchemistry3535detailedstructuralarrangementofsingleproteinmoleculesinsituinparticularcells.
ConclusionsandoutlookAtpresent,analyticalchemistryactsattheinterplaybetweencomposition,structureandstructuraldefectsononesideandpropertiesandfunctionalityofsoftandhardmaterialobjectsontheother.
Itmovedawayfromachemistry-orientedfieldofresearchtooneinamorebroadlydefinedcross-disciplinarydenominator,similartoauxiliaryfieldssuchasspectrometry,materialsscienceorenvironmentalscience.
Whilechemistryremainsthebasisforitsdevelopmentaspects,itsapplicationsinchemicalanalysisrangeovertheentirescientificrealm.
Analyticalequipmentandanalyticalmethodologiesareen-ablingtechnologiesforscienceandsociety.
Inaway,analyt-icalchemistryislikeanexpat,amigrant(notafugitive):ithasitsrootsinchemistry,butitsambitionsandexpectationsaresituatedelsewhere,alloverscience,inindustryandsociety.
The"new"BigDataEraanalyticalchemistryisnotreplac-ingthetraditionalconceptsofanalyticalchemistry;itisanepitome,anavatar,anewconceptualform.
Itstillneedstobefullyintegratedintotheconceptualframeworkofthedis-cipline.
IntheBigDataEraapplications,itcannotrelyany-moreontheaimsandambitionsbasedonthequalityassur-anceoftheindividualmeasurements.
Instead,itsambitionsmustbebasedontherelationofmanyanalyticalresultsincombinationwithotherrelevantinformation.
Thecombineddataaregreaterthanthesumofitsparts,becausethewaytheycombineaddsadifferentquality.
Thisisanage-oldconceptsupposedtooriginatewithAristotle.
Centraltothefullacceptanceofthedisciplineinitsnewformishowitmanifestsitselfinitspracticalutility,inbothsocietyandscience.
BigDataanalyticalchemis-trycannotrelyonhumanjudgment.
Humansaresuscep-tibletocognitivebias;theyhaveatendencytoseekinformationthatconfirmstheirpriorbeliefs.
Also,theapplicationofAIisnotwithoutrisk[47].
Inaworldofincreasinglyautonomouscomputersystems,softwarebugsbecomeabiggerthreatthaneverbefore.
Thereisalotoffundamentalworktodoinensuringthequalityofdatacollection,datahandlinganddatareduction.
Theuseofchemometricsisnecessarytotransformdatainactionableinsight.
Eventually,"smartmetrology"willplayaroleinallthis.
Onlytimewilltellwhenitopensitscurtainshowthedis-ciplinewilleventuallyevolveandwhichnew,nowtotallyunexpectedmetamorphosesitwillundergointhelongrun.
AcknowledgementsTheauthorFAexpresseshisgratitudetotheDivisionofAnalyticalChemistryoftheEuropeanAssociationofChemicalandMolecularSciencesfortheDAC-EuChemSAward2019.
Theawardliesatthebasisofthispaper.
CompliancewithethicalstandardsThischapterdoesnotcontainanystudieswithhumanparticipantsoranimalsperformedbyanyoftheauthors.
ConflictofinterestTheauthorsdeclarethattheyhavenoconflictofinterest.
OpenAccessThisarticleislicensedunderaCreativeCommonsAttribution4.
0InternationalLicense,whichpermitsuse,sharing,adap-tation,distributionandreproductioninanymediumorformat,aslongasyougiveappropriatecredittotheoriginalauthor(s)andthesource,pro-videalinktotheCreativeCommonslicence,andindicateifchangesweremade.
Theimagesorotherthirdpartymaterialinthisarticleareincludedinthearticle'sCreativeCommonslicence,unlessindicatedotherwiseinacreditlinetothematerial.
Ifmaterialisnotincludedinthearticle'sCreativeCommonslicenceandyourintendeduseisnotpermittedbystatutoryregulationorexceedsthepermitteduse,youwillneedtoobtainpermissiondirectlyfromthecopyrightholder.
Toviewacopyofthislicence,visithttp://creativecommons.
org/licenses/by/4.
0/.
References1.
HarveyD.
Analyticalchemistry2.
0.
2009.
http://dpuadweb.
depauw.
edu/harvey_web/eTextProject/version_2.
0.
html.
Accessed26Aug2019.
2.
MurrayRW.
Aneditor'sviewofanalyticalchemistry(thedisci-pline).
AnnuRevAnalChem.
2010;3:1–18.
3.
BrennerS.
Therevolutioninthelifesciences.
Science.
2012;338:1427–8.
4.
DysonFJ.
IssciencemostlydrivenbyideasorbytoolsScience.
2012;338:1426–7.
5.
SchumpeterJA.
Capitalism,socialismanddemocracy(originaledi-tion1942).
London:Routledge;1994.
6.
AdamsF,BarbanteC.
Chemicalimaginganalysis.
Amsterdam:Elsevier;2015.
7.
AdamsF,CollingwoodJ.
Atomicspectrometry|imagingmethods.
In:WorsfoldP,PooleC,TownshendP,MiróM,editors.
Encyclopediaofanalyticalscience.
3rded.
Amsterdam:Elsevier;2019.
p.
239–46.
8.
AlexandrovT,ChernyavskyI,BeckerM,vonEggelingF,NikolenkoS.
Analysisandinterpretationofimagingmassspec-trometrydatabyclusteringmass-to-chargeimagesaccordingtotheirspatialsimilarity.
AnalChem.
2013;85(23):11189–95.
9.
KalininSV,SumpterBG,ArchibaldRK.
Big-deep-smartdatainimagingforguidingmaterialsdesign.
NatMater.
2015;14:973–80.
10.
RaesJ,BorkP.
Moleculareco-systemsbiology:towardsanunder-standingofcommunityfunction.
NatRevMicrobiol.
2008;6:693–9.
11.
IbrahimYM,HamidAM,DengL,GarimellaSV,WebbIK,BakerES,etal.
Newfrontiersformassspectrometrybaseduponstructuresforlosslessionmanipulations.
Analyst.
2017;142:1010–2017.
12.
TeschendorffAE.
Avoidingcommonpitfallsinmachinelearningomicdatascience.
NatMater.
2019;18:422–7.
13.
DoanM,CarpenterAE.
Leveragingmachinevisionincell-baseddiagnosticstodomorewithless.
NatMater.
2019;18:414–8.
14.
GorrochateguiE,JaumotJ,LacorteS,TaulerR.
Dataanalysisstrat-egiesfortargetedanduntargetedLC-MSmetabolomicsstudies.
TrendsAnalChem.
2016;82:425–42.
3536AdamsF.
,AdriaensM.
15.
vanderMaatenLJP,HintonGE.
Visualizingnonmetricsimilaritiesinmultiplemaps.
MachLearn.
2012;8:33–55.
16.
WaltDR.
Opticalmethodsforsinglemoleculedetectionandanal-ysis.
AnalChem.
2013;85:1258–63.
17.
FleischmannM,HendraPJ,McQuillanAJ.
Ramanspectraofpyr-idineadsorbedatasilverelectrode.
ChemPhysLett.
1974;26:163–6.
18.
ZhangR,ZhangY,DongZC,JiangS,ZhangC,ChenLG,etal.
ChemicalmappingofsinglemoleculesbyplasmonenhancedRamanscattering.
Nature.
2013;498:82–6.
19.
GraefeCT,PunihaoleD,HarrisCM,LynchMJ,LeightonR,FrontieraRR.
Far-fieldsuper-resolutionvibrationalspectroscopy.
AnalChem.
2019;91:8723–31.
20.
FeynmanRP.
There'splentyofroomatthebottom.
EngSciMag.
1960;23(5):22–36.
21.
VanAertS,DeBackerA,MartinezGT,denDekkerAJ,VanDyckD,BalsS,etal.
Advancedelectroncrystallographythroughmodelbasedimaging.
IUCrJ.
2016;3:71–83.
22.
LocquetJP,PerretJ,FompeyrineJ,MchlerE,SeoJW,VanTendelooG.
DoublingthecriticaltemperatureofLa1.
9Sr0.
1CuO4usingepitaxialstrain.
Nature.
1998;394:453–6.
23.
FeynmanRP,GatesB,LeightonR.
Surelyyou'rejoking,MrFeynman!
Adventuresofacuriouscharacter.
NewYork:W.
W.
Norton&Company;1985.
24.
Bensaude-VincentB,SimonJ.
Chemistry–theimpurescience.
2nded.
London:ImperialCollegePress;2008.
25.
Bensaude-VincentB.
Thechemists'styleofthinking.
BerWiss.
2009;32(4):365–78.
26.
PaullB.
Analyticalscience–acomplexanddiverseunion.
AnalMethods.
2012;4:19.
27.
AnalyticalMethodsCommittee.
Chemicalmetrology.
AnalMethods.
2016;8:8119–26.
28.
DolmanovaIF.
Metrologyinchemicalanalysis.
In:EncyclopediaofLifeSupportSystems(EOLSS).
2018.
https://www.
eolss.
net.
Accessed26Aug2019.
29.
SweedlerJV,ArmstrongDW,BabaY,DesmetG,DovichiN,EwingA,etal.
Thescopeofanalyticalchemistry.
AnalChem.
2015;87:6425.
30.
AndersenJE,BuchbergerW,WorsfoldP.
Europeananalyticalcol-umnno41.
AnalBioanalChem.
2013;405:5361–4.
31.
PopperK.
Thelogicofscientificdiscovery(firstEnglished.
1959).
London:Routledge;2002.
32.
SweedlerJW.
Reproducibilityandreplicability.
AnalChem.
2019;91:7971–2.
33.
EklundA,NicholsTE,KnutssonH.
Clusterfailure:whyfMRIinferencesforspatialextenthaveinflatedfalse-positiverates.
ProcNatlAcadSci.
2016;113:7900–5.
34.
AdamD.
Thedatadetective.
Nature.
2019;571:462–4.
35.
LazzariA,PouJM,DuboisC,LeblondL.
Smartmetrology:theimportanceofmetrologyofdecisionsintheBigDataEra.
IEEEInstrumMeasMag.
2017;17:1094–6969.
36.
KitchinR.
Bigdataandhumangeography:opportunities,chal-lengesandrisks.
DialoguesHumGeogr.
2013;3(3):262–7.
37.
SchwabK.
WillthefourthindustrialrevolutionhaveahumanheartIn:WorldEconomicForum.
2015.
https://agenda.
weforum.
org/2015/10/will-the-fourth-industrial-revolutionhave-a-human-heart-and-soul.
Accessed26Aug2019.
38.
FeistGJ.
Syntheticandanalyticalthought:similaritiesanddiffer-encesamongartandsciencestudents.
CreatResJ.
1991;4:145–55.
39.
JohnsonRH,HambyB.
Ameta-levelapproachtotheproblemofdefiningcriticalthinking.
Argumentation.
2015;29:417–30.
40.
KingAH.
Ourelementalfootprint.
NatMater.
2019;18:408–9.
41.
LeitoI,TeearuA,BobackaJ,RandonJ,BergquistJ.
EACH(ExcellenceinanalyticalCHemistry),anErasmusMundusjointprogramme:progressandsuccess.
AnalBioanalChem.
2019;411:5913–21.
42.
Montes-BayónM,KneippJ,PanneU.
ReportonKOSMOSSummerUniversityattheSchoolofAnalyticalSciencesAdlershof(Berlin):limitsandscalesinanalyticalsciences.
AnalBioanalChem.
2015;407:4869–72.
43.
GuarinA.
AlexandervonHumboldtandtheoriginsofourmoderngeographicalviewofearth.
In:JanelleDG,WarfB,HansenK,editors.
WorldMinds:geographicalperspectiveson100problems.
Dordrecht:Springer;2004.
p.
607–11.
44.
ValcárcelM.
Quovadis,analyticalchemistryAnalBioanalChem.
2016;408:13–21.
45.
SalzerR,TaylorP,MajcenN,DeAngelisF,WilmetS,VarellaE,etal.
TheprofessionalstatusofEuropeanchemistsandchemicalengineers.
ChemEurJ.
2015;21:9921–35.
46.
AsplundMC,JohnsonJA,PattersonJE.
The2018NobelPrizeinphysics:opticaltweezersandchirpedpulseamplification.
AnalBioanalChem.
2019;411:5001–5.
47.
GauglitzG.
Artificialvs.
humanintelligenceinanalytics.
AnalBioanalChem.
2019;411:5631–2.
Publisher'snoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.
FreddyAdamswasprofessorofchemistryattheUniversityofAntwerp(UA),Belgium,withteachingassignmentsinanalyticalchemistryandradiochemistry.
Hisresearchinvolvedfundamentalanalyticalchemistryandapplica-tionsinthematerialssciences,theenvironmentalsciencesandartandarchaeology.
Hewasco-founderanddirectoroftheMicroandTraceAnalysisCentreattheuniversityandwasrectoroftheUAfor12years.
Atpresent,asemeritusprofessor,heremainsinvolvedinhisformerprofessionalactivitiesandscienceingeneral.
MiekeAdriaensisseniorfullpro-fessorinthefieldofanalyticalchem-istryatGhentUniversity,Belgium.
Shehasbeenworkingforseveralyearsonthedevelopmentandopti-misationofspectroelectrochemicalequipment(i.
e.
thecouplingofelec-trochemicalandspectroscopicmethods)andthestudyofmetalcor-rosioninhibition,includingthede-velopmentofprotectivecoatings.
Shehasgainedexpertiseforover25yearsintheinterdisciplinaryfieldofscienceandculturalheritage.
Themetamorphosisofanalyticalchemistry3537