Frank Vollmer Deshui Yu Optical Whispering Gallery Modes for Biosensing From Physical Principles to Applications Second Edition Optical Whispering Gallery Modes for Biosensing · Frank Vollmer Deshui Yu Optical Whispering Gallery Modes for Biosensing From Physical Principles to Applications Second Edition FrankVollmer DeshuiYu PhysicsandAstronomy PhysicsandAstronomy UniversityofExeter UniversityofExeter Exeter,UK Exeter,UK ISBN 978-3-031-06857-7 ISBN 978-3-031-06858-4 (eBook) https://doi.org/10.1007/978-3-031-06858-4 1stedition:©TheAuthor(s),underexclusivelicensetoSpringerNatureSwitzerlandAG2020 2ndedition:©TheEditor(s)(ifapplicable)andTheAuthor(s),underexclusivelicensetoSpringer NatureSwitzerlandAG2022 Thisworkissubjecttocopyright.AllrightsaresolelyandexclusivelylicensedbythePublisher,whether thewholeorpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuse ofillustrations,recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,and transmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilar ordissimilarmethodologynowknownorhereafterdeveloped. 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ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface to the Second Edition The second edition of our book titled Optical Whispering Gallery Modes for Biosensing now includes extended discussions of advanced topics in microcavity optics such as those on spectroscopy and sensing with optical frequency combs (microcombs),opticalgyroscopes,andoptomechanicalmicrocavitydevices.Further discussionshavebeenaddedonwhisperinggallerymodeatomtrapping,theparity– time symmetry, and the lasing dynamics of macro- and microcavities, down to the one-emitter (one-atom) laser. The book now includes an extended chapter on single-molecule sensing including more details on the optoplasmonic whispering gallery mode single-molecule sensors, an extended discussion of the detection of protein conformational changes and enzyme activity, and a discussion of intracel- lular(invivo)sensingandbarcodingapplicationsbasedonthewhisperinggallery mode microlasers. Nearly 100 pages have been added to our manuscript that was first published as part of the Springer Series on Biological and Medical Physics, BiomedicalEngineeringinNovember2020. Withacomprehensivediscussionofthefundamentalphysicsofopticalmicrocav- itiesandtheinclusionofproblemsetsforeachofthesevenchapters,wehopethat our second edition of Optical Whispering Gallery Modes for Biosensing not only servesasaworkingreferencefortheactiveresearcher,butalsoprovidesascholarly introductiontothefieldofopticalmicrocavitiesforuniversitystudentsandpostgrad- uateresearchers.ThissecondeditionofourbookisastandaloneSpringertextbook that, we believe, will be useful for both introductory and advanced courses about themodernopticsofopticalmicrocavities.Wehopethattheinclusionofthebook cover, which shows a wonderful image of the whispering gallery modes taken by Dr.SamirVartabiKashanianinourlaboratoryattheUniversityofExeter,conveys thebeautyandexcitementthatwe,theauthors,havealwaysfeltfortheresearchon opticalmicrocavitiesandwhisperinggallerymodesundertakenbymanyexcellent researchgroupsaroundtheglobeandwhich,insomanycases,isattheforefrontof opticsandsensing. v vi PrefacetotheSecondEdition In closing, we would like to thank the editors at Springer Nature, especially Dr. Zachary Evenson for their continued and excellent support which made this secondEditiontextbookareality.Thankyoutoo,MayumiNotoandDongjieWang. Exeter,UK FrankVollmer DeshuiYu Preface to the First Edition Theresearchonwhisperinggallerymode(WGM)biosensinghasalwaysbeenvery exciting. It combines interesting physics with emerging applications in biophysics and biology. The idea for writing a book about the physics of WGMs and their applications in sensing and biosensing emerged around the year 2011. I started teaching an interdisciplinary course on the physics of biosensing with WGMs. A morecarefulreviewofthesubjectshowedthatsince2000,manyimportantadvances inphysicsweremadewithWGMs.Thefieldofcavityoptomechanicshademerged; nonlinear optical effects were studied with WGMs including multi-wave mixing, parametericdown-conversion,andfrequencycombgeneration.Thedemonstration ofstrongcouplingbetweenatomsandmoleculeswithWGMssparkedtheinterest for using WGMs in cavity QED. A number of world-leading laboratories joined the effort and made seminal contributions in the research area of optical micro- cavities. The WGMs provide a particularly versatile experimentation platform for those researchers to study the fundamentals of light–matter interactions, from the classical to the quantum regimes. Many of the groundbreaking physics advances weremadewithWGMs,andalmostalwaystheypointtoaninterestingapplication in biosensing. Examples for this are the exceptional points and the quantum light generatedorcollectedwithWGMsthatmightbeabletofurtherenhancedetection sensitivitiesofsinglemolecules.AcomprehensivebookonWGMbiosensingwould have to cover all of these exciting fundamental physics of WGMs. Book chapters on the fundamental understanding of the sensing with light, the physics of WGM inopticalmicrocavities,theapplicationofWGMmicrocavitiesinphysics,andthe fundamentalsofquantumopticsandmolecularcavityQEDwouldbeneeded. Tobeginwith,letalonecompletingsuchacomprehensivebookonthephysicsof WGMsandtheirbiosensingapplicationsdidnotcomeabouteasily.Itrequiredthe rightco-author.AfterImovedmylaboratorytoUniversityofExeter,UK,in2016, the right co-author joined my group: Dr. Deshui Yu. Deshui is an exceptionally talentedtheoristtrainedatPekingUniversity.DeshuijoinedmygroupatUniversity ofExeterin2018toworkonthetheoryofWGMs.Deshuiwasveryexcitedwhen Imentionedthebookprojecttohim.Althoughtheideaforthebookwasstillinits veryearlystagesevenatthattime,Deshuiwasveryenthusiastictojointheproject. vii viii PrefacetotheFirstEdition DeshuiisnotonlyoneofthefinesttheoristsImet,butalsoanexceptionallecturer ofphysics.Deshuicanfindsimpleexplanationsforcomplicatedphysics.Heisable to explain complicated physics without taking shortcuts. Effortlessly, he is able to bridgetheoryandexperiment.Heengageswiththeresearchersfromotherfieldsand disciplines.AlittlemorethanayearlaterafterDeshuijoined,thefirstdraftforour bookwasready.IamdeeplyindebtedtoDeshuiforhishardworkandcommitment tocompletingahigh-qualitybook.Deshui’simmensecontributionsresultedinthe inclusionofadvancedtheoreticalchaptersthatareessentialforadeepunderstanding oftheWGMphysics.Thebooknowfullyconveystheexcitementandappreciations for this exciting research topic. The book covers most of the fundamental WGM physicsandcombinesthemwiththechaptersonsensingwithlight,surfaceplasmon resonance,andsinglemoleculesensing.Thebooktouchesnotonlyoncoresubjectsin physics,butalsoonsomefundamentalaspectsofbiophysicsandchemistry.Itis,we hope,aninspiringandcomprehensivereadforaninterdisciplinaryreadership.Iquote Deshui:“Sciencewithouttheoryislame,theorywithoutexperimentationisblind”. FrankVollmer We hope this book will be a valuable resource for teaching the physics of optical microcavities. We also hope for it to become a valuable resource for the active users of WGMs, in their various applications including biosensing. The future for WGM sensors is bright and just emerging. WGM sensors will help us to explore the biophysics and biochemistry at the very limits of what humans are capable of investigating. They are a platform to develop various nano- and quantum sensing methodologies.TheycanallowustoexploreNature’ssmallestentitiessuchassingle molecules,singlephotons,andfemto-Newtonforces,aswellasintricatemolecular opticalpropertiessuchassingle-moleculechirality.Researchersmayfindthisbook usefulfordevelopingnovelWGMsensingtechniques,suchasthosethatmayfurther enablethedetectionandvisualizationofprocessesatthenanoscale,atultrahighsensi- tivity,andinaspecificandsensitivemanner,downtothelevelofmolecules,atoms, andbonds.TheauthorsbelievethatWGMsensorsandspectrometerswillhavemany importantapplicationsinhealth,nanotechnology,metrology,environment,biology, defense and security, and astronomy. We hope this book may aide in the develop- ment of these next-generation biosensor applications, and that the book may help extendtheseapplicationstoincludechip-scalesingle-moleculelaboratoriesforclin- icaldiagnosticsthatprovidemaximuminformationbyanalyzingabiologicalsample molecule-by-molecule. Insummary,wewouldliketothankSequoiaAlbaWebsterandMithilParekhfor contributingtotheveryearlystagesofthebookproject.Theauthorsthankallwho have directly and indirectly contributed to the successful completion of the book. Thankyoutoo,MayumiNotoandDongjieWang. Exeter,UK FrankVollmer DeshuiYu Contents 1 SensingwithLight ............................................. 1 1.1 Introduction .............................................. 1 1.2 LightPropagationinSpace ................................. 2 1.2.1 VectorandScalarPotentials ........................ 4 1.2.2 WaveEquationsforElectricandMagneticFields ...... 7 1.2.3 BoundaryConditions .............................. 10 1.3 Polarizability ............................................. 12 1.3.1 ElectricDipole ................................... 12 1.3.2 LocalFieldCorrection ............................. 14 1.3.3 LorentzOscillatorModel .......................... 17 1.4 FrequencyandIntensityFluctuationsofLight ................. 21 1.4.1 AutocorrelationFunctionandSpectrum .............. 22 1.4.2 LorentzianandGaussianBroadening ................ 24 1.4.3 PhaseNoise ...................................... 27 1.4.4 HanburyBrown–TwissEffect ....................... 30 1.5 FrequencyStabilization .................................... 32 1.5.1 Fabry–PérotResonator ............................ 32 1.5.2 LC Oscillators ................................... 36 1.5.3 LaserFrequencyLockingtoTransmissionLine ....... 38 1.5.4 Pound–Drever–HallTechnique ..................... 39 1.5.5 ShotNoise ....................................... 43 1.5.6 OpticalHeterodyneandHomodyneDetection ........ 44 1.5.7 MeasuringthePhotonNumber ...................... 47 1.6 OpticalSensingTechnologies ............................... 48 1.6.1 Michelson–MorleyInterferometer ................... 48 1.6.2 OpticalClocks ................................... 49 1.6.3 SingleAtomDetection ............................ 51 1.6.4 OpticalTweezers ................................. 53 Problems ....................................................... 54 References ..................................................... 58 ix x Contents 2 SurfacePlasmonResonance ..................................... 63 2.1 Introduction .............................................. 63 2.2 Plasmonics:InteractionofLightwithMetals .................. 64 2.2.1 Drude–SommerfeldModel ......................... 65 2.2.2 InterbandTransitionsofBoundElectrons ............ 66 2.2.3 Drude–LorentzModel ............................. 69 2.3 SurfacePlasmonPolaritons—SPPs .......................... 69 2.3.1 SPPsatPlaneInterfaces ........................... 70 2.3.2 ExcitationofSPPs ................................ 77 2.3.3 SPRSensors ..................................... 79 2.3.4 SurfacePlasmonOptics ............................ 80 2.4 LocalizedSurfacePlasmonResonances—LSPRs .............. 84 2.4.1 SphericalNanoparticles ............................ 85 2.4.2 EnergyStoredinMetalNanoparticles ................ 89 2.4.3 Nanoellipsoids ................................... 92 2.4.4 MieTheoryofLightScattering ..................... 93 2.4.5 NumericalMethodsforLSPRs ..................... 105 2.5 PlasmonicCouplingofNanoparticles ........................ 110 Problems ....................................................... 114 References ..................................................... 114 3 WhisperingGalleryModesinOpticalMicrocavities ............... 119 3.1 Introduction .............................................. 119 3.2 Microspheres ............................................. 120 3.2.1 StrictAnalyticalEigenmodes ....................... 121 3.2.2 AnalyticalWGMFrequencies ...................... 129 3.2.3 EffectiveModeVolume ............................ 132 3.2.4 ApproximateSolutions ............................ 134 3.2.5 IntrinsicQualityFactor ............................ 138 3.2.6 ExcitationofWGMs .............................. 142 3.3 Microbottles .............................................. 148 3.4 Microdisks ............................................... 153 3.5 Microtoroids .............................................. 158 3.6 Thermo-Refractive-Noise-LimitedFrequencyStability .......... 164 Problems ....................................................... 168 References ..................................................... 171 4 ApplicationsofWGMMicrocavitiesinPhysics .................... 175 4.1 Introduction .............................................. 175 4.2 LaserGeneration .......................................... 176 4.3 NonlinearFrequencyConversion ............................ 178 4.3.1 PockelsEffect .................................... 180 4.3.2 Multiple-WaveMixing ............................ 183 4.3.3 Second-OrderNonlinearity ......................... 184 4.3.4 FrequencyDoubling .............................. 187