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3 Bioanalytical Reviews SeriesEditors Frank-Michael Matysik, Institute of Analytical Chemistry, University of Regensburg,Regensburg,Germany Joachim Wegener, Department of Chemistry, University of Regensburg, Regensburg,Germany Bioanalytical Reviews is the successor of the former review journal with the same name, and it complements Springer’s successful and reputed review book series programintheflourishingandexcitingareaoftheBioanalyticalSciences. Bioanalytical Reviews (BAR) publishes reviews covering all aspects of bioanalytical sciences. It therefore is a unique source of quick and authoritative information for anybody using bioanalytical methods in areas such as medicine, biology,biochemistry,genetics,pharmacology,biotechnology,andthelike. Reviewsofmethodsincludeallmoderntoolsapplied,includingmassspectrom- etry, HPLC (in its various forms), capillary electrophoresis, biosensors, bioelectroanalysis, fluorescence, IR/Raman, and other optical spectroscopies, NMR radiometry, and methods related to bioimaging. In particular the series volumes provide reviews on perspective new instrumental approaches as they apply to bioanalysis, and on the use of micro-/nano-materials such as micro- and nanoparticles.Articlesonμ-totalanalyticalsystems(μ-TAS)andonlabs-on-a-chip alsofallintothiscategory. Intermsofapplications,reviewsonnovelbioanalyticalmethodsbasedontheuse of enzymes, DNAzymes, antibodies, cell slices, to mention the more typical ones, are highly welcome. Articles on subjects related to the areas including genomics, proteomics, metabolomics, high-throughput screening, but also bioinformatics and statisticsastheyrelatetobioanalyticalmethodsareofcoursealsowelcome.Reviews coverbothfundamentalaspectsandpracticalapplications. Reviews published in BAR are (a) of wider scope and authoratively written (rather than a record of the research of single authors), (b) critical, but balanced and unbiased; (c) timely, with the latest references. BAR does not publish (a) reviews describing established methods of bioanalysis; (b) reviews that lack wider scope,(c)reviewsofmainlytheoreticalnature. Tilman E. Schäffer Editor Scanning Ion Conductance Microscopy With contributions by (cid:1) (cid:1) (cid:1) (cid:1) L. A. Baker A. Bhargava M.-H. Choi I. D. Dietzel (cid:1) (cid:1) (cid:1) (cid:1) (cid:1) A. Gesper J. Gorelik A. Haak P. Happel F. Iwata (cid:1) (cid:1) (cid:1) (cid:1) Y. Korchev C. W. Leasor M. V. Makarova Y. Mizutani (cid:1) (cid:1) (cid:1) (cid:1) M. Nakajima P. Novak T. E. Schäffer A. Shevchuk (cid:1) (cid:1) Y. Takahashi T. Ushiki H. von Eysmondt Editor TilmanE.Schäffer InstituteofAppliedPhysics UniversityofTübingen Tübingen,Germany ISSN1867-2086 ISSN1867-2094 (electronic) BioanalyticalReviews ISBN978-3-031-14442-4 ISBN978-3-031-14443-1 (eBook) https://doi.org/10.1007/978-3-031-14443-1 ©TheEditor(s)(ifapplicable)andTheAuthor(s),underexclusivelicensetoSpringerNatureSwitzerland AG2022 Thisworkissubjecttocopyright.AllrightsaresolelyandexclusivelylicensedbythePublisher,whether thewholeorpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseof illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similarordissimilarmethodologynowknownorhereafterdeveloped. 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ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Foreword TilmanE.SchäfferisadistinguishedleaderinthefieldofScanningIonConductance Microscopy[1].Hewasthefirst,asfarasIknow,tousetheSICMtoanswerareal scientificquestion:howabalonenacreforms.Hefounditwasnotbyheteroepitaxial nucleation, as was commonly believed, but instead by growth through mineral bridges that formed in the pores he imaged with the SICM [2]. Together with his coworkers, he also developed an elegant, non-contact method for measuring the stiffness of cells [3] and high-speed SICM with imaging speeds faster than one secondperimage[4].Itisespeciallyimportanttonotethathisworkhasbeenreally focused not just on technique development, but on answering important scientific questions.Forexample,oneofhisrecentpapersrevealsdifferentialstrategiesofhow twohuman-pathogenicviruses manipulateinfectedcells[5]. Oneofhisownchap- tersinthisbook,withvonEysmondt,givesnotonlyacomprehensiveoverview,but arealisticassessmentofboththestrengthsandthelimitationsofthetechnique. Tilmanhasalsodoneanexcellentjobofgettingsomeofthebestandbrightestin the field to contribute chapters to this book. I was particularly interested in poten- tiometric scanning ion conductance microscopy (P-SICM) in the chapter by Choi, Leasor,andBakerandininvestigatingcardiacfunctionwithSICMincombination with other techniques in the chapter by Bhargava and Gorelik. Combining SICM withothertechniques,pioneeredbyTilmanhimself[2]hasbeenparticularlyfruitful –especiallythecombinationwithsuper-resolvedopticalmicroscopyasdiscussedin the chapter by Happel, Gesper, and Haak. A recent, spectacular example in their chapterisfromGeorgFantner’slab(includingoneoftheinventorsofSICM,Barney Drake):a2021NatureCommunicationsarticlewithamazingcorrelative3Dimages of single cells using super-resolution optical fluctuation imaging (SOFI) and scan- ningion-conductancemicroscopy[6].ThechapterbyUshiki,Iwata,Nakajima,and Mizutani describes another fruitful combination: SICM with scanning electron microscopy. Oneoftherealhighlightsofthebookisthechapterbythedistinguishedpioneers Novak, Shevchuk, and Korchev. They do a wonderful job of summarizing their seminal contributions that helped transform SICM into a practical instrument for widespreadapplications. v vi Foreword The chapter by Dietzel, Happel, and Schäffer gives a thorough overview of the intellectualcontextinwhichtheSICMexists.ThoughIwas,ofcourse,wellawareof the scanning probe microscopy component of that intellectual context, I must confessthatIwasunawareofalmostalltherestatthetimeIinventedtheSICM. The path to the invention of the Scanning Ion Conductance Microscope started with a sabbatical I spent studying the vacuum/solid interface with the wonderful surface scientist Gabor Somorjai. Near the end, I asked him if he thought I should continueinthattypeofsurface science.Hesaidno!Hesaidthatthereweremany, many tools for studying the vacuum/solid interface, but very few for studying the much more important liquid/solid interface. He thought that I seemed like an inventive person and that I should use my skills to develop tools for studying the liquid/solidinterface.ProbablythebestcareeradviceIeverreceived! Afternumerousmarginallysuccessfulattemptstodothis,mygroupwasableto design a custom scanning tunneling microscope that got the first atomic resolution image in water [7]. One of the problems with this microscope was noise from ion currentsthatinterferedwithmeasuringthetunnelingcurrent. There is an old saying among physicists that one person’s noise is another person’s signal. I started wondering if it would be possible to build a microscope based on ion currents instead of electron currents. With the long-term goal of imagingapolymerlikeDNAonaninsulatingsurface,IsketchedthisideaonFeb. 18,1986:gluinga¼”Teflonrodtoaplateonthebottomofaglassbeakerandthen scanning a sharpened, insulated stainless steel rod vertically and laterally with a micropositioner. The idea was to lower the rod until the ion current dropped a little, record the micropositionerposition,thenlifttherodandtranslateitlaterallyandloweritagain, recordthemicropositionerpositionagain,andrepeattogetalinescan.Aftertrying insulated sharpened rods, flat rods and rounded rods with some, but very limited success, I tried recessing the rod into the insulation. This worked better, but there was too much drift [8] from electrical changes due to electrochemical reactions on Foreword vii the small area of the electrode. Next, I tried a large area electrode inside an eyedropper.Thisworkedmuchbetter. We then went from eyedroppers to micropipettes and from mechanical micropositioners to the scanners we were using for Atomic Force Microscopy. It was slow going at first, especially because the Atomic Force Microscope was occupying most of our attention, but by Feb. 3, 1989, we had our first publication [1]withimagesofgratings,apolymer,andioncurrentsthroughpores.Thedrawing oftheSICMinthatpublicationremindsmeoftheoneabove. TheuseofScanningIonConductanceMicroscopy increased dramatically afterthe wonderfuladvancesdescribedinthechapterbyNovak,Shevchuk,andKorchevand thechapterbyvonEysmondtandSchäffer.Now,over30yearslater,itisinaperiod of rapid growth. A quick search of Google Scholar with only the search term “SICM”revealedover500publicationsonScanningIonConductanceMicroscopy inthelast4years[9]. Giventhisrapidgrowth,itseemslikeanidealtimeforthisbooktointroducenew researchers to the field and to help existing researchers see the breadth of applications.IamgratefultoTilman,whoIamproudtosaywasmygraduatestudent,and thechapterauthorsforthiswonderfulbook. I believe that the future is bright for Scanning Ion Conductance Microscopy becauseofthededicatedworkofthescientists,physicians,andengineerswhohave advancedthetechnologyanditsapplications. DepartmentofPhysics PaulHansma UniversityofCaliforniaatSantaBarbara USA viii Foreword References 1.HansmaPK,DrakeB,MartiO,GouldSAC,PraterCB(1989)Thescanningion- conductancemicroscope.Science243(4891):641–643 2. Schäffer TE, Ionescu-Zanetti C, Proksch R, Fritz M, Walters DA, Almqvist N, Zaremba CM, Belcher AM, Smith BL, Stucky GD, Morse DE (1997) Does abalone nacre form by heteroepitaxial nucleation or by growth through mineral bridges?ChemMater9(8):1731–1740 3.RheinlaenderJ,SchäfferTE(2013)Mappingthemechanicalstiffnessoflivecells withthescanningionconductancemicroscope.SoftMatter9(12):3230–3236 4. Simeonov S, Schäffer TE (2019) High-speed scanning ion conductance microscopy for sub-second topography imaging of live cells. Nanoscale 11(17):8579– 8587 5.BusingerR,KivimäkiS,SimeonovS,VavourasSyrigosG,PohlmannJ,BolzM, Müller P, Codrea MC, Templin C, Messerle M, Hamprecht K, Schäffer TE, NahnsenS,SchindlerM(2021)Comprehensiveanalysisofhumancytomegalo- virus-andHIV-mediatedplasmamembraneremodelinginmacrophages.Mbio12 (4):e01770–21 6. Navikas V, Leitao SM, Grussmayer KS, Descloux A, Drake B, Yserentant K, WertherP,HertenDP,WombacherR,RadenovicA,FantnerGE(2021)Correl- ative 3D microscopy of single cells using super-resolution and scanning ion- conductancemicroscopy.NatCommun12(1):1–9 7. Sonnenfeld R, Hansma PK (1986) Atomic-resolution microscopy in water. Science232(4747):211–213 8.Perhapsironically,this“drift”becamethesignalfortheScanningElectrochemical Microscope,whichiswelldescribedinthechapterinthisbookbyMakarovaand Takahashi 9. As well as about 100 using the acronym for other thing such as Safety Index Computing Module, Sepsis-induced cardiomyopathy, Simplified Interface to ComplexMemoryandsupervisedintelligencecommitteemachine Preface Scanning ion conductance microscopy (SICM) has undergone a remarkable development since its invention in 1989. Originally devised as a technique for spatially resolvingthetopographyandionpermeabilityofasamplesurface,SICMcannow measure many other sample properties such as surface charge, electrochemical activity, or modulus of elasticity. SICM has thereby evolved into a multisensory, versatile measurement platform with a wide range of applications in physics, biology,chemistry,medicine,andmaterialsscience. This book, Scanning Ion Conductance Microscopy in Springer’s book series BioanalyticalReviews,providesanintroductionandoverviewofSICMtechnology and applications. It is written by pioneers in the field and is intended for both beginnersandexperts. Thefirstchapter,writtenbyProf.Dietzel,Dr.Happel(Ruhr-UniversityBochum, Germany),andProf.Schäffer(UniversityofTübingen,Germany),givesahistorical overview of techniques that paved the way for the development of SICM, starting fromthediscoveryofbioelectricitytwocenturiesago. Inthesecondchapter,vonEysmondtandProf.Schäffer(UniversityofTübingen, Germany)offeradetailedintroductiontothetechnologyofSICManditsstrengths andlimitationsforbiologicalapplicationsincomparisonwithatomicforcemicros- copy(AFM). Thenextchapter,byDr.Choi,Leasor,andProf.LaneBaker(IndianaUniversity, Bloomington,USA),providesacomprehensiveoverviewofelectrochemicalimag- ingbasedonthemeasurementofionsandelectronswithSICM. In the fourth chapter, Dr. Novak, Dr. Shevchuk, and Prof. Korchev (Imperial College London, UK) portray the smart patch-clamp technique, which combines single-channel recordingwith selective probe positioningonacellmembrane with nanoscaleresolution. Prof. Bhargava (Indian Institute of Technology, Hyderabad, India) and Prof. Gorelik (Imperial College London, UK) illuminate in the following chapter how SICM can be used to associate cell signalling pathways with cellular surface structuresincardiacresearch. ix