Springer Handbookof Microscopy

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HHandbookSpringer

of MicroscopyPeter W. Hawkes, John C. H. Spence (Eds.)

With 1140 Figures and 37 Tables

K

EditorsPeter W. HawkesCEMES-CNRSToulouse, France

John C. H. SpenceDept. of PhysicsArizona State UniversityTempe, AZ, USA

ISBN 978-3-030-00068-4 e-ISBN 978-3-030-00069-1https://doi.org/10.1007/978-3-030-00069-1

© Springer Nature Switzerland AG 2019This work is subject to copyright. All rights are reserved by the Publisher,whether the whole or part of the material is concerned, specificallythe rights of translation, reprinting, reuse of illustrations, recitation,broadcasting, reproduction on microfilms or in any other physical way, andtransmission or information storage and retrieval, electronic adaptation,computer software, or by similar or dissimilar methodology now known orhereafter developed.The use of general descriptive names, registered names, trademarks,service marks, etc. in this publication does not imply, even in the absenceof a specific statement, that such names are exempt from the relevantprotective laws and regulations and therefore free for general use.The publisher, the authors and the editors are safe to assume that the adviceand information in this book are believed to be true and accurate at the dateof publication. Neither the publisher nor the authors or the editors give awarranty, express or implied, with respect to the material contained hereinor for any errors or omissions that may have been made. The publisherremains neutral with regard to jurisdictional claims in published maps andinstitutional affiliations.

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V

Preface

Since Science of Microscopy, the predecessor of this book, appeared in 2007, three Nobel prizes of direct relevanceto the field have been awarded. The first of these was the award to Boyle and Smith in 2009 for the invention ofthe charge-coupled device, which was primarily responsible for making digital imaging possible. The second wasthe award to Betzig, Hell, and Moerner in 2014 for the development of superresolution fluorescence microscopy,and the third to Dubochet, Frank, and Henderson in 2017 was given for their work in developing the cryo-electronmicroscopy technique for biology. The fact that radiation damage effects may be out-run by using sufficientlybrief femtosecond x-ray pulses from a hard x-ray laser was also demonstrated in this period. At the same time,there has been a great surge in the application of many tomographic imaging methods in medicine (such as themicroCT method covered in this book); indeed, an imaging revolution is underway in that area. In many hospitals,some form of 3-D imaging is now the first diagnostic method applied to incoming trauma victims.

For this new edition, now published as the Springer Handbook of Microscopy, we have again asked manyof the leaders in the field of modern microscopy to summarize the latest approaches to the imaging of atoms ormolecular structures, and, more especially, the way in which this aids our understanding of atomic processes andinteractions in the organic and inorganic worlds.

Man’s curiosity and the desire to examine the nanoworld goes back at least as far as Ancient Greece. Aristo-phanes, in a fourth-century BC play, refers to a burning glass; the Roman rhetorician Seneca describes hollowspheres of glass filled with water being used as magnifiers, while Marco Polo in the thirteenth century remarks onthe Chinese habit of wearing spectacles. Throughout this time it would have been common knowledge that a dropof water over a particle on glass will provide a magnified image, while a droplet within a small hole does evenbetter as a biconvex lens. By the sixteenth century, magnifying glasses were common in Europe. Kepler appearsto have been the first to draw the correct ray-diagram for image formation, with rays leaving an object point over awide angular range and gathered to a focus by a lens. His book Paralipomena on optics, printed in 1604, shows thecorrect ray diagram for a spherical glass lens, while his Dioptrice (1611) gives an explanation of the functioningof the lenses in Galileo’s telescope. Although Kepler did not derive the lens laws taught to undergraduate sci-ence students today, he does reveal an understanding of the formation of virtual images, which arise with mirrors.These books contain the earliest correct ray diagrams from which the whole subject of geometric optics was laterdeveloped.

It was Anthony van Leeuwenhoek (1632–1723) who first succeeded in grinding lenses accurately enough toproduce a better image with his single-lens instrument than that produced with the primitive compound micro-scopes that were available then. His 112 papers, published in Philosophical Transactions of the Royal Society,brought the microworld to the general scientific community for the first time, covering everything from sperm tothe internal structure of the flea. Robert Hooke (1635–1703) developed the compound microscope, publishing hisresults in careful drawings of what he saw in his Micrographia (1665). The copy of this book in the Universityof Bristol library shows remarkable sketches of faceted crystallites, below which he had drawn piles of cannonballs, whose faces make corresponding angles. This strongly suggests that Hooke believed that matter consists ofthe small spheres (atoms) which could produce these facet angles, and had made this discovery long before itsofficial rediscovery by the first modern chemists, notably Dalton in 1803. Greeks such as Leucippus (450 BC)had long before convinced themselves that a stone, cut repeatedly, would eventually lead to a smallest fragmentor fundamental particle; Democritus once said that “nothing exists except atoms and empty space. All else isopinion.”

This atomic hypothesis has a fascinating history, and is intimately connected with the history of microscopy.It was Brown’s observation in 1827 of the motion of pollen in water by optical microscopy that laid the basis forthe modern theory of matter based on atoms. As late as 1900 many chemists and physicists did not believe inatoms, despite the many independent estimates that could be made of their size. Avogadro’s idea, around 1811 thatequal volumes of gas contained the same number of molecules (regardless of their size) had a powerful influence.This number was first estimated by Johann Loschmidt in 1865. Faraday’s experiments on electrolysis related massto an electron current and the charge it carried. The electron and its charge-to-mass ratio were discovered by

VI Preface

J.J. Thomson in 1897. The evidence for the existence of atoms was summarized by Kelvin and Tait in an appendixto their Treatise on Natural Philosophy, together with an erroneous and rather superficial estimate of the youngage of the Earth, to be used against Darwin. This text was the standard English-language physics text of thelate nineteenth century, despite its failure to cover much of Maxwell’s work. Einstein’s 1905 theory of Brownianmotion, and Perrin’s (1909) more accurate repetition of Brown’s experiment, using microscope observations toestimate Avogadro’s number, finally settled the matter regarding the existence of atoms. Einstein does not referenceBrown’s paper but indicates that he had been told about it. As Professor Archie Howie from Cambridge, UK,commented, it is interesting to speculate how different the history of science would be ifMaxwell had read Brown’spaper and applied his early statistical mechanics to it. By the time of Perrin’s paper, Bohr, Thomson, Rutherford,and others were firmly committed to atomic and even subatomic physics.

In biology, the optical microscope remained an indispensable tool from van Leeuwenhoek’s time with manyincremental improvements. It was able to identify bacteria and their role in disease, but not viruses, which weretoo small. These were first seen with the transmission electron microscope (TEM) in 1938 by Ernst Ruska’sbrother Helmut. With Zernike’s phase contrast theory in the 1930s, a major step forward was taken, but the reallydramatic and spectacular modern advances had to await the widespread use of the modern TEM with new samplepreparation methods and the development of the cryo-EM method. The invention of the laser and superresolutionoptical modes, the charge-coupled device (CCD) and more recent direct-electron detectors, the introduction ofscanning modes and probes, computer control, and data acquisition, powerful new algorithms for data analysisand the production of fluorescent proteins led to further major advances.

The importance of this early history should not be underestimated – in the words of Richard P. Feynman

If in some cataclysm, all scientific knowledge were to be destroyed and only one sentence passed on to the nextgeneration of creatures, what statement would contain the most information in the fewest words? I believe it isthe atomic hypothesis – that all things are made of atoms.

Images of individual atoms were first provided by Erwin Müller’s field-ion microscope in the early 1950s, soonto be followed by Albert Crewe’s scanning transmission electron microscope (STEM) images of heavy atomson thin-film surfaces in 1970. With its sub-ångström resolution, the modern transmission electron microscopescan now routinely image atomic columns in thin crystals in projection, individual atoms in 2-D materials, andeven foreign atoms within a thin crystal using beam-electrons that have excited inner-shell atomic processes.For favorable surface structures, the scanning tunneling microscope has provided us with images of individualsurface atoms since its invention in 1982 and resulted in a rich spin-off of related techniques, such as the scanningtunneling spectroscopy method, the near-field probes, and the atomic force microscope.

The particles used to probe condensed and biological matter must possess a long lifetime if they are to be usedas free-particle beams. For the most part, this has limited investigators to the use of light, x-rays, neutrons, andelectrons. The major techniques can then be classified as imaging, diffraction, and spectroscopy. These may beused in both the transmission and reflection geometries, giving bulk and surface information, respectively. Underthese general headings, in Chap. 9 we review both the low-energy electron microscope (LEEM) and spin-polarizedLEEM methods which, using reflected electrons, have revolutionized surface science and thin-film magnetism.Here, the high cross-section allows movies to made of surface processes at submicrometer resolution, while Augerelectron spectroscopy is conveniently incorporated. Chapter 11 describes the spectacular progress that has beenmade with spectroscopic LEEM since the previous edition of this book. Here, the electron prism in the instrumentprovides dispersion for spectroscopy of the electrons reflected from a clean surface. A remarkable resolution of1.5 nm has now been obtained by such a LEEM at 3.5 eV, and an energy resolution of about 100 meV, bothbeing invaluable for studies aimed at imaging crystal growth, the study of catalysis, and work-function imaging.Chapter 10 deals with the closely related photoelectron microscopy, where a LEEM instrument is used to imagethe photoelectrons excited by a synchrotron beam. Here, the superb energy selectivity of optical excitation canbe used to great advantage. With the importance of 2-D materials, including graphene and all its descendantsthat are now recognized, PEEM studies of the growth of new 2-D materials have taken on a new lease of life.In angle-resolved mode, maps of Fermi surfaces can now be made routinely at synchrotrons, as described alsoin Chap. 11. Chapter 5, based on the earlier chapter by the late Rudi Reichelt, describes advances in scanningelectron microscope (SEM) research, where the lower-energy secondary electrons provide images with a largedepth of focus in the most versatile of all electron-optical instruments. Chapter 6 reviews the functioning of this

Preface VII

instrument at higher pressures than in the conventional SEM and its use for environmental electron microscopy.The numerous modes of operation include x-ray analysis, cathodoluminescence, low-voltage modes for insulators,and the controlled-atmosphere environmental SEM (ESEM). A similar instrument can be devised using a gas field-ion source instead of an electron source. This scanning ion microscope uses the methods of field-ion microscopyto obtain an atomically sharp source of ions (such as 30 kV helium ions), which are focused and scanned acrossthe sample. Chapter 14 gives us a full account of this exciting new microscopy, which has emerged since the firstedition. It includes a full account of ion–sample interactions, the resulting signals that can be detected, contrastmechanisms for transmitted and reflected modes, the analytical capabilities of the instrument, and its applications.The atom probe itself is described in Chap. 15, including a full history of the field-ion microscope, the methodsof the analytical atom probe (which identifies the atoms in the image) including laser pulsing of the tip, and theuse of a smaller counter electrode at lower voltage placed close to the needle-shaped sample, and giving a higherelectric field and better mass resolution. As the summary of applications shows, the resulting instruments havealso emerged as a successful new form of microscopy since the first edition of this book.

Turning now to the transmission geometry, we review the latest work in atomic-resolution transmission elec-tron microscopy (TEM) in Chap. 1, the technique that has transformed our understanding of defect processes incrystalline solids and nanostructures. In that connection, Chap. 12 provides a review of the role of modeling inTEM to obtain higher resolution and decide among the alternative likely structures seen in the images. Chapter 26describes the extension of the high-resolution TEM approach to 3-D image reconstruction, using multiple pro-jections. Given the need to obtain many different projections all at atomic resolution without significant radiationdamage, this has proven to be an enormously difficult problem, for which there has been dramatic progress sincethe previous edition. Chapter 29 reviews the application of this high-resolution TEM approach, combined withother diffraction methods, to the important class of mesoporous materials (zeolites and the newly discovered classof metal-organic framework structures). These highly radiation-sensitive materials are finding many new appli-cations for gas storage and petrochemical catalysis and provide one of the most challenging samples for TEMwork. Spectacular results have been obtained (resulting in high honors for the scientists), and there appears to beno other way to determine the structure of this critical new class of nanostructured material. The scanning trans-mission mode is treated in Chap. 2. The scanning transmission electron microscope (STEM) provides additionalpowerful analytical capability, which, like STM, can provide spectroscopy with atomic-scale spatial resolutionand many other signals, such as cathodoluminescence, energy-loss spectroscopy and characteristic inner-shellx-ray detection. Recently, atomic-resolution images have been produced using this x-ray fluorescence signal. Theclosely-related electron microdiffraction method, which uses the subnanometer probe of the STEM in the trans-mission geometry, is described in Chap. 18. The analysis of the resulting nanodiffraction patterns has provenparticularly powerful for the study of the nanoparticles used in catalysis and their associated strain fields. Anentire chapter (Chap. 7) is then devoted to analytical TEM (AEM), with a detailed analysis of the physics andperformance of its two main detectors, for characteristic x-ray emission and energy-loss spectroscopy. The re-markable recent achievements of in-situ TEM are surveyed in Chap. 3, including transmission imaging of liquidcell electrolysis, observations of the earliest stages of crystal and nanotube growth, phase transitions and catalysts,superconductors, magnetic and ferroelectric domains and plastic deformation in thin films, all at nanometer res-olution or better. Again, the large scattering cross-section of electron probes provides plenty of signal even fromindividual atoms, so that movies can be made. Chapter 8 summarizes the dramatic recent revival of time-resolvedelectron microscope imaging, which uses laser-pulses to excite processes in a sample prior to imaging them. Theexcited state may be imaged by passing the delayed optical pulse to the photocathode of the TEM in the pump-probe mode. Single-shot transmission electron diffraction patterns have now been obtained using electron pulsesas short as a picosecond.

Most of these techniques are undergoing a quiet revolution as aberration corrector devices are being fitted toelectron microscopes. The dramatic revelation that, after 60 years of effort, aberration correction is now a reality,was made about 20 years ago, and we review the relevant electron-optical theoretical background in Chap. 13. Thesame chapter includes an account of monochromators, which help to combat the effects of chromatic aberration,and energy analyzers. Also in the transmission geometry, there have been rapid advances in high-energy pulsedelectron diffraction, with pulses as brief as 10 fs at MeV energies having been generated recently. Pump-probemethods can now be used by this technique to detect time-resolved diffuse scattering between Bragg reflectionsfrom phonons in a thin crystal. This field is reviewed in Chap. 19. Finally, in biology, perhaps the largest scientificpayoff of all has occurred in the field of cryo-electron microscopy, which now seriously challenges all protein

VIII Preface

crystallography performed at synchrotrons. This is largely the result of the recent resolution revolution fueledby the development of new TEM detectors, which can record the arrival of every beam electron under the low-dose conditions used. There are three kinds of cryo-electron microscopy—single-particles, tomography, and 2-Dcrystals. Images of many projections of similar particles are merged in the single particle mode, whereas manyprojections of the same particle are merged in tomography. The increased radiation damage in the tomographymode leads to lower resolution. The grand challenge of locating every protein and molecular machine in a singlecell remains outstanding, but many molecular mechanisms and drug binding processes have now been elucidatedat a resolution of a few ångströms. We summarize this exciting field in Chap. 4.

Electrons, with the largest cross-section, a coherent source brighter than current generation synchrotrons, andnow single-electron detectors, provide the strongest signal and, hence, the best resolution. They do this in a mannerthat can conveniently be combined with spectroscopy, and we now have aberration corrected lenses for them.However, multiple scattering and inelastic background scattering often complicate interpretation. Electrons in abeam continue on to the detector after losing energy while traversing a sample, making an unwanted background,unlike x-rays, which are annihilated after creating a photoelectron, which is not usually detected. X-ray imaging ofnanostructures, even at synchrotrons, involves much longer data acquisition times, but the absence of backgroundand multiple scattering effects greatly improves quantification of data, and thicker samples can be examined. ltcan be shown that the small magnitude of the fine-structure constant will almost certainly never permit imagingof individual atoms using x-rays, unless data from identical particles is merged. We should recall that in proteincrystallography, about 98% of the x-ray beam hits the beam-stop after traversing the sample and does not interactwith the sample at all. Of the remaining 2%, 84% is annihilated in production of photoelectrons, and 8% inCompton scattering, while only the remainder produces Bragg diffraction. By comparison, electron scatteringdepends sensitively on sample thickness, and the direct beam is rapidly both diffracted and inelastically scatteredaway by multiple scattering to negligible intensity with increasing thickness. This thickness sensitivity meansthat, apart from work on monolayers, electron diffraction intensities are far less reproducible than x-ray scatteredintensities, making quantification more difficult. Generally speaking, it is not difficult to record the same Braggintensity ratios from two crystals of the same structure but different size, using x-ray diffraction; this is impossibleusing electron diffraction, unless they both have dimensions of tens of nanometers or less. For light elements theinelastic cross-section for kilovolt electrons is about three times that of the elastic cross-section, unlike hard x-rays,where the photoelectric effect is far stronger than elastic scattering. Success with x-rays has come mainly throughthe use of crystallographic redundancy to reduce radiation damage in protein crystallography. Nevertheless, soft x-ray imaging using zone-plate lenses now provides about 20 nm resolution in thewater window, with the advantagesof thicker samples and imaging in an aqueous environment. Applications of full-field zone-plate microscopy havealso been found in environmental science, materials science, and magnetic materials. In addition, the equivalent ofthe STEM has been developed for soft x-rays: the scanning transmission x-ray microscope (STXM), which usesa zone-plate to focus x-rays onto a sample that can be raster scanned by piezo-electric motors. This arrangementcan then provide spatially-resolved x-ray absorption spectroscopy. That work is reviewed in Chap. 23. Chapter 24reviews the highly successful microcomputed tomography method, in which the absorption of an x-ray beampassing through a sample is recorded from many different directions, allowing a 3-D image to be reconstructed.

Both x-ray and electron-beam imaging methods are limited in biology by the radiation damage they create,unlike microscopy with visible light, which also allows observations in the natural state. Optical microscopyhas now undergone a revolution, with the development of superresolution, two-photon, fluorescent labeling, andscanning confocal methods. These methods are reviewed in Chaps. 21 and 22. Chapter 21 is divided into twoparts, one closely based on Science of Microscopy, the other chronicling later developments. The authors discusstwo-photon confocal microscopy, in which the spot-scanning mode is adopted, and a symmetrical lens beyondthe sample collects light predominantly from the excitation region, thereby eliminating most of the out-of-focusbackground produced in the normal full-field optical sectioningmode. 3-D image reconstruction is then possible.Two-photon microscopy combines this with a fluorescence process in which two low-energy incident photonsare required to excite a detectable photon emitted at the sum of their energies. This has several advantages, byreducing radiation damage and background, and allowing observation of thicker samples. The method can alsobe used to initiate photochemical reactions for study. Chapter 22 describes the latest superresolution schemesfor optical microscopy, which have now brought the lateral resolution down to almost the nanometer size of amolecule. The many methods are known by acronyms such as STED, RESOLFT, PALM, STORM, and PAINT.By the symmetrical lens arrangement, they have increased resolution measured along the optic axis by a largefactor. The lateral resolution can be improved by modulating the illumination field or by using the stimulated

Preface IX

emission depletion microscopy mode (STED), in which saturated excitation of a fluorophore produces nonlineareffects allowing the diffraction barrier to resolution to be broken.

For the scanning near-field probes new possibilities arise. Although restricted to the surface (the site of mostchemical activity) and, in some cases, requiring complex image interpretation, damage is reduced, while thesub-ångström resolution normal to the surface is unparalleled. The method is also conveniently combined withspectroscopy. Early work was challenged by problems of reproducibility and tip artifacts, but several chapters inthis book show the truly remarkable recent progress in surface science, materials science, and biology. Chapter 25describes the various modes of atomic force microscopy which can be used to extract atomic-scale informationfrom the surfaces of modern materials, including oxides and semiconductors. Work functions can be mapped out(by means of a Kelvin probe with good spatial resolution) and a variety of useful signals obtained by modulationspectroscopy methods. This way maps of magnetic force, local dopant density, resistivity, contact potential andtopography may be obtained. Chapter 27 (unchanged from Science of Microscopy) describes applications of thescanning tunnelingmicroscope (STM) in materials science, including inelastic tunneling, surface structure analysisin surface science, the information on electronic structure which may be extracted, atomic manipulation, quantumsize and subsurface effects, and high temperature imaging. Chapter 28 provides a review of low-temperature STMmethods applied to quantum materials and superconductors, allowing impurity atoms to be imaged, energy gapsto be mapped out, and new phases to be identified. Finally, Chap. 31 reviews the special problems that arise whenthe atomic force microscope (AFM) is applied to the imaging of biomolecules; much practical information on in-strumentation and sample preparation is provided, and many striking examples of cell and macromolecule imagesare shown.

We include three chapters on unconventional lensless imaging methods. Chapter 16 deals with electron holog-raphy and Chap. 20 with diffractive imaging. Gabor’s original 1948 proposal for holography was intended toimprove the resolution of electron microscopes. Only recently have his plans been realized, though it has provedeasier to use an aberration-corrected microscope than to employ his two-stage procedure. Meanwhile, electronholography using Möllenstedt’s biprism and the Lorentz mode has proved an extremely powerful method ofimaging the magnetic and electrostatic fields within matter. Dramatic examples have included TEM movies ofsuperconducting vortices as temperature and applied fields are varied, and ferroelectric and magnetic domain im-ages, all within thin self-supporting films. Chapter 20 describes the recent development of new iterative solutions tothe noncrystallographic phase problem, which now allows diffraction-limited images to be reconstructed from thefar-field scattered intensity distribution. This has produced lensless atomic-resolution images of carbon nanotubes(reconstructed from electron microdiffraction patterns) and phase contrast images from both neutron and soft x-rayFraunhofer diffraction patterns of isolated, nonperiodic objects. In this work, lenses are replaced by computers,so that images may now be formed with any radiation for which no lens exists, free of aberrations. As discussed,these methods have been extensively applied to the data collected at x-ray lasers, using femtosecond x-ray pulsesin the diffract-and-destroymode. Here, the elastic scattering is collected (and the incident pulse terminates) beforethe onset of the photoelectron cascade starts to create radiation damage and, subsequently, destroys the sample.The companion Chap. 17 reviews another lensless imaging method, ptychography, and its many applications. Thismethod, which is now rapidly gaining in popularity since the development of ptychography algorithms for nonpe-riodic samples, does not require a rough estimate of the boundary of an isolated sample, unlike most diffractiveimaging methods. Chapter 30 describes recent advances in phase-contrast lensless x-ray imaging, where the useof x-ray phase shifts rather than absorption effects provides images of tissue rather than bone. A pure phase shift,without absorption, would deposit no damaging energy into a patient, while providing potentially high interfero-metric contrast. Propagation (defocus), Talbot (self-imaging) grating methods, and split-beam interferometers areall described for this growing field. Chapter 32 on the uses of microscopy in forensic sciences concludes the book.

Coverage has been limited to high-resolution methods, with the result that some important microscopies havebeen omitted (such as magnetic resonance imaging (MRI) and acoustic imaging).

The ingenuity and creativity of the microscopy community as recorded in these pages are remarkable, as isthe spectacular nature of the images presented. Neither shows any signs of abating. As in the past, we fully expectmajor advances in science to continue to result from breakthroughs in the development of new microscopies.

Peter W. HawkesJohn C.H. Spence

XI

About the Editors

Peter Hawkes looks back at a long career in microscopy. After graduation in 1959,Peter Hawkes joined Ellis Cosslett’s Electron Microscopy Section in the CavendishLaboratory, Cambridge and completed his PhD on electron lens aberrations in 1963.Two books on quadrupole optics resulted from this as well as an introductory text onElectron Optics and Electron Microscopy. He remained in Cosslett’s group, publishingextensively on electron lens properties and later on digital processing of electron mi-croscope images. He was a Research Fellow of Peterhouse and Churchill College. In1975, he moved to the CNRS Laboratory of Electron Optics in Toulouse, of which helater became the Director. In 1980, he joined Hermann Wollnik (University of Gießen)and Karl Brown (SLAC) in organising the first of the series of conferences on Charged-Particle Optics; this was an instant success and the series continues today. He is authorwith Erwin Kasper of a three-volume treatise on the Principles of Electron Optics.

Peter was the Founder-President of the European Microscopy Society and is anHonorary Member of the French Microscopy Society, of which he had been President.He was elected Fellow of the Optical and Microscopy Societies of America and wasawarded the CNRS Silver Medal. He has been an active member of the editorial boardsof Ultramicroscopy and the Journal of Microscopy and editor-in-chief of the long-running Advances in Imaging and Electron Physics. In recent years, he has had moretime to spend on a very different interest, the artists and craftsmen of the nineteenthcentury, with the result that the William Morris Society Newsletter and the Journal ofPre-Raphaelite Studies now appear in his list of publications.

Since 2013, John Spence FRS has been the Director of Science of BioXFEL, a seven-campus consortium in the USA devoted to the application of the recently inventedfree-electron X-ray laser to the study of structure and dynamics in biology.

John completed his PhD in Physics at Melbourne University in Australia, followedby postdoctoral research at the Materials Department in Oxford, UK. He then movedto the Physics Department at Arizona State University in 1976, joining John Cowley’srapidly growing center for electron microscopy. John’s laboratory has since focusedon the development of new forms of atomic-resolution microscopy, from time-of-flightanalysis in scanning tunneling microscopy to the direct imaging of moving dislocationkinks, new electron microscope detectors, and lensless imaging, to name only a few. Hehas authored or coauthored over 500 papers and holds several patents and is the authorof the leading text (4th edition) on atomic-resolution electron microscopy, and a newtext with J.M. Zuo on Advanced Transmission Electron Microscopy. He is also theauthor of “Lightspeed”, a history of measurements of the speed of light and the searchfor an absolute frame of reference in the universe, which led to Einstein’s relativity.

John held a joint appointment with Lawrence Berkeley Laboratory and has spentsabbaticals in Cambridge, UK, the Max Planck Institute at Stuttgart, Oxford, UK, andTrondheim, Norway. He is an overseas Fellow of Churchill College Cambridge, aforeign member of the Royal Society and the Australian Academy of Science, andrecipient of several professional society awards. He enjoys flying large gliders amongthe strong thermals over the Arizona desert mountains and sailing. He is a keen musi-cian devoted to classical piano music, also playing flute and guitar with his jazz quartetWho Knew.

XIII

About the Authors

Matthias W. AmreinDept. of Cell Biology & AnatomyUniversity of CalgaryCalgary, Canadamamrein@ucalgary.ca

Ernst BauerDept. of PhysicsArizona State UniversityTempe, AZ, USAernst.bauer@asu.edu

Wolfgang P. BaumeisterDept. of Molecular Structural BiologyMax Planck Institute of BiochemistryMartinsried, Germanybaumeist@biochem.mpg.de

David C. BellCenter for Nanoscale SystemsHarvard UniversityCambridge, MA, USAdcb@seas.harvard.edu

Paolo BianchiniDept. of NanoscopyItalian Institute of TechnologyGenoa, Italypaolo.bianchini@iit.it

Dawn A. BonnellDept. of Materials Science & EngineeringUniversity of PennsylvaniaPhiladelphia, PA, USAbonnell@upenn.edu

Gianluigi BottonDept. of Materials Science & EngineeringMcMaster UniversityHamilton, Canadagbotton@mcmaster.ca

Isotta CaineroDept. of PhysicsUniversity of GenoaGenoa, Italyisotta.cainero@iit.it

Geoffrey H. CampbellMaterials Science DivisionLawrence Livermore National LaboratoryLivermore, CA, USAghcampbell@llnl.gov

Francesca Cella ZanacchiDept. of NanophysicsItalian Institute of TechnologyGenoa, Italyfrancesca.cella@iit.it

Shery L.-Y. ChangEyring Materials CenterArizona State UniversityTempe, AZ, USAshery.chang@asu.edu

Shunai CheSchool of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai, Chinachesa@sjtu.edu.cn

J.C. Séamus DavisClarendon LaboratoryUniversity of OxfordOxford, UKand

Dept. of PhysicsUniversity College CorkCork, Irelandjcseamusdavis@gmail.com

Alberto DiasproDept. of NanophysicsItalian Institute of TechnologyGenoa, Italyalberto.diaspro@iit.it

Isabel DíazInstitute of Catalysis and Petroleum ChemistrySpanish National Research Council (CSIC)Madrid, Spainidiaz@icp.csic.es

XIV About the Authors

Rafal E. Dunin-BorkowskiErnst Ruska-Centre for Microscopyand Spectroscopy with Electronsand Peter Grünberg InstituteForschungszentrum Jülich GmbHJülich, Germanyr.dunin-borkowski@fz-juelich.de

Stephen D. EdkinsDept. of Applied PhysicsStanford UniversityStanford, CA, USAedkins@stanford.edu

Natasha ErdmanJEOL USA Inc.Peabody, MA, USAerdman@jeol.com

Jun FengAdvanced Light SourceLawrence Berkeley National LaboratoryBerkeley, CA, USAfjun@lbl.gov

Kazuhiro FujitaCondensed Matter Physics& Materials Science Dept.Brookhaven National LaboratoryUpton, NY, USAkfujita@bnl.gov

Robert E. GuldbergPhil and Penny Knight Campusfor Accelerating Scientific ImpactUniversity of OregonEugene, OR, USAguldberg@uoregon.edu

Mohammad H. HamidianDept. of PhysicsHarvard UniversityCambridge, MA, USAm.hamidian@gmail.com

Lu HanDept. of MathematicsTongji UniversityShanghai, Chinaluhan@tongji.edu.cn

Yu HanPhysical Science and Engineering DivisionKing Abdullah Universityof Science and TechnologyThuwal, Saudi Arabiayu.han@kaust.edu.sa

Peter W. HawkesCEMES-CNRSToulouse, Francehawkes@wanadoo.fr

Stefan W. HellDept. of NanoBiophotonics/Dept. of Optical NanoscopyMax Planck Institute for Biophysical Chemistry& Max Planck Institute for Medical ResearchGöttingen, Germanyshell@mpibpc.mpg.de

Gregor HlawacekInstitute for Ion Beam Physics& Materials ResearchHelmholtz Zentrum Dresden RossendorfDresden, Germanyg.hlawacek@hzdr.de

Malcolm HowellsAdvanced Light SourceLawrence Berkeley National LaboratoryBerkeley, CA, USAmrhowells@lbl.gov

Bryan D. HueyDept. of Materials Science & EngineeringUniversity of ConnecticutStorrs, CT, USAbryan.huey@uconn.edu

John L. HutchisonDept. of MaterialsUniversity of OxfordOxford, UKjohn.hutchison@materials.ox.ac.uk

Chris JacobsenAdvanced Photon SourceArgonne National Laboratoryand Northwestern UniversityArgonne, IL, USAcjacobsen@anl.gov

About the Authors XV

Benjamin J. JonesSchool of Science, Engineering & TechnologyAbertay UniversityDundee, UKb.j.jones@physics.org

Takeshi KasamaNational Centre for Nano Fabricationand CharacterizationTechnical University of DenmarkKongens Lyngby, Denmarktakeshi.kasama@cen.dtu.dk

Thomas F. KellySteam Instruments, Inc.Madison, WI, USAthomas.kelly@steaminstruments.com

Angus I. KirklandDept. of MaterialsUniversity of OxfordOxford, UKangus.kirkland@materials.ox.ac.uk

András KovácsErnst Ruska-Centre for Microscopyand Spectroscopy with Electronsand Peter Grünberg InstituteForschungszentrum Jülich GmbHJülich, Germanya.kovacs@fz-juelich.de

Ondrej KrivanekNion CoKirkland, WA, USAkrivanek@nion.com

Luca LanzanòDept. of NanophysicsItalian Institute of TechnologyGenoa, Italy

Rowan K. LearyDept. of Materials Science & MetallurgyUniversity of CambridgeCambridge, UKrkl26@cam.ac.uk

Renkai LiSLAC National Accelerator LaboratoryMenlo Park, CA, USAlrk@slac.stanford.edu

Angela S.P. LinPhil and Penny Knight Campusfor Accelerating Scientific ImpactUniversity of OregonEugene, OR, USAal81@uoregon.edu

Zheng LiuInorganic Functional Materials Research InstituteNational Institute of Advanced Industrial Scienceand Technology (AIST)Nagoya, Japanliu-z@aist.go.jp

Justin LuriaMicroelectronics Engineeringand TechnologyRaytheonAndover, MA, USAjustin.luria@raytheon.com

Yanhang MaSchool of Physical Science and TechnologyShanghaiTech UniversityShanghai, Chinamayh2@shanghaitech.edu.cn

Andrew MaidenDept. of Electronic & Electrical EngineeringUniversity of SheffieldSheffield, UKa.maiden@sheffield.ac.uk

Alvaro MayoralSchool of Science and TechnologyShanghaiTech UniversityShanghai, Chinaamayoral@shanghaitech.edu.cn

Martha R. McCartneyDept. of PhysicsArizona State UniversityTempe, AZ, USAmolly.mccartney@asu.edu

Joseph T. McKeownMaterials Science DivisionLawrence Livermore National LaboratoryLivermore, CA, USAmckeown3@llnl.gov

Paul A. MidgleyDept. of Materials Science & MetallurgyUniversity of CambridgeCambridge, UKpam33@cam.ac.uk

XVI About the Authors

Andrew M. MinorUniversity of California, Berkeley, and LawrenceBerkeley National LaboratoryBerkeley, CA, USAaminor@lbl.gov

Pietro MusumeciDept. of Physics & AstronomyUniversity of California at Los AngelesLos Angeles, CA, USAmusumeci@physics.ucla.edu

Peter D. NellistDept. of MaterialsUniversity of OxfordOxford, UKpeter.nellist@materials.ox.ac.uk

Tetsu OhsunaDept. of Crystaline Materials ScienceNagoya UniversityNagoya, Japanohsuna@mac.com

Peter OleynikovDept. of PhysicsShanghaiTech UniversityShanghai, Chinapoleynikov@shanghaitech.edu.cn

Michele OnetoNikon Imaging CenterItalian Institute of TechnologyGenoa, Italymichele.oneto@iit.it

Ming PanGatan, Inc.Pleasanton, CA, USAmpan@gatan.com

Luca PesceDept. of NanophysicsItalian Institute of TechnologyGenoa, Italyluca.pesce@iit.it

Jürgen PlitzkoDept. of Molecular Structural BiologyMax Planck Institute of BiochemistryMartinsried, Germanyplitzko@biochem.mpg.de

Sagar PrabhudevDept. of Materials Science & EngineeringMcMaster UniversityHamilton, Canadaprabhus@mcmaster.ca

Rudolf Reichelt (deceased)

John RodenburgDept. of Electronic & Electrical EngineeringUniversity of SheffieldSheffield, UKj.m.rodenburg@shef.ac.uk

Frances M. RossDept. of Materials Science and EngineeringMassachusetts Institute of TechnologyCambridge, MA, USAfmross@mit.edu

Steffen J. SahlDept. of NanoBiophotonicsMax Planck Institute for Biophysical ChemistryGöttingen, Germanysteffen.sahl@mpibpc.mpg.de

Yasuhiro SakamotoPhysical ScienceOsaka Prefecture UniversitySakai, Japansakamoto@nano.phys.sci.osaka-u.ac.jp

Melissa K. SantalaSchool of Mechanical, Industrial,and Manufacturing EngineeringOregon State UniversityCorvallis, OR, USAmelissa.santala@oregonstate.edu

Andreas SchollAdvanced Light SourceLawrence Berkeley National LaboratoryBerkeley, CA, USAa_scholl@lbl.gov

Andreas SchönleAbberior Instruments GmbHGöttingen, Germanya.schoenle@abberior-instruments.com

David J. SmithDept. of PhysicsArizona State UniversityTempe, AZ, USAdavid.smith@asu.edu

About the Authors XVII

John C. H. SpenceDept. of PhysicsArizona State UniversityTempe, AZ, USAspence@asu.edu

Peter O. SprauDept. of PhysicsUniversity of California, San DiegoLa Jolla, CA, USApsprau@physics.ucsd.edu

Dimitar StamovBruker Nano GmbHBerlin, Germanydimitar.stamov@bruker.com

Stuart R. StockNorthwestern UniversityChicago, IL, USAs-stock@northwestern.edu

Peter SutterDept. of Electrical & Computer EngineeringUniversity of Nebraska-LincolnLincoln, NE, USApsutter@unl.edu

Osamu TerasakiCentre for High-resolution Electron Microscopy,School of Physical Science and TechnologyShanghaiTech UniversityShanghai, Chinaosamuterasaki@mac.com

Bradley ThielCollege of Nanoscale Engineeringand Technology InnovationSUNY Polytechnic InstituteAlbany, NY, USAbthiel@sunypoly.edu

Rudolf TrompIBM T.J. Watson Research CenterYorktown Heights, NY, USArtromp@us.ibm.com

Sandra Van AertElectron Microscopy for Materials Research (EMAT)University of AntwerpAntwerp, Belgiumsandra.vanaert@uantwerpen.be

Giuseppe VicidominiDept. of NanoscopyItalian Institute of TechnologyGenoa, Italygiuseppe.vicidomini@iit.it

Tony WarwickAdvanced Light SourceLawrence Berkeley National LaboratoryBerkeley, CA, USAwarwick@lbl.gov

Han WenNational Heart, Lung and Blood InstituteNational Institutes of HealthBethesda, MD, USAhan.wen@nih.gov

Yihan ZhuCollege of Chemical EngineeringZhejiang University of TechnologyHangzhou, Chinayihanzhu@zjut.edu.cn

Jian-Min ZuoDept. of Materials Science & Engineeringand Materials Research LaboratoryUniversity of Illinois at Urbana-ChampaignUrbana, IL, USAjianzuo@illinois.edu

XIX

Contents

List of Abbreviations ............................................................. XXVII

Part A Electron and Ion Microscopy

1 Atomic Resolution Transmission Electron MicroscopyAngus I. Kirkland, Shery L.-Y. Chang, John L. Hutchison .................... 31.1 Introduction and Historical Context ................................... 31.2 Essential Theory ......................................................... 71.3 Instrumentation ......................................................... 201.4 Exit-Wave Reconstruction .............................................. 301.5 HRTEM Image Simulation ............................................... 34References ....................................................................... 38

2 Scanning Transmission Electron MicroscopyPeter D. Nellist ................................................................... 492.1 Overview ................................................................. 502.2 The STEM Probe .......................................................... 522.3 Coherent CBED and Ronchigrams....................................... 552.4 Bright-Field Imaging and Reciprocity ................................. 592.5 Annular Dark-Field (ADF) Imaging ..................................... 612.6 Electron Energy-Loss Spectroscopy (EELS).............................. 772.7 X-Ray Analysis and Other Detected Signals in the STEM.............. 832.8 Electron Optics and Column Design .................................... 842.9 Electron Sources ......................................................... 852.10 Resolution Limits and Aberration Correction.......................... 882.11 Conclusions .............................................................. 92References ....................................................................... 93

3 In Situ Transmission Electron MicroscopyFrances M. Ross, Andrew M. Minor............................................. 1013.1 A Working Definition of In Situ Transmission Electron Microscopy .. 1023.2 Phase Transformations .................................................. 1033.3 Surface Reactions, Catalysis, and Crystal Growth ..................... 1163.4 Functional Materials and Devices ...................................... 1303.5 Mechanical Deformation of Materials.................................. 1463.6 Liquid-Phase Processes ................................................. 1603.7 Electron-Beam-Induced Processes .................................... 1653.8 Outlook................................................................... 171References ....................................................................... 173

4 Cryo-Electron TomographyJürgen Plitzko, Wolfgang P. Baumeister ....................................... 1894.1 A Short Overview ........................................................ 1924.2 Cryo-Electron Tomography: The Workflow ............................ 1954.3 Technical Details of the Cryo-ET Workflow ............................ 1994.4 Perspectives and Outlook ............................................... 217References ....................................................................... 218

XX Contents

5 Scanning Electron MicroscopyNatasha Erdman, David C. Bell, Rudolf Reichelt .............................. 2295.1 Conventional Scanning Electron Microscopy .......................... 2315.2 Field-Emission Scanning Electron Microscopy ........................ 2735.3 Scanning Electron Microscopy at Elevated Pressure .................. 2935.4 Microanalysis in Scanning Electron Microscopy ....................... 2985.5 Crystal Structure Analysis

by Electron Backscatter Diffraction..................................... 302References ....................................................................... 305

6 Variable Pressure Scanning Electron MicroscopyBradley Thiel ..................................................................... 3196.1 Variable-Pressure Vacuum Systems .................................... 3216.2 Electron–Gas Interactions .............................................. 3226.3 Imaging Considerations in a Low-Vacuum Environment ............ 3256.4 Working with Hydrated Specimens .................................... 3396.5 Microanalysis in the VPSEM ............................................. 3426.6 Summary ................................................................. 344References ....................................................................... 344

7 Analytical Electron MicroscopyGianluigi Botton, Sagar Prabhudev ........................................... 3457.1 Overview ................................................................. 3467.2 Instrumentation ......................................................... 3527.3 Fundamentals ........................................................... 3747.4 Quantification ........................................................... 3867.5 Resolution in Microanalysis ............................................ 3967.6 Elemental Mapping ..................................................... 4037.7 Detection Limits in Microanalysis ...................................... 4157.8 Energy-Loss Fine Structures ............................................ 4217.9 Atomic-Scale Spectroscopy ............................................. 4337.10 Signal Processing with Advanced Statistical Methods ................ 4407.11 Advanced STEM Detectors ............................................... 442References ....................................................................... 444

8 High-Speed Electron MicroscopyGeoffrey H. Campbell, Joseph T. McKeown, Melissa K. Santala .............. 4558.1 Technologies of High-Speed Electron Microscopy .................... 4568.2 Limitations ............................................................... 4628.3 Applications of High-Speed Electron Microscopy ..................... 4708.4 Outlook................................................................... 4768.5 Conclusions .............................................................. 478References ....................................................................... 478

9 LEEM, SPLEEM and SPELEEMErnst Bauer....................................................................... 4879.1 Electron Beam–Specimen Interactions ................................ 4889.2 Instrumentation ......................................................... 4929.3 Electron Optics ........................................................... 4979.4 Contrast .................................................................. 5009.5 Applications.............................................................. 504

Contents XXI

9.6 Spin-Polarized LEEM (SPLEEM) .......................................... 5129.7 SPELEEM .................................................................. 516References ....................................................................... 523

10 Photoemission Electron MicroscopyJun Feng, Andreas Scholl ....................................................... 53710.1 A Brief History of PEEM.................................................. 53710.2 X-Ray PEEM .............................................................. 53810.3 Uncorrected PEEM Microscopes ......................................... 54110.4 Aberration-Corrected PEEM Microscopes............................... 54510.5 Spectromicroscopy: Electronic Structure, Chemistry,

and Magnetism.......................................................... 55010.6 Time-Resolved Microscopy ............................................. 55610.7 Conclusion ............................................................... 559References ....................................................................... 559

11 Spectroscopy with the Low Energy Electron MicroscopeRudolf Tromp .................................................................... 56511.1 Aspects of the LEEM Instrument ........................................ 56811.2 LEEM-IV................................................................... 57611.3 ARPES and ARRES ........................................................ 58111.4 Potentiometry ........................................................... 58611.5 SPA-LEED ................................................................. 59011.6 LEEM-EELS ................................................................ 59311.7 Radiation Effects with LEEM ............................................ 59511.8 Electron-Volt Transmission Electron Microscopy

in the LEEM Instrument ................................................. 59811.9 Conclusion ............................................................... 600References ....................................................................... 601

12 Model-Based Electron MicroscopySandra Van Aert ................................................................. 60512.1 Model-Based Parameter Estimation ................................... 60612.2 Experiment Design ...................................................... 60812.3 Quantitative Atomic Column Position Measurements ................ 61212.4 Quantitative Composition Analysis..................................... 61412.5 Atom Counting........................................................... 61612.6 Atomic Resolution in Three Dimensions ............................... 61912.7 Conclusions .............................................................. 620References ....................................................................... 621

13 Aberration Correctors, Monochromators, SpectrometersPeter W. Hawkes, Ondrej L. Krivanek........................................... 62513.1 Types of Aberrations..................................................... 62613.2 Aberration Correction ................................................... 63313.3 Practical Aspects of Corrector Operation ............................... 65213.4 Concluding Remarks .................................................... 65913.A Appendix: Power Series Expansions of Electrostatic Potential

and Vector Potential .................................................... 661References ....................................................................... 663

XXII Contents

14 Ion MicroscopyGregor Hlawacek ................................................................ 67714.1 Fundamentals of Beam Formation..................................... 67814.2 Signals.................................................................... 68414.3 Imaging .................................................................. 68914.4 Analytical Approaches to Reveal Composition

and Other Material Parameters......................................... 69914.5 Conclusion ............................................................... 708References ....................................................................... 708

15 Atom-Probe TomographyThomas F. Kelly .................................................................. 71515.1 The History of APT ....................................................... 71515.2 Fundamentals of APT.................................................... 72415.3 Limitations and Strengths of APT....................................... 73515.4 Specimen Preparation .................................................. 73915.5 Applications.............................................................. 74315.6 Developments in Atom-Probe Tomography ........................... 75415.7 Conclusions .............................................................. 758References ....................................................................... 758

Part B Holography, Ptychography and Diffraction

16 Electron HolographyRafal E. Dunin-Borkowski, András Kovács, Takeshi Kasama, MarthaR. McCartney, David J. Smith ................................................... 76716.1 Introduction to Electron Holography .................................. 76716.2 Measurement of Mean Inner Potential and Sample Thickness ...... 77216.3 Measurement of Magnetic Fields....................................... 77416.4 Measurement of Electrostatic Fields ................................... 79116.5 High-Resolution Electron Holography ................................. 80016.6 Alternative Forms of Electron Holography ............................. 80216.7 Discussion and Conclusions ............................................ 805References ....................................................................... 806

17 PtychographyJohn Rodenburg, Andrew Maiden ............................................. 81917.1 Nomenclature............................................................ 82217.2 A Brief History of Ptychography ........................................ 82317.3 How Ptychography Solves the Phase Problem ........................ 82517.4 Sampling and Removal of Artifacts in Images ........................ 83317.5 Experimental Configurations ........................................... 84417.6 Volumetric Imaging ..................................................... 86117.7 Spectroscopic Imaging .................................................. 86717.8 Mixed-State Decomposition and Handling Partial Coherence ....... 86817.9 Theory of Iterative Methods

for the Ptychographic Inverse Problem ................................ 87417.10 Wigner Distribution Deconvolution (WDD) and Its Approximations . 88417.11 Conclusions .............................................................. 899References ....................................................................... 900

Contents XXIII

18 Electron NanodiffractionJian-Min Zuo .................................................................... 90518.1 Electron Diffraction Techniques ........................................ 90618.2 Electron Probes .......................................................... 91918.3 Energy Filtering .......................................................... 92418.4 Diffraction Analysis ...................................................... 92618.5 Conclusions .............................................................. 963References ....................................................................... 964

19 High-Energy Time-Resolved Electron DiffractionPietro Musumeci, Renkai Li ..................................................... 97119.1 Ultrafast Electron Diffraction ........................................... 97119.2 High-Energy Time-Resolved Electron Diffraction Instrumentation.. 97919.3 Applications.............................................................. 99319.4 Future Developments and Outlook..................................... 996References ....................................................................... 1001

20 Diffractive Imaging of Single ParticlesJohn C. H. Spence................................................................ 100920.1 History.................................................................... 101020.2 The Projection Approximation, Multiple Scattering, Objects,

and Images .............................................................. 101220.3 The HIO Algorithm and Its Variants, Uniqueness,

and Constraint Ratio .................................................... 101520.4 Experimental Results.................................................... 101920.5 Iterated Projections ..................................................... 102520.6 Coherence Requirements for CDI Resolution .......................... 102620.7 Single-Particle Image Reconstruction from XFEL Data................ 102720.8 Summary ................................................................. 1032References ....................................................................... 1032

Part C Photon-based Microscopy

21 Fluorescence MicroscopyAlberto Diaspro, Paolo Bianchini, Francesca Cella Zanacchi, LucaLanzanò, Giuseppe Vicidomini, Michele Oneto, Luca Pesce, Isotta Cainero. 103921.1 Brief Chronological Notes ............................................... 104021.2 Basic Principles on Confocal and Two-Photon Excitation

of Fluorescent Molecules................................................ 104121.3 Fluorescent Molecules Under the TPE Regime......................... 104821.4 Optical Consequences of TPE............................................ 104921.5 The Optical Setup ........................................................ 105021.6 Comparison of Confocal and Two-Photon Excitation Microscopy.... 105321.7 Super-Resolved Imaging of Biological Systems ....................... 105521.8 Conclusions .............................................................. 1074References ....................................................................... 1075

XXIV Contents

22 Fluorescence Microscopy with Nanometer ResolutionSteffen J. Sahl, Andreas Schönle, Stefan W. Hell .............................. 108922.1 The Resolution Limit .................................................... 109022.2 Improvement in Axial Resolution by Aperture Enlargement:

4Pi Microscopy and Related Approaches .............................. 109322.3 Breaking the Diffraction Barrier: STED Microscopy

and the RESOLFT Concept ............................................... 110222.4 Coordinate-Stochastic State Transfer at the Single-Molecule

Level: PALM, STORM, PAINT, and Related Approaches ................. 112022.5 Imaging Capabilities for a New Age of Nanobiology ................. 112322.6 Nanoscopy at the MINimum: Molecular Resolution with MINFLUX .. 1127References ....................................................................... 1134

23 Zone-Plate X-Ray MicroscopyChris Jacobsen, Malcolm Howells, Tony Warwick ............................. 114523.1 Background .............................................................. 114523.2 Fresnel Zone Plates...................................................... 115123.3 X-Ray Microscopes ...................................................... 116223.4 Applications.............................................................. 118123.5 Conclusion ............................................................... 1191References ....................................................................... 1191

24 Microcomputed TomographyAngela S.P. Lin, Stuart R. Stock, Robert E. Guldberg .......................... 120524.1 X-Ray CT .................................................................. 120624.2 MicroCT System Components............................................ 121024.3 Data Acquisition and Image Processing ............................... 121424.4 Quantitative Analyses and Advanced Post-Processing Methods..... 122424.5 Other Variants and Recent Developments ............................. 122624.6 Summary ................................................................. 1232References ....................................................................... 1232

Part D Applied Microscopy

25 Scanning Probe Microscopy in Materials ScienceBryan D. Huey, Justin Luria, Dawn A. Bonnell ................................ 123925.1 Imaging at Atomic Resolution with Force Interactions ............... 124025.2 Imaging Properties: Advanced SPM Techniques....................... 124625.3 Future Trends ............................................................ 126225.4 Conclusion ............................................................... 1267References ....................................................................... 1267

26 Electron Tomography in Materials ScienceRowan K. Leary, Paul A. Midgley ............................................... 127926.1 Foundations of Tomography............................................ 128026.2 ET Acquisition............................................................ 128426.3 ET Imaging Modes ....................................................... 128726.4 Tilt Series Alignment .................................................... 130026.5 ET Reconstruction........................................................ 1303

Contents XXV

26.6 Segmentation, Visualization, and Quantitative Analysis ............. 131726.7 Conclusions .............................................................. 1321References ....................................................................... 1321

27 Scanning Tunneling Microscopy in Surface SciencePeter Sutter....................................................................... 133127.1 Basic Principles of STM Imaging ........................................ 133227.2 Tunneling Spectroscopy ................................................. 133927.3 STM at High and Low Temperatures .................................... 134927.4 Heterostructures and Buried Interfaces: Ballistic Electron

Emission Microscopy,Quantum Size Effects, and Cross-Sectional STM....................... 1355

27.5 STM Image Simulation .................................................. 1361References ....................................................................... 1363

28 Visualizing Electronic Quantum MatterKazuhiro Fujita, Mohammad H. Hamidian, Peter O. Sprau, StephenD. Edkins, J.C. Séamus Davis .................................................... 136928.1 Electrons in Crystals ..................................................... 137028.2 Electrons in Crystals: Disorder and Symmetry Breaking .............. 137128.3 Electrons in Crystals: Weakly to Strongly Interacting Phases ......... 137128.4 Spectroscopic Imaging Scanning Tunneling Microscopy .............. 137328.5 Cooper-Pair Condensate Visualization................................. 137628.6 Visualizing Effects of Individual Impurity Atoms

and Dopant Atoms ...................................................... 137728.7 Quasiparticle Interference Imaging .................................... 137928.8 Momentum-Space Imaging of Energy Gaps

of Ordered Phases: Superconductivity ................................. 138128.9 Real-Space Imaging of Energy Gaps of Ordered Phases .............. 138328.10 Visualizing Electronic Symmetry Breaking ............................. 138528.11 Visualizing New Phases of Strong-Correlation Electronic Matter .... 1386References ....................................................................... 1388

29 Microscopy of Nanoporous CrystalsYanhang Ma, Lu Han, Zheng Liu, Alvaro Mayoral, Isabel Díaz, PeterOleynikov, Tetsu Ohsuna, Yu Han, Ming Pan, Yihan Zhu, YasuhiroSakamoto, Shunai Che, Osamu Terasaki ....................................... 139129.1 Classification of Nanoporous Crystals .................................. 139229.2 History of Transmission Electron Microscopy (TEM) Study

of Nanoporous Materials................................................ 139329.3 Comparison with X-Ray Diffraction .................................... 139429.4 Crystal and Crystal Structure Factors ................................... 139629.5 Accidental Extinction.................................................... 139629.6 Double Refraction ....................................................... 139929.7 New Problems Give Exciting Challenges ............................... 140029.8 Recent Technical Developments Important

for the Structural Study of Nanoporous Crystals ...................... 140129.9 Structural Characterization and Solutions ............................. 140629.10 Conclusions .............................................................. 1441References ....................................................................... 1441

XXVI Contents

30 Biomedical X-Ray Phase-Contrast Imaging and TomographyHan Wen ......................................................................... 145130.1 Overview ................................................................. 145130.2 In-Line Phase-Contrast or Free-Space Propagation-Based Method 145330.3 Wavefront Tagging....................................................... 145530.4 Wavefront Tagging with Grating Interferometry ...................... 145630.5 Diffraction-Enhanced Imaging with Monolithic Crystal

Collimator and Analyzer ................................................ 146030.6 Split-Beam Interferometry ............................................. 146130.7 Conclusion ............................................................... 1463References ....................................................................... 1463

31 Atomic Force Microscopy in the Life SciencesMatthias W. Amrein, Dimitar Stamov .......................................... 146931.1 Instrumentation and Imaging.......................................... 147231.2 Sample Preparation ..................................................... 148631.3 Imaging and Locally Probing Macromolecular and Cellular

Samples: Examples...................................................... 149131.4 Outlook and Perspective ................................................ 1499References ....................................................................... 1499

32 Microscopy in Forensic SciencesBenjamin J. Jones ............................................................... 150732.1 Enhancing Forensic Science ............................................ 150732.2 Trace Evidence at the Crime Scene ..................................... 150832.3 Gunshot Residue (GSR).................................................. 150932.4 Glass and Paint .......................................................... 151232.5 Other Trace Evidence Types ............................................. 151332.6 Fingerprints .............................................................. 151432.7 Conclusions .............................................................. 1520References ....................................................................... 1520

Subject Index ...................................................................... 1525

XXVII

List of Abbreviations

1-D one-dimensional2-D two-dimensional2PE two-photon excitation3-D three-dimensional3-D-EBSD three-dimensional electron backscattered

diffraction3-D-XRDM three-dimensional x-ray diffraction

microscopy3-DAP three-dimensional atom probe3M multimessenger microscopy4-D four-dimensional5-D five-dimensional6-D six-dimensional

A

ABF annular bright-fieldACF absorption correction factorADC analog-to-digital-converterADF annular dark-fieldADT automated diffraction tomographyAE Auger electronAEEM Auger electron emission microscopyAEES Auger electron emission spectroscopyAEM analytical electron microscopyAET analytical electron tomographyAFAM atomic force acoustic microscopyAFM atomic force microscopyAIR algebraic iterative reconstructionALS Advanced Light SourceAM amplitude modulationAPFIM atom-probe field ion microscopeAPT atom probe tomographyARPES angle-resolved photoemission

spectroscopyARRES angle-resolved reflected-electron

spectroscopyART algebraic reconstruction techniqueARXPS angle-resolved x-ray photoemission

spectroscopyASEM atmospheric scanning electron

microscopeASR averaged successive reflectionAU Airy unitAWG arbitrary waveform generation

B

BART binary algebraic reconstructiontechnique

bcc body-centered cubicBCS Bardeen–Coopper–SchriefferBEEM ballistic electron emission microscopy

BF bright-fieldBIV best imaging voltageBQPI Bogoliubov quasiparticle interferenceBS backscatter spectrometryBSE backscattered electron

C

CAD computer aided designCAST Centre for Applied Science and

TechnologyCBED convergent-beam electron diffractionCC charge collectionCCD charge-coupled devicecCDI conventional coherent diffractive

imagingccp cubic close-packedCDI coherent diffractive imagingCDW charge density waveCE collection efficiencyCEC constant energy contoursCF charge-flippingCFEG cold field emission gunCFM chemical force microscopyCFT forward cylindrical FTCITS current imaging tunneling spectroscopyCL cathodoluminescenceCLEM correlative light and electron microscopyCLS confocal laser scanningCMC constant mean curvatureCMOS complementary metal–oxide

semiconductorCNT carbon nanotubeCOF covalent organic frameworkCPD critical point dryingCPO charged particle opticsCRB Cramér–Rao boundCRLB Cramér–Rao lower boundcryo-EM cryo-electron microscopycryo-ET cryo-electron tomographycryo-FIB cryo-focused ion beam millingcryo-FLM correlative fluorescence microscopyCS compressed sensingCSEM conventional high-vacuum scanning

electron microscopyCSF crystal structure factorCT computed tomographyCTAFM computed tomography AFMCTEM conventional transmission electron

microscopeCTF coherent transfer functionCVD chemical vapor depositionCW continuous wave

XXVIII List of Abbreviations

CW-STED continuous wave-stimulated emissiondepletion

CXDI coherent x-ray diffractive imaging

D

DAC digital to analog conversionDAM drive amplitude modulationDART discrete algebraic reconstruction

techniqueDAXM differential-aperture x-ray microscopyDCT diffraction contrast tomographyDDC direct detection cameraDDEC direct-detection electron-countingDF dark-fieldDFT density functional theoryDIC differential interference contrastDIRECTT direct iterative reconstruction of

computed tomography trajectoriesDLA delay-line anodeDLS distance least-squaresDLVO Derjaguin, Landau, Verwey, OverbeekDMI Dzyaloshinskii–Moriya interactionDOS density of statesDP diffraction patterndpa displacements per atomDPC defocusing phase contrastDPN dip pen nanolithographyDQE detective quantum efficiencyDREEM double reflection electron emission

microscopedSTORM direct stochastic optical reconstruction

microscopyDTEM dynamic transmission electron

microscopyDWNT double walled nanotubeDWT discrete wavelet transform

E

EBIC electron beam-induced currentEBIV electron beam-induced voltageEBSD electron backscatter diffractionEC electron crystallographyECoPoSAP energy-compensated position-sensitive

atom probeECP electron channeling patternED electron diffractionEDS energy-dispersive spectroscopyEDT electron diffraction tomographyEDX energy-dispersive x-rayEDXS energy-dispersive x-ray spectroscopyEEL electron energy-lossEELM electron energy-loss microscopyEELS electron energy-loss spectroscopyEF energy filteringEFM electrostatic force microscopy

EFTEM energy-filtered transmission electronmicroscopy

EFTEM-SI energy-filtered TEM spectrum imagingELNES energy-loss near-edge structureEM electron microscopyEMC expectation maximization and

compressionEMCCD electron multiplying charge coupled

deviceEMFP elastic mean free pathEMPAD electron microscope pixel array detectorEOM electro-optic modulatorEOS electro-optic samplingePIE extended ptychographical iterative

engineEQM electronic quantum matterESD electron-stimulated desorptioneSE electron-induced secondary electronESEM environmental scanning electron

microscopeESI electron spectroscopic imagingESM electrochemical strain microscopyEST equally sloped tomographyET electron tomographyETD Everhart–Thornley detectorETEM environmental transmission electron

microscopeEUV extreme ultra-violeteV-TEM electron-volt TEMEXAFS extended x-ray absorption fine structureEXELFS extended energy-loss fine structureExM expansion microscopy

F

FC flux closureFCS fluorescence correlation spectroscopyFD Fourier diffractogramFE finite elementFEBID focused electron-beam-induced

depositionFEG field emission gunFEL free-electron laserFEM field electron microscopyFESEM field emission scanning electron

microscopeFET field-effect transistorFFM friction force microscopyFFP front-focal planeFFT fast Fourier transformFIB focused ion beamFIM field ion microscopyFITC fluoresceine isothiocyanateFLICS fluorescence lifetime correlation

spectroscopyFLM fluorescence light microscopyFM frequency modulationFMT fluorescence molecular tomography

List of Abbreviations XXIX

FMTI ferromagnetic topological insulatorFOM figures of meritFOV field of viewFP Fourier ptychographyFPALM fluorescence photoactivation localization

microscopyfps frames per secondFRAP fluorescence recovery after

photobleachingFRC Fourier-ring-correlationFRET fluorescence resonance energy transferFRM fast rotation matchingFT Fourier transformFTIR Fourier transform infrared

microspectroscopyFWHM full width at half maximumFWTM full width at tenth maximum

G

gCW-STED gated continuous wave-stimulatedemission depletion

GED gas-phase electron diffractionGENFIRE generalized Fourier iterative

reconstructionGFIS gas field ion sourceGFP green fluorescent proteinGIS gas injection systemGOF goodness of fitGOS generalized oscillator strengthGPILRUFT global ptychographic iterative linear

retrieval using Fourier transformsGPT general particle tracerGS Gerchberg–Saxton algorithmGSD ground state depletionGSDIM ground state depletion followed by

individual molecule returnGSED gaseous secondary electron detector

H

HAADF high-angle annular dark-fieldhcp hexagonal close-packedHIM helium ion microscopyHOLZ high-order Laue zoneHPI hexagonally packed intermediateHPR hybrid projection reflectionHREM high-resolution electron microscopyHRSEM high-resolution scanning electron

microscopyHRTEM high-resolution transmission electron

microscopyHS Hartree–SlaterHV high vacuum

I

IAP imaging atom probeIBA ion beam analysis

IBF incoherent bright-fieldIBSC ion beam slope cuttingIC intermittent contactICA independent component analysisICL integration classification likelihood

criterionICP-MS inductively coupled plasma mass

spectroscopyIDC indirect detection cameraIETS inelastic electron tunneling spectroscopyIL ionoluminescenceIMFP inelastic mean free pathIML-SPIM individual molecule localization

selective plane illumination microscopyIOM inverted optical microscopeIR infraredIS image scanningiSE ion-induced secondary electroniSEED ion-induced secondary electron energy

distributioniSEY induced secondary electron yieldITA iterative transformation algorithms

K

KCBED kinematic convergent beam blank diskKE kinetic emissionKFM Kelvin probe force microscopyKKA Kramers–Kronig analysisKRIPES k-resolved inverse photoelectron

emission spectroscopy

L

LAADF low-angle annular dark-fieldLACBED large-angle convergent-beam electron

diffractionLARBED large-angle rocking-beam electron

diffractionLCTEM liquid cell transmission electron

microscopyLEAP local-electrode atom probeLEED low-energy electron diffractionLEELM low-electron energy loss microscopyLEEM low-energy electron microscopyLFL Landau–Fermi liquidLIQUITOPY liquid tunable microscopyLMAIS liquid metal alloy ion sourceLMIS liquid metal ion sourceLO longitudinal opticalLPS longitudinal phase spaceLSC longitudinal space chargeLSI linear space invariantLSM laser scanning microscopyLV low vacuumLVFESEM low-voltage field emission scanning

electron microscopeLVSEM low-voltage scanning electron

microscopy

XXX List of Abbreviations

M

MAADF medium-angle annular dark-fieldMAL maximum likelihoodMALDI matrix-assisted laser

desorption/ionizationMAPS monolithic active pixel sensorMDF minimum detectable fractionMDFF mixed dynamic form factorMDN minimum detectable numberMEM mirror electron microscopyMEMS microelectromechanical systemMFM magnetic force microscopyMFP mean free pathmicroCT microcomputed tomographyMIEEM metastable impact electron emission

microscopyMIL Materials of the Institute LavoisierMINFLUX nanoscopy with minimal photon fluxesMIP mean inner potentialMMF minimum mass fractionMMM-4Pi multifocal multiphoton microscopy 4PiMOF metal organic frameworkMOGA multi-objective genetic algorithmMOS metal oxide semiconductorMOSFET metal–oxide–semiconductor field-effect

transistorMOST multiple off-state transitionsMOTIS magneto-optical trap ion sourceMPA magnetic prism arrayMPE multiphoton excitationMRI magnetic resonance imagingMRP mass resolving powerMSA multivariate statistical analysisMSI multivariate statistical methodsMTE mean transverse energyMTF modulated transfer function

N

NA numerical apertureNAD nonlinear anisotropic diffusionNAED nanoarea electron diffractionNBD nanobeam diffractionNC-AFM noncontact atomic force microscopyNCC normalized cross-correlationNEMS nanoelectromechanical systemNEXAFS near-edge x-ray absorption fine structureNFFT nonequispaced fast Fourier

transformationNFMM near-field microwave microscopyNIM nanoimpedance microscopy and

spectroscopyNMR nuclear magnetic resonanceNPC nuclear pore complexNSOM/SNOM near-field scanning optical microscopyNTF noise transfer function

O

OBD optical beam deflectionOIM orientation imaging microscopyOL objective lensOTF optical transfer function

P

PACBED position averaged CBEDPAD pixel area detectorPAINT points accumulation for imaging in

nanoscale topographyPALM photoactivated localization microscopyPALMIRA PALM with independently running

acquisitionPBS polarization beam-splitterPCA principal component analysisPCAFM photoconductive AFMPCD projected charge densityPCF phase-correlation functionpCF pair correlation functionPCI phase contrast index functionPCTF phase contrast transfer functionPDF probability density functionPDW pair density wavePE potential emissionPED precession electron diffractionPEELS parallel electron energy-loss spectrumPEEM photoelectron emission microscopyPFI polychromatic far-field interferometerPFM piezoelectric force microscopyPG point-groupPGA phase grating approximationPIE ptychographical iterative enginePINEM photon-induced near-field electron

microscopyPL photoluminescencePLA pressure-limiting aperturePLD pulsed laser depositionPMQ permanent magnet quadrupolePMT photomultiplier tubePOA phase object approximationPOCS projections onto convex setPoSAP position-sensitive atom probePPFFT pseudopolar fast Fourier transformPR piezoresponsePSD power-spectral-densityPSE-CVD pulsed-spray evaporation chemical vapor

depositionPSF point spread functionPSM presharpened microtipPSRT progressive stochastic reconstruction

techniquePVD physical vapor depositionPXRD powder x-ray diffraction

List of Abbreviations XXXI

Q

QD quantum dotQPI quasiparticle scattering interferenceQSE quantum size effect

R

RAAR relaxed averaged alternating reflectorRBS Rutherford backscattering spectrometryREAP remote-electrode atom probeREM reflection electron microscopyRESOLFT reversible saturable optical fluorescence

transitionRF radio frequencyRI refractive indexRICS raster imaging correlation spectroscopyRIM reflection ion microscopyRMLF reactive multilayer foilRMS root mean squareROI region of interestRP-CVD reduced pressure chemical vapor

depositionRSFP reversibly switchable fluorescent proteinRVM ray–voxel interaction matrix

S

SA selected areaSAED selected area electron diffractionSAP scanning atom probeSAP selected area ptychographySART simultaneous algebraic reconstruction

techniqueSAT single atom tipSAXS small-angle x-ray scatteringSBR signal-to-background-ratioSCBED scanning convergent-beam electron

diffractionSCEM scanning confocal electron microscopySCFS single-cell force spectroscopySCM scanning capacitance microscopySDD silicon drift detectorSDM spatial distribution mapSE secondary electronSEC Schottky emission cathodeSECM scanning electrochemical microscopySED scanning electron diffractionSEED secondary electron energy distributionSEEM secondary electron emission microscopySEM scanning electron microscopySEM-EDX scanning electron microscopy with

energy dispersive x-ray spectroscopySEND scanning electron nanodiffractionSFIM scanning field ion microscopySFXM scanning fluorescence x-ray microprobeSG space groupSGM scanning gate microscopy

SHARP scalable heterogeneous adaptivereal-time ptychography

SI spectrum imageSI-STM spectroscopic imaging scanning

tunneling microscopySIM scanning impedance microscopySIMS secondary ion mass spectroscopySIRT simultaneous iterative reconstruction

techniqueSJTM scanned Josephson tunneling

microscopySLEEM scanning low-energy electron

microscopySMACM single-molecule active-control

microscopySMART spectromicroscope for all relevant

techniquesSMFS single-molecule force spectroscopySMI structure model indexSMIM scanning microwave impedance

microscopySNDM scanning nonlinear dielectric microscopySNOM scanning near-field optical microscopeSNR signal-to-noise-ratioSP single-particleSPA-LEED spot-profile analysis LEEDSPAD single photon avalanche diodeSPELEEM spectroscopic photoemission and

low-energy electron microscopySPEM scanning photoemission microscopeSPIM selective-plane-illumination microscopySPLEEM spin-polarized low-energy electron

microscopySPLIT separation of photons by lifetime tuningSPM scanning probe microscopyspt-PALM single-particle tracking-photoactivation

localization microscopySR-SIM super-resolved structured illumination

microscopySRIM stopping and range of ions in matterSRT spin-reorientation transitionSSIM saturated structured-illumination

microscopySSPM scanning surface potential microscopySSRM scanning spreading resistance

microscopySTED stimulated emission depletionSTEM scanning transmission electron

microscopySTEM-SI scanning transmission electron

microscopy spectrum-imagingstFCS spatiotemporal fluorescence correlation

spectroscopySThM scanning thermal microscopySTIM scanning transmission ion microscopySTM scanning tunneling microscopySTORM stochastic optical reconstruction

microscopySTXM scanning transmission x-ray microscopy

XXXII List of Abbreviations

SW single wavelengthSWM standing wave microscopeSWNT single-walled carbon nanotube

T

t-EBSD transmission EBSDTAP tomographic atom probeTCC transmission cross coefficienttcp tetrahedrally close-packedTDS thermal diffuse scatteringTEEM thermionic emission electron

microscopyTEM transmission electron microscopyTEY total electron yieldTFE thermal field emitterTGA thermogravimetric analysisTI topological insulatorsTIE transport of intensityTIRF total internal reflection fluorescentTKD transmission Kikuchi diffractionTO transverse opticalToA time-of-arrivalToF time-of-flightToF-SIMS time of flight secondary ion mass

spectrometryTPE two-photon excitationTPMS triply periodic minimal surfaceTR-GED time-resolved gas-phase electron

diffractionTR-NIM torsional resonance nanoscale

impedance microscopyTTM two-temperature modelTV total variationTXM transmission x-ray microscope

U

UBMS unbalanced magnetron sputteringUED ultrafast electron diffractionUEM ultrafast electron microscopyUFM ultrasonic force microscopyUHV ultrahigh vacuumUHVTEM ultrahigh vacuum transmission electron

microscopeULV ultralow vibrationUSAXS ultrasmall angle x-ray scatteringUTEM ultrafast TEMUTW ultrathin windowUV ultravioletUVPEEM ultraviolet photoemission electron

microscopy

V

VB valence bandVFP visible fluorescent proteinVLSI very-large-scale integration

VLVSEM very low-voltage scanning electronmicroscopy

VOA virtual objective apertureVP variable pressureVPP Volta phase plateVPSE variable pressure secondary electronVPSEM variable pressure scanning electron

microscopy

W

WAXS wide-angle x-ray scatteringWBP weighted back-projectionWD working distanceWDD Wigner distribution deconvolutionWDS wavelength-dispersive spectrometerWDX wavelength-dispersive x-rayWKB Wentzel–Kramers–BrillouinWPOA weak phase object approximationWSIRT weighted-SIRTWTF wave transfer function

X

X-PEEM x-ray photoemission electronmicroscopy

X-STM cross-sectional scanning tunnelingmicroscopy

XAFS x-ray absorption fine structureXANES x-ray absorption near-edge structureXAS x-ray absorption spectroscopyXASPEEM x-ray absorption PEEMXCF cross-correlation functionXEDS x-ray energy dispersive spectroscopyXFCT x-ray fluorescence CTXFEL x-ray free-electron laserXMCD x-ray magnetic circular dichroismXMCDPEEM x-ray magnetic circular dichroism

photoemission electron microscopyXMLDPEEM x-ray magnetic linear dichroism

photoemission electron microscopyXPEEM x-ray-induced photoemission electron

microscopyXPS x-ray photoelectron spectroscopyXRD x-ray diffraction

Y

YAG yttrium-aluminum-garnetYAP yttrium-aluminum-perovskiteYSZ yttria stabilised zirconia

Z

ZIF zeolitic imidazolate frameworkZL zero-lossZLP zero-loss peakZOLZ zero-order Laue zoneZPP Zernike phase plate