bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface Magneto‐Optic Kerr Effect
Authors: Qiu Ziqiang , Bader Samuel D.
Published: October 2012

In 1845, Michael Faraday found that the polarization plane of linearly polarized light rotates as the light is transmitted through a magnetized medium. Thirty‐two years later the magneto‐optic Kerr effect (MOKE) was discovered by John Kerr when he examined the polarization of light reflected from the polished surface of an electromagnet. These two monumental works heralded the beginnings of magneto‐optics and form the foundation of its modern utilization. As the field of surface and thin‐film magnetism has emerged and blossomed in recent years, so has the need for innovative approaches to study magnetic phenomena on the nanometer‐thickness scale. The application of the Kerr effect to study the surface magnetism was introduced by Moog and Bader (1985) along with the acronym SMOKE to denote the surface magneto‐optic Kerr effect. Since then SMOKE has emerged as a premier surface magnetism technique of choice in many laboratories worldwide. The broad acceptance of the SMOKE technique stems from its simplicity and its ability to generate the “universal currency” in magnetism –the hysteresis loop. Although in this article the SMOKE technique for visible light with fixed wavelength is described, it is easy to extend the technique to wavelength‐dependent measurements such as magneto‐optic spectroscopy and spatially resolved measurements such as magneto‐optic microscopy. The aim of this article is to provide general background about the basic principles and experimental methods of the SMOKE technique.
Cyclic Voltammetry
Authors: Bocarsly Andrew B.
Published: October 2012

The qualitative aspect of cyclic voltammetry has made it a general tool for the evaluation of electrochemical systems. With regard to materials specifically, the technique has found use as a method for investigating the electro‐synthesis of materials (including conducting polymers and redox‐produced crystalline inorganics), the mechanism of corrosion processes, the electrocatalytic nature of various metallic systems, and the photoelectrochemical properties of semiconducting junctions. Here a general description of the cyclic voltammetric technique is provided along with some examples focusing on materials science applications.
Optical Imaging and Spectroscopy, Introduction
Authors: Samuels Alan C.
Published: October 2012

Visual inspection is often the easiest and least expensive means by which materials can be characterized. Optical interrogation of a material, enhanced by microscopy and spectroscopy, is usually completely nondestructive and can be performed with minimal or in some cases no sample preparation whatsoever. This chapter covers the key methods by which optical interrogation may be applied to address materials characterization needs.
Raman Spectroscopy of Solids
Authors: Devine Thomas M. , Adar Fran
Published: October 2012

Raman spectroscopy is based on the inelastic scattering of light by matter and is capable of probing the structure of gases, liquids, and solids, both amorphous and crystalline. In addition to its applicability to most forms of matter, Raman spectroscopy has a number of other advantages. It can be used to analyze tiny quantities of material (e.g., particles that are ≤1 μm3 in dimension), as well as samples exposed to a variety of conditions such as high temperature and high pressure, and samples embedded in other phases, so long as the surrounding media are optically transparent. Succinctly stated, Raman scattering results from incident radiation inducing transitions in the atoms/molecules that make up the scattering medium. The transition can be rotational, vibrational, electronic, or a combination thereof. In most studies of solids by Raman spectroscopy, the transitions observed are vibrational and these will be the focus of this article
X‐Ray Powder Diffraction
Authors: Von Dreele Robert B. , Toby Brian H.
Published: October 2012

X‐ray powder diffraction is used to determine the atomic structure of crystalline materials without the need for large (∼100 μm) single crystals. “Powder” can be a misnomer; the technique is applicable to polycrystalline phases such as cast solids or films grown on a substrate. X‐ray powder diffraction can be useful in a wide variety of situations. Of particular importance are structural studies of materials for which single crystals are unobtainable. A number of questions that can be effectively addressed by this technique are listed in the following. This is an attempt to illustrate the versatility of x‐ray powder diffraction and not, by any means, a complete list. Experiments are described as concrete examples and constitute an assortment of problems of varying difficulty.

X‐ray powder diffraction is an old technique, developed soon after the discovery of x‐rays. The capabilities of the technique have recently grown for two main reasons: the improvement of instrumentation and analysis. This article discusses the fundamental principles of the technique, including the expression for the intensity of each diffraction peak, gives a brief overview of experimental techniques, describes several illustrative examples, gives a description of the procedures to interpret and analyze diffraction data, and discusses weaknesses and sources of possible errors.
Magnetic X‐Ray Scattering
Authors: Nandi Shibabrata
Published: October 2012

Investigations of the structure and dynamics of materials have been an important and essential endeavor in condensed matter physics since the early 20th century. Both neutron and x‐ray scattering techniques have been used extensively to study the crystallographic structure of materials and provide complementary views of structure. For example, x‐ray diffraction has largely been applied to detailed crystallographic structure determination while neutron scattering has traditionally been the standard tool for studies of magnetic structure and the dynamics of condensed matter systems. The principle interaction that makes structure determination possible for x‐rays is the Coulomb interaction between x‐rays and the electronic distribution that gives rise to driven harmonic oscillation of the electrons, and the emission of electric dipole radiation. This is the classical Thomson scattering process. In addition to charge scattering, x‐rays interact with the magnetic moment of the system. When x‐ray energies are tuned through the absorption edges of an element of interest there is a resonant enhancement of the scattering signal now known as x‐ray resonant magnetic scattering. Away from the resonance condition, the magnetic scattering signal is known as nonresonant x‐ray magnetic scattering. In this article, we will concentrate mainly on the basic principles and applications of the x‐ray resonant magnetic scattering and nonresonant magnetic scattering.
Resonant Scattering Techniques
Authors: Finkelstein Kenneth D. , Dmitrienko Vladimir E.
Published: October 2012

This article describes resonant x‐ray scattering by presenting its principles, illustrating them with several examples, providing background on experimental methods, and discussing the analysis of data. Principles of the method presented are the classical picture of x‐ray scattering, including anomalous dispersion, followed by a quantum‐mechanical description for the scattering amplitudes, and ends with a discussion on techniques of symmetry analysis useful in designing experiments. Two examples from the literature are used to illustrate the technique. This is followed by a discussion of experimental aspects of the method, including the principles of x‐ray polarization analysis. A list of criteria is given for selecting systems amenable to the technique, along with an outline for experimental design. A general background on data collection and analysis includes references to sources of computational tools and expertise in the field.
X‐ray Microprobe for Fluorescence and Diffraction Analysis
Authors: Ice Gene E.
Published: October 2012

X‐ray diffraction and x‐ray‐excited fluorescence analysis are powerful techniques for the nondestructive measurement of crystal structure and chemical composition. When a small‐area x‐ray microbeam is used as the probe, chemical composition, crystal structure, crystalline texture, and crystalline strain distributions can be determined. These distributions can be studied both at the surface of the sample and deep within the sample.

This article reviews the physics, advantages, and scientific applications of hard x‐ray (E > 3 keV) microfluorescence and x‐ray microdiffraction analysis. Because practical x‐ray microbeam instruments are extremely rare, a special emphasis is placed on instrumentation, accessibility, and experimental needs which justify the use of x‐ray microbeam analysis.
Electron Techniques, Introduction
Authors: Pennycook Stephen J.
Published: October 2012

Electrons are highly versatile probes of materials because they are first, easily accelerated, second, readily focused by electromagnetic fields and third, they interact strongly with matter. At low energies they interact with materials surfaces, while at high energy they can probe the bulk (at least the interior of a thin specimen). In addition, at high energies they have very short wavelengths, for example, 3.7 pm when accelerated to 100 kV, and, given atomic spacings in materials are 100 – 200 pm, in principle fast electrons are easily capable of providing atomic resolution images. Electrons also lose energy to atomic excitations, bringing another plethora of spectroscopic techniques for analysis of surfaces and bulk compositions and electronic structure. This chapter provides overviews of the key methods developed to exploit these characteristics of electrons to probe the structure, composition and chemical bonding of materials, their internal microstructure and the nature of their surfaces and interfaces.
Transmission Electron Microscopy
Authors: Howe James M. , Fultz Brent , Miao Shu
Published: October 2012

Transmission electron microscopy (TEM) is the premier tool for understanding the internal microstructure of materials at the nanometer level. It allows one to obtain real‐space images of materials with resolutions on the order of a few tenths to a few nanometers, depending on the imaging conditions, and simultaneously obtain diffraction information from specific regions in the images (e.g., small precipitates). Variations in the intensity of electron scattering across a thin specimen can be used to image strain fields, defects such as dislocations and second‐phase particles, and even atomic columns in materials under certain imaging conditions.

In addition to diffraction and imaging, the high‐energy electrons (usually in the range of 100 to 400 keV of kinetic energy) in TEM cause electronic excitations of the atoms in the specimen. Two important spectroscopic techniques make use of these excitations by incorporating suitable detectors into the transmission electron microscope, energy‐dispersive x‐ray spectroscopy (EDS), and electron energy loss spectroscopy (EELS). Nanometer‐scale chemical compositional analysis can be performed by using a focused electron probe. Spatial distribution of elements can be obtained by scanning the probe over the specimen, or by energy‐filtered imaging, a special mode in advanced EELS spectrometer.

The recent advancements in aberration‐correction technologies have improved the image resolution and probe size to sub‐Ångstrom level, and current density in the probe is increased by an order, which catalyze the emergence of new contrast theories and microanalysis techniques. Many other analyses are also possible in TEM with the development of novel detectors.
Scanning Transmission Electron Microscopy:Z‐Contrast Imaging
Authors: Pennycook Stephen J.
Published: October 2012

Scanning transmission electron microscope (STEM) is a combination of the scanning electron microscope and the transmission electron microscope (TEM). Thin specimens are viewed in transmission, while images are formed serially by the scanning of an electron probe. In recent years, through the successful correction of Q2 the intrinsically high aberrations of electron lenses it has become possible to form probes well below atomic dimensions, and as a result, atomic resolution images showing sub‐angstrom resolution may now be routinely achieved in this instrument

The nature of the images obtained in the STEM can differ in significant ways from those formed by the conventional TEM, in particular, multiple signals can be acquired in the STEM including bright field, annular dark field (ADF) images, and spectroscopic images using either electrons that have lost energy by exciting specific inner shell or valence band levels or by detecting emitted characteristic x‐rays. A key difference between STEM and TEM imaging is that the ADF image available on the STEM represents almost perfect incoherent imaging, while the bright field image represents almost perfect coherent imaging, equivalent to the image provided by a conventional high‐resolution TEM. The latter technique has often been simply referred to as high‐resolution electron microscopy (HREM). This article focuses on Z‐contrast imaging of materials at atomic resolution and associated techniques such as electron energy loss spectroscopy (EELS).
Low‐Energy Electron Diffraction
Authors: Pussi Katariina , Diehl Renee D.
Published: October 2012

Low‐energy electron diffraction (LEED) is a common and powerful method for determining the geometric structure of solid surfaces. It has the advantage of being fast and inexpensive relative to many other surface techniques. LEED can provide quick information on the surface unit cell size and geometry of single crystal surfaces, and with more effort can be used to determine the complete surface geometry, i.e. composition, bond lengths and angles. Although LEED has been used primarily as a structural technique, it can be used to determine other surface properties such as atomic and molecular vibration and libration amplitudes and energies. LEED has dominated the study of surface geometries for relatively simple structures, and is expected to become increasingly important in the study of nanostructures, molecular adsorbates, and insulating surfaces.
Energy Dispersive Spectrometry
Authors: Newbury Dale E.
Published: October 2012

Energy dispersive x‐ray spectrometry (EDS) is a widely used measurement technology with particular application to electron beam instruments including the analytical electron microscope and the scanning electron microscope. EDS based on silicon devices provides measurement of the photon energy range from 0.1–30 keV which enables measurement of all elements except H, He, and Li through K‐shell, L‐shell, or M‐shell x‐rays. Quantitative concentration results can be obtained at the major (concentration C > 0.1 mass fraction), minor (0.01 ≤ C ≤ 0.1), and trace level (C < 0.01) with systematic errors in the range of 5% relative when a standard‐based method with calculated corrections for interelement (matrix) effects is used. Silicon drift detector (SDD) EDS is rapidly replacing the classic Si(Li)‐EDS because of superior performance, especially in x‐ray throughput.
Trace Element Accelerator Mass Spectrometry
Authors: McDaniel Floyd Del
Published: October 2012

Accelerator mass spectrometry is a relatively new analytical technique that is being used in over 40 laboratories worldwide for the measurements of cosmogenic long‐lived radioisotopes, as a tracer in biomedical applications, and for trace element analysis of stable isotopes. The use of particle accelerators, along with mass spectrometric methods, has allowed low‐concentration measurements of small‐volume samples. The use of AMS to directly count ions, rather than measure radiation from slow radioactive decay processes in larger samples, has resulted in sensitivities of one part in 1015. The ions are accelerated to mega‐electron‐volt energies and can be detected with 100% efficiency in particle detectors. The improved sensitivities and smaller sample sizes have resulted in a wide variety of applications in anthropology, archaeology, astrophysics, biomedical sciences, climatology, ecology, geology, glaciology, hydrology, materials science, nuclear physics, oceanography, sedimentology, terrestrial studies, and volcanology, among others. Accelerator mass spectrometry has opened new areas of research in the characterization of trace elements in materials.

This article will focus on the technique of trace element accelerator mass spectrometry (TEAMS) and its applications in the analysis of stable isotopes in materials.
Elastic Backscattering of Ions for Compositional Analysis
Authors: Jeynes Chris
Published: October 2012

BS (elastic backscattering spectrometry, either RBS or EBS) using MeV beams is used to obtain elemental depth profiles of thin films up to ∼10 mm thick. Depth resolution degrades with depth but can be ∼1 nm at the surface. Various ion beams and various beam energies can be selected to obtain the optimal analytical conditions for particular samples.

We will briefly mention the use of microbeams since many samples are small or laterally non‐homogeneous. We will also briefly mention the use of ion channelling geometries for characterizing defects in single crystal samples. We should also mention that LEIS and MEIS are both RBS techniques, but they use low energy beams and will not be covered in this article.

We treat all the IBA techniques synergistically. The present article considers the details of analysis using a particle detector placed in the backscattering direction. We explicitly distinguish between RBS and EBS, even though in any particular BS spectrum there may be (and often are) both RBS and EBS signals, since there is a philosophical difference of treatment between a signal resulting from a Coulomb interaction and one resulting from an interaction that must be treated quantum mechanically.
Particle‐InducedX‐Ray Emission
Authors: Reis Miguel A. , Campbell John L.
Published: October 2012

Particle‐Induced X‐Ray Emission (PIXE) is an analytical technique established in the decade of 1970s, which makes use of MeV ion beams (mainly proton beams) to induce x‐ray emission from materials. It is used both in macro mode, where beam spots are of the order of millimeters, and in micro mode, where ion beams are focused to micrometer size (or even below this, since 100 nm spots are already available for PIXE). It has major advantages for the analysis of sensitive and/or complex samples because it is essentially a non‐destructive technique. For example, some laboratories are equipped with facilities where the beam is extracted into the atmosphere, allowing the analysis of paintings and other cultural heritage samples. Recent developments also make possible the analysis of samples that are not homogeneous but composed of different layers. In this case, PIXE has large advantages relative to electron microprobe analysis (EPMA) because the particle beam scattering is very small, such that the micro‐beam remains focused along several micrometers into the sample. Finally, the use of x‐ray detection systems having high resolution (resolving power of the order of 100 or more) is presently moving from pure fundamental work towards applications as more complex samples need to be analyzed.
Medium‐Energy Backscattering and Forward‐Recoil Spectrometry
Authors: Weller Robert A.
Published: October 2012

Medium‐energy backscattering spectrometry is a variation of Rutherford backscattering spectrometry (RBS) using ions with energies ranging from a few tens to a few hundreds of kilo‐electron‐volts. The ion beam, frequently He+, is directed onto a specimen and the number of backscattered ions per incident ion is measured as a function of scattered‐ion energy at one or more angles relative to the beam direction. The fundamental physical process being used is that of a binary collision between the nuclei of an ion in the beam and a near‐stationary atom in the target. In such a collision, the energy of the backscattered ion is determined uniquely by its original energy, the scattering angle (which is the angle between the ion's trajectories before and after the collision), and the ratio of the masses. Consequently, a measurement of the energy of a backscattered ion at a specific angle may be used to infer the mass of the target atom with which it collided. The number of backscattered ions is proportional to the collision cross‐section and the total number of available scattering centers. Since collision cross‐sections are known a priori in this energy range, the number of backscattered ions with a given energy is a direct measure of the number of atoms of the corresponding mass in the target.

The method achieves additional richness as the result of a second physical phenomenon, the gradual loss of kinetic energy through collisions as an ion penetrates through matter. This is measured by stopping power (also called linear energy transfer), which is the average energy lost, typically in electron volts per unit of length (measured in atoms per square centimeter) of trajectory in the target. A second factor controlling the energy of backscattered ions is the depth within the target at which the collision occurs. As a result, it is usually possible to extract quantitative information about the distribution of specific species within the near‐surface region of the specimen. For the purposes of this article, it is sufficient to note that for medium‐energy ions the stopping power is dominated by collisions between the nucleus of the projectile and the electrons of the target, so‐called electronic stopping, which results in relatively uniform loss of energy with minimal angular divergence of the beam. Widely accepted semiempirical procedures are available for computing electronic stopping power.

Particle detection technology is an extremely important issue in medium‐energy ion beam analysis. This article also details time‐of‐flight spectrometry optimized for high‐resolution measurements. Other methods, including magnetic and electrostatic spectrometers, pulsed‐beam accelerator systems, and time‐of‐flight spectrometry optimized for other measurements, are discussed briefly along with several other methods for depth profiling, trace‐element identification, and hydrogen measurement. Throughout, special attention is paid to the relationship between medium‐energy backscattering and conventional high‐energy RBS.
Electrical Measurements on Superconductors by Transport
Authors: Weijers Hubertus W. , Noyes Patrick , Schwartz Justin
Published: October 2012

In this unit, we will focus on techniques for measuring the electrical behavior of technologically important superconducting wires, tapes, and other conductors. Depending on the conditions of measurement, electrical behavior can be interpreted to obtain many technologically important quantities. This article will also discuss the interpretation for some of the most common of these quantities.
Single‐CrystalX‐rayStructure Determination
Authors: Gómez Cesar Pay , Jacobson Robert A.
Published: October 2012

This article is a comprehensive guide to the basics of crystallography and structure determination. We will concentrate here on the use of x‐ray diffraction techniques as would be necessary for the conventional crystal structure investigation; that is, structures which are not twinned, incommensurate, or contain substantial amounts of disorder. A discussion of the basic principles of single‐crystal x‐ray diffraction will be presented first, followed by a discussion of the practical aspects of these techniques. In the course of this discussion, a few of the more widely used methods of overcoming the lack of measured phases, that is, the “phase problem” in crystallography, will be presented.
X‐Ray Photoelectron Spectroscopy
Authors: Weimer Jeffrey J.
Published: October 2012

X‐ray photoelectron spectroscopy (XPS) uses x‐rays of a characteristic energy (wavelength) to excite electrons from orbitals in atoms. Photoelectrons are emitted from the material and collected as a function of their exiting kinetic energy. For single‐step excitation processes, the initial binding energy of the photoelectron is related through energy conservation to its kinetic energy and the x‐ray energy. A typical XPS spectrum shows intensity of electrons as number of electrons per time versus electron binding energy. Features appear in the spectrum due to photoemission from specific binding energy states (excitation from orbitals) in the material and to interactions of the escaping photoelectrons within the material. Chemical elements give rise to peaks at defined binding energies that are from their core levels. The total, integrated photoelectron emission from a core level peak is proportional to the number of orbitals in the analysis volume. This relationship is used to quantify the relative elemental composition of the material in atom percent (at%). The binding energy positions and shapes of the core level peaks and of other excitation features can also be analyzed in detail to determine chemical state information, including oxidation states, partial charges, or hybridization of the elements. The ability to provide both quantitative elemental composition and orbital bonding state information makes XPS unique and gives rise to the additional name as electron spectroscopy for chemical analysis (ESCA).
Nuclear Magnetic Resonance: Basic Principles and Liquid State Spectroscopy
Authors: Hoffmann Markus M.
Published: October 2012

Thermogravimetric analysis (TGA) is an analytical technique for measuring changes in the mass of a material that occur in response to programmed temperature changes. The changes in the mass can be caused by a variety processes such as decomposition, degradation, sublimation, vaporization, adsorption, desorption, oxidation, and reduction. The article explains the principles of TGA and practical aspects of the method that include description of the apparatus, discussion of experimental variables, and applications. Among practical applications, a particular attention is paid to determining composition and thermal stability of materials, evaluating the kinetics of thermally stimulated processes, predicting lifetimes, and studying reactions of materials with gases. The article also addresses the issues of sample preparation as well as of basic analysis and interpretation of data. A special consideration is given to the sources of errors in the mass and temperature measurements as well as to the methods of calibrating both values.
Challenges to Structure Prediction and Structure Characterization at the Nanoscale
Authors: Glotzer Sharon C. , Keys Aaron S. , Jankowski Eric
Published: October 2012

The new revolution in nanoscience, engineering, and technology is being driven by our ability to manipulate matter at the molecular and supramolecular level to create “designer” structures. The parameter space for engineering new materials is indeed vast—structures vary drastically with small changes in interparticle interactions or with small changes to the conditions under which the material is synthesized. Computational simulation offers a means to discover the fundamental principles of how nanoscale systems of molecular building blocks self‐assemble, and how we might control the assembly process to engineer new materials.
Characterizing Micro and Nanomaterials UsingMEMSTechnology
Authors: Isono Yoshitada
Published: October 2012

Micro‐ and nanoelectromechanical system (MEMS and NEMS) technology enables the development of smart products. MEMS and NEMS are not electronic devices such as LSI circuits, but they have distinctive features as mechanical systems consisting of actuators, accelerometers, pressure sensors, optical mirrors, power generators, and micromechanical switches with structures of micro/nanometer scale. For example, the accelerometers and pressure sensors detect the elastic deformation of the microscopic structures induced by the external mechanical force acting on the devices as the change of electric resistance or capacitance. Therefore, the development of MEMS and NEMS products requires the structural design of device that ensures the reliable deformation and movement statically and dynamically. In particular, the size effect of device components on their mechanical properties has to be considered in the structural design of MEMS. As a device size is reduced, the surface effect may begin to dominate the material response. In such a case, bulk properties measured on larger specimens are no longer valid. Knowledge of mechanical properties of MEMS and NEMS materials at the scale of the practical use is essential to the design and optimization of devices. In this chapter, technical issues of typical testing methods are introduced for the mechanical characterization of micro/nanometer scale materials including thin films used in MEMS and NEMS. The mechanical characterization technique using MEMS devices as a testing tool for one‐dimensional nanowire materials is also described.
Magnetization Characterization of Superconductors
Authors: Cave J. R. , Lacroix C.
Published: October 2012

The superconducting state occurs for many elements, alloys, and compounds when cooled to sufficiently low temperatures, specifically, below the critical temperature, Tc. The initial discoveries by Onnes in 1911 and 1914 were of the loss of electrical resistance at very low temperatures and of its reestablishment by applying a strong enough magnetic field or a high enough current. A further discovery by Meissner and Ochsenfeld in 1933 was that a magnetic field could be expelled from a superconducting material as it was cooled through its Tc. This perfect diamagnetic behavior coupled with perfect conductivity led to the derivation of London equations describing the superconducting state in 1935.

At present, there are many known superconducting materials ranging from pure elements such as lead, that are superconducting at liquid helium temperatures, to complex ceramics such as YBaCuO7‐xoperating at liquid nitrogen temperatures. Also, uses of superconductors vary enormously ranging from sensitive magnetic field detectors to electric power cables. Certain engineered superconducting materials and composites can carry very high transport currents in high magnetic fields and much research at this time is being devoted to the development of commercial and also power utility applications. The characterization of these technological materials is a very important part of these activities. Here, we present some basic features of magnetization characterization of superconductors, in particular high temperature superconductors.
Electrochemical Impedance Spectroscopy
Authors: Barsukov Yevgen , Macdonald J. Ross
Published: October 2012

Electrochemical impedance spectroscopy allows access to the complete set of kinetic characteristics of electrochemical systems, such as rate constants, diffusion coefficients, and so on, in single variable‐load experiment. It is restricted to characteristics that describe system behavior in linear range of electrical excitation, for example, when it can be approximated by linear differential equations. It can be contrasted with other methods where explicitly nonlinear properties are investigated, such as cyclic voltammetry (see ChapterCyclic Voltammetry).

A common example of linear conditions is voltage excitation below 25 mV, whereV(I) dependency can be approximated as linear. Some of the parameters remain constant over a wide range of conditions, and once found under linear conditions can also be applied to model much wider ranges. An example of such parameters would be ohmic resistance of electrolyte or thickness of passivating film on the electrode.

Although impedance spectroscopy is sharing the variable‐load experimental method with many other linear excitation electrochemical techniques, its analysis method is distinct, where a time‐domain signal and response are converted to the frequency domain and their relation is found in the form of complex impedance. Complex impedance values over a range of frequencies form an impedance spectrum. Further analysis strives to derive system parameters from the impedance spectrum, typically by developing a model function connecting the impedance spectrum with system parameters and optimizing parameters to obtain a best fit to the impedance spectrum.

This article covers the basics of the experimental implementation of this technique, as well as background and mathematical approaches for developing model functions for most common systems and analysis of the experimental data to obtain system parameters.
X‐Ray Computed Tomography
Authors: Stock Stuart R.
Published: October 2012

X‐ray computed tomography (CT) is a powerful technique for noninvasively characterizing materials. This chapter covers x‐ray computed tomography (CT) in its forms spanning large components (booster rockets) to millimeter‐sized material specimens to micrometer‐sized samples. Emphasis is on contrast produced by differences in x‐ray attenuation, although CT using x‐ray phase contrast, x‐ray fluorescence, or x‐ray diffraction is also covered briefly.
Coherent Diffraction Imaging of Strain on the Nanoscale
Authors: Harder Ross
Published: October 2012

Coherent diffraction imaging (CDI) in the Bragg geometry has gained a niche in recent years for its ability to image strain in a crystalline lattice on the nanoscale. This development is based on the realization that coherently scattered x‐rays, in the vicinity of a Bragg peak of the crystalline sample, have exquisite sensitivity to distortions of the crystal lattice.

The method is dependent on the use of beams of highly brilliant x‐rays available at the third–generation synchrotrons and the new x‐ray–free electron lasers. There are several instruments at these facilities capable of such measurements. Argonne National Laboratory in the United States hosts such an instrument at the Advanced Photon Source.

Computational algorithms are used to retrieve the phases lost in the measurement of the coherently scattered x‐rays and, subsequently, produce the images of the sample. These algorithms are a subject of intense development and in many cases are carefully tuned to a specific application. Phase retrieval for Bragg CDI data will be described in some detail, but similar principles are implemented in all forms of CDI.
Fluctuation Electron Microscopy
Authors: Voyles Paul , Hwang Jinwoo
Published: October 2012

Fluctuation electron microscopy (FEM) is a nanodiffraction technique for measuring nanometer scale order in amorphous materials. Either dark‐field transmission electron microscope imaging or coherent electron nanodiffraction in a scanning transmission electron microscope is used to measure the diffracted intensity from the sample with nanometer spatial resolution. Fluctuations in that intensity from place to place on the sample reveal the size, density, and internal atomic arrangements of nanometer‐scale order. Nanometer scale order in glasses is also called medium‐range order (MRO). Fluctuation microscopy is one of the few experimental techniques sensitive to this type of structure in amorphous materials.
Charged‐Particle Irradiation for Neutron Radiation Damage Studies
Authors: Fluss Michael J. , Hosemann Peter , Marian Jaime
Published: October 2012

The use of energetic charged‐particles are a useful experimental method for producing and studying radiation damage. In addition to producing displacement damage via Coulomb‐moderated ballistic collisions, charged‐particles can also be used to implant specific elements thus changing the chemical and compositional nature of the target material. Charged particle beam studies of radiation damage result in specimens that are usually not any more radioactive than prior to the irradiation. The specific aspect of charged‐particle irradiations that makes them a powerful tool for studying the physics of radiation damage accumulation is the high displacement and implantation rates and that the experimenter can vary important variables of the radiation environment. These include the energy and mass of the charged‐particle, the atomic number of the ion, the temperature, the dose and dose rate, and the mechanical stress of the specimen under test. Experiments can be designed to identify and understand the key mechanisms of radiation damage accumulation. Most importantly, the understanding gained from such experiments can inform and validate models that are then used to make science‐based predictions about material performance under other radiation conditions such as those encountered in a fission reactor or as might be expected in a fusion reactor. Particularly, useful examples of charged‐particle irradiation studies are those experiments that follow the growth of helium bubbles and cavities resulting from the combination of helium implantation and displacement damage
Electrostatic Force Microscopy And Kelvin Probe Force Microscopy
Authors: Sadewasser Sascha , Barth Clemens
Published: October 2012

Studying electrostatic and electronic surface properties such as work function (WF) or local charge phenomena is of high importance not only in surface physics and chemistry, but also in materials science and related fields. Electrostatic force microscopy (EFM) and Kelvin probe force microscopy (KPFM) give access to these properties providing resolution on the nanometer lateral length scale, which explains their large success in science.

Both techniques are based on noncontact atomic force microscopy (nc‐AFM) and use an applied bias voltage to excite a cantilever oscillation, whose amplitude depends on the electrostatic force interaction between the AFM tip and the sample. The EFM directly measures this electrostatic force; however, KPFM uses a compensation technique to allow quantitative determination of the local surface potential. A commonly used method is to apply a static (dc) and alternating (ac) voltage between the tip and surface such that the electrostatic tip–surface interaction is modulated, which greatly helps in detecting small electrostatic forces. Two working modes can be used: the
amplitude modulation
mode is directly sensitive to the electrostatic force, while the
frequency modulation
mode detects the electrostatic force gradient. The methods can be applied to a variety of samples. For instance, on conducting surfaces such as metal and semiconductor surfaces the contact potential difference (CPD) is measured, which represents the WF difference between the tip and sample. An image of the CPD reflects variations of the surface WF at the nanometer scale—an important surface property for any field of research. On the other hand, information about the local charge or dipole distribution is also obtained, which is of utmost importance if insulators are considered.

This article gives an introduction into the principles and practical aspects of the EFM and KPFM techniques and provides a number of application examples.
Scanning Near‐Field Optical Microscopy
Authors: Beversluis Michael R. , Stranick Stephan J.
Published: October 2012

This article describes the setup and use of scanning near‐field optical microscopes for use in nanometer scale material imaging and characterization. We describe the concepts behind near‐field imaging that allow the technique to reach spatial resolution far below the diffraction limit of conventional optical microscopy.
Atomic Excitation Exploited By Energetic‐Beam Characterization Methods
Authors: Jeynes C. , Grime G. W.
Published: October 2012

Many disparate methods of compositional analysis of materials are underpinned by the same fundamental atomic processes: the excitation of the electronic system of the atoms followed by its subsequent relaxation. These methods include the electron spectroscopies (XPS, AES) used for surface studies, the electron microscopies used for elemental and structural characterization (SEM using EDS and WDX; TEM using EELS), and the X‐ray methods (XRF, XAS) and ion beam analysis (PIXE) used for elemental and chemical characterization. All rely on measuring the characteristic energy absorbed or emitted by the unknown target atom when its electronic system is excited by ionization due to charged particles or electromagnetic radiation. This excitation is defined by the energy levels of the atomic electrons, determined primarily by the atomic number of the atom. (Atoms can also be excited without ionization, as in optical and infrared spectroscopy: this is outside the scope of this article.)

The theoretical description of the electronic structure of atoms is a major intellectual triumph of the twentieth century and this body of knowledge is exploited in the theoretical description of each of these methods, but the treatment of any particular method is usually presented by specialists in that method in isolation from all others. In this article we present a brief synthetic overview of materials analysis using atomic excitation, highlighting those features and physical concepts that underpin all these apparently disparate analysis methods. We hope to encourage modern analysts to appreciate the truly complementary nature of the powerful methods at their disposal.
Neutron Reflectometry*
Authors: Fritzsche Helmut
Published: October 2012

Neutron reflectometry (NR) is a versatile technique that has been used in a wide range of research activities in physics, chemistry, biology, and materials science. Specular NR determines the profile of the atomic density and magnetization along the surface normal with nanometer resolution. Therefore, NR experiments address scientific phenomena occurring at the nanoscale, that is, at the surface or interfaces of single thin films or multilayered structures with thicknesses usually in the range from 1 to 100 nm. This provides a brief introduction into the theoretical and practical aspects of specular NR for the nonexpert. A list of references of typical NR experiments covering a wide range of scientific problems is given to help researchers in how NR could be applied to solve scientific problems in their own area of expertise. A few NR experiments are discussed in more detail to showcase the unique capabilities of NR.
Enzyme Kinetics of Drug‐Metabolizing Reactions and Drug–Drug Interactions
Authors: Kramer Melissa A. , Tracy Timothy S.
Published: October 2012

In vitrostudies play an important role in characterizing biotransformation reactions. Kinetic parameters are determined during the early phases of drug discovery and development and provide invaluable information needed to predictin vivometabolism and assess potential interactions with enzyme effectors. In order to obtain reliable and accuratein vitrodata that reflect thein vivosituation, one must employ well‐defined enzyme kinetic practices and reaction conditions. There are multiple factors to consider when conductingin vitrokinetic experiments such as enzyme concentration, addition of co‐substrates, buffering systems, and the effects that each of these may have on the experimental results. Of equal importance is to be aware of the potential caveats that may lead to erroneous results. An overview of the appropriate experimental conditions for kinetic studies is described, as well an explanation of which kinetic model is most appropriate when describing the kinetic results.

Kinetic characterizations of most enzymatic reactions are governed by hyperbolic kinetics that can be described by the Michaelis–Menten equation. In some instances, atypical kinetic profiles have been observed. Atypical kinetics may result from multiple substrate molecules occupying the enzyme active site simultaneously. An overview of the fundamental concepts underlying both typical and atypical kinetic analysis is provided. In addition, the graphical representation and interpretation of the data is reviewed.

In summary, the focus of this chapter is on general enzyme kinetic principles. These principles are presented in the context of defining drug metabolic clearance and drug inhibition potential. It is our hope to provide valuable insight into the complexities ofin vitrokinetics and the many challenges that surround quantitative prediction in drug metabolism.
Solute Carrier (SLC) Family Transporters
Authors: Sahi Jasminder , Lai Yurong , Lee Caroline
Published: October 2012

Xenobiotic transporters are required evaluated by the European and US regulatory agencies for the substrate and inhibition potential of drug candidates, due to the contribution of these to drug‐drug interactions. Interactions involving membrane transporters can alter the blood concentration time profiles of drugs, leading to altered levels of co‐administered drugs. Transporters play a role in toxicities, as inhibition of transporter activity could lead to increased drug concentrations or inhibition clearance of endogenous and exogenous substrates. While the SLC transporter family includes over 300 membrane bound transporters, less than 20 of these are currently considered relevant to drug related interactions. Of these, just eight are recommended by the regulatory agencies ‐ the ABC efflux transporters P‐gp and BCRP and the SLC uptake transporters OATP1B1, OATP1B3, OCT1 and BSEP which are hepatic, and the renal transporters OAT1, OAT3 and OCT2. This chapter discusses the major families of the SLC transporters that are involved in drug transport and provide information on structures, activities, substrates, inhibitors and genetic polymorphisms. Different in vitro and in vivo preclinical models are also discussed, so as to provide a more holistic view of these studies.
Mass Balance Studies in Animals and Humans
Authors: Lin Tsuhan , Heimbach Tycho , Gollen Rakesh , He Handan
Published: October 2012

Before first‐in‐human (FIH) studies with a new drug candidate, preclinical studies need to be conducted to fulfill regulatory requirements or to facilitate regulatory approval. In the United States, investigational new drug (IND) applications with the Food and Drug Administration (FDA) may include IND enabling studies, such as (i)
in vitro
and
in vivo
pharmacology studies for intended use, (ii) toxicology studies supporting the starting dose and duration of an FIH study (such as single‐ or multiple‐dose studies in one rodent and nonrodent species with toxicokinetics, genotoxicity battery, safety pharmacology battery), (iii) single‐dose pharmacokinetics (PKs) in one rodent and nonrodent species, (iv)
in vitro
plasma protein binding in relevant species, and (v)
in vitro
cross species metabolism study in relevant species. While not mandatory for IND submissions, comprehensive preclinical absorption, distribution, metabolism, and excretion (ADME) studies, including biotransformation or metabolite profiling, conventional mass balance, or tissue distribution by quantitative whole‐body autoradiography (QWBA) studies can make a submission package more compelling for progression toward phase I clinical studies. Typically, preclinical ADME together with mass balance studies are recommended before conducting human ADME and mass balance studies, which are generally initiated after the successful synthesis of the radiolabeled drug. For preclinical ADME species, the selection of doses is often based on pre‐existing toxicity information and targeted therapeutic doses. For human ADME studies, which include the evaluation of mass balance, a relevant dose in the anticipated therapeutic range is typically chosen. Conventional mass balance studies only allow the calculation of mass recovery and PK parameters of the radiolabeled drug by quantification of the radioactivity present in excreta such as urine, feces, or bile. Nowadays, these mass balance studies are often conducted as part of more comprehensive ADME studies, where additional information is obtained, including (i) PK properties of the drug and its metabolite(s) in blood or plasma; (ii) absorption estimates via plasma/blood data, urinary data, or fecal data; (iii) elimination pathways and drug metabolism; (iv) total drug exposure and its metabolites in different organs and tissues at different time intervals. In this chapter, fundamental scientific considerations for the successful design, conduct, and interpretation of conventional, basic mass balance and more comprehensive ADME studies are reviewed and discussed.