This book highlights the application of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for high-resolution surface analysis and characterization of materials. While providing a brief overview of the principles of SIMS, it also provides examples of how dual-beam ToF-SIMS is used to investigate a range of materials systems and properties. Over the years, SIMS instrumentation has dramatically changed since the earliest secondary ion mass spectrometers were first developed. Instruments were once dedicated to either the depth profiling of materials using high-ion-beam currents to analyse near surface to bulk regions of materials (dynamic SIMS), or time-of-flight instruments that produced complex mass spectra of the very outer-most surface of samples, using very low-beam currents (static SIMS). Now, with the development of dual-beam instruments these two very distinct fields now overlap.

Time of flight secondary ion mass spectrometry, TOF-SIMS, is a highly surface sensitive analytical technique that can provide information about composition with submicron lateral resolution for a wide variety of materials. In conjunction with the latest cluster ion sources, organic depth profiling is also commonly performed now. For select materials, TOF-SIMS provides unparalleled sensitivity along with excellent reproducibility, and as a mass spectrometric technique, it also provides excellent specificity in the identification of many organic materials. Of the analytical methods available, it is among the most surface sensitive, but the physical principles that underlie it are also the least understood. This volume describes the instrumentation, the physical principles behind the technique to the extent they are understood, and provides a practical approach for the interpretation of TOF-SIMS data. The use of advanced data processing methods such as multivariate statistics are described in a readily approachable manner along with guidelines to help the reader understand where they are or are not really helpful. Given a basic background in undergraduate chemistry and physics, the book will be of use to any student with an interest in the technique. While the analyses are in fact performed in a vacuum, they are conducted in the context of a wider laboratory environment where many other analytical methods are available. The place of TOF-SIMS amongst them, when it is appropriate to use this method or another, or when multiple methods should be used in conjunction with TOF-SIMS is discussed in some depth. Examples of the wide range of applications of TOF-SIMS for research and problem solving in Academic Laboratories, National Laboratories, and Industrial laboratories, as it is applied to polymeric, biological, semiconductor, metallic, insulating, homogeneous, and inhomogeneous surfaces are described.

This book provides an overview of the phenomenology, technology and application of secondary ion mass spectrometry as a technique for materials analysis. This approach is developing into one of the most effective methods of characterizing the composition and chemical state of the surface and sub-surface layers of solid materials. The first three chapters introduce the basic physical and chemical principles involved and the theories which have been proposed to explain the process. Subsequent chapters describe the instrumental components of the SIMS apparatus, the use of SIMS as an analytical tool, and the development of the techniques of sputtered neutral mass spectrometry and laser microprobe and plasma desorption mass spectrometry. Many practical examples are featured to illustrate the application of SIMS to real problems, possible pitfalls are pointed out, and data of use to analysts are collected in appendices. The book is a practical guide suitable for scientists in all fields who wish to use this valuable analytical technique.

In this work the chemical analysis of biological cells and tissues with time-of-flight secondary ion mass spectrometry (ToF-SIMS) was explored. ToF-SIMS has the ability to obtain a mass spectrum with submicron spatial resolution for imaging and is extremely surface sensitive. ToF-SIMS for biological sample analysis is still an emerging field, so the development and characterization of novel sample preparation and analysis methods is key to acquiring useable information. In this work, three different methods to prepare NIH/3T3 fibroblasts were investigated: chemically fixed, freeze-dried and frozen-hydrated. Chemical fixation followed by rinsing removed a majority of intracellular Cl-, improving the secondary ion yields of all organic positively charged secondary ions an average of 2.6x. Damage cross sections were reduced during frozen-hydrated analysis, improving the secondary ion yields of higher mass organic fragments. In a separate experiment, accurate 3D reconstructions of NIH/3T3 fibroblasts were produced. A simple z-correction was applied to the data cube, and the biggest assumption for that correction was validated. An intracellular lipid-rich region surrounding the nucleus was visualized. ToF-SIMS applied to two different breast cancer systems. In the first, eight human breast cancer cell lines were distinguished from one another using mass spectra and principal component analysis (PCA). Not only was PCA to distinguish the cell lines form one another, it also highlighted the largest sources of variance between the cells. Phosphocholine, fatty acids, cholesterol and diacylglycerols (DAGs) were identified as key peaks. The identification of these species indicate that differences in lipid metabolism play an important role in separating the cell types from one another. Breast cancer tumor tissues were also investigated. Data from four tumors was collected. PCA applied to the spectra distinguished the four tissues from one another. Imaging PCA determined the largest sources of variance within an analysis area. Structures were identified by PCA that matched structures observed in serial-sectioned, conventionally-stained slices, and other domains that were not visible in the conventionally-stained slices. As with the breast cancer cell lines, phosphocholine, fatty acids, DAGs, cholesterol and vitamin were found to be large sources of variance, indicating lipid metabolism plays in important role in tumor differentiation.