Time-Of-Flight Mass Spectrometry: Instrumentation and Applications in Biological Research (Acs Professional Reference Book)

Rating:
Summary: Great introduction
Review: I was looking for a quick briefing on the basics of mass spec (MS)for large biomolecules. This book did the job admirably.

Roughly the first half concentrates on the physics and chemistry(!) of MS, although there is a quick tour into protein sequencing early on. Gradually, the book's later chapters switch over to more explicit discussion of biomolecules, proteins in Ch. 10 and RNA/DNA in ch11. I was tempted to jump ahead.

I was very glad I stayed the course. Every beginning physics student knows that there's no such thing as a "measurement". It's really an interaction between the measurement tool and the material under test, in some environment - a fact that people tend to ignore. This fact is central to mass spec: the tool and the way it's used have critical consequences for the measurements that come out.

The first three chapters cover the plumbing and physics of the instruments. Chapters four through nine talk more about the many ways of preparing the ions measured by the mass spectrometer: radioactive decay products, electon beams, lasers of many colors, and more. Each energy source has a different effect on the sample, and different effects on different samples. Modern techniques dilute the sample material in a liquid or solid matrix. That's another variable: reactions between the sample and matrix, depending on energy source. Even the inert gases chosen for the instrument's interior atmosphere can change the results of a measurement.

I would have thought all these reactions were incidental annoyances, unintended degradation of the real sample. Quite the opposite. Reactions with the energy source and matrix define the kinds of chemical features that can be deduced from the MS. They are part of the analytic tool suite. For example, proteins, with generally weak UV absorption, can be handled one way. Nucleotides, with strong UV absorption, need other techniques.

Chapter ten says the most to a biologist. It goes into some detail describing what mass spec can say about proteins. The first thing in most people's minds will be protein sequence: the list of amino acids, and the order in which they occur. MS, with proper help from chemistry, handles that question well.

Other factors affect protein behavior at least as much. Insulin, a protein, can be harvested from animal sources for human use because it lacks sugar side chains. It is almost unique: other proteins fail as human medicines because, not because the animal amino acids are incompatible, but because the sugar side chains are too un-human.

MS deals quite directly with these sugar chains, as well as other chemical tweaks that have biological meaning. In fact, MS may be the most effective tool now in use for analyzing the sugar chains. This book isn't a lab manual, but gives the reader a general idea of the kinds of answers to expect from MS.

The last real chapter, DNA sequencing, decidedly dates the book (1997). DNA has too many chemical quirks to work well; MS can handle strings only a few tens of bases long. The authors hope the MS would been the sequencing tool of choice has been overtaken by technology.

In short, the book is a great intro to mass spec, and has a very effective focus on biological questions. I'm no MS specialist and never will be, but this met my needs very well.

Rating:
Summary: An Outsanding Presentation of TOF Mass Spectrometry
Review: Time-of-Flight Mass Spectrometry: Instrumentation and Applications in Biological Research Robert J. Cotter

Reviewed by: O. David Sparkman Consultant-at-Large 4045 Eagle Ridge Drive Antioch, CA 94509 510-754-5003 [e-mail]

Like Peter Dawson's Quadrupole Mass Spectrometry and Its Applications (AIP, Woodbury, NY, 1995 and Elsevier, Amsterdam, 1976) and Ray March and Richard Hughes' Quadrupole Storage Mass Spectrometry (Wiley-Interscience, New York, 1989), Bob Cotter's 12-chapter, 326-page Time-of-Flight Mass Spectrometry is destined to become one of the classic books on mass spectrometry instrumentation. The book's subtitle, Instrumentation and Applications in Biological Research, is descriptive of the two well-written and organized aspects of this book.

I received a hand-bound copy of this exceptionally well-organized book at the 1997 Pittsburgh Conference. As I made a quick review, I saw that new introductions and applications of TOF mass spectrometry at PittCon®97 were missing; and like many books recently published in the mass spectrometry field, this book would be out of date before it got into extended circulation. After careful reading of the first chapter (Overview and History), it was clear that the author anticipated such an eventuality. At the end of this chapter in a section entitled "About This Book" the author states "...attempting to describe this field, there is a considerable risk in producing a volume that will be quickly outdated. For that reason, there has been a deliberate emphasis on the basic principles of...[TOF mass spectrometry]."

Because this is a single-author book, as opposed to an edited volume with a different author for each chapter, there is a consistent flow and style of writing throughout. A unique feature is the display in highlighted boxes within the text body of equation derivations that describe the principles of TOF mass spectrometry. As the author states in the "About This Book" section of Chapter 1, this was done so these mathematical principles could be omitted by those wanting only an overview of the technology could get the essences without having to create their own abstraction. These highlighted sections make the readability very good for those with only a casual interest of TOF mass spectrometry.

The next two chapters (Time-of-Flight Mass Spectrometers and Reflectrons and Other Energy-Focusing Devices) give a clear understanding of the behavior of ions after they exit the ionization source and before they strike the detector. The importance of these ion-behavior principles to spectral acquisition rates and resolving power of the TOF instrument are clearly explained in well-written easily understood terms. From this material, it is clear as to the advantages and disadvantages of the Linear and Reflectron instruments.

There are chapters on Plasma Desorption, SIMS Instrumentation, and Laser Desorption that include the principles of operations and thoughtfully selected examples to biological applications. The chapter entitled Pulsed Extraction, Continuous Ionization, and Ion Storage Instruments reports the most current work being done in these areas, which are the reason for much of the reassurance of interest in TOF mass spectrometry - especially in chromatography/mass spectrometry hyphenated techniques.

One of the most outstanding features of TOF mass spectrometry has been in the use of post-source decay for peptide sequencing. The chapter devoted to product ion mass spectra from reflectron instruments covers this topic in detail, again with more than adequate application citations. There is also a chapter on peptides, proteins, and glycoproteins that covers peptide mapping and ladder sequencing, post translational modifications, and fragmentation methods. A separate chapter is reserved for oligonucleotides and the human genome.

The more esoteric aspects of TOF instrumentation and applications are detailed in the chapter entitled Tandem TOF and Hybrid Instruments. Time-of-Flight Mass Spectrometry is concluded with an excellent chapter entitled Summary and Future Prospects. In this chapter, the author ties together the current research in TOF mass spectrometry with continued future analytical needs of biological research.

From the historical perceptive in Chapter 1 to the perceived future predicted in Chapter 12, this book includes enough detail to give an overview of TOF mass spectrometry and enough minutia to give an in-depth understanding of the instrument technology and application of TOF mass spectrometry to current (as of later 1996) biological research.

One of the book's shortcomings is the lack of titles with journal citations. A reference work such as this should include the titles of all journal articles. There is enough white space at the end of the references found in each chapter to have included the journal article titles without having added to the number of pages. Another problem is the quality of some of the illustrations. Poor illustration quality has been pervasive in the production of mass spectrometry books by all publishers for the past several years. It appears that authors submit crude illustrations (second- or third-generation photocopies or barely legible outputs from instrument data systems) with the thought that the publisher will provide the level of graphics arts production to produce a good quality - but this is not forthcoming.

Even with some poor quality illustrations, the author and the publisher have produced a better-than-adequate book on time-of-flight mass spectrometry. The organization makes this a book that can be easily read cover-to-cover or one that is a good reference book. Anyone currently working in mass spectrometry or wanting to get a basic understanding of TOF mass spectrometry would be well served by reading this book. Mass spectrometry practitioners and teachers will definitely want this book as a reference source.