MALDI MS
A Practical Guide to Instrumentation, Methods, and Applications

Franz Hillenkamp and Jasna Peter Katalinic, eds.

ALDI (matrix-assisted laser desorption ionization) is a technique that uses laser ablation of a sample-coated target to vaporize molecules for injection into a mass spectrometer. The advantages of MALDI are its gentleness compared to electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), and the fact that MALDI produces mostly singly-charged ions. This means that fragile biomolecules such as proteins can produce a single peak without being fragmented.

Although MALDI can be used on ion traps, it's a bad match because of their limited mass range: ion traps can't detect ions with masses above 2000 Da or so, while masses below 500 Da are not detectable because of saturation by MALDI matrix ions. MALDI is better suited for TOF mass spectrometers. However, most current-generation TOF machines have a limited dynamic range. They typically use only 8-bit A/D converters, which means that only 256 possible peak intensities are possible. Coupled with the inherent variability of laser desorption, signal suppression caused by other sample components, and the huge variabilities (up to 1000×) in the ionization efficiency of different molecules, this means that MALDI mass spectrometry is almost exclusively a qualitative tool, even when isotopic coding is used. As one author points out, no MALDI-MS protein profiling method has yet been validated for clinical studies. This is probably because of the great difficulty in obtaining reliable quantitative results with such machines. Even so, MALDI can be useful in molecule identification and structural studies, where accurate measurements aren't so important.

MALDI MS: A Practical Guide is a collection of nine comprehensive chapters, each written by a different expert in the field. It provides a good basic understanding of the technology for researchers contemplating the use of MALDI in their experiments. Chapters give overviews of the uses of MALDI for analyzing proteins, nucleic acids, glycans, lipids, small molecules, and synthetic polymers. The publication quality is excellent, with clear diagrams and color photos throughout. However, except in the chapter on nucleic acids, most of the authors are too optimistic about the usefulness of MALDI. Like mass spec salesmen, the authors give glowing descriptions of the benefits of MALDI MS while downplaying the many problems and disadvantages. Purchasing a MALDI-ion trap or even a MALDI-FT-ICR machine would be a big mistake for most protein laboratories, yet the reader would have to read carefully between the lines to recognize this.

Another problem with mass spectrometers, including those that use MALDI, is the low level of certainty of identification of biomolecules, especially in real-world biological samples, which may contain hundreds or thousands of other molecules, each accompanied by numerous fragmentation peaks. This is a particular problem for low-resolution instruments like ion traps. Unlike ESI, MALDI cannot be coupled to an LC to assist such overburdened machines in analyzing complex samples. Although this critical fact is mentioned, once again it's glossed over.

Another problem with this book is that specific instruments are only mentioned in passing. This may be understandable, considering that the current crop of instruments will probably be consigned to the scrap heap within a few years, but most readers would expect more specifics in a book with the phrase "practical guide to instrumentation" in the title. This is also not a methods book. Specific procedures for using or calibrating a MALDI mass spectrometer are not discussed. Special techniques, such as ion loss, post-source decay and mass spec imaging, are only mentioned in passing or in brief chapters. Therefore, this book won't be much help to someone already struggling to learn how to use a MALDI mass spectrometer. However, it gives a pretty good executive overview of the capabilities of MALDI for someone trying to decide whether MALDI is worth investing in. The only caveat is, you have to supply your own skepticism.