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Chip‑Based Genotyping by Mass Spectrometry

This chapter appears in the following book:

Integrated Biochips for DNA Analysis

Edited by: Robin Hui Liu and Abraham P. Lee
ISBN: 978-0-387-76758-1
» Get more information about this book at landesbioscience.com «

Chapter authors:
Kai Tang


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DNA analysis by mass spectrometry has the advantage of being the most accurate method for genotyping. Since the mass of molecular ions is measured and each allele has its own intrinsic mass, this method provides direct readout of allele types without the need for any labeling. Coupled with different chip‑based platforms, it has also become one of the highest throughput and most accurate quantitative methods for determining allele frequency. Matrix‑assisted laser desorption/ionization (MALDI) time‑of‑flight mass spectrometry (TOFMS) is the most commonly used genotyping method. Silicon chips have been used as a sample positioning and concentration device for MALDI‑MS. Alternatively, it can also be functionalized and used as a capturing device for DNA template. Subsequent enzymatic reactions and MALDI‑MS can be performed on the chip surface. Electrospray ionization (ESI) has also been used for genotyping, mainly for the analysis of microsatellites. It could also be coupled with chip‑based nano‑electrospray nozzles to increase sensitivity and throughput.

Kai Tang
School of Biological Sciences, Nanyang Technological University

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