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Chip-Based Nanoelectrospray LC/MS Analysis of Biological Samples

presented by

Jack Henion
CEO, Advion BioSciences

May 10, 2005

Pfizer-La Jolla,
CB2 Room 1110 Large Training Room


Background:

Jack Henion is Emeritus Professor of Toxicology at Cornell University where he was a member of the College of Veterinary Medicine since 1976. During his tenure at Cornell Professor Henion conducted research and explored applications in many areas of liquid chromatography/mass spectrometry (LC/MS) and related areas using atmospheric pressure ionization (API) sources. Dr. Henion is Chairman, President, and CEO of Advion BioSciences, Inc., a premier contract research organization that provides LC/MS/MS services and products to the pharmaceutical industry. Advion also has developed and marketed a novel microfabricated chip and associated robot called the NanoMate 400, which it commercialized in mid 2002. This novel product combination offers automated nanoelectrospray mass spectrometry for applications in proteomics and small molecule drug haracterization.


Dr. Henion has received two Doctor Honoris Causa (Honorary Doctorate) degrees in recognition of his international reputation in modern analytical techniques. One is from the University of Ghent, Belgium for his work in trace residue analysis in biological samples, and the other was awarded in May, 2000 from the University of Uppsala, Sweden in recognition of his research in modern LC/MS/MS bioanalytical techniques. In the Spring of 2001 Prof. Henion was recognized as the College of Science outstanding alumnus of the year from the Rochester Institute of Technology where he received his MS degree in analytical organic chemistry in 1967. In the Fall of 2003 Prof. Henion received the Martin Medal for his contributions to the separation sciences coupled with mass spectrometry.

Abstract:

Electrospray mass spectrometry has provided major advances and opportunities for the analytical determination of small and large molecule compounds. This unique ionization mode coupled with on-line LC/MS and LC/MS/MS techniques has essentially revolutionized the bioanalytical sciences. There are now new developments that can provide high-quality analytical data with simpler strategies and faster analytical results. This lecture will describe a novel chip-based commercially available system that delivers this capability.


Recently there have been reports on the miniaturization of analytical techniques. Although the promise of a true ?lab-on-a-chip? system has not yet enjoyed widespread commercialization, important developments are occurring that could lead to this capability. An important analytical opportunity exists if we apply miniaturization techniques to electrospray mass spectrometry. This lecture will present an off-the-shelf commercial example of chip-based nanoelectrospray LC/MS and related techniques that can provide a strategy for rapid, high-quality mass spectrometric analyses of biological samples.


The system described is a chip-based array of 400 microfabricated nanoelectrospray nozzles etched in a silicon substrate. This microfabricated ?chip? is accommodated by a robot (NanoMate HD) which serves to interface the modern world of multi-well plates to the ?ESI Chip? for fully automated nanoelectrospray LC/MS analysis of biological samples. In addition, the same device provides on-line prefractionation of HPLC samples while simultaneously acquiring LC/MS data wherein collected fractions in the ?stored chromatogram? may be subsequently interrogated via infusion signal averaging techniques to obtain high-quality qualitative or quantitative analytical information.


This presentation will summarize the strategies and opportunities afforded by this new approach and present several applications involving small and large molecules that are of interest in pharmaceutical studies.

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