Ian Wilson
Imperial College London
Bio: Ian Wilson trained as a biochemist at the University of Manchester Institute of Science and Technology, going on to a PhD at Keele University on insect moulting hormones. After this he worked in the Pharmaceutical industry, most recently as a Senior Principal Scientist in the Dept of Drug Metabolism and Pharmacokinetics at the AstraZeneca Research site at Alderley Park in Cheshire (UK), joining Imperial College in 2012. He is the author, or co-author, of some 480 papers or reviews, and has received a number of awards in separation and analytical science from the Royal Society of Chemistry, including the Gold Medal of the Analytical Division (2005) and most recently the Knox Medal of the RSC Separation Science Group (2012). He received the Jubilee Medal of the Chromatographic Society in 1994 and gave the inaugural Desty Memorial lecture for Innovation in Separation Science in1996. His research is directed towards the development of hyphenated techniques in chromatography and their application to problems in drug metabolism, toxicology and metabonomics
| Short Abstract For the discovery of biomarkers via MS and LC/MS-based metabolic phenotyping (metabotyping) studies employing untargeted metabonomic/metabolomic methods there is always a tension between maximising throughput and obtaining the most comprehensive metabolic profiles possible. In particular, rapid profiling methods can suffer from ion suppression, leading to analytes being missed, whilst “deep” profiling is time consuming. The introduction of ultra (high) performance LC provided a significant improvement in efficiency and enabled many more metabolites to be detected per unit time compared to conventional HPLC. This presentation will explore further advances resulting from the use of miniaturisation and the combination of U(H)PLC-MS with ion mobility spectrometry (IMS) to enhance the efficiency of metabotyping for both rapid and comprehensive profiling approaches. |
Long Abstract
For the discovery of biomarkers via MS and LC/MS-based metabolic phenotyping (metabotyping) studies employing untargeted metabonomic/metabolomic methods there is always a tension between maximising throughput and obtaining the most comprehensive metabolic profiles. Previously we have described the benefits of moving from 2.1 mm i.d. UHPLC columns for routine metabotyping experiments [1], together with the advantages of adopting a rapid analysis miniaturized metabolic phenotyping (RAMMP) approach in order to increase throughput [2]. In addition to these steps we have now begun to incorporate ion mobility spectrometry (IMS), in a UHPLC/IMS/MS configuration, to maximise feature detection in such experiments [3]. Here the effect of varying both column length (between 30 and 150mm) and the time taken to perform gradient elution (from 3 to 12 min respectively) on the number of features detected when analysing complex biological samples such as urine. As would be expected, and as we have previously shown, a reduction in column length from 150 to 30 mm, and shorter gradients significantly reduces peak capacity with the number of features detected falling from over ca. 16000 to ca. 6500 for a human urine sample. However, the introduction of IMS, thereby providing an additional orthogonal separation, resulted in an increase in the number of MS features detected to nearly ca. 20,000 and ca. 7500 for the 150 mm and the 30 mm columns respectively, for the same chromatographic conditions. Clearly there is significant potential for LC/IMS/MS to be used as a tool for improving throughput and increasing metabolome coverage and both of these possibilities will be illustrated via examples of applications to biological fluids.
References
[1] High-Throughput Microbore UPLC–MS Metabolic Phenotyping of Urine for Large-Scale Epidemiology Studies. Gray N, Lewis M.R, Plumb R.S, Wilson I.D, Nicholson J.K. J. Proteome Res., 14 (2015) 2714–2721.
[2] Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies Nicola Gray, Kyrillos Adesina-Georgiadis, Elena Chekmeneva, Robert S. Plumb, Ian D. Wilson, Jeremy K. Nicholson. Analytical Chemistry, 88 (2016) 5742−5751.
[3] Ion Mobility Spectrometry Combined With Ultra Performance Liquid Chromatography/ Mass Spectrometry For Metabolic Phenotyping of Urine: Effects of Column Length, Gradient Duration and Ion Mobility Spectrometry on Metabolite Detection. Paul D Rainville, Ian D Wilson, Jeremy K Nicholson3 Giorgis Issacs, Lauren Mullin, James I Langridge, Robert S Plumb. Analytica Chimca Acta, in press, 2017
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