Imaging mass spectrometry: fundamentals and applications to drug discovery
ABSTRACT Imaging mass spectrometry (IMS) encompasses a variety of techniques that enable the chemical imaging of analytes, which range in size from atoms and small molecules to intact proteins, directly from biological tissues. IMS is transforming specific areas in biological research with its unique combination of chemical and spatial information. Innovations in instrumentation and imaging protocols will make this approach invaluable at many stages of the drug discovery process, including pharmacological target screening and evaluating the distribution of drug and drug metabolites in cells and tissues. The fundamentals and unique methodology of IMS are discussed, along with exciting new applications to drug discovery science.
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ABSTRACT: In order to detect different substances present in a sample, mass spectrometry is an important option that can be used to answer that question. Thus this method is a standard technique in analytical chemistry laboratories. As the name indicates, mass spectrometers are used for obtaining information about the mass of the sample, in general the mass of its molecules. In all the different techniques and variations of mass spectrometry, ions of the sample are accelerated with help of specially tailored electrical fields and then separated by different means in their mass to charge ratio. One very important method of mass separation is the Time-of-Flight technique (TOF-MS). In this chapter, the development of Time-of-Flight mass spectrometers in recent years regarding their instrumental improvements as well as regarding their applications will be described.Advances in Imaging and Electron Physics, Edited by Peter W. Hawkes, 04/2015: chapter Two: pages 25-78; , ISBN: 978-0-12-802254-2
International Journal of Mass Spectrometry 02/2015; 377:681-689. DOI:10.1016/j.ijms.2014.06.025 · 2.23 Impact Factor
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ABSTRACT: RationaleThere are currently multiple methods available for the preparation of fresh frozen tissue samples for analysis via matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) imaging mass spectrometry (IMS). Although these methods report excellent results, many are expensive automated approaches. With no published attempt to standardise less expensive manual processes, our work aims to provide a robust and repeatable method of sample preparation for MALDI-TOF-IMS that is applicable to a variety of tissue types, well explained, simple and cost effective.Methods Fresh frozen tissue was sectioned at 12 µm and mounted onto liquid nitrocellulose coated slides, washed in a graded alcohol series and then mounted into a modified sublimation apparatus. Matrix is deposited onto the slide to achieve a desired coating of 0.2 mg/cm2. Once coated, the slide is mounted into a custom-built vapor chamber and recrystallised with 50% acetonitrile (ACN), 0.1% trifluoroacetic acid (TFA) for 1 h at 37°C. The slide is then analysed using MALDI-IMS.ResultsWe have successfully implemented this method for a host of tissue samples, including brain, liver, kidney and heart, with no variation in relative spectra or processing method required. When the protocol is followed correctly, sublimations and recrystallisations are highly predictable with limited variation between samples and a very low failure rate. Additional apparatuses can be easily constructed by following the included instructions, that perform as per specifications with no variation.Conclusions We believe that we have described a complete protocol for MALDI-IMS that is easy to use and highly reproducible. The lack of expensive commercially available equipment makes this process very cheap with a relatively low initial outlay and our hope is that more laboratories will begin IMS-based avenues of research based on the work we have performed. Copyright © 2015 John Wiley & Sons, Ltd.Rapid Communications in Mass Spectrometry 04/2015; 29(7). DOI:10.1002/rcm.7138 · 2.64 Impact Factor