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High throughput screening of complex biological samples with mass spectrometry – from bulk measurements to single cell analysis

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Abstract

High throughput screening (HTS) of molecular analytes is in high demand from and implemented in many areas of chemistry, medicine and industrial biotechnology including the discovery of biomarkers and the development of new chemical entities. Despite its prevalence, technical challenges remain in many of the new application areas of HTS which require rapid results from complex mixtures, for example in: screening biotransformations; targeted metabolomics; and in locating drugs and/or metabolites in biological matrices. Common to all of these are lengthy and costly sample preparation stages, involving recovery from cell cultures, extractions followed by low throughput LC-MS/MS methods or specific fluorescence measurements. In the latter the target molecules need to be inherently fluorescent or to include a fluorescent label or tag which can adversely influence a cellular system. Direct infusion mass spectrometry coupled with robotic sample infusion is a viable contender for information rich HTS with sub-second analysis times, and recent developments in ambient ionisation have heralded a new era where screening can be performed on crude cell lysates or even from live cells. Besides commercially available technologies such as RapidFire, Acoustic Mist Ionisation, and the TriVersa ChipMate there are promising new developments from academic groups. Novel applications using desorption electrospray ionisation, microfluidics, rapid LC-separation and ‘one cell’ direct infusion methods offer much potential for increasing throughput from ‘messy’ complex samples and for significantly reducing the amount of material that needs to be analysed. Here we review recent advances in HTS coupled with MS with an emphasis on methods that reduce or remove all sample preparation and will facilitate single cell screening approaches.

Graphical abstract: High throughput screening of complex biological samples with mass spectrometry – from bulk measurements to single cell analysis

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Publication details

The article was received on 30 Jul 2018, accepted on 08 Dec 2018 and first published on 10 Dec 2018


Article type: Critical Review
DOI: 10.1039/C8AN01448E
Citation: Analyst, 2019, Advance Article
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    High throughput screening of complex biological samples with mass spectrometry – from bulk measurements to single cell analysis

    E. E. Kempa, K. A. Hollywood, C. A. Smith and P. E. Barran, Analyst, 2019, Advance Article , DOI: 10.1039/C8AN01448E

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