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Fast Nanoliter-Scale Cell Assays Using Droplet Microarray–Mass Spectrometry Imaging

RamalloGuevara, Carina; Paulssen, Dorothea; Popova, Anna A.; Hopf, Carsten; Levkin, Pavel A.

Abstract:
In pharmaceutical research and development, cell‐based assays are primarily used with readout that rely on fluorescence‐based and other label‐dependent techniques for analysis of different cellular processes. Superhydrophobic–hydrophilic droplet microarrays (DMA) and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS) have recently emerged as key technologies for miniaturized high‐throughput cell assays and for label‐free molecular high‐content drug profiling, respectively. Here, nanoliter‐scale cell assays are integrated on DMAs with MALDI–MS imaging (MALDI–MSI) approaches to a droplet microarray–mass spectrometry imaging (DMA–MSI) platform. Using A549 lung cancer cells, concentration‐response profiling of a pharmaceutical compound, the fatty acid synthase inhibitor GSK2194069, are demonstrated. Direct cell culture on DMAs enables combination of microscopy and high speed, high molecular content analysis using MALDI–MSI. Miniaturization of array spots down to 0.5 mm confining 40 nL droplets allows for MALDI imaging analysis of as few as ten cells per spot. Partial automation ensures a fast sample preparation workflow. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000130340
Veröffentlicht am 12.03.2021
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 2701-0198
KITopen-ID: 1000130340
Erschienen in Advanced Biology
Verlag Wiley-VCH Verlag
Seiten Art.-Nr.: 2000279
Schlagwörter droplet microarray; drug discovery; fatty acid synthase; MALDI imaging; MALDI mass spectrometry; miniaturized cell‐based assay
Nachgewiesen in Scopus
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