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

MALDI imaging MALDI mass spectrometry droplet microarray drug discovery fatty acid synthase miniaturized cell-based assay

Journal

Advanced biology
ISSN: 2701-0198
Titre abrégé: Adv Biol (Weinh)
Pays: Germany
ID NLM: 101775319

Informations de publication

Date de publication:
03 2021
Historique:
revised: 23 12 2020
received: 14 09 2020
entrez: 17 3 2021
pubmed: 18 3 2021
medline: 26 10 2021
Statut: ppublish

Résumé

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. Taken together, the integrated DMA-MSI platform that combines MALDI-MSI, as a label-free analytical readout, with the miniaturized droplet microarray platform is a valuable complement to high throughput cell-based assays technologies.

Identifiants

pubmed: 33729695
doi: 10.1002/adbi.202000279
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2000279

Informations de copyright

© 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH.

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Auteurs

Carina RamalloGuevara (C)

Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack Str. 10, Mannheim, 68163, Germany.

Dorothea Paulssen (D)

Karlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen, 76344, Germany.

Anna A Popova (AA)

Karlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen, 76344, Germany.

Carsten Hopf (C)

Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack Str. 10, Mannheim, 68163, Germany.

Pavel A Levkin (PA)

Karlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen, 76344, Germany.

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