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A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening

Acceleration and unification of drug discovery is important to reduce the effort and cost of new drug development. Diverse chemical and biological conditions, specialized infrastructure and incompatibility between existing analytical methods with high-throughput, nanoliter scale chemistry make the w...

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Autores principales: Benz, Maximilian, Asperger, Arndt, Hamester, Meike, Welle, Alexander, Heissler, Stefan, Levkin, Pavel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589500/
https://www.ncbi.nlm.nih.gov/pubmed/33106489
http://dx.doi.org/10.1038/s41467-020-19040-0
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author Benz, Maximilian
Asperger, Arndt
Hamester, Meike
Welle, Alexander
Heissler, Stefan
Levkin, Pavel A.
author_facet Benz, Maximilian
Asperger, Arndt
Hamester, Meike
Welle, Alexander
Heissler, Stefan
Levkin, Pavel A.
author_sort Benz, Maximilian
collection PubMed
description Acceleration and unification of drug discovery is important to reduce the effort and cost of new drug development. Diverse chemical and biological conditions, specialized infrastructure and incompatibility between existing analytical methods with high-throughput, nanoliter scale chemistry make the whole drug discovery process lengthy and expensive. Here, we demonstrate a chemBIOS platform combining on-chip chemical synthesis, characterization and biological screening. We developed a dendrimer-based surface patterning that enables the generation of high-density nanodroplet arrays for both organic and aqueous liquids. Each droplet (among > 50,000 droplets per plate) functions as an individual, spatially separated nanovessel, that can be used for solution-based synthesis or analytical assays. An additional indium-tin oxide coating enables ultra-fast on-chip detection down to the attomole per droplet by matrix-assisted laser desorption/ionization mass spectrometry. The excellent optical properties of the chemBIOS platform allow for on-chip characterization and in-situ reaction monitoring in the ultraviolet, visible (on-chip UV-Vis spectroscopy and optical microscopy) and infrared (on-chip IR spectroscopy) regions. The platform is compatible with various cell-biological screenings, which opens new avenues in the fields of high-throughput synthesis and drug discovery.
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spelling pubmed-75895002020-11-10 A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening Benz, Maximilian Asperger, Arndt Hamester, Meike Welle, Alexander Heissler, Stefan Levkin, Pavel A. Nat Commun Article Acceleration and unification of drug discovery is important to reduce the effort and cost of new drug development. Diverse chemical and biological conditions, specialized infrastructure and incompatibility between existing analytical methods with high-throughput, nanoliter scale chemistry make the whole drug discovery process lengthy and expensive. Here, we demonstrate a chemBIOS platform combining on-chip chemical synthesis, characterization and biological screening. We developed a dendrimer-based surface patterning that enables the generation of high-density nanodroplet arrays for both organic and aqueous liquids. Each droplet (among > 50,000 droplets per plate) functions as an individual, spatially separated nanovessel, that can be used for solution-based synthesis or analytical assays. An additional indium-tin oxide coating enables ultra-fast on-chip detection down to the attomole per droplet by matrix-assisted laser desorption/ionization mass spectrometry. The excellent optical properties of the chemBIOS platform allow for on-chip characterization and in-situ reaction monitoring in the ultraviolet, visible (on-chip UV-Vis spectroscopy and optical microscopy) and infrared (on-chip IR spectroscopy) regions. The platform is compatible with various cell-biological screenings, which opens new avenues in the fields of high-throughput synthesis and drug discovery. Nature Publishing Group UK 2020-10-26 /pmc/articles/PMC7589500/ /pubmed/33106489 http://dx.doi.org/10.1038/s41467-020-19040-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Benz, Maximilian
Asperger, Arndt
Hamester, Meike
Welle, Alexander
Heissler, Stefan
Levkin, Pavel A.
A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
title A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
title_full A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
title_fullStr A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
title_full_unstemmed A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
title_short A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
title_sort combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589500/
https://www.ncbi.nlm.nih.gov/pubmed/33106489
http://dx.doi.org/10.1038/s41467-020-19040-0
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