A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
| Autor: | Benz, Maximilian, Asperger, Arndt, Hamester, Meike, Welle, Alexander, Heissler, Stefan, Levkin, Pavel A. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Dendrimers
Technology Lab-on-a-chip Cell Survival Science High-throughput screening Drug Evaluation Preclinical Tin Compounds Article Combinatorial libraries Cell Line High-Throughput Screening Assays Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization 2019-023-027909 Humans Drug discovery and development lcsh:Q ToF-SIMS lcsh:Science ddc:600 |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020) Nature Communications, 11 (1), Art.Nr. 5391 Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-19040-0 |
| Popis: | 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. On-chip synthesis and screening has been used to automate drug discovery but on-chip analysis still remains a major limitation. Here, the authors report on a dendrimer-based surface patterning method to create nanodroplet arrays on materials which allow for on-chip high-throughput analysis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|