Detection of cell aggregation and altered cell viability by automated label-free video microscopy: A promising alternative to endpoint viability assays in high throughput screening
2015 (English)In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 20, no 3, 372-381 p.Article in journal (Refereed) Published
Automated phase-contrast video microscopy now makes it feasible to monitor a high-throughput (HT) screening experiment in a 384-well microtiter plate format by collecting one time-lapse video per well. Being a very cost-effective and label-free monitoring method, its potential as an alternative to cell viability assays was evaluated. Three simple morphology feature extraction and comparison algorithms were developed and implemented for analysis of differentially time-evolving morphologies (DTEMs) monitored in phase-contrast microscopy videos. The most promising layout, pixel histogram hierarchy comparison (PHHC), was able to detect several compounds that did not induce any significant change in cell viability, but made the cell population appear as spheroidal cell aggregates. According to recent reports, all these compounds seem to be involved in inhibition of platelet-derived growth factor receptor (PDGFR) signaling. Thus, automated quantification of DTEM (AQDTEM) holds strong promise as an alternative or complement to viability assays in HT in vitro screening of chemical compounds.
Place, publisher, year, edition, pages
2015. Vol. 20, no 3, 372-381 p.
time-lapse microscopy, video microscopy, phase contrast microscopy, differentially time evolving morphologies, high throughput screening (HTS), cell aggregation, PDGFR signalling.
Bioinformatics (Computational Biology) Social and Clinical Pharmacy
Research subject Bioinformatics; Clinical Pharmacology
IdentifiersURN: urn:nbn:se:uu:diva-234561DOI: 10.1177/1087057114562158ISI: 000350310000007PubMedID: 25520371OAI: oai:DiVA.org:uu-234561DiVA: diva2:757066