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27 November 2018 Multimodal imaging and high-throughput image-processing for drug screening on living organisms on-chip
Daniel Migliozzi, Matteo Cornaglia, Laurent Mouchiroud, Virginie Uhlmann, Michael A. Unser, Johan Auwerx, Martin A. M. Gijs
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Funded by: European Union Ideas Program, EU Ideas Program, Gebert Ruf Stiftung
Journal of Biomedical Optics, Vol. 24, Issue 2, 021205 (November 2018). https://doi.org/10.1117/1.JBO.24.2.021205
Abstract
A major step for the validation of medical drugs is the screening on whole organisms, which gives the systemic information that is missing when using cellular models. Caenorhabditis elegans is a soil worm that catches the interest of researchers who study systemic physiopathology (e.g., metabolic and neurodegenerative diseases) because: (1) its large genetic homology with humans supports translational analysis; (2) worms are much easier to handle and grow in large amounts compared with rodents, for which (3) the costs and (4) the ethical concerns are substantial. Here, we demonstrate how multimodal optical imaging on such an organism can provide high-content information relevant to the drug development pipeline (e.g., mode-of-action identification, dose–response analysis), especially when combined with on-chip multiplexing capability. After designing a microfluidic array to select small separated populations of C. elegans, we combine fluorescence and bright-field imaging along with high-throughput feature recognition and signal detection to enable the identification of the mode-of-action of an antibiotic. For this purpose, we use a genetically encoded fluorescence reporter of mitochondrial stress, which we studied in living specimens during their entire development. Furthermore, we demonstrate real-time, very large field-of-view capability on multiplexed motility assays for the assessment of the dose–response relation of an anesthetic.
CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
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Daniel Migliozzi, Matteo Cornaglia, Laurent Mouchiroud, Virginie Uhlmann, Michael A. Unser, Johan Auwerx, and Martin A. M. Gijs "Multimodal imaging and high-throughput image-processing for drug screening on living organisms on-chip," Journal of Biomedical Optics 24(2), 021205 (27 November 2018). https://doi.org/10.1117/1.JBO.24.2.021205
Received: 15 March 2018; Accepted: 2 November 2018; Published: 27 November 2018
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Cited by 10 scholarly publications.
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KEYWORDS
Microfluidics
Organisms
Multimodal imaging
Luminescence
Multiplexing
Diffusion
Imaging systems
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