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      Microfluidic Approaches for Manipulating, Imaging, and Screening C. elegans

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          Abstract

          The nematode C. elegans (worm) is a small invertebrate animal widely used in studies related to fundamental biological processes, disease modelling, and drug discovery. Due to their small size and transparent body, these worms are highly suitable for experimental manipulations. In recent years several microfluidic devices and platforms have been developed to accelerate worm handling, phenotypic studies and screens. Here we review major tools and briefly discuss their usage in C. elegans research.

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          Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications.

          Daniel Mark, Stefan Haeberle, Günter Roth … (2010)
          This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays (see S. Haeberle and R. Zengerle, Lab Chip, 2007, 7, 1094-1110, for an earlier review). In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the easy, fast, and cost-efficient implementation of different application-specific (bio-)chemical processes. In our review we focus on recent developments from the last decade (2000s). We start with a brief introduction into technical advances, major market segments and promising applications. We continue with a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations of every platform. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and dedicated systems for massively parallel analysis. This review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposability, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols (295 references).
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            Finding function in novel targets: C. elegans as a model organism.

            Titus Kaletta, Michael O. Hengartner (2006)
            Despite its apparent simplicity, the nematode worm Caenorhabditis elegans has developed into an important model for biomedical research, particularly in the functional characterization of novel drug targets that have been identified using genomics technologies. The cellular complexity and the conservation of disease pathways between C. elegans and higher organisms, together with the simplicity and cost-effectiveness of cultivation, make for an effective in vivo model that is amenable to whole-organism high-throughput compound screens and large-scale target validation. This review describes how C. elegans models can be used to advance our understanding of the molecular mechanisms of drug action and disease pathogenesis.
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              Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology

              Maxwell C. K. Leung, Phillip L Williams, Alexandre Benedetto … (2008)
              The nematode Caenorhabditis elegans has emerged as an important animal model in various fields including neurobiology, developmental biology, and genetics. Characteristics of this animal model that have contributed to its success include its genetic manipulability, invariant and fully described developmental program, well-characterized genome, ease of maintenance, short and prolific life cycle, and small body size. These same features have led to an increasing use of C. elegans in toxicology, both for mechanistic studies and high-throughput screening approaches. We describe some of the research that has been carried out in the areas of neurotoxicology, genetic toxicology, and environmental toxicology, as well as high-throughput experiments with C. elegans including genome-wide screening for molecular targets of toxicity and rapid toxicity assessment for new chemicals. We argue for an increased role for C. elegans in complementing other model systems in toxicological research.
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                Author and article information

                Contributors
                Manabu Tokeshi: Role: Academic Editor
                Kiichi Sato: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Micromachines (Basel)
                Journal ID (iso-abbrev): Micromachines (Basel)
                Journal ID (publisher-id): micromachines
                Title: Micromachines
                Publisher: MDPI
                ISSN (Electronic): 2072-666X
                Publication date (Electronic): 19 July 2016
                Publication date Collection: July 2016
                Volume: 7
                Issue: 7
                Electronic Location Identifier: 123
                Affiliations
                [1 ]Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
                [2 ]Department of Mechanical Engineering, York University, Toronto, ON M3J 1P3, Canada; prezai@ 123456yorku.ca
                Author notes
                [* ]Correspondence: guptab@ 123456mcmaster.ca ; Tel.: +905-525-9140 (ext. 26451)
                Article
                Publisher ID: micromachines-07-00123
                DOI: 10.3390/mi7070123
                PMC ID: 6190076
                PubMed ID: 30404296
                SO-VID: 880bbd60-c9a0-4153-ab94-ed7265b2730b
                Copyright © © 2016 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 19 April 2016
                Date accepted : 11 July 2016
                Categories
                Subject: Review

                Keywords: c. elegans,microfluidics,live imaging,electrotaxis,neurobiology,high-throughput screening,drug discovery
                Data availability:
                Keywords: c. elegans, microfluidics, live imaging, electrotaxis, neurobiology, high-throughput screening, drug discovery

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