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NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae

NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae
NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae
Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.
1932-6203
e64297-[17pp]
Hu, Chunxiao
4892b566-6809-42a8-8285-1c1e93aac730
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Kearn, James
f10467c2-3498-4f7f-affc-0a528252245d
Murray, Caitriona
6fcb874d-75d7-49aa-9219-8f9723d862fe
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Morgan, Hywel
de00d59f-a5a2-48c4-a99a-1d5dd7854174
Hu, Chunxiao
4892b566-6809-42a8-8285-1c1e93aac730
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Kearn, James
f10467c2-3498-4f7f-affc-0a528252245d
Murray, Caitriona
6fcb874d-75d7-49aa-9219-8f9723d862fe
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Morgan, Hywel
de00d59f-a5a2-48c4-a99a-1d5dd7854174

Hu, Chunxiao, Dillon, James, Kearn, James, Murray, Caitriona, O'Connor, Vincent, Holden-Dye, Lindy and Morgan, Hywel (2013) NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae. PLoS ONE, 8 (5), e64297-[17pp]. (doi:10.1371/journal.pone.0064297). (PMID:23717588)

Record type: Article

Abstract

Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.

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Published date: 22 May 2013
Organisations: Nanoelectronics and Nanotechnology, Centre for Biological Sciences

Identifiers

Local EPrints ID: 352078
URI: https://eprints.soton.ac.uk/id/eprint/352078
ISSN: 1932-6203
PURE UUID: 851f743b-f240-40f0-a1c9-c09c7ef2add9
ORCID for Hywel Morgan: ORCID iD orcid.org/0000-0003-4850-5676

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Date deposited: 11 Jul 2013 09:32
Last modified: 17 Sep 2019 00:52

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