Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires invasive dissections and is low-throughput. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the first extracellular recordings of body-wall muscle electrophysiology inside an intact roundworm, Caenorhabditis elegans. We can also use nano-SPEARs to record from multiple animals in parallel and even from other species, such as Hydra littoralis. Furthermore, we use nano-SPEARs to establish the first electrophysiological phenotypes for C. elegans models for amyotrophic lateral sclerosis and Parkinson's disease, and show a partial rescue of the Parkinson's phenotype through drug treatment. These results demonstrate that nano-SPEARs provide the core technology for microchips that enable scalable, in vivo studies of neurobiology and neurological diseases.
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We thank C. Kemere for discussions on extracellular recordings and spectral analysis. Several strains were provided by the Caenorhabditis Genetics Center, which is funded by National Institutes of Health (NIH) Office of Research Infrastructure Programs (P40 OD010440). J. Wang provided the ALS worm strains and A. Fouad from the Fang-Yen Lab provided the YX9 animals. This work is funded by the Defense Advanced Research Projects Agency Young Faculty Award D14AP00049 (J.T.R.), NIH grant DA018341 (W.Z.) and the Hamill Foundation (J.T.R. and W.Z.). D.L.G. is funded by the National Science Foundation (NSF) Graduate Research Fellowship Program 0940902. D.L.G. and K.N.B. are funded by training fellowships from the Keck Center of the Gulf Coast Consortia on the NSF Integrative Graduate Education and Research Traineeship (IGERT): Neuroengineering from Cells to Systems 1250104. We also thank the Rice Shared Equipment Authority and the University of Houston Nanofabrication Facility where devices were fabricated.
The authors declare no competing financial interests.
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Gonzales, D., Badhiwala, K., Vercosa, D. et al. Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays. Nature Nanotech 12, 684–691 (2017). https://doi.org/10.1038/nnano.2017.55
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