Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays

Abstract

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 low-throughput and invasive dissections. 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.

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials

“…Electrodeposited gold nanoelectrodes have similarly been used for sensing and stimulating fibroblast, myotube, and neuronal assemblies . Gonzales et al recently demonstrated an interesting alternative to vertically aligned nanoelectrodes, instead fabricating horizontally orientated, high‐aspect‐ratio (25:1), suspended electrodes (named nano‐SPEARs), which they used to measure the electrophysiology of roundworms and other animals . The lateral fabrication process is notably different to the majority of other approaches in this field and has the potential to be laterally scaled across relatively large distances.…”

Rethinking the Role of the Nervous System: Lessons From the Hydra Holobiont

“…[17]). The combination of diverse in vitro techniques, such as in situ hybridization, [20] immunofluorescence, [12] and electrophysiological measurements, [21,22] and recently developed in vivo imaging [23] and behavioral recordings, [24] promises deep insights into the molecular architecture and function of the nervous system in Hydra (for review see ref. [18,19] In addition to this conventional role in coordinating motor activities, the nervous system in Hydra appears to be orchestrating other organismal functions, such as development, tissue homeostasis, and immune function.…”

Satiety, Thermosensation and Mechanosensation Regulate a Spontaneous C. elegans Sleep State

“…When confined to microfluidic chambers we found that adult C. elegans rapidly and spontaneously switch between normal activity and brief quiescent bouts without any additional stimuli ( Figure 1A). We initially observed this behavior when immobilizing worms for recording body-wall muscle electrophysiology [50]. In these electrical recordings we observed minutes-long periods of muscle inactivity that corresponded to whole-animal quiescence [50].…”

“…We initially observed this behavior when immobilizing worms for recording body-wall muscle electrophysiology [50]. In these electrical recordings we observed minutes-long periods of muscle inactivity that corresponded to whole-animal quiescence [50].…”