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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 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.

SUBMITTER: Gonzales DL

PROVIDER: S-EPMC5500410 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays.

Gonzales Daniel L DL Badhiwala Krishna N KN Vercosa Daniel G DG Avants Benjamin W BW Liu Zheng Z Zhong Weiwei W Robinson Jacob T JT

Nature nanotechnology 20170417 7

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 fi ...[more]

PMID: 28416816

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Project description:The number of people aged 12 years and older using illicit drugs reached 59.3 million in 2020, among which 5.2 million are cocaine users based on the national data. In order to fully understand cocaine addiction and develop effective therapies, a tool is needed to reliably measure real-time cocaine concentration and neural activity in different regions of the brain with high spatial and temporal resolution. Integrated biochemical sensing devices based upon flexible microelectrode arrays (MEA) have emerged as a powerful tool for such purposes; however, MEAs suffer from undesired biofouling and inflammatory reactions, while those with immobilized biologic sensing elements experience additional failures due to biomolecule degradation. Aptasensors are powerful tools for building highly selective sensors for analytes that have been difficult to detect. In this work, DNA aptamer-based electrochemical cocaine sensors were integrated on flexible MEAs and protected with an antifouling zwitterionic poly (sulfobetaine methacrylate) (PSB) coating, in order to prevent sensors from biofouling and degradation by the host tissue. In vitro experiments showed that without the PSB coating, both adsorption of plasma protein albumin and exposure to DNase-1 enzyme have detrimental effects on sensor performance, decreasing signal amplitude and the sensitivity of the sensors. Albumin adsorption caused a 44.4% sensitivity loss, and DNase-1 exposure for 24 hr resulted in a 57.2% sensitivity reduction. The PSB coating successfully protected sensors from albumin fouling and DNase-1 enzyme digestion. In vivo tests showed that the PSB coated MEA aptasensors can detect repeated cocaine infusions in the brain for 3 hrs after implantation without sensitivity degradation. Additionally, the same MEAs can record electrophysiological signals at different tissue depths simultaneously. This novel flexible MEA with integrated cocaine sensors can serve as a valuable tool for understanding the mechanisms of cocaine addiction, while the PSB coating technology can be generalized to improve all implantable devices suffering from biofouling and inflammatory host responses.

Dataset Information

Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays.

Publications

Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays.

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