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Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening

Zhang, Xiaoxiao and Beebe, Tyler and Jen, Nelson and Lee, Chia-An and Tai, Yuchong and Hsiai, Tzung K. (2015) Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening. Biosensors and Bioelectronics, 71 . pp. 150-157. ISSN 0956-5663. PMCID PMC4457543. doi:10.1016/j.bios.2015.04.027.

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Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (µECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) ( Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young’s modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm^(−3). These innovations enabled physiological ECG telemetry in the fish’s natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24 h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for µECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery.

Item Type:Article
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URLURL TypeDescription CentralArticle
Tai, Yuchong0000-0001-8529-106X
Hsiai, Tzung K.0000-0003-1734-0792
Additional Information:© 2015 Elsevier B.V. Received 29 January 2015; Received in revised form 30 March 2015; Accepted 12 April 2015; Available online 14 April 2015. This study was supported by the National Institutes of Health: HL083015 (T.K.H., N.C.C.) and HD069305 (N.C.C., T.K.H.).
Funding AgencyGrant Number
Subject Keywords:Zebrafish; Circadian Rhythm; Flexible and waterproof multi-electrode arrays; Drug screening; Toxicity testing
PubMed Central ID:PMC4457543
Record Number:CaltechAUTHORS:20150717-091904516
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Official Citation:Xiaoxiao Zhang, Tyler Beebe, Nelson Jen, Chia-An Lee, Yuchong Tai, Tzung K. Hsiai, Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening, Biosensors and Bioelectronics, Volume 71, 15 September 2015, Pages 150-157, ISSN 0956-5663, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58916
Deposited By: Tony Diaz
Deposited On:21 Jul 2015 21:55
Last Modified:10 Nov 2021 22:12

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