Accurate and stable chronic in vivo voltammetry enabled by a replaceable subcutaneous reference electrode

Robbins, Elaine; Castagnola, Elisa; Cui, Xiufang

doi:10.1016/j.isci.2022.104845

Cited by 12 publications

(7 citation statements)

References 82 publications

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“…Figure 4B shows the in vivo 5-HT SWV detection at PEDOT/CNT coated MEAs at one day (black) and one week (blue) post-implant in anesthetized mice, demonstrating that the PEDOT/CNT-coated MEA can stably detect tonic 5-HT for at least seven days. Though the peak amplitude is consistent along the first week of implantation, we observed a 0.03 V anodic shift in the oxidation peak during chronic experiments, which is likely caused by the de-chlorination of the chronically implanted Ag/AgCl reference electrodes, resulting in errors in the potential reading at the working electrode (Robbins et al 2022). Subcutaneous Ag/AgCl reference freshly inserted at each day of measurement will solve this problem (Robbins et al 2022).…”

Section: Resultsmentioning

confidence: 76%

“…Though the peak amplitude is consistent along the first week of implantation, we observed a 0.03 V anodic shift in the oxidation peak during chronic experiments, which is likely caused by the de-chlorination of the chronically implanted Ag/AgCl reference electrodes, resulting in errors in the potential reading at the working electrode (Robbins et al 2022). Subcutaneous Ag/AgCl reference freshly inserted at each day of measurement will solve this problem (Robbins et al 2022).…”

Section: Resultsmentioning

confidence: 76%

“…Meunier 2019;Hashemi et al 2009;Saylor et al 2019). While FSCV is effective at measuring phasic 5-HT release at fast temporal resolutions (hundreds of milliseconds (Hashemi et al 2009;Jacobs et al 2014;Keithley et al 2011;Robinson et al 2003;Saylor et al 2019)), the necessity for background subtraction has prevented its use for tonic 5-HT measurement (Carl J. Meunier 2019;Mark DeWaele 2017). Modified voltammetry techniques based on FSCV, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

Castagnola

Robbins

Krahe

et al. 2023

Preprint

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Real-time multi-channel measurements of tonic serotonin (5-HT) concentrations across different brain regions are of utmost importance to the understanding of 5-HT role in anxiety, depression, and impulse control disorders, which will improve the diagnosis and treatment of these neuropsychiatric illnesses. Chronic sampling of 5-HT is critical in tracking disease development as well as the time course of pharmacological treatments. Despite their value, in vivo chronic multi-site measurements of 5-HT have not been reported. To fill this technological gap, we batch fabricated implantable glassy carbon (GC) microelectrode arrays (MEAs) on a flexible SU-8 substrate to provide an electrochemically stable and biocompatible device/tissue interface. Then, to achieve multi-site detection of tonic 5-HT concentrations, we incorporated the poly(3,4-ethylenedioxythiophene)/functionalized carbon nanotube (PEDOT/CNT) coating on the GC microelectrodes in combination with a new square wave voltammetry (SWV) approach, optimized for selective 5-HT measurement. In vitro, the PEDOT/CNT coated GC microelectrodes achieved high sensitivity towards 5-HT, good fouling resistance in the presence of 5-HT, and excellent selectivity towards the most common neurochemical interferents. In vivo, our PEDOT/CNT-coated GC MEAs were able to successfully detect basal 5-HT concentrations at different locations of the CA2 hippocampal region of mice in both anesthetized and awake head-fixed conditions. Furthermore, the implanted PEDOT/CNT-coated MEA achieved stable detection of tonic 5-HT concentrations for one week. Finally, histology data in the hippocampus shows reduced tissue damage and inflammatory responses compared to stiff silicon probes. To the best of our knowledge, this PEDOT/CNT-coated GC MEA is the first implantable flexible multisite sensor capable of chronic in vivo multi-site sensing of tonic 5-HT. This implantable MEA can be custom-designed according to specific brain region of interests and research questions, with the potential to combine electrophysiology recording and multiple analyte sensing to maximize our understanding of neurochemistry.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

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Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

Castagnola

Robbins

Krahe

et al. 2023

Preprint

Self Cite

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“…In addition, an IrO x coating is being considered as a reference electrode candidate for in vivo biosensing due to its biocompatibility [ 46 ]. Ag/AgCl reference electrodes commonly used lack the in vivo potential stability required for long-term measurements, and their cytotoxicity affects animal experiments and human implantation [ 47 , 48 ]. The biocompatibility of IrO x minimizes the disruption of proton balance to maintain constant potential [ 46 ], and the coating stability could help keep its function.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study on the Effect of Substrate Structure on Electrochemical Performance and Stability of Electrodeposited Platinum and Iridium Oxide Coatings for Neural Electrodes

Li,

Jiang,

2023

Micromachines

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Implantable electrodes are crucial for stimulation safety and recording quality of neuronal activity. To enhance their electrochemical performance, electrodeposited nanostructured platinum (nanoPt) and iridium oxide (IrOx) have been proposed due to their advantages of in situ deposition and ease of processing. However, their unstable adhesion has been a challenge in practical applications. This study investigated the electrochemical performance and stability of nanoPt and IrOx coatings on hierarchical platinum-iridium (Pt-Ir) substrates prepared by femtosecond laser, compared with the coatings on smooth Pt-Ir substrates. Ultrasonic testing, agarose gel testing, and cyclic voltammetry (CV) testing were used to evaluate the coatings’ stability. Results showed that the hierarchical Pt-Ir substrate significantly enhanced the charge-storage capacity of electrodes with both coatings to more than 330 mC/cm2, which was over 75 times that of the smooth Pt-Ir electrode. The hierarchical substrate could also reduce the cracking of nanoPt coatings after ultrasonic, agarose gel and CV testing. Although some shedding was observed in the IrOx coating on the hierarchical substrate after one hour of sonication, it showed good stability in the agarose gel and CV tests. Stable nanoPt and IrOx coatings may not only improve the electrochemical performance but also benefit the function of neurobiochemical detection.

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“…Glutamate was detected in vivo using a 3-electrode setup. The reference electrode was a silver wire coated with silver chloride inserted into the muscle of the pig near the working electrode insertion site ( 53 ). A metal retractor was utilized as a counter electrode.…”

Section: Methodsmentioning

confidence: 99%

Real-time in vivo thoracic spinal glutamate sensing reveals spinal hyperactivity during myocardial ischemia

Salavatian

Robbins

Kuwabara

et al. 2023

Preprint

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Myocardial ischemia-reperfusion (IR)-induced ventricular arrhythmias are the leading cause of death. The spinal cord neural network plays a critical role in triggering ventricular arrhythmias. Assessing the spinal neural signaling during IR is essential to develop neuromodulation therapies that target the spinal neural network. In this study, we have developed a flexible glutamate-sensing multielectrode array to evaluate the spinal cord network activity in a large animal model using amperometry. IR injury was induced by ligating the left anterior descending artery for 1 hour and releasing the ligation suture. A glutamate sensing probe was inserted into the dorsal horn of the thoracic spinal cord at the T2-T3 level which processes the neural information that is generated by the cardiac sensory neurons and provides sympathoexcitatory feedback to the heart. Using the glutamate sensing probe, we have shown that the spinal neural network is excited during the IR, particularly after 15 mins of the onset of the ischemia and it is elevated even during the reperfusion. The glutamate release signal is correlated with the reduction in the cardiac myocyte activation recovery interval which is a surrogate for the action potential duration, as well as dispersion of the repolarization which is a marker for increased risk of arrhythmias. This study illustrates a new technique that is capable of measuring the spinal glutamate at different levels of the spinal cord as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway.

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Accurate and stable chronic in vivo voltammetry enabled by a replaceable subcutaneous reference electrode

Cited by 12 publications

References 82 publications

Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

A Comparative Study on the Effect of Substrate Structure on Electrochemical Performance and Stability of Electrodeposited Platinum and Iridium Oxide Coatings for Neural Electrodes

Real-time in vivo thoracic spinal glutamate sensing reveals spinal hyperactivity during myocardial ischemia

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