Dataset Information

Flexible Fiber Probe for Efficient Neural Stimulation and Detection.

ABSTRACT: Functional probes are a leading contender for the recognition and manipulation of nervous behavior and are characterized by substantial scientific and technological potential. Despite the recent development of functional neural probes, a flexible biocompatible probe unit that allows for long-term simultaneous stimulation and signaling is still an important task. Here, a category of flexible tiny multimaterial fiber probes (<0.3 g) is described in which the metal electrodes are regularly embedded inside a biocompatible polymer fiber with a double-clad optical waveguide by thermal drawing. Significantly, this arrangement enables great improvement in mechanical properties, achieves high optical transmission (>90%), and effectively minimizes the impedance (by up to one order of magnitude) of the probe. This ability allows to realize long-term (at least 10 weeks) simultaneous optical stimulation and neural recording at the single-cell level in behaving mice with signal-to-noise ratio (SNR = 30 dB) that is more than 6 times that of the benchmark probe such as an all-polymer fiber.

SUBMITTER: Du M

PROVIDER: S-EPMC7404151 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Flexible Fiber Probe for Efficient Neural Stimulation and Detection.

Du Minghui M Huang Lu L Zheng Jiajun J Xi Yue Y Dai Yi Y Zhang Weida W Yan Wei W Tao Guangming G Qiu Jianrong J So Kwok-Fai KF Ren Chaoran C Zhou Shifeng S

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200609 15

Functional probes are a leading contender for the recognition and manipulation of nervous behavior and are characterized by substantial scientific and technological potential. Despite the recent development of functional neural probes, a flexible biocompatible probe unit that allows for long-term simultaneous stimulation and signaling is still an important task. Here, a category of flexible tiny multimaterial fiber probes (<0.3 g) is described in which the metal electrodes are regularly embedded ...[more]

PMID: 32775173

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Project description:The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits, which provides a promising approach for the study of progressive neurophysiological phenomena. Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance. However, lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness. Herein, we report a hybrid probe (Silk-Optrode) consisting of a silk protein optical fiber and multiple flexible microelectrode arrays. The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals. Silk plays an important role due to its high transparency, excellent biocompatibility, and mechanical controllability. Through the hydration of the silk optical fiber, the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue. The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses, surpassing previous work of a similar type. Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions. A silk optical fiber-based Silk-Optrode probe consisting of a natural silk optical fiber and a flexible micro/nano electrode array is reported. The multifunctional soft probe can modify its own Young's modulus through hydration to achieve accurate implantation into the brain. The low optical loss and single-unit recording abilities allow simultaneous optogenetic stimulation and multichannel readout, which expands the applications in the operation and parsing of neural circuits in behavioral animals.

Project description:Vagus nerve stimulation (VNS) is being actively explored as a treatment for multiple conditions as part of bioelectronic medicine research. Reliable and safe VNS in mouse models is a critical need for understanding mechanisms of these. We report on the development and evaluation of a microfabricated cuff electrode (MouseFlex) constructed of polyimide (PI) and with iridium oxide (IrOx) electrodes that is thermoformed to 86 µm ± 12 µm radius to interface the mouse cervical vagus nerve (r ≈ 50 µm). Innovative bench-top methods were used to evaluate the stimulation stability and electrochemical properties of electrodes. Our aggressive stimulation stability (Stim-Stab) test utilized 1 billion pulses at a 1000 Hz with a current density of 6.28 A/cm2 (1.51 mC/cm2/phase) delivering 3023 × 103 C/cm2 to evaluate electrode lifetimes, and all electrodes remained functional. We also investigated the effects of thermoforming on their impedance, charge storage capacity (CSC), and charge injection capacity (CIC). The modest changes in electrochemical properties indicate that the thermoforming process was well tolerated. Thermoformed electrode safety and efficacy were evaluated in-vivo by performing acute VNS in mice and monitoring their heart and respiration rate as biomarkers. Their electrochemical properties were also measured before, during and after VNS. Bradycardia and bradypnea were reliably induced at stimulation currents of 100 to 200 µA, well below the in-vivo CIC of ∼1250 µA (∼0.5 mC/cm2), supporting their safety and efficacy. The electrode impedance increased and CIC decreased during in-vivo use, but largely reversed these changes in in-vitro testing after enzymatic cleaning, supporting their tolerance for surgical use. STATEMENT OF SIGNIFICANCE: Vagus nerve stimulation (VNS) is a rapidly growing aspect of healthcare and bioelectronic medicine research. Reliable and safe VNS in mice with small diameter (d ≈ 100 µm) nerves has been a challenge due to achieving intimate contact with the nerve, and the stimulation stability of commonly used electrodes. We demonstrate a microfabricated (MouseFlex) cuff electrode constructed of polyimide with IrOx electrodes that is thermoformed to contact the mouse cervical vagus. Bench studies highlight the stimulation stability exceeded 109 pulses at 6.28 A/cm2 and their electrochemical properties were measured before, during, and after bench and nerve stimulation. Nerve stimulation induced bradycardia and bradypnea at currents below the in-vivo charge injection capacity, supporting their safety, efficacy, and tolerance for surgical handling.

Dataset Information

Flexible Fiber Probe for Efficient Neural Stimulation and Detection.

Publications

Flexible Fiber Probe for Efficient Neural Stimulation and Detection.

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