Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve

Ghazavi, Atefeh; González-González, María Alejandra; Romero-Ortega, Mario I.; Cogan, Stuart F.

doi:10.1016/j.bios.2020.112608

Cited by 11 publications

(8 citation statements)

References 46 publications

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“…The fact that this intraneural approach is more invasive compared to the approach of cervical VNS using cuff electrodes, however, limits this kind of study to acute investigations. Nevertheless, this approach of intraneural stimulation provides a potential improvement of acute experiments for selective cardiac VNS with recruitment of an increased number of cardiac and less off-target fibers 30,[50][51][52] .…”

Section: Discussionmentioning

confidence: 99%

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation

Kronsteiner

Haberbusch

Aigner

et al. 2023

Sci Rep

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The cardiac responses to vagus nerve stimulation (VNS) are still not fully understood, partly due to uncontrollable confounders in the in-vivo experimental condition. Therefore, an ex-vivo Langendorff-perfused rabbit heart with intact vagal innervation is proposed to study VNS in absence of cofounding anesthetic or autonomic influences. The feasibility to evoke chronotropic responses through electrical stimulation ex-vivo was studied in innervated isolated rabbit hearts (n = 6). The general nerve excitability was assessed through the ability to evoke a heart rate (HR) reduction of at least 5 bpm (physiological threshold). The excitability was quantified as the charge needed for a 10-bpm HR reduction. The results were compared to a series of in-vivo experiments rabbits (n = 5). In the ex-vivo isolated heart, the baseline HR was about 20 bpm lower than in-vivo (158 ± 11 bpm vs 181 ± 19 bpm). Overall, the nerve remained excitable for about 5 h ex-vivo. The charges required to reduce HR by 5 bpm were 9 ± 6 µC and 549 ± 370 µC, ex-vivo and in-vivo, respectively. The charges needed for a 10-bpm HR reduction, normalized to the physiological threshold were 1.78 ± 0.8 and 1.22 ± 0.1, in-vivo and ex-vivo, respectively. Overall, the viability of this ex-vivo model to study the acute cardiac effects of VNS was demonstrated.

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Section: Discussionmentioning

confidence: 99%

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation

Kronsteiner

Haberbusch

Aigner

et al. 2023

Sci Rep

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“…In this work we focused on exploring the mechanical properties of different nerve modalities, somatic with a higher number of myelinated fibers and autonomic with primarily unmyelinated fibers. The sciatic nerve is a model used to study somatic neves 24,25 , while the vagus nerve has gained attention as a main autonomic nerve connecting the brain with peripheral organs and is a main focus for neuromodulation as a treatment for bioelectronic medicine 11,13,37,38 .…”

Section: Discussionmentioning

confidence: 99%

Biomechanics Characterization of Autonomic and Somatic Nerves by High Dynamic Closed-Loop MEMS force sensing

González-González

Alemansour

Maroufi

et al. 2023

Preprint

Self Cite

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The biomechanics of peripheral nerves are determined by the blood-nerve barrier (BNB), together with the epineural barrier, extracellular matrix, and axonal composition, which maintain structural and functional stability. These elements are often ignored in the fabrication of penetrating devices, and the implant process is traumatic due to the mechanical distress, compromising the function of neuroprosthesis for sensory-motor restoration in amputees. Miniaturization of penetrating interfaces offers the unique opportunity of decoding individual nerve fibers associated to specific functions, however, a main issue for their implant is the lack of high-precision standardization of insertion forces. Current automatized electromechanical force sensors are available; however, their sensitivity and range amplitude are limited (i.e. mN), and have been tested only in-vitro. We previously developed a high-precision bi-directional micro-electromechanical force sensor, with a closed-loop mechanism (MEMS-CLFS), that while measuring with high-precision (−211.7μN to 211.5μN with a resolution of 4.74nN), can be used in alive animal. Our technology has an on-chip electrothermal displacement sensor with a shuttle beam displacement amplification mechanism, for large range and high-frequency resolution (dynamic range of 92.9 dB), which eliminates the adverse effect of flexural nonlinearity measurements, observed with other systems, and reduces the mechanical impact on delicate biological tissue. In this work, we use the MEMS-CLFS for in-vivo bidirectional measurement of biomechanics in somatic and autonomic nerves. Furthermore we define the mechanical implications of irrigation and collagen VI in the BNB, which is different for both autonomic and somatic nerves (~ 8.5-8.6 fold density of collagen VI and vasculature CD31+ in the VN vs ScN). This study allowed us to create a mathematical approach to predict insertion forces. Our data highlights the necessity of nerve-customization forces to prevent injury when implanting interfaces, and describes a high precision MEMS technology and mathematical model for their measurements.

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“…In order to fabricate 3D helical MEAs, planar spiral MEAs were first made in a cleanroom using thin film fabrication processes similar to our previously reported work [ 24 , 25 ] ( Figure 1 A.1). First, 5 µm polyimide was spin-coated on silicon wafer.…”

Section: Methodsmentioning

confidence: 99%

A Novel 3D Helical Microelectrode Array for In Vitro Extracellular Action Potential Recording

Geramifard

Lawson²,

Cogan³

et al. 2022

Micromachines

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Recent advances in cell and tissue engineering have enabled long-term three-dimensional (3D) in vitro cultures of human-derived neuronal tissues. Analogous two-dimensional (2D) tissue cultures have been used for decades in combination with substrate integrated microelectrode arrays (MEA) for pharmacological and toxicological assessments. While the phenotypic and cytoarchitectural arguments for 3D culture are clear, 3D MEA technologies are presently inadequate. This is mostly due to the technical challenge of creating vertical electrical conduction paths (or ‘traces’) using standardized biocompatible materials and fabrication techniques. Here, we have circumvented that challenge by designing and fabricating a novel helical 3D MEA comprised of polyimide, amorphous silicon carbide (a-SiC), gold/titanium, and sputtered iridium oxide films (SIROF). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) testing confirmed fully-fabricated MEAs should be capable of recording extracellular action potentials (EAPs) with high signal-to-noise ratios (SNR). We then seeded induced pluripotent stems cell (iPSC) sensory neurons (SNs) in a 3D collagen-based hydrogel integrated with the helical MEAs and recorded EAPs for up to 28 days in vitro from across the MEA volume. Importantly, this highly adaptable design does not intrinsically limit cell/tissue type, channel count, height, or total volume.

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Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve

Cited by 11 publications

References 46 publications

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation

Biomechanics Characterization of Autonomic and Somatic Nerves by High Dynamic Closed-Loop MEMS force sensing

A Novel 3D Helical Microelectrode Array for In Vitro Extracellular Action Potential Recording

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