Flexible microelectrode array for interfacing with the surface of neural ganglia

Sperry, Zachariah; Na, Kyounghwan; Parizi, Saman Salemizadeh; Chiel, Hillel J.; Seymour, John P.; Yoon, Euisik; Bruns, Tim M.

doi:10.1088/1741-2552/aab55f

Cited by 31 publications

(37 citation statements)

References 67 publications

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“…A flexible electrode array was fabricated broadly as we and others have described 33,54 . One layer of 2.2 µm-thick polyimide (PI-2610 from HD Microsystems) was spin-coated on a sacrificial layer and fully cured at 350˚C.…”

Section: Polymer Array Fabricationmentioning

confidence: 99%

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Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

Sperry

et al. 2018

Preprint

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The ability to deliver highly compliant biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural engineering.Bioelectronic devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of interest. We demonstrate that a novel diamond shuttle can deliver ultra-compliant polymer microelectrodes to intraneural structures with the smallest cross-sectional area and dimpling reported to date. This was demonstrated in vivo through rat dura mater and feline dura and dorsal root epineurium. The dorsal root ganglia are an especially relevant target for organ function and pain research, and unlike dura mater over the brain, its outer membrane cannot be removed surgically. We present a method of creating a unique diamond shuttle, only 11 microns thick with a T-beam vertical support, that pierces dura and epineurium. This T-beam structure reduced the cross-sectional area of the shuttle by 58% relative to an equivalently stiff silicon shuttle. We also discovered that higher frequency oscillation of the shuttle, at 200 Hz, significantly reduced tissue compression regardless of the insertion speed, while slow speeds independently also reduced tissue compression. Finally, we demonstrate the shuttle delivery of and neural recordings from ultra-fine, flexible arrays (5-µm thick, 65-µm wide) with 60 microelectrodes in a 1.2-mm span from different neural targets. This novel microelectrode shuttle has a large design space making it suitable for research in a variety of central and peripheral nervous system targets and animal models. IntroductionImplantable sensor arrays, especially when deployed in neural mapping studies, are most accurate and insightful when damage and disruption to nervous system circuitry is minimized. Minimizing damage and reactivity has been emphasized by recent global initiatives including the BRAIN Initiative, the NIH SPARC program, the GSK Innovation Challenge, and several DARPA funding programs, which have supported the development of new technology for mapping, monitoring, and/or controlling the nervous system with higher fidelity and longevity. Previous work demonstrated that size of an implant effects the neuron count and several glia markers of reactivity 12 . A precise implant size to tissue damage function is still missing, but evidence suggests that care should be taken to minimize the damage to blood vessels which densely permeate nervous tissue 3,4 . Central nervous system (CNS) neurons, for example, are located within ~15 µm of a capillary vessel 5-7 so damage to the blood-brain barrier is unavoidable.When designing an implantable device, the penetrating structure must be stiff enough to reach the desired target with accuracy and, more challenging, piercing a tough fibrous outer membrane protecting the neurons.These challenges have opposing solutions -make the device as fine as possible for minimal bleeding and cellular disruption, yet ens...

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Section: Polymer Array Fabricationmentioning

confidence: 99%

“…All steps were approved by the University of Michigan Institutional Animal Care and Use Committee (IACUC; protocol PRO00007296). As described elsewhere 54…”

Section: In Vivo Experiment Feline Drgmentioning

confidence: 99%

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

Sperry

et al. 2018

Preprint

Self Cite

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“…With more precise information on sensory inputs, both conventional intracellular electrophysiological approaches (in reduced and semiintact preparations) and modern alternatives, such as multi-unit and implantable recording electrodes (e.g. Cullins andChiel, 2010, 2010;Hanein et al, 2002;Lu et al, 2013;Saha et al, 2013;Sperry et al, 2018), can be used to unravel the neural circuits that integrate sensory information to control locomotion. Just like the slugs and snails, the field of research may be relatively slow, but much is afoot.…”

Section: Prospectivementioning

confidence: 99%

Olfactory navigation in aquatic gastropods

Wyeth

2019

Journal of Experimental Biology

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Gastropod diversity is substantial in marine and freshwater habitats, and many aquatic slugs and snails use olfactory cues to guide their navigation behaviour. Examples include finding prey or avoiding predators based on kairomones, or finding potential mates using pheromones. Here, I review the diversity of navigational behaviours studied across the major aquatic taxa of gastropods. I then synthesize evidence for the different theoretical navigation strategies the animals may use. It is likely that gastropods regularly use either chemotaxis or odour-gated rheotaxis (or both) during olfactory-based navigation. Finally, I collate the patchwork of research conducted on relevant proximate mechanisms that could produce navigation behaviours. Although the tractability of several gastropod species for neurophysiological experimentation has generated some valuable insight into how turning behaviour is triggered by contact chemoreception, there remain many substantial gaps in our understanding for how navigation relative to more distant odour sources is controlled in gastropods. These gaps include little information on the chemoreceptors and mechanoreceptors (for detecting flow) found in the peripheral nervous system and the central (or peripheral) processing circuits that integrate that sensory input. In contrast, past studies do provide information on motor neurons that control the effectors that produce crawling (both forward locomotion and turning). Thus, there is plenty of scope for further research on olfactory-based navigation, exploiting the tractability of gastropods for neuroethology to better understand how the nervous system processes chemosensory input to generate movement towards or away from distant odour sources.

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“…[17] Aiming to biomedical applications, the flexibility of the electrodes becomes an essential factor to minimize the mechanical mismatch at the interface and guarantee an effective coupling. [5] In this line, a series of flexible electrodes have been proposed, [18][19][20] but only a few combine flexibility with nanostructure. [21,22,23] For instance, Rogers and colleagues described a bio-interfaced system based on ultrathin electronics supported by bioresorbable substrates of silk fibroin, [18] which assures minimal stresses on the tissue and highly conformal coverage.…”

Section: Introductionmentioning

confidence: 99%

Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features

et al. 2020

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Understanding neural physiopathology requires advances in nanotechnology‐based interfaces, engineered to monitor the functional state of mammalian nervous cells. Such interfaces typically contain nanometer‐size features for stimulation and recording as in cell‐non‐invasive extracellular microelectrode arrays. In such devices, it turns crucial to understand specific interactions of neural cells with physicochemical features of electrodes, which could be designed to optimize performance. Herein, versatile flexible nanostructured electrodes covered by arrays of metallic nanowires are fabricated and used to investigate the role of chemical composition and nanotopography on rat brain cells in vitro. By using Au and Ni as exemplary materials, nanostructure and chemical composition are demonstrated to play major roles in the interaction of neural cells with electrodes. Nanostructured devices are interfaced to rat embryonic cortical cells and postnatal hippocampal neurons forming synaptic circuits. It is shown that Au‐based electrodes behave similarly to controls. Contrarily, Ni‐based nanostructured electrodes increase cell survival, boost neuronal differentiation, and reduce glial cells with respect to flat counterparts. Nonetheless, Au‐based electrodes perform superiorly compared to Ni‐based ones. Under electrical stimulation, Au‐based nanostructured substrates evoke intracellular calcium dynamics compatible with neural networks activation. These studies highlight the opportunity for these electrodes to excite a silent neural network by direct neuronal membranes depolarization.

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Flexible microelectrode array for interfacing with the surface of neural ganglia

Abstract: Overall, the GSEA has been shown to provide a variety of information types from ganglia neurons and to have significant potential as a tool for neural mapping and interfacing.

Cited by 31 publications

References 67 publications

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

Olfactory navigation in aquatic gastropods

Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features

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