Engineering microscale systems for fully autonomous intracellular neural interfaces

Abstract

Conventional electrodes and associated positioning systems for intracellular recording from single neurons in vitro and in vivo are large and bulky, which has largely limited their scalability. Further, acquiring successful intracellular recordings is very tedious, requiring a high degree of skill not readily achieved in a typical laboratory. We report here a robotic, MEMS-based intracellular recording system to overcome the above limitations associated with form factor, scalability, and highly skilled and tedious manual operations required for intracellular recordings. This system combines three distinct technologies: (1) novel microscale, glass-polysilicon penetrating electrode for intracellular recording; (2) electrothermal microactuators for precise microscale movement of each electrode; and (3) closed-loop control algorithm for autonomous positioning of electrode inside single neurons. Here we demonstrate the novel, fully integrated system of glass-polysilicon microelectrode, microscale actuators, and controller for autonomous intracellular recordings from single neurons in the abdominal ganglion of Aplysia californica (n = 5 cells). Consistent resting potentials (<−35 mV) and action potentials (>60 mV) were recorded after each successful penetration attempt with the controller and microactuated glass-polysilicon microelectrodes. The success rate of penetration and quality of intracellular recordings achieved using electrothermal microactuators were comparable to that of conventional positioning systems. Preliminary data from in vivo experiments in anesthetized rats show successful intracellular recordings. The MEMS-based system offers significant advantages: (1) reduction in overall size for potential use in behaving animals, (2) scalable approach to potentially realize multi-channel recordings, and (3) a viable method to fully automate measurement of intracellular recordings. This system will be evaluated in vivo in future rodent studies.

Biomedical and Tissue Engineering Strategies to Control Foreign Body Reaction to Invasive Neural Electrodes

“…Accordingly, the use of dexamethasone could be combined with tissue engineering strategies, such as substrate functionalization with biodegradable hydrogels and porous CPs, for its controlled local release in order to specifically target its activity around the implant, while reducing potential side effects caused by its systemic toxicity at too high doses. In relation to this approach, one of the first in vitro attempts to control the release of dexamethasone from a conducting polymer coating of PPy on Au electrode 2018) Lago et al, 2007;Garde et al, 2009;Mercanzini et al, 2010;Chang et al, 2013;Hassler et al, 2016;Oddo et al, 2016;Boehler et al, 2017;Delgado-Martínez et al, 2017;Wurth et al, 2017;de la Oliva et al, 2018b,c;Ji et al, 2018;Kang et al, 2019;Lee et al, 2019;Rombaut et al, 2019 Parylene C Reviewed in Fekete andPongrácz (2017) Ziegler et al, 2006;Sohal et al, 2014;Xie et al, 2014;Lecomte et al, 2017;Mueller et al, 2017;de la Oliva et al, 2018a,b;Vitale et al, 2018;Kang et al, 2019PDMS Blau et al, 2011Gao et al, 2013;Guo et al, 2014;Minev et al, 2015;Chatzimichail et al, 2018;Kumar et Poly(carboxybetaine) and pCBMA Jiang and Cao, 2010;Carr et al, 2011;Zhang et al, 2013;Trel'Ová et al, 2019 Phosphorylcholine self-assembled monolayers Chen et al, 2005 Poly(sulfobetaine) and pSBMA Reviewed in Sin et al (2014a) Jiang and...…”

“…Strategies based on microfluidic, microscale and nanoscale technologies provide scalability. They can lead from the long-term and stable neurotransmission simultaneously to many tissue points, to an enhancement of spatial selectivity stimulation, through implantable microelectrode arrays and microscale actuators ( Kozai, 2018 ; Kumar et al, 2020 ). Even more so because conventional electrodes and recording systems are bulky and unsuitable for single cell resolution.…”

Resonant scanning design and control for fast spatial sampling

“…The goal is to achieve uniform spatial sampling in a normalized Field-of-View (FoV). We use fill-factor and scanning range to characterize the spatial coverage of scanning patterns, following common usage in the literature 15 , 18 . The fill factor characterizes the spatial coverage within a normalized scanning range.…”

“…Multiple scanning pattern designs have been proposed 9 , 10 , 15 – 18 . Hwang et al proposed a frequency selection rule for high frame-rate Hz operation 15 , 16 .…”

“…These designs tend to focus on actuation frequency selection while ignoring the phase. More recent work discussed both frequency and phase in scanning pattern design 18 , but they are limited to patterns that repeat in each frame. Moreover, none of these designs considered physical constraints such as actuation signal amplitude, which are important in real-world systems.…”