Timko, B. P. | Search bioRxiv

bioRxiv2023

An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function

We report an integrated optogenetic and bioelectronic platform for stable and long-term modulation and monitoring of cardiomyocyte function in vitro. Optogenetic inputs were achieved through expression of a photoactivatable adenylyl cyclase (bPAC), that when activated by blue light caused a dose-dependent and time-limited increase in autonomous cardiomyocyte beat rate. Bioelectronic readouts were achieved through an integrated planar multi-electrode array (MEA) that provided real-time readouts of electrophysiological activity from 32 spatially-distinct locations. Irradiation at 27 W/mm2 resulted in a ca. 14% increase in beat rate within 20-25 minutes, which remained stable for at least 2 hours. The beating rate could be cycled through repeated "on" and "off" states, and its magnitude was a monotonic function of irradiation intensity. Our integrated platform opens new avenues in bioelectronic medicine, including closedloop feedback systems, with potential applications for cardiac regulation including arrhythmia diagnosis and intervention. TeaserA system that integrates optogenetic stimulation and bioelectronic recording capabilities allows for on-demand regulation of cardiac cell function.

bioengineering↗

bioRxiv2021

Transparent and Conformal Microcoil Arrays for Spatially Selective Neuronal Activation

Micromagnetic stimulation (MS) using small, implantable microcoils is a promising modality for achieving neuronal activation with high spatial resolution and low toxicity. Microcoils can be designed to achieve localized, spatially asymmetric fields that target neurons of a particular orientation. Insulation of the coil avoids the direct contact between metal and tissue and the use of specialized biopolymers may help to further reduce chronic inflammation and glial scarring. Studies to date have largely focused on single channel devices; herein, we report the design and development of a microcoil array for localized activation of cortical neurons and retinal ganglion cells. We utilized a computational model that related the activation function to the geometry and arrangement of coils and selected a coil design that maintained a region of activation <50 {micro}m wide. The device was composed of an SU8/Cu/SU8 tri-layer structure, which was flexible, transparent and conformal and featured four individually-addressable microcoil stimulation elements. Interfaced with ex vivo cortex or retina slices from GCaMP6-transfected mice, we observed that individual neurons localized within 40 {micro}m of the element tip could be activated repeatedly and in a dose (power) dependent fashion. Taken together, these results highlight the potential of magnetic stimulation devices for brain-machine interfaces and could open new routes toward bioelectronic therapies including prosthetic vision devices.

neuroscience↗