bioRxiv Science⌕ Search

Biology subjects

Shepard, K.

Publications and source records attributed to Shepard, K..

5 recordsLinked to original sources

A Fully Endovascular Neural Interface

Electrical stimulation of neural circuits is expanding therapeutic strategies to modulate brain, autonomic, and immune functions. Devices delivered endovascularly offer a less invasive alternative to conventional implanted electrodes, while delivering spatio-temporal specificity superior to noninvasive techniques. We demonstrate a fully endovascular sub-1-mm3 implant, utilizing ultrasound for wireless power delivery and data telemetry in a fashion invariant to device orientation. The implant consists of piezoelectric transducers, an energy storage capacitor, an application-specific integrated circuit, and electrodes packaged on a 7-{micro}m-thick polyimide scaffold. The implant can be delivered through a microcatheter in a manner analogous to conventional neurovascular stents, and self-expands upon deployment to appose the vessel walls. We demonstrate intravascular stimulation of the autonomic nervous system from the carotid artery, achieving modulation of blood pressure in rabbits. This approach establishes a broadly applicable platform for neural interfaces enabling both stimulation and recording.

neuroscience↗

Cell-scale autonomous CMOS motes for intracellular bioelectronics

Integrating autonomous electronics within single cells has remained beyond the reach of modern bioelectronics. Miniaturization at this scale could transform our ability to study and actuate biological processes at the cellular level, complementing existing molecular and fluorescent approaches. As these devices approach the sub-100-{micro}m length scale, volumetric constraints demand fundamentally new approaches to power delivery and telemetry. Here, we report an optically powered 10-picoliter complementary metal oxide semiconductor (CMOS) mote that operates with a power density of 1 pW/pL, comparable to the metabolic rate of cellular systems. These fully CMOS motes can be manufactured at scale yielding 1000 motes from a 4-mm2 silicon die. Multiple motes can be simultaneously powered and interrogated within a single optical field of view using epifluorescence microscopy. We demonstrate intracellular implantation of these motes within the single-celled mixotrophic dinoflagellate Noctiluca scintillans with negligible cytoplasmic displacement, pushing the boundaries of active CMOS bioelectronics to the intracellular domain and establishing a next-generation of truly cell-scale bioelectronic interfaces TeaserA 10-pL autonomous CMOS mote with fluorescence-based backscatter communication enables cell-scale sensing.

bioengineering↗

Ultralight Solar Transmitter Enables Fine-Scale Movement Ecology in North American Hummingbird Migration

O_LIDue to attachment weight limitations, animals under 5g have remained a major methodological barrier in movement ecology, limiting tracking options for many small-bodied organisms. C_LIO_LIWe developed and field-tested an ultra-light solar powered transmitter (Bl[u]Morpho 0.058-0.060g) designed to enable continuous, near real-time tracking using a broad, crowd sourced network. C_LIO_LIWe validated the system on two North American hummingbird species during spring migration, demonstrating reliable detection, multi-week retention, broad spatial coverage (United States, Mexico and Canada), and long-distance migration paths including a 6,526km cumulative track. C_LIO_LIOur results highlight the ability to track the smallest of species across the full migratory range with fine-scale spatial resolution and high temporal resolution using the Bl[u]Morpho transmitter. Importantly, we present the first migratory tracks known to exist on North American hummingbird species. C_LI Data/Code for peer review statementsR Code used for all analyses is attached for peer review.

ecology↗

Wearable, High-Density, Time-Domain Diffuse Optical Tomography Array for Functional Neuroimaging

Noninvasive functional neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), are essential tools for understanding brain activity and cognition for various neurological and mental health conditions. While fMRI offers high spatial resolution, its limited temporal resolution and costly large-form-factor restricts its accessibility and practicality for many applications. In contrast, EEG is more affordable and portable but has limited spatial resolution. In the present study, we overcome the limitations of existing neuroimaging technologies with the development of Micro-DOT, a functional near-infrared spectroscopy (fNIRS) system capable of high-density, time-domain diffuse optical tomography (HD-TD-DOT). Micro-DOT tackles the tradeoff between form factor and spatial resolution that has been a longstanding issue with existing fNIRS systems through the use of a unique hardware architecture that arrays HD-TD-DOT-capable electronics directly at the tissue surface. This is made possible with complementary-metal-oxide-semiconductor (CMOS) source-detector chiplets that contain all the electronics and optics necessary for HD-TD-DOT operation, and can be mounted on flexible polyimide packaging with a very minimal footprint. Pairing these hardware innovations with an advanced volumetric reconstruction software, Micro-DOT achieves in-plane spatial resolution, depth resolution, and localization accuracy comparable to fMRI, while maintaining the wearable form factor and portability of EEG, making it a viable stand-alone system for measuring subject-specific brain activation.

neuroscience↗

SARS-CoV-2 envelope-protein corruption of homeostatic signaling mechanisms in mammalian cells

During a SARS-CoV2 infection, host cells produce large amounts of the viral envelope protein (Ep-CoV2). Ep-CoV2 is partially inserted into the membrane of nascent viral particles and into cellular membranes. To mimic the pathophysiological impact of the cellular protein fraction, Ep-CoV2 was overexpressed in mammalian cells and effects on key signaling parameters were monitored. By tagging with green fluorescent protein (GFP), we found that Ep-CoV2 protein is mostly present in the endoplasmic reticulum with additional trace amounts in the plasma membrane. We observed that wild-type Ep-CoV2 and, to a lesser extent, its mutants (N15A, V25F) corrupted some of the most important homeostatic mechanisms in cells. The same was observed with isolated transmembrane domains of the protein. The Ep-CoV2-evoked elevation of intracellular Ca2+ and pH as well as the induced membrane depolarization produced by the presence of the protein interfere with major signal transduction cascades in host cells. These functions of Ep-CoV2, which likely contribute to the pathogenesis of the viral protein, result from the ion-channel activity of the viral protein. Two independent assays, a functional reconstitution of Ep-CoV2 protein in artificial membranes and a rescue of K+-deficient yeast mutants, confirm that Ep-CoV2 generates a cation-conducting channel with a low unitary conductance and a complex ion selectivity. The data presented here suggest that specific channel function inhibitors of Ep-CoV2 can provide cell protection and virostatic effects.

pathology↗