Serrano, R. R.-M. | Search bioRxiv

bioRxiv2025

NeuroSuite for Long-term Functional and Structural Studies of Air-Liquid Interface Cerebral Organoids

Over the past decade, air-liquid interface cerebral organoids (ALI-COs) have emerged as powerful in vitro models that capture essential structural and functional traits of the human brain, offering an exciting alternative to traditional animal models in neuroscience. Yet, the full potential of these systems has remained untapped due to the lack of non-invasive, long-term electrophysiological tools capable of preserving organoid integrity. Existing techniques, ranging from patch clamping to rigid and 3D microelectrode arrays, often compromise organoid growth and disrupt delicate cytoarchitecture. Here, we present NeuroSuite, an innovative bioelectronic platform designed to overcome these challenges. At its core is Neuroweb, a perforated, ultra-thin, and conformable organic microelectrode array engineered for minimal disruption of nutrient and oxygen exchange. Neuroweb is reusable and supports stable recordings for over six months, making it uniquely suited for longitudinal studies. Coated with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a high-performance mixed ionic-electronic conductor, Neuroweb delivers exceptional signal-to-noise ratio recordings with high spatial precision. By pairing Neuroweb with NeuroMaps, an intuitive software for interactive analysis and visualisation, NeuroSuite enables long-term, non-invasive tracking and spatial mapping of electrical activity from brain organoids and ex vivo brain slices at the air-liquid interface. Following rigorous validation, we demonstrate that NeuroSuite can capture both high- and low-frequency throughout maturation. Our pipeline reveals evolving network connectivity, including the development of GABA-ergic interneurons, and concurrent shifts in high-frequency spiking and low-frequency oscillations indicative of a refinement in the excitatory-inhibitory balance. Finally, automated data acquisition and spatial spike mapping highlight local activity changes in response to media composition, a factor often overlooked in conventional recordings. NeuroSuite thus opens a new frontier in organoid neuroscience, enabling precise, long-term monitoring essential for modelling neurological diseases, understanding human brain development, and accelerating drug discovery. TeaserConformal organic bioelectronic arrays, combined with an open-access toolbox for analysis and visualisation, reveal real-time and long-term neural dynamics in brain organoid slices at the air-liquid interface.

neuroscience↗

bioRxiv2024

Development of novel signal and spike velocity analysis tools in peripheral nerve cuffs

ObjectivePeripheral nerve neurotechnologies hold significant promise as avenues for new closed-loop clinical treatments. However, analysis tools for nerve recordings - a key component of closed-loop nerve technologies - remain underdeveloped compared to brain-focused methods. This study introduces and explores the performance of two novel nerve signal analysis techniques which rely on a defining feature of peripheral nerve signals: the reliable conduction velocity of signals transmitted by axons in nerves. ApproachWe test the capabilities of the introduced cross-correlation and spike delay velocity analysis techniques both in silico on synthetic nerve signals and on in vivo nerve signals acquired from freely-moving rats. Main resultsOur findings show that both techniques can be successfully employed to extract transmission direction and velocity information from nerve cuff recordings. Notably, cross-correlation analysis can be employed to detect neural signals of very low signal-to-noise ratio, otherwise undetectable by typical spike detection approaches. SignificanceOur findings provide new techniques to both enhance detection and extract new information in the form of velocity data from nerve recordings. As axon signal conduction direction and velocity is tightly linked to neural function, these techniques can support new research into peripheral nervous system function and new therapeutic approaches driven by neural interfaces.

neuroscience↗