Biology subjects

Jones, P. D.

Publications and source records attributed to Jones, P. D..

7 recordsLinked to original sources

bioRxiv2026

A scalable mesh microelectrode array platform for longitudinal electrophysiology in neural spheroids

Electrophysiological interfacing remains difficult in three-dimensional in vitro models, when using planar microelectrode arrays or optical methods. This challenge limits experimental progress using such models, despite their promise of better physiological relevance than monolayer cell culture. Mesh MEAs which can integrate conformally on or even within tissue offer a possible solution but are not yet widely accessible. Here, we present a mesh MEA device, designed as a simple, manufacturable platform for spheroid electrophysiology. In neural spheroids, the device enabled longitudinal electrophysiological recordings and pharmacological modulation of spontaneous electrical activity. On native polyimide meshes, spheroids maintained their shape while cells enveloped the mesh, embedding electrodes to a depth of 100 {micro}m after 2 weeks. In contrast, laminin biofunctionalization of the mesh promoted outgrowth and migration of cells. This device and associated methods should be adaptable to organoids, ex vivo tissue, or bioengineered in vitro models.

neuroscience↗

bioRxiv2026

Electrophysiological profiling of hiPSC-derived neurospheres using a novel NeuroMPS with integrated electrodes

Despite advances in microphysiological systems, in vitro platforms for neuronal models remain limited by insufficient electrophysiological resolution, poor structural compatibility with 3D tissue architecture, and an inability to capture functional network dynamics alongside morphological and metabolic readouts. Here, we develop a neuromicrophysiological system (NeuroMPS) that pairs human iPSC-derived neurospheres, comprising neurons and glial cells, with tailored microelectrode arrays (MEAs) for non-invasive, high-resolution monitoring of neuronal network dynamics and functional maturation in vitro. The NeuroMPS combines a custom MEA with capped electrodes optimized for neurite-level signal detection and a glass microwell module that provides structural confinement and optical compatibility for imaging. Importantly, this configuration enables stable, longitudinal electrophysiological recordings from 3D neural constructs while supporting multimodal analyses. Following exposure to pharmacological modulators (PTX, TTX, bicuculline, CNQX, and 4-AP) and the neurotoxin rotenone, NeuroMPS detects alterations in network activity within minutes, even at the lowest concentrations tested, whereas morphological and metabolic changes emerge only at higher doses and later time points. This work provides a physiologically relevant, scalable, non-invasive platform that integrates high-sensitivity electrophysiological readouts with morphological and metabolic profiling to enable early prediction of compound-induced effects in human iPSC-derived 3D neural networks, with applications in neuropharmacology, neurotoxicology, and disease modeling.

bioengineering↗

bioRxiv2026

Nanopore event detection in a simple and adaptive way

Nanopore read-out, that is the current signals measured across nanometer-sized openings in dielectric membranes or through natural protein channels, enables the detection, identification and sequencing of individual molecules. The detection can take place by analyzing the events of single biomolecules interacting with the pore. The accuracy in the detection of these single events is key for identification of physicochemical properties of analyte molecules. To this end, we further develop a very simple, fast, almost parameter-free, and adaptable cluster-based event detection (CBED) algorithm that clusters the nanopore signals prior to detecting nanopore events. The algorithm is validated against two other event detection schemes with respect to simplicity and efficiency. For this, nanopore data from four different experiments stemming from different laboratories that vary in the nanopore type, size, and analyte are considered. The comparison is made on the basis of the number of events detected, their quality, and the most important features extracted from nanopore events. Our results underline the higher efficiency and less noise of the CBED detected events for biological nanopore data and the need for an on-the-fly adaptivity of the baseline current for a class of solid-state nanopore data.

bioinformatics↗

bioRxiv2023

A microphysiological system for parallelized morphological and electrophysiological read-out of 3D neuronal cell culture

Three-dimensional in vitro models in microfluidic systems are promising tools for studying cell biology, with complex models using multiple cell types combined with high resolution imaging. Neuronal models demand electrical readout of the activity of networks of single neurons, yet classical planar microelectrode arrays struggle to capture extracellular action potentials when neural soma are suspended distant from the microelectrodes. This study introduces sophisticated microfluidic microelectrode arrays, specifically tailored for electrophysiology of 3D neuronal cultures. Using multilayer photolithography of permanent epoxy photoresists, we developed devices having 12 independent culture modules in a convenient format. Each module has two adjacent compartments for hydrogel-based 3D cell culture, with tunnels allowing projection of neurites between compartments. Microelectrodes integrated in the tunnels record action potentials as they pass between the compartments. Mesh ceilings separate the compartments from overlying wells, allowing for simple cell seeding and later nutrient, gas and waste exchange and application of test substances. Using these devices, we have demonstrated 3D neuronal culture, including electrophysiological recording and live imaging. This microphysiological platform will enable high-throughput investigation of neuronal networks for investigation of neurological disorders, neural pharmacology and basic neuroscience. Further models could include cocultures representing multiple brain regions or innervation models of other organs.

neuroscience↗

bioRxiv2023

A flexible implant for acute intrapancreatic electrophysiology

Microelectrode arrays (MEAs) have proven to be a powerful tool to study electrophysiological processes over the last decades with most technology developed for investigation of the heart or brain. Other targets in the field of bioelectronic medicine are the peripheral nervous system and its innervation of various organs. Beyond the heart and nervous systems, the beta cells of the pancreatic islets of Langerhans generate action potentials during the production of insulin. In vitro experiments have demonstrated that their activity is a biomarker for blood glucose levels, suggesting that recording their activity in vivo could support patients suffering from diabetes mellitus with long-term automated read-out of blood glucose concentrations. Here, we present a flexible polymer-based implant having 64 low impedance microelectrodes designed to be implanted to a depth of 10 mm into the pancreas. As a first step, the implant will be used in acute experiments in pigs to explore the electrophysiological processes of the pancreas in vivo. Beyond use in the pancreas, our flexible implant and simple implantation method may also be used in other organs such as the brain.

bioengineering↗

bioRxiv2021

A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes

Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neural tissues. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell-derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.

neuroscience↗

bioRxiv2020

A mesh microelectrode array for non-invasive electrophysiology within neural organoids

Organoids are emerging in vitro models of human physiology. Neural models require the evaluation of functional activity of single cells and networks, which is best measured by microelectrode arrays. The characteristics of organoids clash with existing in vitro or in vivo microelectrode arrays. With inspiration from implantable mesh electronics and growth of organoids on polymer scaffolds, we fabricated suspended hammock-like mesh microelectrode arrays for neural organoids. We have demonstrated the growth of organoids enveloping these meshes and the culture of organoids on meshes for up to one year. Furthermore, we present proof-of-principle recordings of spontaneous electrical activity across the volume of an organoid. Our concept enables a new class of microelectrode arrays for in vitro models of three-dimensional electrically active tissue.

neuroscience↗