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 commonly 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.

A flexible protruding microelectrode array for neural interfacing in bioelectronic medicine.

Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a low-invasive neural interface with highly selective, micrometer-sized electrodes. This paper reports on the development of a three-dimensional (3D) protruding thin-film microelectrode array (MEA), which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons. Cylindrical gold pillars (Ø 20 or 50 µm, ~60 µm height) were fabricated on a micromachined polyimide substrate in an electroplating process. Their sidewalls were insulated with parylene C, and their tips were optionally modified by wet etching and/or the application of a titanium nitride (TiN) coating. The microelectrodes modified by these combined techniques exhibited low impedances (~7 kΩ at 1 kHz for Ø 50 µm microelectrode with the exposed surface area of ~5000 µm²) and low intrinsic noise levels. Their functionalities were evaluated in an ex vivo pilot study with mouse retinae, in which spontaneous neuronal spikes were recorded with amplitudes of up to 66 µV. This novel process strategy for fabricating flexible, 3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine, e.g., for the control of vital digestive functions.

The noise and impedance of microelectrodes.

OBJECTIVE: While the positive correlation between impedance and noise of microelectrodes is well known, their quantitative relationship is too rarely described. Knowledge of this relationship provides useful information for both microsystems engineers and electrophysiologists. APPROACH: We discuss the physical basis of noise in recordings with microelectrodes, and compare measurements of impedance spectra to noise of microelectrodes. MAIN RESULTS: Microelectrode recordings intrinsically include thermal noise, [Formula: see text], with the real component of impedance integrated over the recording frequency band. Impedance spectroscopy allows the quantitative prediction of thermal noise. Optimization of microelectrode noise should also consider the contribution of amplifier noise. These measures enable a quantitative evaluation of microelectrodes' recording quality which is more informative than common but limited comparisons based on the impedance magnitude at 1 kHz. SIGNIFICANCE: Improved understanding of the origin of microelectrode noise will support efforts to produce smaller yet low noise microelectrodes, capable of recording from higher numbers of neurons. This tutorial is relevant for single microelectrodes, tetrodes, neural probes and microelectrode arrays, whether used in vitro or in vivo.