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.

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.