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The development of three-dimensional (3D) tissues derived from single- and multi-lineage-directed human-induced pluripotent stem cells (hiPSCs) has significantly enhanced our capacity to mimic more complex cellular and physiological environments but creates new challenges for their analysis. Electrophysiology is crucial for elucidating electrical properties within neuronal and cardiac networks; however, traditional methods are poorly adapted to capturing activity throughout the 3D tissue structure, primarily due to limited spatial resolution. To address this limitation, we have developed 3D Flexible, Self-folding Microelectrode Array (FSMEA) devices comprised of a polyimide and SU-8 photoresist bilayer or an SU-8/SU-8 bilayer, which utilizes strain differences between the layers. We demonstrate that FSMEA devices can effectively record spontaneous action potentials and local field potentials in two 3D tissues, cortical organoids ranging from 800 to 1,500 µm in diameter and human elongating multi-lineage organized cardiac (EMLOC) gastruloids. These FSMEAs represent a new class of strain-based 3D MEA devices. 

The biocompatibility of materials used in electronic devices is critical for the development of implantable devices like pacemakers and neuroprosthetics, as well as in future biomanufacturing. Biocompatibility refers to the ability of these materials to interact with living cells and tissues without causing an adverse response. Therefore, it is essential to evaluate the biocompatibility of metals and semiconductor materials used in electronic devices to ensure their safe use in medical applications. Here, we evaluated the biocompatibility of a collection of diced silicon chips coated with a variety of metal thin films, interfacing them with different cell types, including murine mastocytoma cells in suspension culture, adherent NIH 3T3 fibroblasts, and human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs). All materials tested were biocompatible and showed the potential to support neural differentiation of iPSC-NPCs, creating an opportunity to use these materials in a scalable production of a range of biohybrid devices such as electronic devices to study neural behaviors and neuropathies.