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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.more » « lessFree, publicly-accessible full text available August 1, 2026
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