Stretchable Microelectrode Arrays for Electro-Mechanical Probing of Brain Spheroids

Mechanical forces shape brain development and contribute to pathological conditions such as traumatic brain injury. However, their direct effects on neural electrophysiology remain difficult to elucidate. Here, we introduce a multimodal system capable of delivering controlled mechanical actuation to brain spheroids while simultaneously recording their spontaneous electrophysiological activity. The platform enables culturing spheroids onto kirigami-patterned stretchable thin-film microelectrode arrays over multiple days. The array reliably records spontaneous spheroid activity and sustains uniaxial mechanical stimulation with controlled elongation and speed, ranging from manual precision stretching to high-velocity impacts. We capture spheroid deformation during slow stretch (∼100 µm/s) and detect acute electrophysiological changes following high-velocity stimulation (∼1-2 m/s). This multimodal platform establishes a foundational system for systematic in vitro investigations of how mechanical forces regulate functional activity in 3D tissues.