A thermally actuated 3D foldable bioelectronic interface for multimodal electrophysiological and cytokine profiling of human spinal cord organoids.

Three-dimensional (3D) organoids provide physiologically relevant models for studying human neural development and disease; however, stable bioelectronic interfacing with curved and dynamic organoid surfaces remains challenging. Here, we present a thermally actuated, shape-memory polymer (SMP)-based foldable bioelectronic interface for simultaneous electrophysiological recording and electrochemical cytokine sensing in human spinal cord organoids (hSCOs). Near physiological temperature (36-37 °C), the SMP substrate undergoes pronounced mechanical softening, enabling conformal 3D wrapping around organoids without external mechanical compression. The platform integrates gold microelectrodes for extracellular neural recording and antibody-functionalized sensing electrodes for label-free cytokine detection. Finite element simulations and experimental mechanical analyses confirmed temperature-dependent bending, enhanced conformal contact, low interfacial stress, and mechanically stable biointerfacing. Electrochemical characterization demonstrated linear cytokine sensing responses over 1-100 ng/ml, with calculated limits of detection (LOD) of 0.44 ng/ml for TNF-α and 0.41 ng/ml for IL-8. Using this multimodal platform, stable electrophysiological recordings and cytokine monitoring were simultaneously obtained from hSCOs under inflammatory stimulation. TNF-α treatment induced dose-dependent increases in neural firing activity together with corresponding electrochemical cytokine responses. Collectively, this thermally adaptive bioelectronic interface provides a minimally invasive platform for integrated electrical and biochemical profiling of intact organoids and offers a promising tool for neuroinflammatory organoid studies.