In situ graphene-seq: spatial transcriptomics and chronic electrophysiological characterization of tissue microenvironments
2026-06-19
Biological systems comprise diverse, interconnected cell types whose functional dynamics and molecular identities are tightly coupled, yet difficult to capture simultaneously at high spatiotemporal resolution. Electrophysiology provides real-time measurements of cellular activity but with limited molecular context, whereas transcriptomics profiles gene expression without dynamic physiological readouts. Here, we introduce in situ graphene-sequencing, a platform that integrates chronic electrophysiology with imaging-based, spatially resolved transcriptomics. The system combines stretchable mesh nanoelectronics for long-term, single-cell-level interfacing with transparent graphene/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate electrodes, enabling seamless integration of electrical recording and optical imaging. By coupling electrophysiology with high-throughput, imaging-based in situ sequencing, the platform enables multimodal analysis of heterogeneous tissue microenvironments. We demonstrate in situ graphene-sequencing by charting multimodal profiles of human-induced pluripotent stem cell-derived cardiomyocyte and endothelial cell co-cultures, examining how spatial heterogeneity is associated with electrophysiological activity and gene expression. This approach provides an integrative framework for studying how tissue microenvironments shape cell behavior and molecular states.