In Situ Graphene-Seq: Spatial Transcriptomics and Chronic Electrophysiological Characterization of Tissue...

Area of Science:

• Biotechnology
• Molecular Biology
• Systems Biology

Background:

• Understanding biological systems requires simultaneous analysis of cellular function and molecular identity.
• Current methods like electrophysiology and transcriptomics offer limited, separate insights.
• Bridging these modalities is crucial for deciphering molecular mechanisms of cellular activity.

Purpose of the Study:

• To introduce in situ graphene-sequencing (graphene-seq), an integrated platform for multimodal, high-spatiotemporal resolution analysis.
• To overcome limitations of existing approaches by combining chronic electrophysiology with imaging-based 3D transcriptomics.
• To enable comprehensive analysis of cell microenvironments within heterogeneous tissues.

Main Methods:

• Development of a platform using stretchable mesh nanoelectronics and transparent graphene/PEDOT:PSS electrodes.
• Integration of chronic electrophysiology with imaging-based, spatially resolved 3D transcriptomics.
• Validation using human-induced pluripotent stem cell-derived cardiomyocyte and endothelial cell co-cultures.

Main Results:

• Demonstration of seamless integration of electrical recordings and optical imaging for multimodal analysis.
• Characterization of multimodal profiles in co-cultures, revealing spatial heterogeneity effects.
• Successful charting of gene expression and electrophysiological activity in relation to cell composition.

Conclusions:

• In situ graphene-seq provides a scalable, integrated approach for studying cellular function and molecular identity interplay.
• The platform offers insights into how tissue microenvironments influence cell behavior and molecular states.
• This technology advances regenerative medicine, stem cell therapy, and disease modeling.