A Dual-Function Micropatterned Gold Platform for Cell Patterning and Optical Imaging Applications.

How can we reliably study cellular interactions and molecular responses in well-defined microenvironments while maintaining compatibility with high-sensitivity optical imaging techniques? Addressing this question is critical for understanding tissue development, disease progression, and cellular heterogeneity. Despite the promise of Raman spectroscopy for label-free molecular analysis, a major bottleneck lies in the lack of platforms that combine precise spatial control of cell placement with seamless integration into optical workflows. Here, we present CELLPAC a high-throughput, biocompatible cell-patterning platform that integrates micropatterned gold substrates, self-assembled PEG monolayers, and c-RGD peptides to create microscale adhesive domains for controlled cell confinement. CELLPAC enables the localization and co-localization of single or multiple human keratinocytes into tailored geometric patterns, supporting detailed studies of intercellular communication and migration. Crucially, the platform's gold component supports surface-enhanced Raman spectroscopy (SERS), and our measurements reveal ~3-fold signal enhancement for intrinsic cellular biomolecules. This dual functionality allows CELLPAC to not only direct cell behavior with high spatial fidelity but also to probe associated molecular processes. With its modular design and optical compatibility, CELLPAC provides a versatile foundation for studying curvature-guided migration, biochemical signaling, and other microenvironment-dependent cell responses advancing biomedical research in areas such as tissue engineering, drug screening, and biosensing.