Bio-inspired rational design of multiscale topographical interfaces: pansy petal replicas as high-fidelity SERS platforms for single-cell analysis.

Engineering biointerfaces that provide both robust cell capture and optimal signal enhancement is a central challenge in the development of materials for cellular diagnostics. Conventional top-down fabrication methods are often complex and costly, limiting their widespread application. Here, we introduce a bio-inspired rational design strategy for creating high-performance SERS platforms for single-cell analysis. By developing a quantitative image analysis methodology, we define a surface complexity coefficient, α, which serves as a predictive metric for the cell-adhesion capacity of a given topography. We demonstrate that pansy petal replicas, identified through this strategy, possess a unique multiscale architecture ideal for erythrocyte analysis. These interfaces exhibit a synergistic interplay between high submicron complexity (α > 20) for robust cell immobilization and cell-conformable micron-scale semi-cavities (8-10 μm) that maximize the interaction area with plasmonic Au nanoparticles (∼30 nm). This optimized topography results in a 2- to 7-fold enhancement of SERS signals from individual erythrocytes compared to other floral-templated substrates. This work not only provides a scalable and cost-effective manufacturing route for advanced SERS materials but also establishes a quantitative framework for designing next-generation biointerfaces for a host of diagnostic and biomedical applications.