Virtual Overlay Staining With Plasmonic Oligomer Metasurface

Abstract

We here present a label-free virtual staining technique using plasmonic oligomer metasurfaces fabricated through a scalable, lithography-free method. This approach enables morphological analysis of cells with enhanced colorful contrast based on refractive index differences between the cells and their surrounding medium. Unlike conventional methods that rely on molecular dyes and regularly patterned plasmonic structures, our technique employs electrostatic nanoparticle assembly to rapidly create oligomeric plasmonic arrays across an entire wafer. These oligomers provide far-reaching optical near-field enhancement, exceeding 30nm, approximately 10 times greater than that provided by monomeric nanoparticles, allowing for the visualization of cellular components located above the cellular membrane. This advancement not only simplifies the imaging process but also opens new avenues for label-free cellular imaging, offering significant potential for broader applications in biological imaging and diagnostics. © 2026 The Author(s). Small published by Wiley-VCH GmbH.