Plasmonic Optical Tweezers and Surface-Enhanced Raman Spectroscopy: Fundamentals, Single-Entity Applications, and the...

The ability to manipulate and probe individual nano-particles, viruses, and organelles with high sensitivity and specificity is an essential part of modern nanoscience and molecular biology. Plasmonic optical tweezers (POT), which use localized surface plasmons to create nanoscale-confined optical fields, have emerged as a powerful platform for trapping and manipulating single nano-bio entities at low optical powers. When combined with surface-enhanced Raman spectroscopy (SERS) from the same plasmonic nanostructures, these platforms offer a unique multi-modal capability: simultaneous optical manipulation and label-free chemical fingerprinting of a single specimen. However, the field faces critical challenges, including low throughput, thermal noise, photothermal damage, and the overwhelming complexity of interpreting dynamic, single-molecule SERS data. This review examines the transformation of plasmonic optical trapping and spectroscopy as they evolve toward autonomous operation and intelligent decision-making. We begin with the fundamental principles that enable these tools to manipulate and probe single viruses, organelles, and nano-particles. Building on this foundation, we explore how computational intelligence is being integrated into the field to address long-standing challenges. This includes the emergence of data-driven methods for designing optimized plasmonic nanostructures, for decoding the complex molecular fingerprints hidden in single-molecule SERS spectra, and for creating feedback-driven systems capable of adaptive, real-time experiment control. By synthesizing these developments, we illustrate a clear trajectory: from manually operated instruments toward fully integrated intelligent nanophotonic laboratories that can autonomously discover and characterize the nano-world. We conclude by discussing the remaining challenges-from data acquisition and model interpretability to the mitigation of photothermal effects-and the most promising pathways toward realizing this transformative vision for virology, cell biology, and nanomedicine.