Plasmonic Optical Tweezers and Surface-Enhanced Raman Spectroscopy: Fundamentals, Single-Entity Applications, and the Evolving Role of Artificial Intelligence

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.