The future of metal nanostructure optical tweezers

Abstract

Optical tweezers using metal nanostructures have leveraged extreme subwavelength focusing to circumvent the diffraction limit, enabling the isolation and label-free sensing of single nanoparticles. Over the past two decades, nanoaperture optical tweezers (NOTs) have matured into a useful tool for biophysical analysis, monitoring the conformational dynamics, binding affinities, and structural mutations of single proteins without perturbing labels or tethers. Driven by a post-machine-learning shift in biophysics toward understanding the sequence-structure-dynamics-function paradigm, NOTs have recently achieved real-time mapping of single-protein energy landscapes. Future improvements will aim to resolve the sub-microsecond protein folding dynamics by improving the signal-to-noise ratio while navigating the impacts of surface interactions and thermophoresis. This work forecasts key technical innovations over the next five years to achieve nanosecond-scale temporal resolution. By transitioning to smaller metal nanostructures (which includes moving away from nanoapertures) and operating at longer near-infrared wavelengths, near-field sensitivity can be maximized while mitigating laser-induced heating. Augmented functionalities—including integrated Raman spectroscopy (for applications like peptide identification and single-cell proteomics), and enantioselective chiral trapping will expand the utility of metal nanostructure optical tweezers. Combined with machine learning models to maximize data extraction from low signal-to-noise environments and train future predictive models on protein dynamics, these advances aim to deliver a robust platform to understand the dynamics of biomolecules.