Scattered Light Imaging Enables Real-Time Monitoring of Label-Free Nanoparticles and Fluorescent Biomolecules in Live Cells

Simultaneously monitoring label-free nanoparticles (NPs) and fluorescent biomolecules inside the live cell in real time is challenging because both imaging methods require different instrumentation and measuring principles. Here we report a novel scattered light imaging (SLi) technique that allows label-free NPs to be monitored using a conventional confocal microscope. The method shows a high spatial resolution and can distinguish label-free silver nanoparticles (AgNPs) with a 10 nm size difference in live cells. We performed SLi to observe the uptake, movement, distribution, and transformation of AgNPs in live cells at a single-particle level. The method is applicable to accurately track the localization of a variety of nanomaterials inside the cell. With this approach, label-free NP and fluorescent-labeled biomolecules are imaged simultaneously making it possible to real-time monitor nanobio interactions.