Gigantic optical non‐linearities from nanoparticle‐enhanced molecular probes with potential for selectively imaging the structure and physiology of nanometric regions in cellular systems

The requirement to functionally probe biological structures, with ever increasing selectivity and three-dimensional resolution is a frontier area in microscopy. Non-linear optics has a unique potential in this regard with numerous studies focused on the potential of three-dimensional imaging with super-resolution. In this paper we demonstrate that non-linear optical phenomena, such as second harmonic (SH) generation, which is very sensitive to the membrane potential, can be locally enhanced by complexing or approaching a SH generating molecular probe to a nanoantenna of a silver or gold nanoparticle. This gives complexes with gigantic optical non-linearities. These contrast enhancing non-linear optical complexes have the potential to be directed selectively to specific nanometric regions in cells in order to report on alterations on the structure and the function in such regions while overcoming the inherent inefficiency of non-linear optical interactions.