Development of a Differential Interference Contrast Thermal Lens Microscope for Sensitive Individual Nanoparticle Detection in Liquid

Abstract

A thermal lens microscope (TLM) with a new principle was developed to improve the detection limit of conventional TLM. The detection limit was decreased by introducing a differential interference contrast (DIC) method which realizes background-free photodetection. The new differential interference contrast thermal lens microscope (DIC-TLM) exploits phase contrast resulting from a photothermal effect instead of refraction used in conventional TLM. In order to produce high phase contrast, we fabricated a pair of DIC prisms with a large shear value of 5 microm which is in accordance with the thermal diffusion length. First, we verified the principle of DIC-TLM. The background of TLM measurement was reduced to 1/100 by differential interference, and the signal-to-background (S/B) ratio was improved by 1 order of magnitude. The signal was confirmed to originate from phase contrast, and the expansion of the shear value was effective. Furthermore, we demonstrated counting of individual gold nanoparticles (5 nm) using DIC-TLM. The particles were counted with high signal-to-noise (S/N) ratio, and the S/N ratio was improved by 1 order of magnitude. Finally, we discuss the possibility of single molecule counting in a liquid.