Nonfluorescent Molecule Detection in 10² nm Nanofluidic Channels by Photothermal Optical Diffraction

Abstract

Integrating analytical systems in 101–103 nm spaces provides ultrasensitive analytical devices at the single cell and the single molecule levels due to the ultrasmall space, and fundamental technologies for nanofluidics are developed. A simple and ultrasensitive detection method is one of the essential technologies for nanofluidics; however, it is still challenging due to the ultrasmall volume at the attoliter to femtoliter scale. In this study, we report a new photothermal detection method of nonfluorescent molecules for a 102 nm space, photothermal optical diffraction (POD), which utilizes light absorption and heat generation by an analyte and optical diffraction by a nanochannel after heat diffusion. Concentration determination of nonfluorescent molecules in a 400 nm channel was successfully demonstrated, and a limit of detection (LOD) of 5.0 μM was achieved, corresponding to 500 molecules (0.84 zmol) in a detection volume of 230 aL. Also, detection in a 200 nm channel was successfully demonstrated without degradation of the LOD. Our method can be widely used for chemical and biological analyses in 102–103 nm nanofluidics.