Optical microscopy for monitoring liquids and nanoparticles inside nanofluidic channels

Licentiate thesis, 2025

Nanofluidics constitutes a promising platform for studying properties of single particles in a confined environment. Single particle studies can provide unique insights into the fields of chemistry, biophysics, and material science, that extend beyond the knowledge gained when ensembles of billions of particles, with either slightly, or sometimes vastly, varying properties, are studied simultaneously. Robust and high-precision characterization methods are required to realize studies of single particles. In this context, optical microscopy, which can be employed to detect tiny changes of the refractive index of a liquid or solid medium, constitutes a non-invasive approach allowing to monitor the flow of particles and liquids through nanochannels with, potentially, high spatial and temporal resolution. In this work, I examine two techniques – dark-field scattering microscopy and cross-grating wavefront microscopy – and successfully determine solute concentration within sub-100 nm nanofluidic channels using them. While dark-field provides higher signal-to-noise ratios within my studies, cross-grating wavefront microscopy provides the benefit of quantitative measurements of liquid refractive index below the diffraction limit. Additionally, I investigated the light scattering signatures of metal nanoparticles contained within nanofluidic channels and found peculiar relationships between particle dimensions and their visibility when observed in a dark-field microscope. I developed a theoretical framework to aid the interpretation of scattering signals from such combined channel-particle systems.