Monitoring Liquid Concentration Changes in Nanofluidic Channels Using Cross-Grating Wavefront Microscopy

Journal article, 2026

Optical microscopy that employs intensity measurements of scattered, transmitted, or emitted light is critical to study micro- and nanofluidic systems widely used in, e.g., biology, chemistry, and materials science. Since such fluidic systems often are transparent, simple bright-field microscopy observations are bound to yield low-contrast images. Fluorescence labeling or Raman imaging can be used to overcome this limitation and yield high contrast. However, these approaches are invasive or complex and slow and do not yield direct quantitative information about a liquid inside a micro- or nanofluidic structure. Quantitative phase microscopy techniques on the other hand are very efficient in enhancing the contrast of transparent samples, in a noninvasive manner. However, they have never been applied to nanofluidic systems. To fill this gap, we demonstrate how cross-grating wavefront microscopy enables the quantitative characterization of liquids in terms of concentration and refractive index, as well as solute diffusion, inside a single nanofluidic channel embedded in a SiO2 matrix in general and from diffraction-limited nanofluidic channel volume fractions as small as ∼45 aL. In a wider perspective, this study thus demonstrates the applicability of cross-grating wavefront microscopy to the characterization of processes taking place in volumes smaller than the diffraction limit of light, such as, e.g., nanofluidic systems, nanopores, or nanocavities.