Development of a Lensless Compact Optical System for Ultrasensitive Nanomaterial Detection in Liquid Media via Exploiting Multiple Light Scattering

Accurate detection of nanoparticles in liquids is essential across drug delivery, diagnostics, and environmental monitoring. Dynamic light scattering (DLS), the current gold‐standard technique, relies on single‐scattering events and requires prior knowledge of sample temperature and optical properties, limiting its sensitivity at low particle concentrations and increasing system cost and complexity. Here, we present a lensless, cost‐effective speckle‐based method that exploits multiple light scattering to overcome these limitations. A custom‐machined aluminum sample holder uniformly illuminates the entire sample volume with a randomized coherent light field via repeated diffuse reflections. Subtle nanoparticle motions modulate the phase of the scattered light, producing time‐varying speckle patterns captured by a CMOS camera without any imaging optics. Temporal correlation analysis of the speckle time series quantifies nanoparticle dynamics without requiring prior sample information. The method detects nanoparticles at concentrations as low as 10 5 particles/mL, which is at least 10 3 –10 4 ‐fold below the DLS detection limit for sub‐200 nm particles. Under fixed‐concentration conditions, an empirical calibration model achieves semi‐quantitative size determination in the 100–200 nm range with 95% prediction intervals within ± 7 nm. The proposed platform therefore offers a versatile, field‐deployable solution for ultrasensitive nanoparticle characterization in liquid media.