Label-Free Nanostructured Biosensing Platform Based on Depolarized Dynamic Light Scattering for Rapid and Portable Detection of Immunoglobulins in Complex Biological Samples

The dynamic behavior of nanoparticles in solution provides valuable insights for biomolecular detection. When nanoparticles exhibit optical anisotropy, their Brownian rotational diffusion can be monitored through depolarized dynamic light scattering (DDLS). For anisotropic particles such as gold nanorods (GNRs), the rotational diffusion coefficient scales inversely with the cube of their hydrodynamic radius, making DDLS highly sensitive to nanoscale binding events. Here, we report a label-free nanostructured biosensing platform based on DDLS that enables rapid, sensitive, and portable detection of immunoglobulins in complex samples. The system integrates bioconjugated GNRs with a custom-built, miniaturized DDLS device to achieve real-time, in loco measurements within approximately ≈10 s, without extensive sample preprocessing. As a proof-of-concept, GNRs functionalized with SARS-CoV-2 nucleocapsid proteins were used to detect specific immunoglobulins in clinical samples. The nanobiosensor exhibited high analytical sensitivity, with a detection limit of 0.16 ng/mL, as determined using spiked samples containing commercial monoclonal anti-N antibodies, highlighting its potential for rapid point-of-care immunoassays in complex biological environments.