Digital nanophotonic biosensing empowered by silicon Mie voids

Abstract

Optical biosensors are indispensable in medical and environmental diagnostics, yet existing approaches are fundamentally limited in their sensitivity due to ensemble-averaged measurements. Digital biosensing has emerged as a promising solution for resolving individual binding events, thereby providing signals at very low analyte concentrations down to the single-molecule level. Here, we present a novel concept for digital optical biosensing empowered by dielectric Mie voids, combining nanoparticle-based contrast enhancement and deep learning for ultrasensitive biomarker detection. The resonantly trapped light in the air cavities of the periodic Mie void arrays ensures strong overlap between the near-fields and the single gold nanoparticles that are captured on the surface in the presence of the protein biomarker. Remarkably, this strong interaction creates high-contrast digital signals for the precise counting of single nanoparticles located both within and outside the voids, yielding efficient use of the entire sensor area for high sensitivity. We employ deep-ultraviolet (DUV) lithography for the scalable and low-cost production of Mie voids in silicon wafers and automated image analysis with a convolutional neural network for robust nanoparticle counting. As a proof of our concept, we demonstrate the detection of an important disease biomarker, interleukin-6 (IL-6), from small sample volumes at concentrations as low as 1.84 pg/ml, within the physiological range of healthy individuals. Owing to its scalability, precision, and adaptability, our digital nanophotonic biosensing approach based on silicon Mie voids establishes a versatile route for applications ranging from bioanalytics to health and environmental monitoring.