Multiplexed Nanophotonic Sensor Arrays for Time-resolved Biomolecular Analysis

Complex diseases arise from networks of interacting biomolecules, yet most analytical technologies measure only a limited number of interactions simultaneously. Here, we present a chirped guided-mode resonance (cGMR) photonic biosensor array for multiplexed, label-free analysis of biomolecular kinetics across hundreds of sensing sites. The platform integrates 322 photonic sensors on a single chip that are fabricated using a CMOS process ensuring high reproducibility (wavelength sensitivity of 36.8 pixels/nm with a standard deviation of 1.37 pixels/nm). Shifts in the photonic resonance due to molecular binding are recorded using a conventional CMOS camera allowing time-resolved and simultaneous measurements across the entire array. We demonstrate the platform's versatility by monitoring real-time binding of antibodies, aptamers, and synthetic glycopolymers where the parallel measurements reveal distributions of binding responses arising from surface heterogeneity and multivalency that are inaccessible to conventional, single biosensor platforms. As a model, wheat germ agglutinin binding to a GlcNAc-displaying glycopolymer yielded sub-micromolar equilibrium dissociation constants (KD = 28-564 nM). Crucially, the array successfully resolves the kinetics of lectin-glycopolymer binding interactions using a portable optical setup, even in a complex biological matrix. By combining scalable CMOS fabrication with portable, highly parallel interrogation, this cGMR array provides a robust route toward high-throughput biomolecular profiling in point-of-care diagnostics and drug discovery.