Wei Li, Yuqian Wang, Lianghui Fan, Runpu Shen, Zhikang Xiao, Jianzhong Xu, Junyang Chen, Gaoxiang Xu
The evolution of biosensors demands synergistic improvements in signal transduction and data processing. We present a universal biosensing platform that combines dual-mode signal responses from silver-modulated gold nanorods (AuNRs) and gold–silver nanoclusters (AuAgNCs) (including localized surface plasmon resonance (LSPR) shifts and fluorescence variations) with machine learning (ML)-enhanced image analysis. Initially, AuNR was synthesized and transformed into silver-coated gold nanorods (AuNR@Ag) via silver reduction, with LSPR shifts precisely characterized. Concurrently, AuAgNCs were engineered to enhance their fluorescence through antigalvanic reactions between surface Ag(I) and Au(0) cores. The dual-mode platform leverages the silver-linked fluorescence intensity of AuAgNCs and LSPR of AuNR@Ag, as well as the increasingly enhanced inner filter effect between AuAgNCs and the evolving LSPR of AuNR@Ag, enabling simultaneous fluorescence and colorimetric readouts. The platform achieved high-precision detection of alkaline phosphatase via dual-signal correlation ( R 2 > 0.99), demonstrating robustness in complex matrices. Furthermore, to facilitate point-of-care testing applications, an ML algorithm encompassing feature extraction, dimensionality reduction, and model validation was integrated to process bimodal signal images. The subsequent data analysis exhibited robust correlations ( R 2 > 0.95), thereby substantiating the effectiveness of this approach in analyzing bimodal data. The ML-augmented analytics was validated for the analysis of serum samples, giving results that matched well with those from the spectra-based standard method. This work bridges nanomaterial engineering with ML-augmented analytics, offering a versatile framework for next-generation biosensors with clinical diagnostic potential.