Biosensing with Fluorescent Metal Nanoclusters

Luminescent metal nanoclusters (MNCs), consisting of a few metal atoms, have emerged as a frontier in biosensors due to their ultrasmall size and unique optical and electronic properties. Their exclusive optoelectronic characteristics, and enzyme mimicking activities with flexibility in terms of numerous types of surface functionalization, photostability and high biocompatibility, enable the design of advanced biosensors with high sensitivity and specificity. This chapter comprehensively explores the design and fabrication principles of MNC-based biosensors, followed by an in-depth analysis of core sensing mechanisms. Optical sensing approaches include fluorometric detections, aggregation-induced emission, Förster resonance energy transfer, colorimetric assays, and surface-enhanced Raman scattering. In parallel, electrochemical sensing strategies utilize techniques like cyclic voltammetry, differential pulse voltammetry, amperometry, electrochemical impedance spectroscopy, linear sweep voltammetry, electrochemiluminescence, and photoelectrochemical detection. These multi-modal platforms have demonstrated wide applicability in detecting various biomolecules and metabolites such as glucose, nucleic acids, proteins, amino acids, and cholesterol, as well as in identifying heavy metal ions, environmental bio-toxins, and disease biomarkers through responsive assays. Recent advances further highlight pH-sensitive diagnostics, fluorescence recovery via displacement assays, and electrochemical signaling readouts. Through integrated design strategies, MNC-based biosensors provide a versatile toolkit for disease diagnostics and clinical monitoring, reflecting a future precision molecular detection strategy linking nanoscience with biomedical applications.