Dual-locked spectroscopic probes for sensing and therapy

Optical imaging probes allow us to detect and uncover the physiological and pathological functions of an analyte of interest at the molecular level in a non-invasive, longitudinal manner. By virtue of simplicity, low cost, high sensitivity, adaptation to automated analysis, capacity for spatially resolved imaging and diverse signal output modes, optical imaging probes have been widely applied in biology, physiology, pharmacology and medicine. To build a reliable and practically/clinically relevant probe, the design process often encompasses multidisciplinary themes, including chemistry, biology and medicine. Within the repertoire of probes, dual-locked systems are particularly interesting as a result of their ability to offer enhanced specificity and multiplex detection. In addition, chemiluminescence is a low-background, excitation-free optical modality and, thus, can be integrated into dual-locked systems, permitting crosstalk-free fluorescent and chemiluminescent detection of two distinct biomarkers. For many researchers, these dual-locked systems remain a ‘black box’. Therefore, this Review aims to offer a ‘beginner’s guide’ to such dual-locked systems, providing simple explanations on how they work, what they can do and where they have been applied, in order to help readers develop a deeper understanding of this rich area of research. Dual-locked optical probes change their optical signals when they respond to two biomarkers of interest. This facilitates real-time imaging of multiple interrelated biomarkers in living systems and, thus, provides opportunities to better understand pathological events and enhanced diagnostic specificity.