Body fluid diagnostics using activatable optical probes

In vitro diagnostics often detects biomarkers in body fluids (such as blood, urine, sputum, and cerebrospinal fluids) to identify life-threatening diseases at an early stage, monitor overall health, or provide information to help cure, treat, or prevent diseases. Most clinically used optical in vitro diagnostic tests utilize dye-labeled biomolecules for biomarker recognition and signal readout, which typically involve complex steps and long processing times. Activatable optical probes (AOPs), which spontaneously activate their optical signals only in the presence of disease biomarkers, offer higher signal-to-background ratios and improved detection specificity. They also have the potential to simplify detection procedures by eliminating multiple washing steps. In this review, we summarize recent advances in the use of AOPs for pre-clinical and clinical body fluid diagnostics across various diseases, including cancer, nephro-urological disorders, infectious diseases, and digestive diseases. We begin by discussing the molecular design strategies of AOPs to achieve different optical signal readouts and biomarker specificity. We then highlight their diagnostic applications in various disease models and body fluids. Finally, we address the challenges and future perspectives of AOPs in enhancing body fluid diagnostics and advancing precision medicine.