Unravelling the Labyrinth of Organic Semiconducting Chromophores for Fluorescence Bioimaging beyond 1500 nm

Fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700 nm) provides great promise for the visualization of pathology and physiology at the molecular level, with high spatial resolution and deep tissue penetration. Particularly, increasing studies focus on creating organic semiconducting chromophores (OSCs) for noninvasive NIR-IIb imaging (1500–1700 nm) with near-zero tissue autofluorescence and a greatly enhanced penetration. This review aims to unravel the labyrinth of engineering highly bright OSCs for advancing NIR-IIb imaging. We summarize and highlight five strategic designs for boosting NIR-IIb fluorescence emission, containing manipulation of intramolecular motions, an atom-programming strategy, construction of semiconducting polymer dots, a J-aggregation regulation strategy, and the creation of molecule–protein complexes. Eventually, the potential directions for improving and advancing the application of NIR-IIb fluorophores toward clinical practices are emphasized. We envision that this review will provide a design reference for creating high-performance long-wavelength fluorescent emitters, thereby paving the way for the future of NIR-IIb FLI.