Multiscale and Stimuli-Responsive Biosensing in Biomedical Applications: Emerging Biomaterials Based on Aggregation-Induced Emission Luminogens

Biosensors play a critical role in the diagnosis, treatment, and prognosis of diseases, with diverse applications ranging from molecular diagnostics to in vivo imaging. Conventional fluorescence-based biosensors, however, often suffer from aggregation-caused emission quenching (ACQ), limiting their effectiveness in high concentrations and complex environments. In contrast, the phenomenon of aggregation-induced emission (AIE) has emerged as a promising alternative, where luminescent materials exhibit strong emission in the aggregated state with good photostability, biocompatibility, large Stokes shift, high quantum yield, and tunable emission. This review article discusses the development of AIEgen-based biosensors for multiscale biosensing in biomedical applications. The integration of AIEgens with nanomaterials, such as graphene oxide and stimuli-responsive nanomaterials, can further improve the selectivity and multifunctionality of biomolecule detection. By careful molecular design, the affinity between AIEgens and specific biomolecules can be tuned, enabling the selective detection of targets like DNA, RNA, and proteins ex vivo, in vitro and in vivo, which can be applied across multiple scales, from detecting biomolecules and cellular structures to analyzing tissues and organs, underscoring their growing importance in disease diagnosis. Furthermore, we explore the potential integration of AIEgen-based biosensors with artificial intelligence (AI) technologies, offering promising avenues for future advancements in this field. •A comprehensive overview of the design and applications of AIEgens for biosensing•Elucidating mechanisms for multiscale detection of biomarkers•Discussing the critical impacts of stimuli responsivenesses for enhanced selectivity•Delving into the challenges and future prospects of AIEgens for biosensing