Chemiluminescence resonance energy transfer (CRET) has evolved into a robust tool in biosensing and bioimaging, offering extraordinary signal-to-noise ratios without the need for external excitation. The performance of CRET platforms is fundamentally governed by the CRET efficiency between donor and acceptor pairs, and elevating this efficiency remains the central challenge for advancing next-generation CRET technology. This review systematically elucidates the fundamental principles of CRET, the advanced engineering of donor-acceptor pairs, the critical factors influencing transfer efficiency, and emerging applications, underscoring the rational tactics to maximize CRET efficiency. Specifically, recent advancements in chemiluminescent (CL) donors including luminol, Cypridina luciferin analogs, acridinium derivatives, peroxyoxalates, and dioxetanes are critically evaluated, alongside the evolution of diverse acceptors, encompassing organic dyes and advanced nanomaterials. Five precision-driven strategies are subsequently summarized to improve CRET efficiency, comprising enhancing donor CL intensity, prolonging chemiluminescence duration, minimizing donor-acceptor distance, enhancing acceptor quantum yield, and expanding the donor-acceptor spectral overlap area. Furthermore, the cutting-edge applications of CRET systems, including food safety screening, environmental pollutant sensing, clinical diagnostics, as well as bioimaging and theranostics are showcased. Ultimately, current technical challenges and future trajectories are discussed. By centering on the overarching theme of optimizing efficiency, this review offers a definitive roadmap for engineering highly sensitive CRET systems and expanding their broad-spectrum applications.
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Bu et al. (2026) studied this question.
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