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Bioluminescence resonance energy transfer (BRET) techniques offer a high degree of sensitivity, reliability and ease of use for their application to sensing biomolecules. BRET is a distance dependent, non-radiative energy transfer, which uses a bioluminescent protein to excite an acceptor through the resonance energy transfer. A BRET sensor can quickly detect the change of a target biomolecule quantitatively without an external electromagnetic field, e.g., UV light, which normally can damage tissue. Having been developed quite recently, this technique has evolved rapidly. Here, different bioluminescent proteins have been reviewed. In addition to a multitude of bioluminescent proteins, this manuscript focuses on the recent development of BRET sensors by utilizing quantum dots. The special size-dependent properties of quantum dots have made the BRET sensing technique attractive for the real-time monitoring of the changes of target molecules and bioimaging in vivo. This review offers a look into the basis of the technique, donor/acceptor pairs, experimental applications and prospects., Competing Interests: The authors declare no conflict of interest.

Carbon-dots (CDs), the emerging fluorescent nanoparticles, show special multicolor properties, chemical stability, and biocompatibility, and are considered as the new and advanced imaging probe in replacement of molecular fluorophores and semiconductor quantum dots. However, the requirement of external high power light source limits the application of fluorescent nanomaterials in bio-imaging. The present study aims to take advantage of bioluminescence resonance energy transfer mechanism (BRET) in creating self-illuminating C-dots. Renilla luciferase (Rluc) is chosen as the BRET donor molecule. Conjugation of Renilla luciferase and C-dots is necessary to keep their distance close for energy transfer. The optimal condition for achieving BRET is investigated by studying the effects of different factors on the performance of BRET, including the type of conjugation, concentration of carbon dots, and conjugation time. The linear relationship of BRET efficiency as a function of the amount of C-dots in the range of 0.20–0.80 mg/mL is observed. The self-illuminating carbon dots could be applied in bioimaging avoiding the tissue damage from the external high power light source. [ABSTRACT FROM AUTHOR]