Amphiphile-Mediated Ultrasmall Aggregation Induced Emission Dots for Ultrasensitive Fluorescence Biosensing

The development of ultrasensitive and highly selective fluorescence biosensors for diverse analytes is highly desirable but remains a challenge. It is attributable to the scarcity of fluorogens with promising brightness, stability, and nontoxicity, which primarily determine the performance of fluorescence biosensors. Herein, we report the design and preparation of aggregation induced emission (AIE) dots with high brightness, exceptional colloidal stability, ultrasmall size, and functional groups for developing ultrasensitive biosensor through the electrostatic conjugation to biological molecules, and use blemycin (BLM) as the proof-of-concept analyte. The recognition and the subsequent cleavage of the quencher-labeled DNA (Q-DNA) by BLM result in the formation of three-mer quencher-linked oligonucleotide fragments (Q-DNA-1), which significantly decreases the amount of quenchers anchored on AIE dot surfaces and subsequently reduces the fluorescence resonance energy transfer (FRET) effect. As compared to the case in which BLM is absent, remarkable fluorescence enhancement is observed, and is dependent on BLM concentration. Thus, ultrasensitive fluorescence detection of target BLM is realized, with a detection limit down to 3.4 fM, the lowest value reported so far. Moreover, the proposed fluorescence biosensor has also been successfully utilized for detection of BLM spiked in human serum samples. The as-proposed strategy not only significantly improves the selectivity and sensitivity of BLM assay, but also allows the ultrasensitive detection of a variety of bioactive molecules by simply changing the specific target recognition substances, thus providing a versatile fluorescence platform, and showing great potential to be applied in chemo-/bioanalysis and clinical biomedicine.