Protein-Induced Electrochemiluminescence Enhancement of Tetraphenylvinyl Derivatives for Ultrasensitive Bioanalysis

Herein, the bovine serum albumin (BSA)-loaded tetrakis[4-(4′-cyanophenyl)phenyl]ethane nanoaggregates (NAs) (BSA@TBPE-(CN)4 NAs) as a novel electrochemiluminescence (ECL) emitter were first prepared, which exhibited superior ECL performance via the newly defined protein-induced ECL enhancement. Impressively, BSA not only restricted the intramolecular motions by its hydrophobic cavity to improve optical radiation for enhancing ECL efficiency but also promoted the electrochemical excitation of BSA@TBPE-(CN)4 NAs in which amino acid residues of BSA altered the surface states and narrowed the energy gap of BSA@TBPE-(CN)4 NAs for further boosting the ECL efficiency. Furthermore, the BSA@TBPE-(CN)4 NAs displayed a more dispersed state due to electrostatic repulsion caused by its considerable negative charges, which was conducive to reacting more fully with coreactants for improving ECL emission. Excitingly, the BSA@TBPE-(CN)4 NAs exhibited a threefold stronger ECL intensity and a 4.8-fold higher ECL efficiency compared to those of TBPE-(CN)4 NAs. Thus, as an application, an ECL biosensor was fabricated based on the BSA@TBPE-(CN)4 NAs as an efficient emitter and the mismatch-fueled three-dimensional (3D) DNA walker as an effective signal amplifier for the rapid and ultrasensitive detection of microRNA-21 with a detection limit (LOD) of 19.1 aM, and it was successfully applied to assess the microRNA-21 expression of human cancer cells MCF-7 and HeLa. This work developed a novel avenue to reasonably synthesize highly efficient organic ECL emitters for motivating their potential application in ultrasensitive biosensing and high-resolution ECL bioimaging.