Discovery of a new coreactant for highly efficient and reliable electrochemiluminescence

Using luminophore and coreactant pairs increases light emission in electrochemiluminescence (ECL) reactions, improving the overall sensitivity of ECL assays. The most commonly used coreactant is tri- n -propylamine (TPrA) for its capability as a reducing agent. However, TPrA is hydrophobic and readily oxidized, which limits its utility in biosensing. Here, we report the discovery and characterization of the new coreactant 4-(dimethylamino)pyridine (4-DMAP). The compound is highly water soluble and chemically stable under ambient conditions. Most importantly, 4-DMAP generated ECL signals >180 times higher than TPrA in tris(bipyridine)ruthenium(II) [Ru(bpy) 3 ] 2+ . The 4-DMAP ECL enabled ultra-sensitive and robust immunoassays. For example, the 4-DMAP ECL reliably detected protein markers in extracellular vesicles from the plasma samples of cancer patients. It also achieved >200-fold higher sensitivity than TPrA-ECL did in quantifying neutralizing antibodies against SARS-CoV-2 in human saliva. These findings could lead to exciting new opportunities for using ECL-based sensing in a range of clinical applications. • 4-DMAP is a potent alternative to TPrA, generating 180-fold stronger ECL intensities • It is highly water soluble and chemically stable at room temperature • 4-DMAP excites oxidized luminophores through a radical process • The [Ru(bpy) 3 ] 2+ /4-DMAP system enabled highly sensitive detection of biomarkers The sensitivity of electrochemiluminescence (ECL) assays relies on effective luminophore-coreactant pairs. Cho et al. introduce 4-(dimethylamino)pyridine (4-DMAP), a stable, water-soluble coreactant that enhances [Ru(bpy) 3 ] 2+ ECL by over 180-fold compared to tri- n -propylamine (TPrA), providing strong signal amplification and versatile biosensing performance in aqueous diagnostic applications.