A dual-signal strategy for the solid detection of both small molecules and proteins based on magnetic separation and highly fluorescent copper nanoclusters

Recently, a variety of analytical methods for the detection of small molecules or proteins based on small molecule-protein interaction have been developed. However, these methods often focus on either small molecules or proteins. Few efforts are made to detect both of them in the same system. In this work, a dual-signal strategy for the solid detection of both small molecules and proteins based on small molecule-protein interaction is proposed by using the streptavidin-biotin couple as a model. In our strategy, magnetic nanoparticles (MNPs) are adopted for target separation, and highly fluorescent copper nanoclusters (CuNCs) are synthesized in situ to give signals. In the absence of the targets, CuNCs are associated with the MNPs and present in the precipitate under magnetic field; whereas in the presence of either streptavidin or biotin, the CuNCs will present in the supernate. By monitoring the fluorescent intensity of each, dual-signal can be obtained for the solid detection of either the protein or the small molecule. Results show that sensitive and specific detection of both streptavidin (detection limit: 0.47 nM) and biotin (detection limit: 3.1 nM) can be achieved. This method can be extended for the detection of other small molecule-protein couples, and thereby has the potential for biomedical and clinical applications.