Coupling of an antifouling and reusable nanoplatform with catalytic hairpin assembly for highly sensitive detection of nucleic acids using zeta potential as signal readout

Abstract

Zeta potential analyzer has been becoming a routine instrument for nanomaterial characterization, which allows simple, non-invasive, highly sensitive, and reagentless measurement. However, its application in quantitative bioanalysis is greatly hampered by the dearth of appropriate sensing strategy, high background signal of nanomaterials and severe interference in complex biofluids. Herein, we develop a highly sensitive method to detect nucleic acids based on an antifouling and reusable nanoplatform using zeta potential as signal readout. In this work, the nanoplatform, composed of a magnetic nanoparticle (MNP) core and an antifouling zwitterionic lipid membrane, not only resists on the nonspecific adsorption of proteins, but facilitates its separation from complex detection system, enabling accurate measurement of zeta potential. After conjugation of uncharged peptide nucleic acids, the resultant nanoconjugates can capture negatively charged target nucleic acids, significantly reducing interfacial zeta potential. The proposed method can detect picomolar analyte in a single incubation step or fetomolar analyte with the use of chain hairpin assembly. Additionally, the nanoplatform can be reused by mild nuclease treatment, which is rather difficult to be achieved by other nanoparticle-based detection methods. Overall, this method provides a new insight to use zeta potential as signal output for quantitative bioanalysis.