Developing
novel strategies for sensitive and specific detection
of protein biomarkers is a field of active research. Here, we report
an ultrasensitive biosensor to detect protein tyrosine kinase-7 (PTK7),
an important protein biomarker on the cell surface, by aptamer conformation-cooperated
enzyme-assisted surface-enhanced Raman scattering (SERS) (ACCESS)
technology. Our approach features a synergistic combination of the
conformational alteration of the anglerfish aptamer triggered by the
recognition of the membrane protein (PTK7) and Exo III enzyme-assisted
nucleic acid amplification. It transduces the specific binding events
between the aptamer and PTK7 protein into dramatically improved SERS
signals. Sensitive and specific detection of PTK7 protein has been
demonstrated both in the solution and directly on the surface of live
CCRF-CEM cells, with a limit of detection better than the commercial
enzyme-linked immunosorbent assay method by nearly 5 orders of magnitude.
As a flexible, ultrasensitive, and specific approach, ACCESS promises
important applications in clinical diagnostics, where only a very
limited amount of the biological sample is available.