Electrically switchable DNA interface for the detection and size-analysis of DNA and protein targets

We introduce a chip-compatible scheme for the label-free detection of proteins in real-time that is based on the electrically driven conformation-switching of DNA oligonucleotides on metal surfaces. The switching behavior is a sensitive indicator for the specific recognition of IgG antibodies, antibody-fragments, and small proteins like cytochrome c, which can be detected in quantities of less than 1 amol on the sensor surface. We show how the dynamics of the induced molecular motion can be monitored by measuring the high-frequency switching response as well as by time-resolved fluorescence measurements. When proteins bind to the layer, the increase in hydrodynamic drag slows the switching dynamics, which allows us to determine the size of the captured proteins. We demonstrate the identification of different antibody fragments and small proteins by means of their kinetic fingerprint. The switchDNA method represents a generic approach to simultaneously detect and size target molecules using a single analytical platform.