Label-Free Monitoring of Single Molecule Immunoreaction with a Nanopipette

The nanopipette has been employed for the single molecule analysis due to its advantage of easy fabrication and controllable diameter. Herein, we present that the single molecule immunoreaction could be monitored by using the quartz nanopipette through the discrimination of characteristic blockade current, which reflect the intrinsic character of the individual unlabeled protein molecules due to its heterogeneous motion in solution. Our methods show the ability to monitor the immunoreaction between single α-fetal protein (AFP) and its specific antibody in aqueous solution without any labeling. Our studies may open a new door to comprehensively understand the single molecule immunoreaction, which gain more insight into the molecular dynamic of elementary steps.