A tip-attached tuning fork sensor for the control of DNA translocation through a nanopore

In this work, we demonstrate that a tuning fork can be used as a force detecting sensor for manipulating DNA molecules and for controlling the DNA translocation rate through a nanopore. One prong of a tuning fork is glued with a probe tip which DNA molecules can be attached to. To control the motion and position of the tip, the tuning fork is fixed to a nanopositioning system which has sub-nanometer position control. A fluidic chamber is designed to fulfill many requirements for the experiment: for the access of a DNA-attached tip approaching to a nanopore, for housing a nanopore chip, and for measuring ionic current through a solid-state nanopore with a pair of electrodes. The location of a nanopore is first observed by transmission electron microscopy, and then is determined inside the liquid chambers with an optical microscope combined with local scanning the probe tip on the nanopore surface. When a DNA-immobilized tip approaches a membrane surface near a nanopore, free ends of the immobilized DNA strings can be pulled and trapped into the pore by an applied voltage across the nanopore chip, resulting in an ionic current reduction through the nanopore. The trapped DNA molecules can be lifted up from the nanopore at a user controlled speed. This integrated apparatus allows manipulation of biomolecules (DNA, RNA, and proteins) attached to a probe tip with sub-nanometer precision, and simultaneously allows measurement of the biomolecules by a nanopore device.