Optical tweezers for force measurements on DNA in nanopores

We demonstrate the means to integrate two powerful and widely used single-molecule techniques, viz., optical tweezers and solid-state nanopores. This setup permits simultaneous spatial sampling and high-resolution force measurements of nucleic acids and proteins. First, we demonstrate the rapid spatial localization of nanopores using our custom-built inverted microscope and ionic current measurements. This is made possible by including a specialized flow cell for silicon-based nanopores with an optical window for a high-numerical aperture microscope. Subsequently, we can insert individual DNA molecules into a single nanopore and arrest the DNA during voltage-driven translocation. To detect the position of the trapped particle in the optical trap with high accuracy in the presence of the nanopore, the optical tweezers uses reflected light from the bead for detection. Consequently, we can use our setup to directly determine the force on a DNA molecule in a solid-state nanopore. Finally, we suggest a number of new experiments that become possible with this unique technique.