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The aim of this proposal is to use solid-state interfaced with biological nanopores to develop a novel force spectroscopy on the single molecule level. Nanopores offer a unique possibility for analysis of molecules in a volume of ~10^-23 l. Electric fields allow to pull charged macromolecules into and through the pore, while the ion current contains information about the molecule and its interaction with the channel surface. Here we use optical tweezers with ion current detection to apply forces and position a molecule in a pore. This leads to a novel, nanopore-based force spectroscopy enabling pN force detection while controlling the distance with nm resolution along a molecule in a biological nanopore. Our tool will be used to investigate the underlying physics of interaction, translocation or unfolding of macromolecules in pores. The current consortium will claim a worldwide lead position with this technique. Our proposed technology could lead to groundbreaking experiments.
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