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2D materials offer huge potential as substrates to build devices for biosensing applications but are plagued by unwanted interactions such as binding/sticking. Controlling such interactions will be critical for the continued exploration of 2D materials in biosensing. In this work, we engineer and tune the surface interactions of hexagonal boron nitride (hBN) to direct the motion and diffusion of DNA. Using ISCAT and fluorescence microscopy techniques, we explore the nanoscopic interactions of DNA with different 2D materials. We show that pristine hBN flakes exhibit the lowest surface interactions and DNA bind preferentially to the edges and regions of high defect density of the hBN flake. We tap into a recently reported Xenon Focused Ion Beam (FIB) technique to engineer edges and defects on hBN flakes. Our technique harnesses a Xenon-FIB to lightly irradiate the desired regions of the hBN flake followed by …