Abstract

Rapid, label-free analysis of individual biopolymers, specifically of individual DNA fragments is of great importance to many areas of biology and medicine. In recent years, translocation experiments within solid-state pores and protein channels combined with ionic current blockade measurements have become the technology of choice when detection is needed at the single molecule level. For linear biopolymers such as DNA and RNA however, detection based on ionic current blockade seem to lack the signal sensitivity necessary to obtain structural information with single base resolution. Transverse (perpendicular to the helix axis) conductance measurements of DNA in nanometer-sized tunneling junctions promise current detection limits within single nucleotide resolution. Yet, the exact alignment of nanoscale electrodes in tunneling regime to a solid-state nanopore has proven to be a significant challenge. We address this shortcoming by developing a novel method for aligning nanopore and tunneling junction in a nanoscale tunneling architecture by electrochemical metal deposition. As a result, tunnelling electrodes can be fabricated with atomic sharpness and precisely aligned to the nanopore. DNA can be driven electrophoretically through the tunneling architecture and it may be possible to detect modulations in the tunneling current specific to each base in the DNA.

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