Fabrication and characterization of solid-state nanopore arrays for high-throughput DNA sequencing

We report the fabrication and characterization of uniformly sized nanopore arrays, integrated into an optical detection system for high-throughput DNA sequencing applications. Nanopore arrays were fabricated using focused ion beam milling, followed by TiO(2) coating using atomic layer deposition. The TiO(2) layer decreases the initial pore diameter down to the sub-10 nm range, compatible with the requirements for nanopore-based sequencing using optical readout. We find that the TiO(2) layers produce a lower photoluminescence background as compared with the more widely used Al(2)O(3) coatings. The functionality of the nanopore array was demonstrated by the simultaneous optical detection of DNA-quantum dot conjugates, which were electro-kinetically driven through the nanopores. Our optical scheme employs total internal reflection fluorescence microscopy to illuminate a wide area of the TiO(2)-coated membrane. A highly parallel system for observing DNA capture events in a uniformly sized 6 × 6 nanopore array was experimentally realized.