(736d) Fabrication and Control of Nanopore Devices for Ultra-Rapid Biomolecule Analysis Applications

This talk will describe the nanofabrication and control of solid-state nanopore devices for advanced biomolecule analysis applications. Specifically, a wafer-scale process has been developed for the fabrication of solid-state nanopore devices. In addition, modeling and simulation of transport of individual DNA strands through the nanopores indicate that the performance of these devices under combined AC-DC fields using an optimization engine has the potential to approach high-resolution, ultra-rapid DNA sequencing.

The intersection of nanofabrication technologies (originating in the semiconductor industry) with biology/biophysics has great potential for creating a next generation of bioanalytical systems. For example, one ?grand challenge? is to be able to inexpensively and readily sequence the genomes of all individuals on the planet, which would be a substantial step forward in our understanding of genome variation and its implication on susceptibility to disease. Other implications include the possibility of ?personalized medicine? as well as fast genotyping of pathogens or biological warfare agents to allow rapid responses. In recent years ?Engineered Nanopore Devices? (ENDs) have become attractive candidates to achieve the ?$1000-genome?, viz. the ability to sequence mammalian genomes within hours-days at a cost of ~$1000 (compared to 1-5 years and > $10 million with current technology). These devices are based upon electric-field-driven translocation of single DNA strands through individual nanopores of diameter < 5 nm and length < 20 nm (fabricated using lithographic patterning and high-resolution electron beams).

Two critical unresolved issues in END science and technology are: 1) fabrication of large arrays of extremely small (1-5 nm) nanopore devices, and 2) controlling the dynamics of DNA transport in engineered nanopores in order to achieve the highest resolution. Here a novel fabrication strategy is introduced, which employs electron beam lithography (EBL) in combination with atomic layer deposition (ALD) to produce nanopores and nanopore arrays. Since these methods are easily scaleable, END devices can be mass produced using an optimized variation of the methods described here. To address the second issue, recent theoretical work from our group will be highlighted. Based upon mesoscopic (Brownian dynamics) simulations, t is proposed that the control of biopolymer transport through the nanopore via carefully optimized AC electric fields could dramatically increase the resolution of the device to reach single-nucleotide levels.