Nanopore Systems for Biomolecular Analysis
"Nanopore Systems for Biomolecular Analysis"
Dr. Michael Goryll, Associate Professor, School of ECEE, Arizona State University
Nanopore systems exhibit tremendous potential for molecular analysis. One example that has attracted considerable interest is the ability to perform direct DNA sequencing using electrical current modulation through nanopores. Engineered natural nanopores have demonstrated excellent capabilities; however, they need to be embedded in a lipid bilayer membrane to ensure their functionality. This talk will present how a silicon micropore platform can be adapted to host ion channels in planar lipid membranes. The silicon platform presented provides excellent electrical properties concerning the biomembrane seal resistance and the membrane capacitance, resulting in a low noise of the recordings. While biochemically modified natural protein nanopores have shown to be able to accomplish sensitive and selective biomolecule detection and even DNA sequencing, there are concerns regarding their chemical stability in different pH buffers and their temperature sensitivity. Replacing natural protein nanopores with solid-state nanopores in materials like silicon, silicon dioxide or silicon nitride not only enhances the stability of the platform but also enables easy integration with VLSI electronics into a high-throughput sensing platform. The main obstacle preventing adoption of solid-state nanopores thus far is the required size range on the order of single nanometers and the available materials and manufacturing technologies. This talk will introduce a solid-state manufacturing pathway using silicon-on-insulator substrate technology that not only is compatible with established industrial manufacturing processes, but allows electrostatic trapping of biomolecules using lateral electrostatic fields and the design of hybrid nanopores, in which polymers are being used to line the inside of the solid-state structure. An alternative to lithographically defined nanopores can be found in the biomineralized silica shells of marine diatom algae. Their hierarchical pore architecture with pore sizes down to 40 nm in diameter makes these nanomembranes exceptionally mechanically stable. These nanopores are homogeneous in size and have a low aspect ratio, enabling fast diffusion-driven transport. The presentation will show how the combination of bottom-up biomineralized nanopores and top-down silicon structures forms a pathway for integrating low-cost nanostructures with BioMEMS devices to form large area nanopore membranes. Such hybrid devices exhibit a low probability of complete clogging, due to the large (>200) number of nanopores available. Besides nanoparticle translocation measurements via the reduction in ionic current through the nanopore membrane, functionalized biomineralized nanopore membranes can act as lipid bilayer hosts. In addition to nanopore technology, the talk will address recent developments in transimpedance amplifier frontend technology for wide-bandwidth recording and show opportunities how signal processing can be employed for de-noising and event classification.