This project aims to develop a technology based on nanopore biosensor arrays for applications in single molecule analysis. Current single molecule techniques have several limitations. They do not allow study of molecules in their native environment, they are not high throughput, and they are expensive and labor-intensive. Furthermore, these methods have been limited in both their throughput capability and spatial resolution (e.g. their ability to distinguish features within a single macromolecule). To address these technological shortcomings and enable the high-throughput study of single molecule biophysics in solution, a semiconductor nanopore sensor array technology will be developed. The basis of the detection methodology is that sensitive charge sensors detect multiple characteristics of individual molecules as they are driven through a nanopore by an applied electric field. The nanopore sensors provide a unique opportunity for label-free, ultra-fast, high spatial resolution, and highly parallel detection of single macromolecules. This technology has applications in several fields by providing a label-free method to sensitively identify and quantify biological material, including proteins, DNA, viruses, and cells. Initial work will focus on developing the technology for protein analysis. To date, single molecule technologies have contributed detailed and quantitative information about structure-function relationships, concentrations, and interaction kinetics of biological molecules. Such knowledge has increased our understanding of biochemical pathways while revealing mechanisms of normal and disease states. This understanding is necessary for future medical advances. The proposed technology will enable the rapid, low cost study of proteins in solution phase at the single molecule level. This technology will speed the development of many aspects of biomedical research, including diagnostic tools, drug discovery, and proteomics.
