The nucleotide sequence of DNA and mRNA and its expression in various cells is of utmost importance to life scientists because every disease state of biological function could be traced back to a single or a group of genes (DNA sequences). Thus the knowledge of the sequence of these genes and their subsequent regulation should provide powerful therapeutic approaches for disease control at the source of the problem (i.e. genetic level). The objective of the investigators work is to design and implement a silicon- based nano-electro-mechanical-system for the study, characterization and sequencing of individual polynucleotide molecules of DNA and RNA using conductance techniques. Such a system has never been demonstrated in silicon. The proposal takes a new step in fabricating the system in a silicon wafer. The project is high risk and can have significant impact to the area of single molecule electronic detection. The device will consist of two chambers in a silicon wafer with integrated electrodes. These chambers will be separated by a thin membrane with nano-pores defined in it. The DNA molecule will be introduced in chamber 1 and a voltage will be applied across the silicon membrane between electrodes 1 and 2. Since DNA is negatively charged, it will be pulled through the pore under the electric field at a controllable speed. The chambers will be filled with a conducting solution and the conductance measured across the pore will change when the DNA strand passes through the pore. The device described in the proposal will use silicon micro-machining techniques for the fabrication. Silicon processing and micro-machining techniques have been used to develop various micro-electro-mechanical structures for bio-medical application over the past few years. The processing dimensions are approaching regimes where these devices can be interfaced with biological molecules. For instance, lateral features down to 200A (e.g. using electron beam or X-ray lithography) and vertical features down to a 20A (e.g. using growth of oxide or controlled deposition) could be defined. For the device described the thin membrane will be made of silicon using epitaxial lateral overgrowth (ELO) and or made of silicon nitride deposited using low pressure chemical vapor deposition (LPCVD). """"""""Nanapores"""""""" (diameter < 50A) will be formed in the membrane (thickness < 500A) which will separate the two chambers. The initial size of the pores will be controlled using direct write electron beam lithography and dry gas phase etching and the final dimension will be achieved using formation of sidewall. The ability to build the system described in this application will further enable the fabrication of other bio-electronic interface devices such as protein separation and purification of charged molecules. In addition, once the basic challenge of moving a single DNA molecule through a silicon pore under and electric field has been demonstrated in a silicon based device, further enhancements can be made by adding fluorescence related components, the next step of the long term goal of the research.
| Iqbal, Samir M; Akin, Demir; Bashir, Rashid (2007) Solid-state nanopore channels with DNA selectivity. Nat Nanotechnol 2:243-8 |
