Silicon-based, single molecule, DNA analysis prototype

Period of Performance: 09/01/2003 - 12/31/2005

$187K

Phase 1 SBIR

Recipient Firm

Eagle Research and Development, LLC
Boulder, CO 80301
Principal Investigator

Abstract

DESCRIPTION (provided by applicant): The ultimate goal of this project is a silicon chip with a fabricated, well-instrumented nanopore capable of discriminating between the bases of long strands of DNA. This occurs as they thread through the pore at MHz rates. Discrimination is done through the image charge induced in the gate region of the semiconductor sensors placed to detect the unique, asymmetric charge distributions of single-stranded DNA (ssDNA) at the narrowest part of the nanopore. Such a chip would then be the core device of an inexpensive, ultra-fast sequencing system. This final system would transform diagnostic medicine by enabling exquisitely targeted treatments using sequencing data both from the patient and from the disease-causing pathogen. For example, an AIDS patient violently allergic to some antibiotics could be treated with an anti-viral medicine for the specific mutant AIDS strain affecting him/her. The specific device to be developed in the initial phase contains all the essential elements of the final system - a V-groove pore and local electronics - but is built at the 100 nm scale instead of the 1 nm scale needed to sequence ssDNA. The immediate goal is to obtain bio-compatible, rugged and low-cost nanopores suitable for immersion into a liquid. It will be both a proof-of-principle demonstration and an engineering evaluation of many of the techniques and procedures needed in the final system. This initial device will be fabricated in silicon with state-of-the-art, but well-established, technology including sub-micron feature sizes, V- groove etching, and a vertical architecture. Arrays of 1 - 100 nm size nanopores will be fabricated on a silicon substrate, which also contains local electrodes and electronics to facilitate and enhance the measurements. The fabricated device will be first characterized and tested with larger molecules such as proteins to prepare for designing and constructing the final phase, scaled-down device. Its use will be demonstrated by detecting, identifying and sizing individual DNA molecules and proteins as a necessary step towards developing the sensitivity and resolution required for DNA sequencing.