The aim of this program is to develop a novel genetic analysis platform that will provide multiple cost, time and sensitivity advantages over conventional technologies. The ability to diagnose the susceptibility to diseases such as breast or colorectal cancer provides valuable information for affected individuals that can lead to early detection and treatment of the disease. Current technologies for identifying genetic mutations and polymorphisms are limited in their diagnostic utility because of the complex sample processing, amplification steps and expensive detection instrumentation. Most genetic analyses is thus relegated to sophisticated and costly testing laboratories. The nanotechnology enabled sensor described in this proposal will be capable of highly selective and sensitive detection of nucleic acid hybridization in an array based format without the need for sample labeling or amplification. Furthermore, instead of expensive optical detection this nanosensor will detect hybridization by changes in electrical conductivity that can be made with a simple, low cost, low power instrument compatible with a point of care or even portable sensor platform. This detection system is based on the discovery that nanoscale materials such as nanotubes and nanowires can act as field effect transistors (FET's) at room temperature. This effect is termed NanoChemFET and it works because the conductive properties of exquisitely sensitive nanowires are modulated by charges on the analyte molecule that act like a gate voltage in a conventional field effect transistor. Because captured DNA or RNA would deliver a defined number of negative charges, proportional to the number of nucleotides brought into the vicinity of the nanowire, nucleic acids are well-suited to sensitive, quantitative analysis by a NanoChemFET sensor. As described in this proposal we will develop processes to controllably manufacture nanowires and assemble them on functional devices. We will use these devices to test the sensor performance for sensing and discriminating specific DNA sequences. In phase I of the program we will detect hybridization of a specific DNA sequence and we will determine the basal sensitivity and discriminatory capabilities of the sensor. This will provide the baseline from which to develop multiple genomic analysis applications including expression arrays, SNP genotyping and the detection of infectious agents in an exquisitely sensitive, rapid and cost effective manner.
