SBIR Phase I: Extraordinary Electroconductance Label-Free Breast Cancer Arrays

This Small Business Innovation Research (SBIR) Phase I project develops a prototype gene expression platform for accurate cancer diagnosis, prognosis and treatment monitoring. Current platforms have many limitations, including slow, complex, labor-intensive processes; and suboptimal sensitivity. The proposed device will 1) provide similar or better net sensitivity compared to existing multivariate gene-expression assays, 2) is free of labels; 3) offers the flexibility of much smaller array elements; and, 4) is manufactured inexpensively compared to competing technologies. The sensor uses novel, proprietary, metal-semiconductor hybrid structures that exhibit strongly enhanced sensitivity to external electric fields. The sensor device geometry has been shown to have much higher sensitivity and lower noise than other electric field detection devices that are deployable as array-based sensors. The objectives are to develop the essential components of an initial prototype that is able to image, with high spatial resolution, individual ionic events associated with nucleic acid base pairing; test the dynamic range and limits of detection in a complex background, where the target sequence is present within a relatively large excess of non-complimentary nucleic acids; and, validate and benchmark a 12-pixel array for breast cancer and reference genes in normal human breast and breast cancer ribonucleic acid. The broader impact/commercial potential of this project centers on the global deoxyribonucleic acid and gene chip market, which is expected to reach $1,425.2 million by 2015. Gene expression products have diverse usage in areas such as clinical diagnostics, biodefense, and agriculture. Cancer diagnosis and treatment application is expected to dominant the applications market through 2015; accounting for about a 24% market share. The proposed technology excels over current gene expression assays, offering significant improvements in sensitivity, specificity and an array format, with the promise of driving feature sizes into the nanoscale regime - all in a label-free format. The label-free format eliminates time-consuming chemical labeling; the need for high power excitation sources as well as sophisticated scanning instrumentation; and, potential biasing of results. With significantly improved sensitivity and specificity smaller samples can be used and/or less processing will be required; and, some of the more interesting biomarkers with low copy number can be reliably used. The potential advantages of achieving such ultra-high resolution without compromising sensitivity and specificity include the ability to consolidate several predictive cancer-related biomarkers into a single diagnostic test. Because the proposed sensors are produced using traditional methods, they can be economically produced as high-density arrays.