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

这个小型企业创新研究（SBIR）第一阶段项目开发了一个原型基因表达平台，用于准确的癌症诊断，预后和治疗监测。目前的平台有许多局限性，包括缓慢，复杂，劳动密集型的过程;和次优的灵敏度。所提出的装置将1）与现有的多变量基因表达测定相比提供类似或更好的净灵敏度，2）不含标记物; 3）提供小得多的阵列元件的灵活性;以及4）与竞争技术相比制造成本低廉。该传感器采用新颖的专有金属-半导体混合结构，对外部电场具有强烈的增强灵敏度。传感器装置几何形状已被证明具有比可部署为基于阵列的传感器的其它电场检测装置高得多的灵敏度和低得多的噪声。目标是开发能够以高空间分辨率对与核酸碱基配对有关的单个离子事件成像的初始原型的基本组成部分;测试在复杂背景下的动态范围和检测极限，其中靶序列存在于相对大量过量的非互补核酸中;以及，验证和基准测试乳腺癌和正常人乳腺和乳腺癌核糖核酸中的参考基因的12像素阵列。该项目更广泛的影响/商业潜力集中在全球脱氧核糖核酸和基因芯片市场，预计到2015年将达到14.252亿美元。基因表达产物在临床诊断、生物防御和农业等领域具有多种用途。预计到2015年，癌症诊断和治疗应用将占据应用市场的主导地位，约占24%的市场份额。所提出的技术优于目前的基因表达测定，在灵敏度、特异性和阵列格式方面提供了显着的改进，并有望将特征尺寸驱动到纳米级范围内-所有这些都以无标记的形式进行。无标记格式消除了耗时的化学标记;对高功率激发源以及复杂的扫描仪器的需求;以及结果的潜在偏差。随着灵敏度和特异性的显著提高，可以使用更小的样品和/或需要更少的处理;并且，可以可靠地使用一些具有低拷贝数的更有趣的生物标志物。实现这种超高分辨率而不影响灵敏度和特异性的潜在优势包括将几种预测性癌症相关生物标志物整合到单一诊断测试中的能力。由于所提出的传感器是使用传统方法生产的，因此它们可以经济地生产为高密度阵列。

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.