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

这个小企业创新研究（SBIR）一期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。目前的平台有很多局限性，包括缓慢、复杂、劳动密集型的流程；和次优灵敏度。与现有的多变量基因表达检测相比，该设备将提供类似或更好的净灵敏度，2)不需要标签；3)提供更小数组元素的灵活性；4)与竞争技术相比，制造成本低廉。该传感器采用新颖的、专有的金属-半导体混合结构，对外部电场的灵敏度大大提高。该传感器设备的几何形状已被证明比其他可部署为阵列传感器的电场探测设备具有更高的灵敏度和更低的噪声。目标是开发初始原型的基本组件，该原型能够以高空间分辨率成像与核酸碱基配对相关的单个离子事件；测试在复杂背景下的动态范围和检测限，其中目标序列存在于相对大量的非互补核酸中；并且，验证和基准的12像素阵列的乳腺癌和参考基因在正常的人乳房和乳腺癌核糖核酸。该项目的更广泛的影响/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有着广泛的应用。预计到2015年，癌症诊断和治疗应用将主导应用市场；约占24%的市场份额。拟议的技术优于当前的基因表达分析，在灵敏度、特异性和阵列格式方面提供了显著的改进，有望将特征尺寸驱动到纳米级——所有这些都是在无标签格式下进行的。无标签格式消除了耗时的化学标签；需要高功率励磁源以及精密的扫描仪器；还有，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；而且，一些更有趣的低拷贝数生物标志物可以可靠地使用。在不影响灵敏度和特异性的情况下实现这种超高分辨率的潜在优势包括能够将几种预测癌症相关的生物标志物整合到一个单一的诊断测试中。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成高密度阵列。

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.