Integrated Biochip Sensors for Detection of Cancer

描述（由申请人提供）：自上而下的硅纳米技术和半导体材料的微机械加工的最新技术进步为小型、灵敏、一次性使用、能够快速和高度准确地分析体液样本的护理点诊断器械提供了新的机会。纳米传感器和微流体生物芯片已经成功地证明用于检测流体中的蛋白质，但仍有待以稳健的阵列形式实现，检测多种蛋白质，其可用于临床前研究或临床样品。在这项提案中，我们组建了一个真正全面的跨学科研究人员团队，目标是应用和转化多学科研究，以设计和生产强大的自上而下的硅基场效应纳米传感器平台技术，该技术集成在一次性使用的即时诊断生物芯片中，用多种抗体功能化，用于从乳腺抽吸物的细胞裂解物中离体检测癌症蛋白。这些任务将由我们的研究人员团队完成，他们具有临床翻译（ILJSOM的Susan克莱尔），硅基场效应器件的微/纳米制造和片上样品浓缩和分离（普渡大学的Rashid Bashir和加州大学伯克利分校的Luke Lee），纳米传感器的模拟和计算（普渡大学的Ashraf Alam）以及癌症生物化学（普渡大学的Don Bergstrom）。该项目的具体目标如下：（i）开发来自乳房抽吸物的芯片上细胞裂解方法，（ii）开发新技术以用抗体使传感器阵列表面功能化，同时使非特异性吸附和生物污染最小化，（iii）开发新的计算和模拟策略以用于对流体中蛋白质结合时的场效应传感器响应进行建模，（iv）开发强大的自上而下的硅基场效应纳米板阵列，用于癌症蛋白质和标志物的多重检测，以及（v）开发集成生物芯片传感器，并进行广泛的测试和临床前研究。我们将继续专注于检测开发的问题和要求，以使用人体样本进行离体临床前研究。

DESCRIPTION (provided by applicant): The recent technological advances in top-down silicon nanotechnology and micromachining of semiconductor materials present themselves with new opportunities for small, sensitive, one time use, point of care diagnostic devices capable of rapid and highly accurate analysis of samples of body fluid. Nano- sensors and microfluidic biochips have been successfully demonstrated for the detection of proteins in fluids, yet still to be realized in a robust array format, with detection of multiple proteins, which can be used in preclinical studies or clinical samples. In this proposal, we have assembled a truly comprehensive team of interdisciplinary researchers with the goal of applied and translational multidisciplinary research for designing and producing robust top-down silicon-based field-effect nano-sensor platform technologies integrated in one-time-use point-of-care diagnostic biochips, functionalized with multiple antibodies, for the ex-vivo detection of cancer proteins from cell lysate from breast aspirates. These tasks will be accomplished by our team of researchers with expertise in clinical translation (Susan Clare at ILJSOM), micro/nano-fabrication of silicon based field effect devices and on-chip sample concentration and separation (Rashid Bashir at Purdue and Luke Lee at UC Berkeley), Simulation and computation of nanosensors (Ashraf Alam at Purdue), and Cancer bio-chemistry (Don Bergstrom at Purdue). The following are the specific aims of the project: (i) Develop on chip cell lysing approaches from breast aspirates, (ii) Develop novel techniques to functionalize the sensor array surfaces with antibodies, while minimizing non-specific adsorption and bio-fouling, (iii) Develop novel computational and simulation strategies for modeling the field effect sensor response upon protein binding in fluids, (iv) Develop robust top-down silicon-based field-effect nano-plate arrays for multiplexed detection of cancer proteins & markers, and (v) Develop integrated biochip sensors and perform extensive tests and preclinical studies. We will keep the focus on the issues and requirements towards assay development to perform ex-vivo preclinical studies with human samples.