Integrated Biochip Sensors for Detection of Cancer

描述（由申请人提供）：最近在自上而下的硅纳米技术和半导体材料微加工方面的技术进步为小型、敏感、一次性使用、护理点诊断设备提供了新的机会，这些设备能够快速、高度准确地分析体液样本。纳米传感器和微流体生物芯片已经成功地用于检测液体中的蛋白质，但仍然需要在一个强大的阵列格式中实现，可以检测多种蛋白质，这可以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团队，目标是应用和转化多学科研究，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，集成在一次性使用的护理点诊断生物芯片中，具有多种抗体功能，用于从乳腺吸出物的细胞裂解液中检测癌症蛋白。这些任务将由我们的研究团队完成，他们具有临床翻译（ILJSOM的Susan Clare），硅基场效应器件的微/纳米制造和片上样品的浓度和分离（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）和癌症生物化学（普渡大学的Don Bergstrom）的专业知识。以下是该项目的具体目标：(i)开发利用乳腺吸吸器的芯片细胞溶解方法；（ii）开发新技术，用抗体使传感器阵列表面功能化，同时最大限度地减少非特异性吸附和生物污染；（iii）开发新的计算和模拟策略，对液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，用于多路检测癌症蛋白质和标志物；㈤开发综合生物芯片传感器，进行广泛的试验和临床前研究。我们将继续关注分析开发的问题和要求，以进行人类样本的离体临床前研究。

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.