Semiconductor Nanosensors for Label-Free Detection of Antigens and Cellular Immun

描述(由申请人提供)：纳米级电子设备有可能实现作为传感器的精密灵敏度，用于检测可溶性抗原和对这些抗原的免疫反应。我们的实验室一直专注于纳米材料的设计和开发，以实现这一目的。例如，里德实验室利用cmos(互补金属氧化物半导体)-fet(场效应晶体管)技术开发了一种半导体固态技术，这是将这些传感器集成到标准电子设备中的系统规模的关键一步。这些设备可以进行化学表面修饰，对结合分子电荷高度敏感，能够快速、无标记地检测溶液中DNA和蛋白质的毫微摩尔浓度(在几秒钟内)。此外，这些新设备能够感应到刺激诱导的微升体积的微小细胞胞外酸化。Fahmy实验室专注于新型生物材料在检测和调节免疫反应方面的应用。在这里，这些经验的结合将集中于这些纳米传感器的优化和测试，作为检测抗原、抗体和抗原反应性淋巴细胞的诊断。我们的应用程序旨在展示这项技术在癌症诊断应用中的实用性。我们的工作假设是，纳米级的CMOS线可以被开发成对可溶性抗原以及对这些抗原的免疫反应的快速、定量诊断装置。为了验证这一假设，我们建议：1)制造集成的半导体纳米传感器，结合芯片上的流体，以实现高通量采样能力。2)优化这些传感器的化学表面修饰以进行配基结合，并测试传感器检测癌症标记物和生产疫苗介导的抗体的灵敏度极限。3)展示了该系统在检测抗原特异性淋巴细胞反应和肿瘤相关疫苗反应方面的应用。由于该方法的优势在于新颖的纳米线制造方案和与CMOS技术的无缝集成，因此我们的方法便于在需要对样本进行敏感和高通量筛选的基础和诊断临床环境中广泛使用。 相关声明：我们开发了一种合成纳米线(NW)的新技术，使其首次能够与微电子系统直接集成，并具有作为高灵敏度生物分子检测器的能力，可能会给生物诊断应用带来革命性的变化。我们提出的工作概述了下一代便携式电子纳米传感器的研究计划，并展示了其在癌症生物标志物读出和免疫反应中的应用。这些纳米传感器可以用一种强大的固态设备取代当前的技术，有助于在临床环境中进行快速诊断。

DESCRIPTION (provided by applicant): Nanoscale electronic devices have the potential to achieve exquisite sensitivity as sensors for the detection of soluble antigens and the immune response to those antigens. Our laboratories have focused on the design and development of nanomaterials to achieve this purpose. For example, the Reed laboratory has developed a semiconductor solid-state technology using CMOS (complementary metal-oxide-semiconductor)-FET (field effect transistor) technology, a critical step in system-scale integration of these sensors into standard electronics. These devices are amenable to chemical surface modification and are highly sensitive to bound molecular charge, enabling rapid, label-free detection (within seconds) of femtomolar concentrations of DNA and proteins in solution. In addition, these new devices enable sensing of stimulus induced extracellular acidification of a minute number of cells in microliter volumes. The Fahmy laboratory is focused on the application of novel biomaterials to detection and modulation of the immune response. Here, this combination of experience will be focused on the optimization and testing of these nanosensors as a diagnostic for detection of antigens, antibodies and antigen-responsive lymphocytes. Our application aims to demonstrate the utility of this technology for cancer diagnostic applications. Our working hypothesis is that nanoscale CMOS wires can be developed as rapid, quantitative diagnostic devices of soluble antigens as well as the immune response to those antigens. To test this hypothesis, we propose to: 1) Fabricate integrated semiconducting nanosensors incorporating on-chip fluidics for high throughput sampling capability. 2) Optimize chemical surface modification of these sensors for ligand binding, and test the limits of sensitivity of the sensor for detection of cancer markers and production of vaccine-mediated antibodies. 3) Demonstrate the utility of this system in the detection of antigen- specific lymphocyte responses and tumor-associated vaccine response. Because the strength of the approach lies in a novel fabrication scheme of nanowires and seamless integration with CMOS technology, our approach facilitates wide use in basic and diagnostic clinical settings requiring sensitive and high-throughput screening of samples. Relevance Statement: We have developed a novel technology to synthesizing nanowires (NWs) allowing their direct integration with microelectronic systems for the first time, as well as their ability to act as highly sensitive biomolecule detectors that could revolutionize biological diagnostic applications. Our proposed work outlines a research plan for the development of the next generation portable electronic nanosensor and demonstrates its application in the read-out of cancer biomarkers and the immune response. These nanosensors can replace current technology with a powerful solid-state device useful for rapid diagnosis in clinical settings.