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

用于无标记检测抗原和细胞免疫的半导体纳米传感器

• 批准号: 7499641
• 负责人: Tarek Fahmy
• 金额: $ 36.49万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-24 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7499641
• 关键词: Acidity; Affinity; Animals; Antibodies; Antigens; B-Lymphocytes; Binding; Biocompatible Materials; Biological; Biological Markers; Blood; CD3 Antigens; Calibration; Cancer Detection; Cancer Diagnostics; Cancer Vaccines; Cell Count; Cell surface; Charge; Chemicals; Clinical; Communicable Diseases; DNA; DNA Viruses; Detection; Development; Development Plans; Devices; Diagnostic; Drops; Early Diagnosis; Electronics; Extracellular Fluid; Frequencies; Goals; Histocompatibility Antigens Class II; Immune response; Immunity; In Vitro; Individual; Ions; Label; Laboratories; Lead; Ligand Binding; Ligands; Lymphocyte; MHC antigen; Major Histocompatibility Complex; Malignant Neoplasms; Mediating; Medical; Metabolic; Methods; Microfluidics; Modeling; Modification; Molecular; Monitor; Mus; Parasitic Diseases; Peptide/MHC Complex; Peptides; Performance; Phase; Physiological; Point-of-Care Systems; Process; Proteins; Purpose; Reading; Research; Sampling; Scheme; Semiconductors; Serum; Solutions; Specificity; Standards of Weights and Measures; Stimulus; Surface; System; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Techniques; Technology; Testing; Time; Transgenic Organisms; Transistors; Translating; Tumor Antigens; Vaccinated; Vaccine Production; Vaccines; Viral; Work; base; clinically relevant; concept; cost; crosslink; design; detector; experience; extracellular; high throughput screening; macromolecule; metal oxide; nanomaterials; nanoscale; nanosensors; nanowire; new technology; next generation; novel; preclinical study; prototype; rapid detection; rapid diagnosis; research study; response; sensor; small molecule; solid state; tumor

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.

描述（由申请人提供）：纳米级电子器件具有作为传感器实现灵敏度的潜力，用于检测可溶性抗原和对这些抗原的免疫应答。我们的实验室专注于纳米材料的设计和开发，以实现这一目的。例如，Reed实验室开发了一种使用CMOS（互补金属氧化物半导体）-FET（场效应晶体管）技术的半导体固态技术，这是将这些传感器系统规模集成到标准电子产品中的关键一步。这些设备适合化学表面改性，对结合的分子电荷高度敏感，能够快速，无标记检测（几秒钟内）溶液中的DNA和蛋白质的飞摩尔浓度。此外，这些新设备能够感测刺激诱导的微升体积中的微小数量的细胞的细胞外酸化。Fahmy实验室专注于新型生物材料在检测和调节免疫反应中的应用。在这里，这种经验的结合将集中在这些纳米传感器的优化和测试，作为抗原，抗体和抗原反应淋巴细胞检测的诊断。我们的应用旨在展示该技术在癌症诊断应用中的实用性。我们的工作假设是，纳米CMOS线可以开发为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，我们提出：1）制造集成的半导体纳米传感器，结合芯片上的流体高通量采样能力。2)优化这些传感器的配体结合的化学表面修饰，并测试传感器检测癌症标志物和疫苗介导抗体产生的灵敏度极限。3)证明该系统在检测抗原特异性淋巴细胞应答和肿瘤相关疫苗应答中的实用性。由于该方法的优势在于纳米线的新型制造方案和与CMOS技术的无缝集成，因此我们的方法有助于在需要灵敏和高通量筛选样品的基础和诊断临床环境中广泛使用。 相关性声明：我们已经开发出一种新的技术来合成纳米线（NW），使其首次与微电子系统直接集成，以及它们作为高灵敏度生物分子检测器的能力，这可能会彻底改变生物诊断应用。我们提出的工作概述了下一代便携式电子纳米传感器的发展研究计划，并展示了其在癌症生物标志物和免疫反应的读出中的应用。这些纳米传感器可以用强大的固态设备取代当前的技术，用于临床环境中的快速诊断。