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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

基本信息

批准号：
7873020
负责人：
Tarek Fahmy
金额：
$ 36.13万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-24 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7873020
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 Reading Research Sampling Scheme Semiconductors Serum Solutions Specificity Stimulus Surface System T cell response 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 cost crosslink design detector efficacy testing 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

项目摘要

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检测可溶性抗原和对这些抗原的免疫反应的传感器的高灵敏度的潜力。我们的实验室一直致力于纳米材料的设计和开发，以实现这一目的。例如，里德实验室开发了一种使用CMOS（互补金属氧化物半导体）-场效应晶体管（fet）技术的半导体固态技术，这是将这些传感器集成到标准电子产品中的系统规模的关键一步。这些装置可以进行化学表面修饰，对结合的分子电荷高度敏感，能够在几秒钟内快速、无标记地检测出溶液中DNA和蛋白质的飞摩尔浓度。此外，这些新设备能够感知刺激诱导的微升体积的细胞外酸化。Fahmy实验室专注于应用新型生物材料来检测和调节免疫反应。在这里，这些经验的结合将集中在这些纳米传感器的优化和测试上，作为检测抗原、抗体和抗原反应淋巴细胞的诊断。我们的应用程序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，纳米级CMOS导线可以发展为可溶性抗原的快速、定量诊断设备，以及对这些抗原的免疫反应。为了验证这一假设，我们建议：1)制造集成半导体纳米传感器，结合片上流体，以获得高通量采样能力。2)优化这些传感器的化学表面修饰，用于配体结合，并测试传感器检测癌症标志物和产生疫苗介导抗体的灵敏度极限。3)证明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中的实用性。由于该方法的优势在于纳米线的新颖制造方案和与CMOS技术的无缝集成，我们的方法有助于广泛应用于需要敏感和高通量样品筛选的基础和诊断临床环境。