Nanowire Devices for Ultrasensitive, Multiplexed Detection of Cancer Markers

用于超灵敏、多重检测癌症标记物的纳米线设备

• 批准号: 7597118
• 负责人: CHARLES M LIEBER
• 金额: $ 16.98万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7597118
• 关键词: Address; Affect; Antibodies; Antigens; Area; Binding; Biological; Biological Assay; Biological Models; Biological Testing; Buffers; Cancer Detection; Characteristics; Classification; Competence; Coupled; Detection; Development; Devices; Diagnosis; Diagnostic; Discrimination; Electronics; Environment; Equilibrium; Fc Receptor; Fluorescence; Goals; Growth; Ionic Strengths; Link; Liquid substance; Malignant Neoplasms; Measurement; Methodology; Methods; Modeling; Modification; Monitor; Monoclonal Antibodies; Operative Surgical Procedures; Performance; Play; Process; Property; Proteins; Protocols documentation; Reproducibility; Research; Sampling; Serum; Serum Proteins; Silicon; Solutions; Staging; Surface; Technology; Testing; Time; Transistors; base; cancer recurrence; design; detector; electrical measurement; falls; human disease; improved; link protein; nanodevice; nanoelectronics; nanowire; public health relevance; receptor; response; sensor; Address; Affect; Antibodies; Antigens; Area; Binding; Biological; Biological Assay; Biological Models; Biological Testing; Buffers; Cancer Detection; Characteristics; Classification; Competence; Coupled; Detection; Development; Devices; Diagnosis; Diagnostic; Discrimination; Electronics; Environment; Equilibrium; Fc Receptor; Fluorescence; Goals; Growth; Ionic Strengths; Link; Liquid substance; Malignant Neoplasms; Measurement; Methodology; Methods; Modeling; Modification; Monitor; Monoclonal Antibodies; Operative Surgical Procedures; Performance; Play; Process; Property; Proteins; Protocols documentation; Reproducibility; Research; Sampling; Serum; Serum Proteins; Silicon; Solutions; Staging; Surface; Technology; Testing; Time; Transistors; base; cancer recurrence; design; detector; electrical measurement; falls; human disease; improved; link protein; nanodevice; nanoelectronics; nanowire; public health relevance; receptor; response; sensor

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a robust silicon nanowire-based nanoelectronic sensor technology for rapid, ultra-sensitive and quantitative multiplexed detection of cancer marker proteins. Chemically-synthesized silicon nanowires can provide the uniformity needed for assembly of arrays of reproducible field-effect detectors, and modification of the surfaces of these nanodevices with specific receptors will enable real-time, ultra-sensitive electronic detection of cancer markers. The proposed research will address four specific research areas. First, a robust, addressable nanowire sensor chip and effective chip interface will be developed. Large-scale silicon nanowire growth will be coupled with wafer scale assembly, and the results will be optimized to yield an efficient chip fabrication process that enables good device yield and efficient chip through-put. A new chip interface that enables simple `plug-and-play' interconnection to measurement apparatus will be developed and validated. Large-scale device characterization will be carried out to determine statistical reproducibility of the nanowire transistor properties, and to optimize these properties. Second, a reproducible methodology for linking antibody receptor arrays to functional nanowire device arrays will be developed. Monoclonal antibodies arrays for cancer markers will be linked to the nanowire device arrays using a microarrayer, and the fidelity and competence of the receptors arrays will determine using fluorescence and electrical binding assays. Third, key factors and limits on the nanowire sensor performance will be defined. Systematic studies of the antibody-modified nanowire device array chips will be used to determine key performance factors, including (i) device baseline and detection stability, (ii) detection sensitivity as a function of buffer ionic strength, (iii) selectivity and discrimination against false positive/false negative responses, and (iv) methods for quantitative concentration analysis. In addition, limits for multiplexed detection in the nanowire device arrays will be investigated. Fourth, nanowire device chip characteristics and limits for serum samples will be determined. Protein detection limits in serum analysis as a function of ionic strength, and limits for selective multiplexed detection, including discrimination of false positives from nonselective binding and quantitative concentration analysis will be characterized. The proposed research has broad significance and (1) could enable early stage diagnosis and detection of recurrence of cancer using current diagnostic markers, (2) allow for highly robust diagnosis and treatment by detection and monitoring of panels of emerging cancer markers, and (3) could be generally applied for early stage diagnosis and monitoring of other human diseases. PUBLIC HEALTH RELEVANCE The overall goal of this project is to develop a nanoelectronic sensor technology for rapid, ultra-sensitive and quantitative simultaneous detection of multiple cancer marker proteins. The proposed research has broad significance and promises to (1) enable early stage diagnosis and detection of recurrence of cancer using current diagnostic markers, (2) allow for highly robust diagnosis and treatment by detection and monitoring of panels of emerging cancer markers, and (3) become a general technology for rapid early stage diagnosis and monitoring of human disease.

描述（由申请人提供）：该项目的总体目标是开发一种稳健的硅基纳米电信传感器技术，用于快速，超敏感和定量的癌症标志物蛋白的多重多路复用检测。化学合成的硅纳米线可以提供组装可再现现场效应探测器阵列所需的均匀性，并且对这些纳米构件的表面进行修饰，将其带有特定受体的表面将实现实时的实时，超敏感的癌症标记的超敏感电子检测。拟议的研究将解决四个特定的研究领域。首先，将开发出可靠的，可寻址的纳米线传感器芯片和有效的芯片接口。大规模硅纳米线的生长将与晶圆尺度组装相结合，结果将进行优化，以产生有效的芯片制造工艺，该工艺能够促进良好的设备产量和有效的芯片穿越。将开发和验证一个新的芯片接口，该芯片接口可以使简单的“插件”互连与测量设备进行验证。将进行大规模的设备表征，以确定纳米晶体管特性的统计重复性，并优化这些特性。其次，将开发用于将抗体受体阵列与功能性纳米线阵列联系起来的可重现方法。用于癌症标志物的单克隆抗体阵列将使用微阵列链接到纳米线器件阵列，并且受体阵列的保真度和能力将使用荧光和电结合测定确定。第三，将定义纳米线传感器性能的关键因素和限制。对抗体修饰的纳米线设备阵列芯片的系统研究将用于确定关键性能因素，包括（i）设备基线和检测稳定性，（ii）检测敏感性作为缓冲离子强度的函数，（iii）选择性和对假阳性/假阴性响应的选择性和歧视性，以及（IV）浓度分析。此外，将研究纳米线阵列中多路复用检测的限制。将确定第四，纳米线设备芯片特性和血清样品的限制。血清分析中的蛋白质检测极限是离子强度的函数，以及选择性多重检测的限制，包括从非选择性结合中歧视假阳性和定量浓度分析。拟议的研究具有广泛的意义，（1）可以使用当前的诊断标记来实现早期诊断和检测癌症的复发，（2）允许通过检测和监测新兴癌症标志物的检测和监测来高度稳健的诊断和治疗，并且（3）通常可以用于早期阶段诊断和其他人类疾病的早期诊断和监测。 公共卫生相关性该项目的总体目标是开发一种纳米电子传感器技术，以快速，超敏感和定量的同时检测多种癌症标记蛋白。拟议的研究具有广泛的意义，并承诺（1）使用当前诊断标志物实现早期诊断和检测癌症的复发，（2）允许通过检测和监测新兴癌症标志物的检测和监测来高度鲁棒的诊断和治疗，（3）成为快速的早期阶段诊断和监测人类疾病的一般技术。