Nanowire DNA hybridization sensor

纳米线 DNA 杂交传感器

• 批准号: 6719100
• 负责人: R HUGH DANIELS
• 金额: $ 19.98万
• 依托单位: NANOSYS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-14 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719100
• 关键词: biomedical equipment development; biosensor device; biotechnology; electrical conductance; electrical property; electrochemistry; nanotechnology; nucleic acid hybridization; nucleic acid sequence; oligonucleotides

DESCRIPTION (provided by applicant): The aim of this program is to develop a novel genetic analysis platform that will provide multiple cost, time and sensitivity advantages over conventional technologies. The ability to diagnose the susceptibility to diseases such as breast or colorectal cancer provides valuable information for affected individuals that can lead to early detection and treatment of the disease. Current technologies for identifying genetic mutations and polymorphisms are limited in their diagnostic utility because of the complex sample processing, amplification steps and expensive detection instrumentation. Most genetic analyses is thus relegated to sophisticated and costly testing laboratories. The nanotechnology enabled sensor described in this proposal will be capable of highly selective and sensitive detection of nucleic acid hybridization in an array based format without the need for sample labeling or amplification. Furthermore, instead of expensive optical detection this nanosensor will detect hybridization by changes in electrical conductivity that can be made with a simple, low cost, low power instrument compatible with a point of care or even portable sensor platform. This detection system is based on the discovery that nanoscale materials such as nanotubes and nanowires can act as field effect transistors (FET's) at room temperature. This effect is termed NanoChemFET and it works because the conductive properties of exquisitely sensitive nanowires are modulated by charges on the analyte molecule that act like a gate voltage in a conventional field effect transistor. Because captured DNA or RNA would deliver a defined number of negative charges, proportional to the number of nucleotides brought into the vicinity of the nanowire, nucleic acids are well-suited to sensitive, quantitative analysis by a NanoChemFET sensor. As described in this proposal we will develop processes to controllably manufacture nanowires and assemble them on functional devices. We will use these devices to test the sensor performance for sensing and discriminating specific DNA sequences. In phase I of the program we will detect hybridization of a specific DNA sequence and we will determine the basal sensitivity and discriminatory capabilities of the sensor. This will provide the baseline from which to develop multiple genomic analysis applications including expression arrays, SNP genotyping and the detection of infectious agents in an exquisitely sensitive, rapid and cost effective manner.

描述(由申请人提供)：该项目的目标是开发一种新的基因分析平台，该平台将提供比传统技术更多的成本、时间和灵敏度优势。诊断乳腺癌或结直肠癌等疾病易感性的能力为受影响的个人提供了宝贵的信息，有助于及早发现和治疗这种疾病。由于复杂的样品处理、扩增步骤和昂贵的检测仪器，目前用于识别基因突变和多态的技术在诊断方面的实用价值有限。因此，大多数基因分析都被降级到复杂而昂贵的测试实验室。这项建议中描述的纳米技术传感器将能够以基于阵列的形式高度选择性和灵敏地检测核酸杂交，而不需要对样品进行标记或放大。此外，这种纳米传感器将通过电导率的变化来检测杂交，而不是昂贵的光学检测，这可以通过与护理点甚至便携式传感器平台兼容的简单、低成本、低功耗的仪器来实现。这种检测系统是基于这样一个发现，即纳米级材料，如纳米管和纳米线，在室温下可以充当场效应管(FET)。这种效应被称为纳米化学场效应管，它的工作原理是因为高度敏感的纳米线的导电特性受到分析物分子上的电荷的调制，这些电荷的作用就像常规场效应晶体管中的栅极电压。由于捕获的DNA或RNA将提供一定数量的负电荷，与带入纳米线附近的核苷酸数量成正比，因此核酸非常适合通过NanoChemFET传感器进行灵敏的定量分析。正如这项提案中所描述的，我们将开发可控地制造纳米线的工艺，并在功能设备上组装它们。我们将使用这些设备来测试传感器的性能，以感应和区分特定的DNA序列。在该计划的第一阶段，我们将检测特定DNA序列的杂交，并确定传感器的基本灵敏度和识别能力。这将为开发多种基因组分析应用程序提供基线，包括表达阵列、SNP基因分型和以极其敏感、快速和成本效益的方式检测感染性病原体。