Nanowire DNA hybridization sensor

描述（由申请人提供）：该计划的目的是开发一种新的遗传分析平台，与传统技术相比，该平台将提供多种成本，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体提供了有价值的信息，可以导致疾病的早期发现和治疗。由于复杂的样品处理、扩增步骤和昂贵的检测仪器，目前用于鉴定基因突变和多态性的技术在其诊断实用性方面受到限制。因此，大多数遗传分析都被交给了复杂而昂贵的测试实验室。在该提议中描述的纳米技术使能的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，而不需要样品标记或扩增。此外，代替昂贵的光学检测，这种纳米传感器将通过电导率的变化来检测杂交，这可以用与护理点或甚至便携式传感器平台兼容的简单、低成本、低功率仪器来实现。这种检测系统是基于纳米级材料如纳米管和纳米线在室温下可以充当场效应晶体管（FET）的发现。这种效应被称为NanoChemFET，它的工作原理是因为精密敏感的纳米线的导电性能是由分析物分子上的电荷调制的，这些电荷的作用就像传统场效应晶体管中的栅极电压。由于捕获的DNA或RNA会传递与进入纳米线附近的核苷酸数量成比例的确定数量的负电荷，因此核酸非常适合通过NanoChemFET传感器进行灵敏的定量分析。如本提案所述，我们将开发可控制造纳米线并将其组装在功能器件上的工艺。我们将使用这些设备来测试传感器的性能，用于传感和区分特定的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辨别能力。这将为开发多个基因组分析应用提供基线，包括表达阵列，SNP基因分型和以灵敏，快速和成本效益的方式检测感染因子。

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.