Nanowire DNA hybridization sensor

描述（由申请人提供）：该项目的目的是开发一种新的基因分析平台，该平台将比传统技术提供多重成本，时间和灵敏度优势。诊断对乳腺癌或结直肠癌等疾病的易感性的能力为受影响的个人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，目前用于识别基因突变和多态性的技术在其诊断效用方面受到限制。因此，大多数基因分析都被转移到复杂而昂贵的测试实验室。本提案中描述的纳米技术传感器将能够以阵列为基础的格式进行高选择性和敏感的核酸杂交检测，而无需样品标记或扩增。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，这可以用一种简单、低成本、低功耗的仪器来实现，这种仪器与护理点甚至便携式传感器平台兼容。这种检测系统是基于纳米材料如纳米管和纳米线在室温下可以作为场效应晶体管（FET）的发现。这种效应被称为纳米化学场效应管（NanoChemFET），它之所以起作用，是因为极为敏感的纳米线的导电特性被分析物分子上的电荷调制，这种电荷就像传统场效应晶体管中的栅极电压一样。由于捕获的DNA或RNA会传递一定数量的负电荷，与带入纳米线附近的核苷酸数量成正比，因此核酸非常适合于由纳米化学场效应管传感器进行敏感的定量分析。如本提案所述，我们将开发可控制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，以感知和区分特定的DNA序列。在项目的第一阶段，我们将检测特定DNA序列的杂交，我们将确定传感器的基础灵敏度和区分能力。这将为开发多种基因组分析应用提供基础，包括表达阵列、SNP基因分型和以极其敏感、快速和经济有效的方式检测传染性病原体。

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.