Nanopore array force spectroscopy chip for rapid clinical genotyping

用于快速临床基因分型的纳米孔阵列力谱芯片

• 批准号: 7317184
• 负责人: ANDRE MARZIALI
• 金额: $ 22.79万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7317184
• 关键词: Adoption; Applications Grants; Base Sequence; Biological Assay; Blood; Caliber; Clinical; Communities; Complex; DNA; DNA Sequence; Detection; Development; Devices; Disease; Electronics; Elements; Facility Construction Funding Category; Genes; Genetic; Genetic Polymorphism; Genomics; Genotype; Grant; Healthcare; Hour; Individual; Industry; Intervention; Label; Membrane; Methods; Microfluidics; Mutation; Mutation Detection; Noise; Nucleic Acids; Patients; Performance; Predisposition; Process; Rate; Research Personnel; Resolution; Scheme; Sensitivity and Specificity; Signal Transduction; Solutions; Spectrum Analysis; Testing; Time; Variant; Work; base; commercialization; concept; data acquisition; design; drug metabolism; genotyping technology; hydrophilicity; improved; insertion/deletion mutation; method development; nanopore; nanoscale; prototype; response; sensor; single molecule; size; solid state; tool

DESCRIPTION (provided by applicant): A major barrier to utilization of genotype information in personalized health care is the complexity and time required by existing genotyping processes. Rapid clinical intervention that is guided by genetic information from individual patients will require determination of tens of mutations per patient in less than one hour. Though methods currently exist that are capable of analyzing a single mutation in 30-60 minutes, this greatly limits the utility of genotype information to diseases and predispositions that depend on a single mutation. Methods for analyzing tens to hundreds of mutations require several hours to carry out, and are too slow for an appropriate clinical response. Likewise, high throughput genotyping technologies that can analyze thousands of patients simultaneously are inappropriate for the single-patient/rapid response required in a clinical setting. There is therefore a pressing need, driven by clinical experts and industry, for simple and rapid genotyping technologies capable of analyzing on the order of a hundred loci in a matter of minutes. Nanometer-sized pores in an insulating membrane represent an important new mode of detection and analysis of biomolecules. Though nanopore-based single-molecule detection schemes are already candidates for high throughput DMA sequencing, genotyping is a nearer-term application that is clinically important and will produce benefits to the DMA sequencing community. Multi-nanopore force spectroscopy promises to be a rapid, sensitive and label-free nucleic acid analysis scheme. In previous work we demonstrated the ability to detect sequence at single base resolution using organic nanopore force spectroscopy. In this continuation of our previous work, we aim at the development of solid-state nanopore- based force spectroscopy for rapid electronic detection of sequence variation. We envision the eventual development of a commercial device based on an array of nanoporous membrane elements, each designed to recognize a particular sequence. In this grant application, we propose the development of a device and methods to serve as a proof-of-concept of one element of such an array. We will construct a prototype element, and iterate on fabrication and methods development while testing its sensitivity, and specificity.

描述（由申请人提供）：个性化医疗保健中基因型信息利用的主要障碍是现有基因分型过程所需的复杂性和时间。由个别患者的遗传信息引导的快速临床干预将需要在不到一小时的时间内确定每位患者数十个突变。尽管目前存在能够在30-60分钟内分析单个突变的方法，但这极大地将基因型信息的实用性限制在依赖于单个突变的疾病和倾向。分析数十至数百个突变的方法需要几个小时才能进行，并且对于适当的临床反应而言太慢了。同样，可以同时分析数千名患者的高吞吐基因分型技术不适合临床环境中所需的单患者/快速反应。因此，在临床专家和行业的驱动下，有一个紧迫的需求，用于简单而快速的基因分型技术，能够在几分钟之内分析一百个基因座的顺序。绝缘膜中的纳米尺寸孔代表了生物分子的检测和分析的重要新模​​式。尽管基于纳米孔的单分子检测方案已经是高吞吐量DMA测序的候选者，但基因分型是一种近期的应用，在临床上很重要，将为DMA测序社区带来好处。多纳米孔力光谱有望成为一种快速，敏感和无标记的核酸分析方案。在先前的工作中，我们证明了使用有机纳米孔力光谱法以在单碱基分辨率下检测序列的能力。在我们以前的工作的延续中，我们旨在开发固态纳米孔的力光谱，以快速电子检测序列变化。我们设想基于一系列纳米方膜元素的商业设备的最终开发，每个元素旨在识别特定序列。在此赠款应用程序中，我们建议开发一种设备和方法，以作为该数组中一个元素的概念概念。我们将构建一个原型元素，并在测试其敏感性和特异性的同时进行制造和方法开发。