New Platform for Ionic Current Measurement with Application to DNA Sequencing

应用于 DNA 测序的离子电流测量新平台

• 批准号: 7692710
• 负责人: ANDREW D HIBBS
• 金额: $ 37.34万
• 依托单位: ELECTRONIC BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-19 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692710
• 关键词: Area; Benchmarking; Binding; Biological; Blood capillaries; Chemicals; Communities; DNA; DNA Sequence; Data; Devices; Diffusion; Documentation; Electric Capacitance; Electronics; Facility Construction Funding Category; Freedom; Frequencies; Funding; Goals; Hemolysin; Individual; Ion Channel; Laboratories; Legal patent; Lipid Bilayers; Measurement; Measures; Mechanics; Medicine; Membrane; Methods; Modality; Molecular; Names; Nanotechnology; Noise; Numbers; Operating System; Operative Surgical Procedures; Performance; Pharmacologic Substance; Phase; Physiological; Pore Proteins; Process; Property; Public Health; Rate; Reagent; Research; Research Personnel; Resolution; Science; Signal Transduction; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Structure; System; Technology; Temperature; Thick; Time; Training; Update; Work; base; capillary; cold temperature; cost; design; improved; innovation; insight; nanochannel; nanopore; nanoscale; next generation; novel; patch clamp; programs; prototype; solid state; usability; voltage

DESCRIPTION (provided by applicant): This Phase II SBIR program aims to develop and demonstrate an innovative AC measurement system for measuring ionic current in biological and artificial nanoscale channels. Nanopores and nanochannels represent a key emerging component of nanotechnology, as well as a continuing focus of much biophysical and pharmacological research. AC measurement enables new time and amplitude degrees of freedom, such as measurement of the unbiased (zero DC) properties of analyte binding interactions, and new opportunities to study fundamental phenomena. A particular benefit of AC probing is that it permits a significant improvement in measurement sensitivity. In Phase II, our goal is to demonstrate the full capability of the AC method through construction of an optimized sensing platform. Many aspects of this platform will be taken from an ongoing DARPA funded effort to develop protein pore measurement technology for use outside the laboratory, and this Phase II effort will make a number of significant practical advances available to the research community. Specific Phase II objectives are to build a prototype AC system that provides a net increase in measurement signal-to-noise ratio of 10 over present commercial technology, and to demonstrate its capability in an area of active research. The Phase II system will be offered to the research community as an integrated standalone system for basic measurements under the product name: Individual Molecule Analysis Platform (IMAP). A particular application of the AC method is that it potentially offers a means to sequence DNA at a cost much lower than any method that relies on chemical reagents. The potential performance was studied in Phase I with excellent results, and we will continue this effort in Phase II. Indeed, preliminary calculations that were updated based on the Phase I results show that it is just possible that the Phase II system will be able to differentiate the bases of DNA in a true sequencing modality. However, even if that tremendous result is not achieved, the Phase II prototype will provide the next generation in nanopore ionic current measurement capability. PUBLIC HEALTH RELEVANCE: Nanoscale biological channels underlie many of the basic physiologic properties in the body and are targeted by approximately 13% of all pharmaceuticals. In addition, artificial nanoscale structures offer tremendous possibilities to improve medicine and advance basic scientific understanding of molecular processes. The workhorse technology to study such channels and structures has not advanced in 10 years. This program will provide experimental results that were not previously possible, and greatly improve the methods ease of use, thereby reducing operational costs and making the capabilities more available to new researchers.

描述（由申请人提供）：第二阶段 SBIR 计划旨在开发和演示一种创新的交流测量系统，用于测量生物和人造纳米级通道中的离子电流。纳米孔和纳米通道代表了纳米技术的一个关键新兴组成部分，也是许多生物物理和药理学研究的持续焦点。交流测量实现了新的时间和幅度自由度，例如测量分析物结合相互作用的无偏（零直流）特性，以及研究基本现象的新机会。交流探测的一个特殊优点是它可以显着提高测量灵敏度。在第二阶段，我们的目标是通过构建优化的传感平台来展示 AC 方法的全部功能。该平台的许多方面将取自 DARPA 资助的一项正在进行的开发实验室外使用的蛋白质孔测量技术的工作，第二阶段的工作将为研究界带来许多重大的实际进展。第二阶段的具体目标是构建一个原型交流系统，与目前的商业技术相比，该系统的测量信噪比净增加 10 倍，并展示其在积极研究领域的能力。第二阶段系统将作为一个集成的独立系统提供给研究界，用于基本测量，产品名称为：个体分子分析平台（IMAP）。 AC 方法的一个特殊应用是，它可能提供一种 DNA 测序方法，其成本远低于任何依赖化学试剂的方法。第一阶段的潜在性能研究取得了优异的结果，我们将在第二阶段继续这一努力。事实上，根据第一阶段结果更新的初步计算表明，第二阶段系统有可能能够以真正的测序方式区分 DNA 碱基。然而，即使没有实现这一巨大成果，第二阶段原型也将提供下一代纳米孔离子电流测量能力。公共卫生相关性：纳米级生物通道是体内许多基本生理特性的基础，大约 13% 的药物都以纳米级生物通道为目标。此外，人造纳米结构为改善医学和促进对分子过程的基本科学理解提供了巨大的可能性。研究此类通道和结构的主力技术在过去十年中并未取得进展。该计划将提供以前不可能的实验结果，并大大提高方法的易用性，从而降低运营成本并使新研究人员更容易使用这些功能。