New Platform for Ionic Current Measurement with Application to DNA Sequencing

描述（由申请人提供）：该二期SBIR项目旨在开发和演示一种创新的交流测量系统，用于测量生物和人工纳米级通道中的离子电流。纳米孔和纳米通道是纳米技术的一个重要新兴组成部分，也是许多生物物理和药理学研究的持续焦点。交流测量提供了新的时间和振幅自由度，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。交流探测的一个特别好处是它可以显著提高测量灵敏度。在第二阶段，我们的目标是通过构建一个优化的传感平台来展示交流方法的全部能力。该平台的许多方面将从DARPA资助的一项正在进行的工作中获得，该工作旨在开发用于实验室之外的蛋白质孔隙测量技术，该第二阶段的工作将为研究界提供许多重要的实际进展。第二阶段的具体目标是建立一个原型交流系统，该系统的测量信噪比比目前的商业技术净增加10，并在一个活跃的研究领域展示其能力。II期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，它有可能提供一种比任何依赖化学试剂的方法成本低得多的DNA测序方法。我们在第一期研究了潜在的性能，并取得了良好的结果，我们将在第二期继续这项工作。事实上，基于第一阶段结果更新的初步计算表明，第二阶段系统将有可能以真正的测序方式区分DNA的碱基。然而，即使这个巨大的结果没有实现，第二阶段的原型将提供下一代纳米孔离子电流测量能力。公共卫生相关性：纳米级生物通道是人体许多基本生理特性的基础，是大约13%的药物的靶点。此外，人造纳米结构为改善医学和推进对分子过程的基本科学理解提供了巨大的可能性。研究这类通道和结构的主力技术10年来一直没有进步。该项目将提供以前不可能的实验结果，并大大提高方法的易用性，从而降低操作成本，使新研究人员更容易获得这些能力。

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.