New Platform for Ionic Current Measurement with Application to DNA Sequencing

描述(由申请人提供)：该第二阶段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。纳米孔和纳米通道是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重点。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。交流探头的一个特别优点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AC方法的全部能力。该平台的许多方面将来自DARPA资助的正在进行的开发实验室外使用的蛋白质孔测量技术的努力，这一第二阶段的努力将使研究界获得一些重要的实际进展。第二阶段的具体目标是建立一个原型交流系统，提供比目前商业技术净增加10%的测量信噪比，并在一个活跃的研究领域展示其能力。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：单个分子分析平台(IMAP)。AC方法的一个特殊应用是，它潜在地提供了一种以比任何依赖化学试剂的方法低得多的成本对DNA进行排序的方法。在第一阶段对潜在的性能进行了研究，取得了很好的结果，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，第二阶段系统将能够以真正的测序方式区分DNA的碱基。然而，即使没有取得如此巨大的结果，第二阶段原型也将提供下一代纳米孔离子流测量能力。与公共健康相关：纳米尺度的生物通道是人体许多基本生理特性的基础，大约13%的药物以纳米生物通道为靶标。此外，人工纳米结构为改进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。研究这种渠道和结构的主力技术已经有10年没有进步了。该计划将提供以前无法提供的实验结果，并极大地提高方法的易用性，从而降低操作成本，使新的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.