Nanopatch System for Next Generation Ion Channel Recordings

用于下一代离子通道记录的 Nanopatch 系统

• 批准号: 7272507
• 负责人: ANDREW D HIBBS
• 金额: $ 15.3万
• 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: 2007-08-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7272507
• 关键词: Adverse effects; Amplifiers; Architecture; Area; Arts; Axon; Biological Process; Biology; Biophysics; Biosensor; Communities; Custom; Development; Devices; Disease; Electric Capacitance; Electronics; Elements; Event; Frequencies; Funding; Glass; Investigation; Ion Channel; Laboratories; Lead; Left; Link; Lipid Bilayers; Lipids; Measurement; Measures; Medical; Membrane; Methods; Molecular Biology; Molecular Medicine; Noise; Performance; Pharmaceutical Preparations; Phase; Process; Range; Reaction; Reaction Time; Records; Research; Research Personnel; Screening procedure; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Source; Speed; Structure; Surface; System; Technology; Testing; Thick; Time; Universities; Utah; Variant; base; concept; cost; day; design; drug development; electrical measurement; electrical property; improved; instrument; millimeter; nanopore; nanoscale; next generation; patch clamp; programs; prototype; radius bone structure; single molecule; size; voltage; volunteer

DESCRIPTION (provided by applicant): Ion channels are the control mechanisms of an enormous range of biological functions. Medical researchers are discovering tens or hundreds of new channelopathies per year as many diseases are being recognized that arise from channel malfunction. In addition, the adverse side effects of some drugs on ion channels have the potential to cause lethal reactions within the body. The entire biology, molecular biology, and biophysics of ion channels is thus of great medical importance. Channels are also inherently multiscale devices that link atomic scale structures to macroscopic flows responding to single molecules with substantial current flow. Current patch clamp methods used to study this current flow are limited in two key areas to maximize the information that can be gained from studying these channels. First, current systems cannot achieve a low enough noise level to measure many channels with low conductances, such as the Ca channels. Secondly, these systems are unable to reach a large enough bandwidth to detect many short duration single channel events seen in many channels such as the Na channel. The proposed project aims to further develop a glass nanopore system, previously developed under a DARPA project, into a nanopatch device capable of measuring single channel currents. This device consists of a new membrane configuration comprised of a nanometer-scale pore (10 nm to 75 nm radius) in a millimeter-scale glass surface covered by a lipid bilayer. The new nanopatch technology offers the possibility of increasing measurement sensitivity at low frequencies, and increasing the upper operating frequency, which would represent a real advance in scientific measurement capability. The overall aim of this Phase I SBIR program is to establish the specific embodiment, or combination of embodiments, for which the new lipid on glass nanopore configuration can best be applied to improve on the state-of-the-art in laboratory ion channel measurements. This investigation will be conducted with Dr. Henry White from the University of Utah, whose lab helped develop the glass nanopores. This project proposes a new system to improve the quality of ion channel current measurement technology. Such an improvement in the technology could lead to better methods for drug development and screening and offer the capability to test experimental drugs' effect on ion channels, and thus on many processes in the body, without actually having to give the drug to volunteers. In addition, the proposed technology could make possible accurate measurements of specific ion channel currents and might enable development of new drugs to target the activities in those channels. Finally, the technological improvements proposed would bring considerable benefit to the biomolecular research community.

描述（由申请人提供）：离子通道是多种生物功能的控制机制。随着许多疾病被认为是由通道故障引起的，医学研究人员每年都会发现数十或数百种新的通道病。此外，一些药物对离子通道的不良副作用有可能在体内引起致命反应。因此，离子通道的整个生物学、分子生物学和生物物理学具有重要的医学意义。通道本质上也是多尺度装置，它将原子尺度结构与宏观流动联系起来，响应具有大量电流的单分子。目前用于研究这种电流的膜片钳方法仅限于两个关键领域，以最大限度地提高从研究这些通道中获得的信息。首先，当前系统无法实现足够低的噪声水平来测量许多低电导通道，例如 Ca 通道。其次，这些系统无法达到足够大的带宽来检测在许多通道（例如 Na 通道）中看到的许多短持续时间的单通道事件。该项目旨在将先前在 DARPA 项目下开发的玻璃纳米孔系统进一步开发为能够测量单通道电流的纳米贴片装置。该装置由一种新的膜结构组成，该结构由毫米级玻璃表面上的纳米级孔（半径为 10 nm 至 75 nm）组成，表面覆盖有脂质双层。新的纳米贴片技术提供了提高低频测量灵敏度和提高工作频率上限的可能性，这将代表科学测量能力的真正进步。该第一阶段 SBIR 计划的总体目标是建立具体的实施方案或实施方案的组合，其中玻璃纳米孔结构上的新脂质可以最好地应用于改进实验室离子通道测量的最先进水平。这项研究将由犹他大学的亨利·怀特博士进行，他的实验室帮助开发了玻璃纳米孔。该项目提出了一种新系统来提高离子通道电流测量技术的质量。这种技术的改进可以带来更好的药物开发和筛选方法，并提供测试实验药物对离子通道的影响的能力，从而测试对体内许多过程的影响，而无需实际将药物给予志愿者。此外，所提出的技术可以准确测量特定离子通道电流，并可以开发针对这些通道活动的新药物。最后，所提出的技术改进将为生物分子研究界带来相当大的好处。