Nanopatch System for Next Generation Ion Channel Recordings

描述（由申请人提供）：该二期SBIR项目旨在进一步开发用于离子通道测量的电子生物科学（EBS）纳米贴片系统。该系统将允许在平面脂质双分子层（PLB）系统上使用膜片钳方法进行高灵敏度测量。该系统依靠石英纳米孔膜平台上的纳米级双层结构和EBS设计的电子元件来降低传统PLB系统的噪声。该项目的目的是提高低频噪声性能，以与贴片夹紧相媲美，适应已建立的协议，并开发新的方法来增加可纳入纳米贴片系统的离子通道类型，并展示该系统使用具有低电导和快速动力学的细胞内通道的能力。四个纳米贴片系统原型也将被生产出来。与目前可用的离子通道测量设备相比，这种改进的纳米贴片系统将具有几个明显的优势，包括低噪声，高带宽平台，坚固且可重复的双层形成，精细的温度和压力控制以及自动双层形成和离子通道合并。所提出的纳米贴片系统将使大范围的低电导通道和具有快速动力学的通道能够在PLB中以以前无法达到的分辨率和灵敏度进行评估。

DESCRIPTION (provided by applicant): This Phase II SBIR program aims to further develop Electronic Bio Sciences' (EBS) Nanopatch system for ion channel measurements. The proposed system will allow high sensitivity measurements previously only attainable with the patch clamp method to be performed on a planar lipid bilayer (PLB) system. The system relies on a nanometer scale bilayer on the quartz nanopore membrane platform and EBS designed electronics to reduce the noise typically associated with a traditional PLB system. The aims of this program are to improve the low frequency noise performance to rival that of patch clamping, adapt established protocols and develop new methods to increase the types of ion channels that can be incorporated into the Nanopatch system and demonstrate the capabilities of the system using an intracellular channel with low conductance and fast kinetics. Four prototype Nanopatch systems will also be produced. This improved Nanopatch system will have several distinct advantages over currently available ion channel measurement apparatus including a low noise, high bandwidth platform, robust and reproducible bilayer formation, fine temperature and pressure control and automated bilayer formation and ion channel incorporation. The proposed Nanopatch system will enable a large range of low conductance channels and channels with fast kinetics to be evaluated in a PLB at previously unattainable resolution and sensitivity. PUBLIC HEALTH RELEVANCE: Ion channels are critical in an enormous range of physiological functions ranging from control of nerve impulses to cardiac regulation and medical researchers are discovering tens to hundreds of new channelopathies per year as many diseases are being recognized that arise from channel malfunction. In order to exploit this knowledge for new drugs targeting these channels, a complete characterization of the individual channel conductance is needed. The Nanopatch system will provide a means to achieve this characterization as well as increase the number of channels that can be investigated, substantially decrease the difficulty in obtaining these measurements and allow complete dose effect curves to be obtained due to increased measurement times with the robust bilayer platform.