Nanopatch System for Next Generation Ion Channel Recordings

描述(由申请人提供)：该第二阶段SBIR计划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。所提出的系统将允许在平面脂质双层(PLB)系统上进行以前只能用膜片钳方法获得的高灵敏度测量。该系统依赖于石英纳米孔膜平台上的纳米级双层薄膜和EBS设计的电子设备，以降低传统PLB系统通常相关的噪音。该计划的目的是提高低频噪声性能，使之与膜片钳相媲美，调整已有的协议并开发新的方法，以增加可纳入Nanopatch系统的离子通道类型，并展示使用低电导和快速动力学的细胞内通道的系统能力。还将生产四个Nanopatch原型系统。与现有的离子通道测量仪器相比，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、坚固和可重复的双层形成、精细的温度和压力控制以及自动双层形成和离子通道并入。所提出的Nanopatch系统将能够在PLB中以以前无法达到的分辨率和灵敏度来评估大范围的低电导通道和具有快速动力学的通道。 与公共卫生相关：离子通道在从控制神经冲动到心脏调节的广泛生理功能中都是关键的，医学研究人员每年都会发现数十到数百种新的通道病变，因为人们认识到许多疾病都是由通道故障引起的。为了利用针对这些通道的新药的这一知识，需要对单个通道电导进行完整的表征。Nanopatch系统将提供一种手段来实现这一特征，并增加可调查的通道数量，大大降低获得这些测量的难度，并允许由于使用坚固的双层平台增加测量时间而获得完整的剂量效应曲线。

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.