IDBR: Nanoengineered Enhancements to the Patch-Clamp Technique

该奖项支持一个项目，该项目将改进用于记录单个细胞电位的膜片钳测量仪器。膜片钳法是用于此目的的最广泛的方法；自1975年以来，已有2.6万份研究出版物引用了这种方法，其中一半是在过去5年里发表的。尽管这种方法被广泛使用，但由于所使用的设备，该方法有许多众所周知的局限性。特别是，很难同时获得和维持一个以上的记录，这使得对蜂窝网络单个成员的电活动的研究变得困难。此外，录音质量会随着时间的推移而下降，而且录音带宽有限。通过在该合同的支持下开发新的仪器，将更容易获得长时间、多地点的记录，并且更容易获得高带宽信号。传统的膜片钳系统采用玻璃移液器与位于远离移液器尖端的固定位置的Ag/AgCl电极接触细胞。在尖端附近引入任何蜂窝或其他碎片会干扰可靠的测量。在即将开发的设备中，一个可移动的纳米电极可以向前推进并穿过尖端来清除这些碎片。仅这一修改就有望缓解目前大多数膜片钳的局限性。虽然拟议的设备将比标准的膜片钳电极更复杂，但该项目的目标是开发一种能够轻松集成到现有膜片钳系统中的设备。这种使设计适应当前使用的系统的方法应该会鼓励电生理学家迅速接受这种新工具，显著增加它对未来十年生物学研究进展的可能影响。PI一直积极开发新课程和其他活动，为神经科学和生物工程服务。由于膜片钳广泛应用于神经科学和细胞生物学的各个领域，因此该装置的成功开发有望对生物学研究产生广泛的影响。

This award supports a project that will improve instrumentation used for patch-clamp measurements for recording the electrical potential of individual cells. The patch-clamp method is the most widely used method for this purpose; 26,000 research publications have cited the method since 1975, half of these appearing in the last five years. Despite this widespread use, the method has a number of well known limitations that arise from the equipment used. In particular, it is difficult to obtain and to sustain more than one recording at a time, making studies of the electrical activity of individual members of cellular networks difficult. Moreover, the quality of recordings deteriorates with time, and the recording bandwidth is limited. Through the development of new instrumentation undertaken with the support of this award, long-duration, multiple-site recordings will be easier to obtain, and high bandwidth signals will be more accessible. Traditional patch clamp systems employ a glass pipette to contact the cell with an Ag/AgCl electrode located at a fixed position far from the pipette tip. Introduction of any cellular or other debris near the tip interferes with reliable measurement. In the device to be developed, a movable nanoelectrode can be advanced forward and through the tip to clear such debris. This modification alone is expected to alleviate most of the current patch clamp limitations. While the proposed device will be more complex than a standard patch clamp electrode, the project's goal is development of a device that will integrate easily into existing patch clamp systems. This approach of adapting the design to systems currently in use should encourage rapid acceptance of the new tool among electrophysiologists, significantly increasing the likely impact it will have on the progress of biological research over the next decade. The PI has been active in development of new curricula and other activities that serve both neuroscience and bioengineering. Because of the extensive use of the patch-clamp in a variety of areas of neuroscience and cell biology, successful development of the proposed device can be expected to have a broad impact on biological research.