Advanced Dynamic Clamp for Neuroscience

项目摘要 这一第二阶段提案的目标是开发一个商业的“即插即用”、用户友好、功能强大和 专为神经元应用而设计的可靠的动态钳位系统。我们的产品将使所有人 神经元电生理学家能够进行复杂的动态钳制实验，而不需要任何 要求具备编程、工程或数学建模技能。我们的产品是一个集成的 专门用于神经科学应用的硬件和软件包，专注于特定的稳定性 以及常规神经电生理学所需的可靠性以及在 神经系统。在第一阶段，我们开发了软件、操作系统和硬件的关键组合 以实现高速度，最重要的是，该产品所需的高可靠性。硬件和 使该系统可靠和稳定的软件创新包括数字调制电导钳位 模式。这一新的创新极大地扩展了系统在快速电压变化期间的稳定性 发生在神经元动作电位期间。我们的进步是由专利软件实现的，该软件包含 商业秘密，新颖的专利和正在申请专利的仪器，以及我们团队的独特技能。我们的 该系统也是第一个能够使用钙离子(和其他荧光信号)相互作用的动态钳制系统 具有电流幅度和选通行为。在第一阶段，我们发现引入光纤的主要限制 进入动态钳位的信号是带宽。在第二阶段，我们有一个匹配的正在申请专利的定制低延迟 我们专门开发的用于动态夹具的光电探测器系统。这项计划的三个目标是： 1)开发面向图形的验证模型通道库。这一目标强烈地以客户为导向， 根据我们I-Corps采访的反馈。在实验室使用动态夹具的最大障碍是 很难实现模型。我们将使动态夹具像手机上的应用程序一样易于使用。 2)开发和验证用于直观建模的高级版本的CyberSolver。我们将建立一个 直观的界面，与电生理学家实际分析数据的方式相匹配。机器智能将会 帮助指导用户完成该过程并避免常见错误。他们将能够生产定制的模型 这在网络细胞上运行，没有问题。 3)针对客户驱动的功能开发和优化硬件。这包括需要的不仅仅是 膜电压作为输入。我们将整合光学输入信号。我们还将包括经常请求的内容 功能，以提高易用性，响应速度，和一个替代的“合成电池”模式的运作。 这些目标的完成将导致先进的商业神经元动态钳夹系统，这是 功能强大、可靠，但即插即用，安装方便，使用简单。

Project Summary The goal of this Phase II proposal is to develop a commercial “plug and play”, user-friendly, powerful and reliable dynamic clamp system specifically designed for neuronal applications. Our product will enable all neuronal electrophysiologists to be able to perform sophisticated dynamic clamp experiments, without any requirement for programming, engineering, or mathematical modeling skills. Our product is an integrated package of hardware and software specifically for neuroscience applications, focusing on the specific stability and reliability needed for routine neuronal electrophysiology and the large array of ion channels found in the nervous system. In Phase I, we developed the critical combination of software, operating system, and hardware to achieve high speeds, and, most importantly, the high reliability needed for this product. The hardware and software innovations that make this system reliable and stable include a digitally modulated conductance clamp mode. This new innovation greatly expands the stability of the system during the rapid voltage changes that occur during neuronal action potentials. Our advances are made possible by proprietary software containing trade secrets, novel patented and patent pending instrumentation and the unique skill set of our team. Our system is also the first dynamic clamp system capable of using Ca2+ (and other fluorometric signals) to interact with current amplitudes and gating behavior. In Phase I, we found that the main limitation to introducing optical signals into dynamic clamp was bandwidth. In Phase II, we have a matched a patent-pending custom low-latency photodetector system that we developed explicitly for use in dynamic clamp. The three aims of this project are: 1) Develop Graphically Oriented Validated Model Channel Libraries. This aim is strongly customer driven, based on feedback from our I-Corps interviews. The biggest barrier to using dynamic clamp in the laboratory is difficulty implementing models. We will make dynamic clamp as easy to use as an app on your phone. 2) Develop and validate an advanced version of the Cybersolver for intuitive model building. We will build an intuitive interface that matches how electrophysiologists actually analyze their data. Machine intelligence will help guide users through the process and avoid common errors. They will be able to produce custom models that run, without problem, on the Cybercyte. 3) Develop & Optimize Hardware for Customer-driven Features. This includes the need for more than just membrane voltage as an input. We will incorporate optical input signals. We will also include frequently requested features to improve the ease of use, speed of response, and an alternate “synthetic cell” mode of operation. Completion of these aims will result in an advanced commercial neuronal dynamic clamp system, which is powerful, reliable, but plug and play to install, and simple to use.