Advanced Dynamic Clamp for Neuroscience

用于神经科学的先进动态钳

• 批准号: 10868186
• 负责人: Mark W Nowak
• 金额: $ 37.86万
• 依托单位: CYTOCYBERNETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-19 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10868186
• 关键词: Action Potentials; Artificial Intelligence; Behavior; Cells; Closure by clamp; Computer software; Computers; Custom; Data; Disease; Electrophysiology (science); Engineering; Feedback; Goals; Innovation Corps; Interview; Intuition; Ion Channel; Laboratories; Legal patent; Libraries; Medicine; Membrane; Mental disorders; Modeling; Mutation; Nervous System; Neurons; Neurosciences; Operating System; Optics; Phase; Play; Process; Running; Seizures; Signal Transduction; Speed; Stimulus; System; Telephone; design; digital; experimental study; improved; innovation; instrumentation; mathematical model; model building; nervous system disorder; novel; operation; response; skills; user-friendly; voltage

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.

项目概要 第二阶段提案的目标是开发一个商业“即插即用”、用户友好、功能强大且 专为神经应用而设计的可靠动态夹具系统我们的产品将使所有这些成为可能。 神经元电生理学家能够执行复杂的动态钳实验，无需任何 对编程、工程或数学建模技能的要求我们的产品是一个集成的产品。 专门针对神经科学应用的硬件和软件包，重点关注特定的稳定性 常规神经元电生理学和在神经元中发现的大量离子通道所需的可靠性和可靠性 在第一阶段，我们开发了软件、操作系统和硬件的关键组合。 实现高速度，最重要的是，实现该产品所需的高可靠性。 使该系统可靠稳定的软件创新包括数字调制电导钳 这项新的创新极大地提高了系统在电压快速变化期间的稳定性。 发生在神经动作电位期间的软件使我们的进步成为可能。 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。 该系统也是第一个能够使用 Ca2+（和其他荧光信号）相互作用的动态钳系统 在第一阶段，我们发现引入光学的主要限制。 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。 我们专门开发用于动态钳位的光电探测器系统该项目的三个目标是： 1) 开发面向图形的验证模型通道库 这一目标是由客户驱动的。 根据我们对 I-Corps 采访的反馈，在实验室中使用动态夹具的最大障碍是。 实现模型的困难。我们将使动态夹具像手机上的应用程序一样易于使用。 2) 开发并验证 Cyber​​solver 的高级版本，以进行直观的模型构建。 直观的界面与电生理学家实际分析数据的方式相匹配。 帮助指导用户完成整个过程并避免常见错误他们将能够生成自定义模型。 在 Cyber​​cyte 上运行没有问题。 3) 为客户驱动的功能开发和优化硬件这不仅仅需要。 我们还将包含经常要求的光输入信号。 提高易用性、响应速度和替代“合成电池”操作模式的功能。 完成这些目标将产生先进的商业神经动态钳系统，该系统是 功能强大、可靠，但即插即用，安装简单，使用简单。