Advanced Dynamic Clamp for Neuroscience

用于神经科学的先进动态钳

• 批准号: 10577885
• 负责人: Mark W Nowak
• 金额: $ 85.89万
• 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/10577885
• 关键词: Action Potentials; Address; Artificial Intelligence; Basic Science; Behavior; Cardiac Myocytes; Cells; Closure by clamp; Computer software; Computers; Coupling; Custom; Data; Dedications; Development; Disease; Electrical Engineering; Electrophysiology (science); Engineering; Feedback; Friends; Genetic; Goals; Innovation Corps; Interruption; Interview; Intuition; Ion Channel; Laboratories; Legal patent; Libraries; Location; Mathematics; Medicine; Membrane; Mental disorders; Modeling; Mutation; National Institute of Mental Health; Nervous System; Neurons; Neurosciences; Operating System; Optics; Patients; Phase; Play; Process; Publishing; Recurrence; Request for Applications; Research; Research Personnel; Resources; Role; Running; Seizures; Signal Transduction; Site; Speed; Stimulus; System; Techniques; Technology Transfer; Telephone; Testing; Therapeutic; Therapeutic Intervention; Time; Work; cell type; commercialization; design; digital; directed differentiation; experimental study; genetic analysis; graphical user interface; improved; innovation; insight; instrumentation; interest; mathematical ability; mathematical model; model building; nerve stem cell; nervous system disorder; novel; novel therapeutics; operation; patch clamp; programs; response; skills; software systems; stem cells; tool; 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.

项目摘要 该第二阶段建议的目标是开发商业“插头”，用户友好，强大和 可靠的动态夹具系统专为神经元应用而设计。我们的产品将启用所有 神经元电生理学家能够执行复杂的动态夹具实验，而无需任何 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 专门用于神经科学应用的硬件和软件包，重点是特定稳定性 常规神经元电生理学和大量离子通道所需的可靠性和可靠性 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 为了达到高速，最重要的是，该产品所需的高可靠性。硬件和 使该系统可靠且稳定的软件创新包括数字调制电导夹 模式。这种新的创新大大扩展了在快速电压变化期间系统稳定性 发生在神经元动作电位期间。包含专有软件使我们的进步成为可能 商业秘密，新颖的专利和专利等待仪器以及我们团队的独特技能。我们的 系统也是第一个能够使用Ca2+（和其他荧光信号）进行交互的动态夹具系统 具有当前的放大器和门控行为。在第一阶段，我们发现引入光学的主要限制 带宽的信号是带宽。在第二阶段，我们有一个匹配的申请专利的自定义低延迟 我们明确开发用于动态夹具的光电探测器系统。该项目的三个目标是： 1）开发以图形为导向的验证模型通道库。这个目标是强烈的客户驱动的， 根据我们的I-Corps访谈的反馈。在实验室中使用动态夹具的最大障碍是 难以实施模型。我们将使动态夹具易于用作手机上的应用。 2）开发和验证用于直观模型构建的网络层的高级版本。我们将建立一个 直观界面与电生理学家如何实际分析其数据相匹配。机器智能会 帮助指导用户完成整个过程，并避免常见错误。他们将能够制作自定义模型 在网络中毫无问题地运行。 3）为客户驱动的功能开发和优化硬件。这不仅包括在内 膜电压作为输入。我们将结合光学信号。我们还将包括经常要求的 提高易用性，响应速度和替代“合成单元”操作方式的功能。 这些目标的完成将导致先进的商业神经元动态夹具系统，这是 功能强大，可靠，但可以安装插件，并且易于使用。