Advanced Dynamic Clamp for Neuroscience

用于神经科学的先进动态钳

• 批准号: 10483575
• 负责人: Mark W Nowak
• 金额: $ 86.08万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483575
• 关键词: Action Potentials; Address; Artificial Intelligence; Basic Science; Behavior; Cardiac Myocytes; Cells; Closure by clamp; Computer software; Computers; Coupling; Custom; Data; Development; Disease; Electrical Engineering; Electrophysiology (science); Engineering; Feedback; Genetic; Goals; Gold; Home; 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 structure; Neurons; Neurosciences; Operating System; Optics; Patients; Phase; Play; Process; Publishing; 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; base; cell type; commercialization; design; digital; 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 第二阶段提案的目标是开发一种商业“即插即用”、用户友好、功能强大且 专为神经元应用设计的可靠动态夹系统。我们的产品将使所有 神经电生理学家能够进行复杂的动态钳实验，没有任何 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，专注于特定的稳定性 和可靠性所需的常规神经元电生理学和大阵列的离子通道中发现的 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 以实现该产品所需的高速度以及最重要的高可靠性。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中。我们的进步是由专有软件， 商业秘密，新颖的专利和正在申请专利的仪器和我们团队的独特技能。我们 该系统也是第一个能够使用Ca 2+（和其他荧光信号）相互作用的动态夹钳系统。 具有电流幅度和选通行为。在第一阶段，我们发现引入光学的主要限制是， 信号进入动态钳位是带宽。在第二阶段，我们有一个匹配的专利申请中的自定义低延迟 光电探测器系统，我们明确开发用于动态钳位。该项目的三个目标是： 1)开发面向图形的验证模型通道库。这一目标是由客户强烈驱动的， 根据我们对I-Corps的采访反馈在实验室中使用动态夹的最大障碍是 实施模式困难。我们将使动态夹钳像手机上的应用程序一样易于使用。 2)开发和验证Cybersolver的高级版本，用于直观的模型构建。我们将建立一个 与电生理学家实际分析数据的方式相匹配的直观界面。机器智能将 帮助指导用户完成整个过程并避免常见错误。他们将能够生产定制模型 在赛博细胞上运行毫无问题 3)为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。我们将结合光学输入信号。我们还将包括经常要求 这些功能提高了易用性、响应速度和替代的“合成细胞”操作模式。 这些目标的完成将导致先进的商业神经元动态钳系统， 功能强大，可靠，但即插即用安装，使用简单。