A custom microchip amplifier for patch clamp electrophysiological recording

用于膜片钳电生理记录的定制微芯片放大器

• 批准号: 8832629
• 负责人: Reid Harrison
• 金额: $ 35.61万
• 依托单位: INTAN TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832629
• 关键词: Adopted; Adoption; Amplifiers; Architecture; Automation; Boxing; Cell model; Cells; Computer software; Computers; Custom; Data; Development; Documentation; Economic Development; Electric Capacitance; Electrodes; Electronics; Electrophysiology (science); Evaluation; Exhibits; Financial compensation; Floor; Glass; Goals; In Vitro; Individual; Ion Channel; Kilogram; Laboratory Research; Life; Manufacturer Name; Marketing; Measurement; Measures; Medical; Medical Research; Microscope; Monitor; Neurons; Neurosciences; Noise; Patch-Clamp Techniques; Performance; Pharmacologic Substance; Phase; Postage Stamps; Protocols documentation; Publishing; Research; Research Personnel; Resistance; Robotics; Scientist; Series; Signal Transduction; Silicon; Synapses; System; Technology; Testing; Training; Work; analog; cost; design; improved; in vivo; innovation; instrument; instrumentation; microchip; micromanipulator; new technology; next generation; novel; open source; patch clamp; programs; prototype; public health relevance; relating to nervous system; research study; sound; success; tool; voltage; voltage clamp; web site

DESCRIPTION (provided by applicant): Patch clamp electrophysiology has been a central tool of neuroscience and pharmaceutical research since its advent in the late 1970s. Whole-cell patch clamping utilizes glass micropipettes and sensitive analog electronics to monitor the ion-channel currents and intracellular voltages of individual neurons or other cells. For decades, this has been performed by highly trained scientists using micromanipulators under a microscope to painstakingly guide an electrode to contact (or "patch clamp") a single cell. Once in contact, large, expensive amplifier modules are used to monitor or manipulate the small cellular electrical signals. In the last ten years, advances in automation have led to the development of inexpensive robotic systems capable of automatically patch clamping many neurons in vivo in minutes, with success rates matching or exceeding those of skilled investigators. As a result of this innovation, patch clamp techniques are being adapted to a wider variety of experimental protocols and target species, and researchers are now recording from multiple cells simultaneously. However, the size and expense of the traditional rack-mounted amplifier electronics systems present a significant bottleneck in the continued development of large-scale highly automated intracellular recording systems. Single-channel amplifiers capable of current-clamp and voltage- clamp measurements are typically large rack-mounted boxes weighing several kilograms and costing more than $10,000 per channel. At least eight companies produce such instruments, which represent the dominant component of modern patch clamp recording systems in terms of size, mass, and cost. The move to multi- channel automated systems will only exacerbate this problem. Intan Technologies proposes to integrate all the sensitive electronics needed for patch clamp recording onto a small, low-power, inexpensive silicon microchip ("PatchChip") that will replace traditional patch clamp amplifiers. The use of advanced microelectronics will reduce the bulky and expensive amplifier systems down to the size of a postage stamp. Integrated amplifiers could be mounted in close proximity to each micropipette in a large-scale automated recording system, reducing noise pickup and size. The PatchChip will have the capability to conduct both voltage-clamp and current-clamp measurements, and will have sufficient sensitivity to resolve picoampere-level synaptic currents and millivolt-level intracellular voltages. A novel circuit architecture eliminates the need for of-chip precision resistors and allows for standard patch clamp functions like series resistance compensation and fast transient capacitance compensation. An easy-to-use USB interface circuit board will be designed for the chip; this evaluation system with open-source software will allow instrumentation manufacturers to incorporate this new technology into advanced patch clamp systems.

描述（由申请人提供）：自1970年代后期出现以来，斑块夹电生理学一直是神经科学和药物研究的中心工具。全细胞斑块夹紧利用玻璃微孔和敏感的模拟电子来监测单个神经元或其他细胞的离子通道电流和细胞内电压。几十年来，这个 已经由训练有素的科学家使用显微镜下的显微镜进行了艰苦的指导电极（或“贴片夹”）单个单元的电极。接触后，使用大型，昂贵的放大器模块来监视或操纵小细胞电信号。在过去的十年中，自动化的进步导致了廉价的机器人系统的发展，能够在几分钟内自动修补体内的许多神经元，成功率匹配或超过了熟练的研究人员的神经元。由于这种创新，斑块夹技术正在适应更广泛的实验方案和目标物种，现在研究人员正在同时从多个细胞记录。然而，传统机架安装式电子系统的规模和费用在持续开发高度自动化的细胞内记录系统的持续开发中具有重要的瓶颈。能够使用电流钳和电压夹具测量的单通道放大器通常是重量数公斤的机架安装箱，每个频道的成本超过10,000美元。至少八家公司生产这种工具，这些工具代表了现代贴片夹记录系统的主要组成部分，其规模，质量和成本。多通道自动化系统的转移只会加剧此问题。 Intan Technologies建议将贴片夹记录所需的所有敏感电子设备集成到一个小型，低功率，廉价的硅微芯片（“ PatchChip”）上，这些硅微芯片（“ PatchChip”）将取代传统的补丁夹放大器。高级微电子的使用将使庞大且昂贵的放大器系统降低到邮票的大小。可以在大规模自动记录系统中近距离安装集成的放大器，以降低噪音拾取和尺寸。 PatchChip将具有进行电压夹和电流钳测量的能力，并具有足够的灵敏度来解决PicoAmpere级突触电流和毫伏级的细胞内电压。一种新型的电路结构消除了对芯片精度电阻的需求，并允许标准的贴片夹函数（例如串联电阻补偿和快速瞬态电容补偿）。易于使用的USB接口电路板将为芯片设计；带有开源软件的评估系统将使仪器制造商能够将此新技术纳入高级贴片夹系统。