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: 8520846
• 负责人: Reid Harrison
• 金额: $ 18.48万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8520846
• 关键词: Amplifiers; Architecture; Automation; Award; Boxing; Cell model; Cells; Computer software; Computers; Custom; Data; Development; Devices; Electric Capacitance; Electrodes; Electronics; Electrophysiology (science); Emerging Technologies; Evaluation; Financial compensation; Glass; Goals; In Vitro; Individual; Ion Channel; Kilogram; Life; Manufacturer Name; Marketing; Measurement; Measures; Medical Research; Membrane; Microscope; Monitor; Neurons; Neurosciences; Nobel Prize; Noise; Patch-Clamp Techniques; Pharmacologic Substance; Phase; Postage Stamps; Production; Protocols documentation; Research; Research Personnel; Resistance; Robotics; Scientist; Series; Signal Transduction; Silicon; Specific qualifier value; Stream; Synapses; System; Techniques; Technology; Testing; Training; Work; analog; cost; design; digital; in vivo; innovation; instrument; instrumentation; microchip; micromanipulator; new technology; novel; open source; patch clamp; programs; prototype; public health relevance; relating to nervous system; research study; software development; success; tool; trend; voltage; voltage clamp

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 nearly $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 off-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 20 世纪 70 年代末出现以来，膜片钳电生理学一直是神经科学和药物研究的核心工具。全细胞膜片钳利用玻璃微量移液器和敏感的模拟电子器件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 是由训练有素的科学家在显微镜下使用显微操作器精心引导电极接触（或“膜片钳”）单个细胞。一旦接触，就会使用大型、昂贵的放大器模块来监视或操纵小的蜂窝电信号。在过去的十年中，自动化的进步导致了廉价机器人系统的发展，该系统能够在几分钟内自动对体内许多神经元进行膜片钳，其成功率与熟练研究人员的成功率相当或超过。由于这项创新，膜片钳技术正在适应更广泛的实验方案和目标物种，研究人员现在可以同时从多个细胞进行记录。然而，传统机架式放大器电子系统的尺寸和费用成为大规模高度自动化细胞内记录系统持续发展的重大瓶颈。能够进行电流钳和电压钳测量的单通道放大器通常是重达数公斤的大型机架安装盒，每个通道的成本接近 10,000 美元。至少有八家公司生产此类仪器，从尺寸、质量和成本来看，它们代表了现代膜片钳记录系统的主要组成部分。转向多渠道自动化系统只会加剧这个问题。 Intan Technologies 提议将膜片钳记录所需的所有敏感电子器件集成到小型、低功耗、廉价的硅微芯片（“PatchChip”）上，以取代传统的膜片钳放大器。先进微电子学的使用将把笨重且昂贵的放大器系统缩小到邮票的大小。集成放大器可以安装在大型自动记录系统中靠近每个微量移液器的位置，从而减少噪声拾取和尺寸。 PatchChip 将能够进行电压钳和电流钳测量，并且具有足够的灵敏度来解析皮安级突触电流和毫伏级细胞内电压。新颖的电路架构消除了对片外精密电阻的需求，并允许标准膜片钳功能，例如串联电阻补偿和快速瞬态电容补偿。将为该芯片设计一个易于使用的USB接口电路板；这个带有开源软件的评估系统将使仪器制造商能够将这项新技术融入先进的膜片钳系统中。