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: 8919470
• 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/8919470
• 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; Health; 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; 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20世纪70年代末问世以来，膜片钳电生理学一直是神经科学和药物研究的核心工具。全细胞贴片夹紧利用玻璃微移液管和敏感的模拟电子学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，