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首页> 外文期刊>Journal of Neurophysiology >Microchip amplifier for in vitro, in vivo, and automated whole cell patch-clamp recording
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Microchip amplifier for in vitro, in vivo, and automated whole cell patch-clamp recording

机译：用于体外，体内和自动全细胞膜片钳记录的Microchip放大器

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Patch clamping is a gold-standard electrophysiology technique that has the temporal resolution and signal-to-noise ratio capable of reporting single ion channel currents, as well as electrical activity of excitable single cells. Despite its usefulness and decades of development, the amplifiers required for patch clamping are expensive and bulky. This has limited the scalability and throughput of patch clamping for single-ion channel and single-cell analyses. In this work, we have developed a custom patch-clamp amplifier microchip that can be fabricated using standard commercial silicon processes capable of performing both voltage- and current-clamp measurements. A key innovation is the use of nonlinear feedback elements in the voltage-clamp amplifier circuit to convert measured currents into logarithmically encoded voltages, thereby eliminating the need for large high-valued resistors, a factor that has limited previous attempts at integration. Benchtop characterization of the chip shows low levels of current noise [1.1 pA root mean square (rms) over 5 kHz] during voltage-clamp measurements and low levels of voltage noise (8.2 mu V rms over 10 kHz) during current-clamp measurements. We demonstrate the ability of the chip to perform both current- and voltage-clamp measurement in vitro in HEK293FT cells and cultured neurons. We also demonstrate its ability to perform in vivo recordings as part of a robotic patch-clamping system. The performance of the patch-clamp amplifier microchip compares favorably with much larger commercial instrumentation, enabling benchtop commoditization, miniaturization, and scalable patch-clamp instrumentation.
机译：膜片钳是一种金标准的电生理技术，具有时间分辨率和信噪比，能够报告单个离子通道电流以及可激发单个细胞的电活动。尽管其有用性和数十年的发展，但膜片钳位所需的放大器昂贵且笨重。这限制了用于单离子通道和单细胞分析的膜片钳的可扩展性和吞吐量。在这项工作中，我们开发了定制的膜片钳放大器微芯片，可以使用能够执行电压和电流钳测量的标准商用硅工艺来制造该芯片。一项关键创新是在电压钳位放大器电路中使用非线性反馈元件，将测得的电流转换为对数编码的电压，从而消除了对大型高阻值电阻器的需求，而这是先前集成尝试所受限制的因素。芯片的台式特性显示在电压钳测量期间显示出低水平的电流噪声[5 kHz上1.1 pA均方根（rms）]，在电流钳测量期间显示出低水平的电压噪声（10μs时，在8.2μV rms均方根）。我们展示了该芯片在HEK293FT细胞和培养的神经元中进行电流和电压钳位测量的能力。我们还展示了其作为机器人膜片钳系统的一部分进行体内录音的能力。膜片钳放大器微芯片的性能优于大型商用仪器，可实现台式商品化，小型化和可扩展的膜片钳仪器。

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