A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording.
A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording.
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DOI：
10.3390/s16050709
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发表时间：
2016-05-19
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影响因子：
--
通讯作者：
Tartagni M
中科院分区：
文献类型：
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作者：
Crescentini M;Bennati M;Saha SC;Ivica J;de Planque M;Morgan H;Tartagni M
利用离子通道记录的高通量筛选（HTS）是药理学中一种强有力的药物发现技术。用平面双层类脂膜（BLM）记录离子通道是可扩展的并且具有非常高的灵敏度。基于BLM离子通道记录的HTS系统面临三个主要挑战：（i）可扩展的微流体装置的设计;（ii）能够检测带宽>10 kHz的pA范围内的电流的紧凑型超低噪声跨导放大器的设计;（iii）集成这两个元件的紧凑型、鲁棒性和可扩展的系统的设计。本文介绍了一种采用0.35 μm CMOS工艺实现的集成A/D转换的低噪声跨阻放大器。CMOS放大器采集±200 pA至±20 nA范围内的电流，带宽为100 kHz，功耗为41 mW。集成的数字偏移补偿环路平衡Ag/AgCl电极的任何电压偏移。在±200 pA范围内，测得的开路输入参考噪声电流低至4 fA/kHz。电流放大器与微流体装置一起嵌入集成平台中，用于从离子通道记录电流。短杆菌肽-A、α-溶血素和KcsA钾通道已用于验证平台和电流-数字转换器。
High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 μm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/√Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, α-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter.