Kim Jungsuk, Maitra Raj, Pedrotti Kenneth D, Dunbar William B
Department of Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
IEEE Trans Biomed Circuits Syst. 2013 Jun;7(3):285-95. doi: 10.1109/TBCAS.2012.2200893.
In this paper, a fully integrated high-sensitivity patch-clamp system is proposed for single-molecule deoxyribonucleic acid (DNA) analysis using a nanopore sensor. This system is composed of two main blocks for amplification and compensation. The amplification block is composed of three stages: 1) a headstage, 2) a voltage-gain difference amplifier, and 3) a track-and-hold circuit, that amplify a minute ionic current variation sensed by the nanopore while the compensation block avoids the headstage saturation caused by the input parasitic capacitances during sensing. By employing design techniques novel for this application, such as an instrumentation--amplifier topology and a compensation switch, we minimize the deleterious effects of the input-offset voltage and the input parasitic capacitances while attaining hardware simplicity. This system is fabricated in a 0.35 μm 4M2P CMOS process and is demonstrated using an α-hemolysin protein nanopore for detection of individual molecules of single-stranded DNA that pass through the 1.5 nm-diameter pore. In future work, the refined system will functionalize single and multiple solid-state nanopores formed in integrated microfluidic devices for advanced DNA analysis, in scientific and diagnostic applications.
本文提出了一种完全集成的高灵敏度膜片钳系统，用于使用纳米孔传感器进行单分子脱氧核糖核酸（DNA）分析。该系统由用于放大和补偿的两个主要模块组成。放大模块由三个阶段组成：1）前置级，2）电压增益差分放大器，3）跟踪保持电路，用于放大纳米孔感测到的微小离子电流变化，而补偿模块则避免在传感期间由输入寄生电容引起的前置级饱和。通过采用针对该应用新颖的设计技术，如仪表放大器拓扑结构和补偿开关，我们在实现硬件简单性的同时，将输入失调电压和输入寄生电容的有害影响降至最低。该系统采用0.35μm 4M2P CMOS工艺制造，并使用α-溶血素蛋白纳米孔进行了演示，用于检测穿过1.5nm直径孔的单链DNA单个分子。在未来的工作中，经过改进的系统将使集成微流控设备中形成的单个和多个固态纳米孔功能化，用于科学和诊断应用中的高级DNA分析。
