Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring

Jun-Chau Chien; Sam W. Baker; H. Tom SohAmin Arbabian

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Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring

机译：Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring

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In this article, we present the design and analysis of an electrochemical circuit for measuring the concentrations of therapeutic drugs using structure-switching aptamers. Aptamers are single-stranded nucleic acids, whose sequence is selected to exhibit high affinity and specificity toward a molecular target, and change its conformation upon binding. This property, when coupled with a redox reporter and electrochemical detection, enables reagent-free biosensing with a subminute temporal resolution for italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"in vivo/italic therapeutic drug monitoring. Especially, we design a chronoamperometry (CA)-based electrochemical circuit that measures the direct changes in the electron transfer (ET) kinetics of a methylene blue reporter conjugated at the distal end of the aptamer. To overcome the high-frequency noise amplification issue when interfacing with a large-size ( 0.25 mmsup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"2/sup) implantable electrode, we present a sample-and-hold (S/H) circuit technique in which the desired electrode potentials are held onto noiseless capacitors during the recording of the redox currents. This allows disconnecting the feedback amplifiers to avoid its noise injection while reducing the total power consumption. A prototype circuit implemented in 65-nm CMOS demonstrates a cell-capacitance-insensitive input-referred noise (IRN) current of 15.2 pAsub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"rms/sub at a 2.5-kHz filtering bandwidth. We tested our system in human whole blood samples and measured the changes in the ET kinetics from the redox-labeled aptamers at different kanamycin concentrations. By employing principal component analysis (PCA) to compensate for the sampling errors, we report a molecular noise floor (at SNR = 1) of 3.1 inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" tex-math notation="LaTeX"$mu text{M}$ /tex-math/inline-formula with sub-1-s acquisition time at 0.22-mW power consumption.

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《IEEE Journal of Solid-State Circuits》 |2020年第11期|2914-2929|共16页
作者
Jun-Chau Chien; Sam W. Baker; H. Tom SohAmin Arbabian;
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作者单位

Stanford University, Stanford, CA, USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);
原文格式 PDF
正文语种英语
中图分类基本电子电路;
关键词
Drugs; In vivo; Monitoring; Kinetic theory; Electrodes; Current measurement; Electric potential;

Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring

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