Abstract
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 in vivo therapeutic drug monitoring. Especially, we design a chronoamperometry (CA)-based electrochemical cir- cuit 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 ampli- fication issue when interfacing with a large-size ( >0.25 mm 2) 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 pA rms 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 diffe