26.4 A Cell-Capacitance-Insensitive CMOS Sample-and-Hold Chronoamperometric Sensor for Real-Time Measurement of Small Molecule Drugs in Whole Blood

The capability of adjusting a drug-dosing profile in real time based on personalized pharmacokinetics plays a crucial role in achieving optimal therapeutic outcomes at minimal toxicity [1]. Achieving this requires biosensors that can continuously measure drug concentrations at sub-minute temporal resolution. Today, the gold standard methods such as immunoassays and liquid chromatography are not able to achieve this because they require long assay times (typically hours). Recently, structure-switching aptamers have drawn great attention for in vivo realtime monitoring [2]-[4]. As shown in Fig. 26.4.1, aptamers are single-stranded DNA molecules whose sequences are selected to bind target molecules with high affinity [2]. To achieve electrochemical detection, redox reporters (such as methylene blue, MB) are conjugated to these aptamers such that conformation changes in the aptamer caused by target binding leads to a direct electrical readout in proportional to the target concentration. Such a reagent-free capability has been demonstrated using microfluidics and implanted probes measuring chemotherapeutics and aminoglycoside antibiotics [2]-[4]. To generalize the technology for ambulatory patients, [5] presents a system integrating an aptamer-interfacing electrochemical circuit with wireless powering and telemetry.