Abstract: As the need grows for alternatives to cumbersome, laboratory-dependent analytical methods, researchers are increasingly focused on developing versatile tools for point-of-care testing and therapeutic drug monitoring (TDM). Conventional TDM relies on intermittent venous blood sampling, a practice that is particularly ill-suited for drugs with rapid onset, short half-lives (t₁/₂ < 4 h), and narrow therapeutic windows. Consequently, clinicians are often limited to a handful of concentration measurements, providing only sparse snapshots of drug exposure and insufficient temporal resolution for timely clinical decision-making.
To address these limitations, my team is developing portable biosensing platforms capable of delivering continuous, real-time measurements directly in undiluted complex biological matrices and in vivo environments. Our approach centers on DNA-based biosensor architectures integrated with electrochemical transduction mechanisms for signal generation. Although these sensors offer significant advantages for decentralized and continuous monitoring, several key challenges remain. First, the design of DNA architectures is still largely guided by empirical trial-and-error approaches rather than predictive engineering principles. Second, DNA-based sensors remain susceptible to degradation in biological environments. Third, most current platforms are restricted to the detection of a single analyte per electrode, limiting their utility for multiplexed monitoring.
In this lecture, I will highlight our recent efforts to overcome these challenges through the development of DNA aptamer selection and engineering strategies, electrochemical impedimetric sensing approaches, and redox reporters that enable multiplexed measurements on a single electrode platform. These advances are paving the way toward more robust, informative, and clinically relevant biosensing technologies for real-time therapeutic monitoring.