Electrochemical Biosensors for Whole Blood Analysis: Recent Progress, Challenges, and Future Perspectives.

Whole blood, as one of the most significant biological fluids, provides critical information for health management and disease monitoring. Over the past 10 years, advances in nanotechnology, microfluidics, and biomarker research have spurred the development of powerful miniaturized diagnostic systems for whole blood testing toward the goal of disease monitoring and treatment. Among the techniques employed for whole-blood diagnostics, electrochemical biosensors, as known to be rapid, sensitive, capable of miniaturization, reagentless and washing free, become a class of emerging technology to achieve the target detection specifically and directly in complex media, e.g., whole blood or even in the living body. Here we are aiming to provide a comprehensive review to summarize advances over the past decade in the development of electrochemical sensors for whole blood analysis. Further, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms.

Employing a Redox Reporter-Modified Self-Assembly Monolayer in Electrochemical Aptamer-Based Sensors to Enable Calibration-Free Measurements.

Electrochemical aptamer-based (E-AB) sensors suffer from sensor-to-sensor signal variations due to the variation in the total number of probes immobilized on the sensor surface, the effective working area, and the heterogeneity properties of the electrode surface, thus requiring a calibration step prior to each measurement. This is impractical, if not possible, for some cases, e.g., in a complex matrix including blood samples. In response, we propose a calibration-free approach to achieve the measurement of biorelevant small-molecule and protein analytes. Specifically, we employed one reporter labeled onto an aptamer (e.g., methylene blue) for redox signaling, and the other reporter (e.g., ferrocene) was modified onto a self-assembly monolayer as a reference signal. By taking the ratio of the two signals, we achieved a much improved baseline stability and sensor-to-sensor reproducibility, which allows the calibration-free measurement of the analysis of the respective targets, including doxorubicin, vancomycin, and thrombin in both simple buffer and even directly complex samples including serum and whole blood.