Man Zhu

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.

The ability to track the levels of specific molecules, such as drugs, metabolites, and biomarkers, in the living body, in real time and for long durations, would improve our understanding of health and our ability to diagnose, treat, and monitor disease. To this end, we are developing electrochemical aptamer-based (EAB) biosensors, a general platform supporting high-frequency, real-time molecular measurements in the living body. Here we report that the use of an agarose hydrogel protective layer for EAB sensors significantly improves their signaling stability when deployed in the complex, highly time-varying environments found in vivo. The improved stability is sufficient that these hydrogel-protected sensors achieved good baseline stability and precision when deployed in situ in the veins, muscles, bladder, or tumors of living rats without the use of the drift correction approaches traditionally required in such placements. Finally, our implantable gel-protective EAB sensors achieved good biocompatibility when deployed in vivo in the living rats without causing any severe inflammation.

in the jugular veins of live rats over multi-hour measurements runs that achieve time resolution of seconds and concentration precision of a few micromolar.

Electrochemical aptamer-based (E-AB) biosensors suffer from sensor-to-sensor signal variations due to the variation of the total number and the heterogeneity of probes immobilized on the electrode surface, with the former attracting more attention. As such, a calibration process to correct for such variations is required for this type of sensor, causing inconvenience and inaccessibility in harsh sensing environments such as blood samples, which has dramatically limited the widespread clinical use of biosensors. In response, here, we have adopted E-AB sensors to achieve calibration-free measurements of small biological/drug molecules. Specifically, we employ one probe-attached redox reporter and a second intercalated redox reporter to generate two signals, achieving good sensor-to-sensor reproducibility and thus obviating the need for calibration. We first demonstrated the capability of E-AB sensors for the accurate measurement of kanamycin, tobramycin, and adenosine triphosphate (ATP) in phosphate-buffered saline (PBS) buffer, achieving concentration ranges of approximately 4.7 × 103-, 2.0 × 103-, and 12.7-fold, respectively. Then, we applied this calibration-free approach to the measurement of these three target molecules directly in undiluted serum, achieving a concentration precision of a few micromolars.

An electrochemical aptamer-based sensor, enabling in vivo measurements of drug concentrations directly in the bladder of living rats under pH-variable conditions, was developed employing a π-extended tetrathiafulvalene (exTTF) as redox reported.