Rapid and Continuous Simultaneous Monitoring of Interleukin-6 and Lactate Using a Bioelectronic Sensor Platform: toward Early Sepsis Prediction.

Timely and precise monitoring of inflammatory biomarkers is essential for the effective management of sepsis and related acute conditions. Current monitoring strategies depend mostly on centralized, benchtop systems. Here, we present compact in vitro and in vivo bioelectronic sensor platforms capable of rapid and simultaneous detection of lactate and interleukin-6 (IL-6) in human serum and interstitial fluid. The dual-analyte sensor integrates an enzymatic amperometric lactate sensor with an aptamer-based voltammetric IL-6 sensor on single microchips and microneedle arrays toward rapid decentralized and on-body testing, respectively. Lactate is measured via a first-generation enzymatic oxidation strategy, while IL-6 is quantified using a methylene blue-tagged aptamer through square wave voltammetry. These compact systems address key challenges in combining distinctly different surface chemistries, assay formats, and electrochemical transduction mechanisms, enabling simultaneous real-time and crosstalk-free detection. The resulting platforms demonstrate robust analytical performance and represent a significant step toward rapid, continuous, and decentralized monitoring of sepsis biomarkers. Furthermore, the underlying aptamer-enzyme integration strategy along with the multiplexed capabilities of both platforms offers broad potential for simultaneous measurements of a wide range of inflammatory and metabolic biomarkers in various clinical diagnostic applications.