Bridging sepsis physiology and biosensor engineering: a clinical perspective on electrochemical cytokine sensor...

Sepsis remains one of the most critical challenges in contemporary intensive care medicine, characterized by profound immunological and physiological heterogeneity. Cytokines have gained increasing attention as dynamic biomarkers that can complement conventional markers and bedside clinical assessment, enabling more refined diagnosis, risk stratification, and monitoring of treatment response. Most current work on cytokine biosensing is organized around a technological ambition: continuous, minimally invasive, wearable measurement. In this Perspective, we invert that starting point and derive sensor specifications from the pathophysiology and workflow of the septic patient in intensive care. Doing so yields a different set of priorities. Because septic concentrations of the principal mediators span three to four orders of magnitude, a wide linear range matters more than the lowest attainable limit of detection. Because resuscitation and antimicrobial decisions are made within the first hours, response times must be measured in minutes rather than tens of minutes. Because reference ranges, kinetics and outcome associations have been established only in blood, and because vascular access is already present in these patients, whole blood remains the medium of choice, and a discrete, single-use format is preferable to continuous operation in a fouling-prone matrix. Several of these conclusions run counter to the direction the field is currently taking. We argue that aligning sensor architecture with the pathophysiological context of sepsis is a precondition for cytokine-targeted biosensing to support decision-making at the bedside.