Continuous blood biochemical monitoring in ECMO: from clinically actionable biomarkers to extracorporeal circuit-integrated analytical systems

Extracorporeal membrane oxygenation (ECMO) is an essential life-support therapy for patients with severe cardiopulmonary failure, yet its clinical outcomes remain substantially limited by life-threatening complications. Therefore, early identification of ECMO-related complications requires a transition from intermittent laboratory testing toward continuous multiparametric biochemical surveillance. However, reliable monitoring during ECMO remains challenging due to the complexity of whole-blood matrices, dynamic flow conditions, and biofouling. In this review, we propose a framework for continuous blood biochemical monitoring during ECMO. Representative biomarkers are stratified into three monitoring tiers according to clinical actionability, temporal responsiveness, analytical accessibility, and system integrability. We then evaluate electrochemical sensing strategies matched to different biomarkers and identify the major technical barriers to sustained operation under extracorporeal conditions. A central focus is an in situ, extracorporeal circuit-coupled sampling-conditioning-sensing architecture that combines microfluidic plasma access, cross-scale fluidic coupling, interfacial stabilization, and calibration methods to reduce cellular interference, matrix effects, and long-term signal drift. However, such an architecture remains subject to important practical constraints, including circuit perturbation and thrombogenic risks at sampling interfaces, pressure and flow mismatches between the ECMO circuit and microfluidic modules, cumulative blood loss, and long-term fouling, blockage, and module reliability. We further look ahead to how continuous multiparametric biochemical data could be combined with AI-assisted interpretation, knowledge-guided models, and clinical decision-support systems. By linking biomarker prioritization, fluidic conditioning, electrochemical sensing, long-term reliability, and intelligent interpretation, this review outlines a practical pathway toward next-generation extracorporeal circuit-integrated biochemical monitoring systems for extracorporeal life support.