Multiplexed centrifugal microfluidic system for rapid and non-invasive detection of myocardial fibrosis†

Abstract

Myocardial fibrosis is a pathological condition characterized by the excessive accumulation of extracellular matrix proteins, primarily collagen, within the myocardium. Early symptoms of myocardial fibrosis are often subtle, leading to late detection. As the disease progresses, it is often associated with life-threatening complications. Therefore, myocardial fibrosis urgently demands a diagnostic system that is rapid, effective, and preferably non-invasive. In this study, we developed a highly sensitive microfluidic light-initiated chemiluminescent assay (LICA) for the simultaneous detection of cTnI, NT-proBNP, HA, LN, PICP, and PIIINP, the key biomarkers involved in the occurrence and development of myocardial fibrosis. The system is highly integrated and compact, incorporating reagent lyophilization and whole blood separation technologies, and is suitable for point-of-care testing. By combining advantages of centrifugal microfluidics and LICA, the system effectively shortens the detection time for key biomarkers associated with MACEs. Moreover, the system provides optimal analytical performance, with LoDs of 0.0018 ng mL⁻¹, 0.0127 ng mL⁻¹, 3.52 ng mL⁻¹, 6.88 ng mL⁻¹, 4.68 ng mL⁻¹, and 0.072 ng mL⁻¹ for cTnI, NT-proBNP, HA, LN, PIIINP and PICP, respectively. Ultimately, the system can achieve an AUC of 0.548, 0.670, 0.772, 0.752, 0.833 and 0.713 for cTnI, NT-proBNP, HA, LN, PIIINP, and PICP, respectively, and an overall combined ROC of 0.946 for the detection of myocardial fibrosis, indicating its excellent efficacy and potential for widespread clinical applications.