Paper-based multiplexed colorimetric biosensing of cardiac and lipid biomarkers integrated with machine learning for accurate acute myocardial infarction early diagnosis and prognosis

Abstract

This study demonstrates how a colorimetric biosensor based on microfluidic paper can swiftly diagnose a disease and predict its prognosis to triage patients effectively. This was the first biosensor to quantify the gold standard cardiac troponin (cTnI) and lipid biomarkers, including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) simultaneously. Prior research encountered obstacles or limitations, such as measuring a single biomarker or total cholesterol, which cannot distinguish between LDL and HDL. CatBoost, an advanced machine learning (ML) technique used for diagnosis that combines the predictive power of ML algorithms obtained an impressive area under the receiver operating curves (AUROC) of 0.97 ± 0.018 for all possible classification thresholds. CatBoost is a brand-new ensemble framework based on the interaction of multiple health parameters that can generate AUROC values of 0.897 ± 0.047 for the accurate prognosis of recurrent acute myocardial infarction (AMI), demonstrating remarkably accurate AMI diagnosis and prognosis. In addition, this paper-based analytical device (µPAD) biosensor employs an electrophoretic method to overcome the challenges posed by non-specific adsorption. This is accomplished by isolating non-specific biomolecules based on differences in their isoelectric points and removing non-specifically adsorbing colorimetric markers. The limits of detection (LoD) for cTnI in AMI were lower than their respective clinical cutoff values. This study also demonstrated that the proposed ML framework produced significantly better results than conventional statistical analysis. High correlation filtering and (t-SNE) dimensionality reduction were utilized for a limited number of data points. The respectable accuracy and AUROC of this method were also validated using cross-validation.