Three-Biomarker Joint Strategy for Early and Accurate Diagnosis of Acute Myocardial Infarction via a Multiplex Electrochemiluminescence Immunoarray Coupled with Robust Machine Learning

Mingquan Guo; Dexin Du; Jue Wang; Yao Ma; Di Yang; Mohammad A Haghighatbin; Jiangnan Shu; Wei Nie; Ruoxian Zhang; Zhiping Bian; Liansheng Wang; Zachary J Smith; Hua Cui

doi:10.1021/cbmi.3c00035

Three-Biomarker Joint Strategy for Early and Accurate Diagnosis of Acute Myocardial Infarction via a Multiplex Electrochemiluminescence Immunoarray Coupled with Robust Machine Learning

Chem Biomed Imaging. 2023 Apr 28;1(2):179-185. doi: 10.1021/cbmi.3c00035. eCollection 2023 May 22.

Authors

Affiliations

¹ Key Laboratory of Precision and Intelligent Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
² Institute of Cardiovascular Disease, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
³ Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

Abstract

Acute myocardial infarction (AMI) represents a leading cause of death globally. Key to AMI recovery is timely diagnosis and initiation of treatment, ideally within 3 h of symptom onset. Cardiac troponin T (cTnT) is the gold standard yet a low cTnT result cannot rule out AMI at early times. Here, we develop a three-biomarker joint strategy for early and accurate diagnosis of AMI via an electrochemiluminescence (ECL) immunoarray coupled with robust machine learning. The ECL immunoarray is based on an array microchip with a single-electrode and chemiluminescent immuno-Gold (ciGold) nanoassemblies. The ciGold immunoarray was obtained by successively assembling nanocomposites of Cu²⁺/cysteine complexes and N-(aminobutyl)-N-(ethylisoluminol) bifunctionalized gold nanoparticles combined with chitosan and antibody conjugated gold nanoparticles on the surface of a microchip. Three biomarkers, including cardiac troponin I, heart type fatty acid binding protein, and copeptin, were simultaneously detected in 260 serum samples from patients presenting with chest pain by an innovative multiplexed ECL immunoarray, and classified via the three-biomarker joint assessment model using support vector machines. The model achieved perfect discrimination (100% sensitivity and specificity) for AMI vs non-AMI patients, substantially higher than cTnT alone. Within 12 h of symptom onset, high-sensitivity cardiac troponin T (hs-cTnT) misclassified >20% of patients, while the joint biomarker assessment model retained perfect accuracy. As the time between symptom onset and testing became shorter, the degree to which the joint assessment model outperformed hs-cTnT increased. The proposed three-biomarker joint strategy is obviously superior to hs-cTnT for early and accurate diagnosis of AMI, hopefully reducing AMI mortality and saving limited medical resources.