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 singleelectrode and chemiluminescent immuno-Gold (ciGold) nanoassemblies. The ciGold immunoarray was obtained by successively assembling nanocomposites of Cu 2+ /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 threebiomarker joint strategy is obviously superior to hs-cTnT for early and accurate diagnosis of AMI, hopefully reducing AMI mortality and saving limited medical resources.
Recently,
our group reported a chemical timer approach
to manipulate
the onset time of chemiluminescence (CL) emission. However, it is
still in the proof-of-concept stage, and its analytical applications
have not been explored yet. Nanomaterials have merits of good catalytic
effect, large specific surface area, good biocompatibility, and ease
of self-assembly, which are ideal for constructing analytical-interfaces
for bioassays. Herein, an emission onset time-adjustable chemiluminescent
L012-Au/Mn2+ was synthesized for the first time by modifying
Mn2+ on the surface of L012-protected gold nanoparticle.
By using H2O2 and NaHCO3 as coreactants,
L012-Au/Mn2+ could not only generate an ultrastrong and
long-time CL emission but also its CL emission onset time could be
adjusted by the addition of thiourea, which could effectively eliminate
interference from the addition of coreactants, shorten the exposure
time, reduce the detection background, and finally achieve high sensitivity
CL imaging analysis. On this basis, a label-free CL immunoassay was
constructed with a smartphone-based imaging system for high-throughput
and sensitive determination of severe acute respiratory syndrome coronavirus
2 nucleocapsid (N) protein. The CL image of the immunoassay with different
concentrations of N proteins was captured in one photograph 100 s
after the injection of H2O2 with a short exposure
time of 0.5 s. The immunoassay showed good linearity over the concentration
range of 1 pg/mL to 10 ng/mL with a detection limit of 0.13 pg/mL,
which was much lower than the reported CCD imaging detection method.
In addition, it showed good selectivity and stability and was successfully
applied in serum samples from healthy individuals and COVID-19 rehabilitation
patients.
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