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

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 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.

Near-IR Photoinduced Electrochemiluminescence Imaging with Structured Silicon Photoanodes

“…Electrochemiluminescence (ECL) is the generation of light induced by an electrochemical reaction. It generally produces the excited state of a luminophore at an electrode surface, leading to the emission of visible photons. , It has been widely used in clinical assays, sensing, imaging, and microscopy, especially with the following water-based anodic coreactant ECL systems: (i) tris­(bipyridine)­ruthenium­(II) complex with tri- n -propylamine ([Ru­(bpy) 3 ] 2+ -TPrA) and (ii) 3-aminophthalhydrazide with hydrogen peroxide (luminol-H 2 O 2 ). − Photoinduced electrochemiluminescence (PECL) is an ECL variant that is based on photogenerated charge transfer at the semiconductor/liquid interface. − Because it converts optical signals through a photoelectrochemical mechanism, PECL can, in principle, also be employed for revealing projected patterns, which is particularly interesting when the excitation wavelength is invisible to the human eye. Localized PECL photoconversion of visible light (λ exc = 674 to λ ECL = 413 nm) via the annihilation of a diphenylanthraceme derivative on p -Si has been early mentioned by Laser and Bard and, more recently, Ciampi et al.…”

Dynamic Mapping of Electrochemiluminescence Reactivity in Space: Application to Bead-Based Assays

“…Since it gives an optical readout, the spatial distribution of this signal can be mapped easily and offers the opportunity to perform microscopy experiments. ,,− Given the high sensitivity and spatiotemporal controllability of ECL, ,, the combination between ECL and imaging enables the visualization of a variety of microscopic objects and cells. ,,− ECL generation itself is a dynamic electrochemical process that integrates many elementary steps: the initial electrochemical reactions at the electrode surface, the exergonic electron-transfer reactions populating the excited state of the luminophore, and finally its radiative relaxation to the ground state with the light emission. Most of the ECL imaging works study and visualize static entities such as micro/nanoparticles, cells, or organelles and require long exposure time of the 2D photodetector (typically, a CCD camera). − Indeed, a few seconds or tens of seconds are classically used to accumulate enough photons in order to obtain a clear image of the analyzed objects. ,− This is due to the low number of generated photons during the ECL process and to the limited ECL efficiency of the luminophores . This limitation implies that dynamic processes in the subsecond or millisecond timescales are rarely investigated by ECL. ,, For example, Zhu and co-workers imaged the collisions of single [Ru­(bpy) 3 ] 2+ -doped silica nanoparticles by ECL with a 0.2 s exposure time .…”

Local reactivity of metal–insulator–semiconductor photoanodes imaged by photoinduced electrochemiluminescence microscopy

“…26 The light originates from a luminophore molecule that is brought to its excited state by a highly exergonic electron-transfer reaction and relaxes to its ground state by emitting a photon. 27,28 This phenomenon is widely used for medical diagnosis applications and immunoassays, 29–36 with the ECL model system comprising tris(bipyridine)ruthenium( ii ) complex ([Ru(bpy) 3 ] 2+ ) and tri- n -propylamine (TPrA) as the luminophore and the co-reactant, respectively. Since ECL offers an optical readout, it has evolved progressively into a microscopy technique.…”