Framework and Spherical Nucleic Acids Synergistically Enhanced Electrochemiluminescence Nanosensors for Rapidly Diagnosing Acute Myocardial Infarction Based on Circulating MicroRNA Levels

Acute myocardial infarction (AMI)-related microRNAs (miRNAs) in circulating blood have been proved as promising biomarkers for AMI diagnosis. The detection of these miRNAs at ultralow levels usually requires nucleic acid amplification strategies to improve the sensitivity at the cost of time. Given that the first hour after an AMI attack is the golden time for saving AMI patients' lives, shortening the time of ultrasensitive miRNA analysis is of great significance for clinical AMI diagnosis. Toward this goal, here we present a direct electrochemiluminescence (ECL) sensing strategy for fast and ultrasensitive miRNA detection, circumventing the time-consuming signal amplification steps. Target miRNAs are directly hybridized with two probe strands that are attached to a covalently hemin-modified spherical nucleic acid enzyme (SNAzyme) and a truncated triangular pyramid DNA nanoplatform on the electrode, respectively. Both of them improve the ECL signal and meanwhile reduce the background, thereby remarkably promoting the detection sensitivity of target miRNAs. It enables the rapid detection of an AMI-related miRNA (miR-499) at 10 aM in human serum within 30 min using the SNAzyme-catalyzed luminol-H2O2 ECL reaction. This sensing strategy is then utilized for AMI diagnosis via probing endogenous miR-499 in patients' circulating blood with endogenous miR-16 as an intrinsic reference, showing a significant difference (P < 0.001) between the miR-499 levels of patients and the healthy.

Automated summary

This study presents a fast and ultrasensitive miRNA detection method using a direct electrochemiluminescence sensing strategy, which avoids time-consuming signal amplification steps. The method enables the detection of AMI-related miRNA in human serum within 30 minutes and is of great significance for clinical AMI diagnosis.