A multiplexed ion-exchange membrane-based miRNA (MIX·miR) detection platform for rapid diagnosis of myocardial infarction

Abstract

Micro RNAs (miRNAs) have shown great potential as rapid and discriminating biomarkers for acute myocardial infarction (AMI) diagnosis. We have developed a multiplexed ion-exchange membrane-based miRNA (MIX.miR) preconcentration/sensing amplification-free platform...

Human Heart Anoxia and Reperfusion Tissue (HEART) Model for the Rapid Study of Exosome Bound miRNA Expression As Biomarkers for Myocardial Infarction

“…Recently, circulating microRNAs (miRNAs) have been proposed as potential biomarkers for rapid and accurate assessment of cardiovascular diseases, including MI, due to distinct changes observed during hypoxic and oxidative stress events. [15,[17][18][19][20][21] Interestingly, many of these miRNAs have been demonstrated to be packaged in small extracellular vesicles with diameters between 30 and 200 nm, also known as exosomes and have been shown to promote beneficial clinical effects both in vivo and in vitro. [22] Both exosome contents, including miRNAs, and surface properties have been shown to be potential biomarkers in cancer models, but this has not yet been translated to the realm of cardiovascular disease.…”

“…[15,21] As miRNA turnover is much quicker than that of proteins such as troponin, the current gold standard, miRNAs have demonstrated the potential of being able to distinguish between MI patients suffering from II or RI-phase damage, significantly decreasing the amount of testing needed prior to diagnosis. [15,[17][18][19][20][21] Unfortunately, these bring forth additional challenges that must be addressed to reliably utilize miRNAs as clinical biomarkers on a broad scale.…”

“…[24,25] Additionally, because these miRNAs are typically packaged in exosomes, additional sample preparation steps are necessary, thus increasing both sample processing time and potential sample loss. [20,[24][25][26] Our recent development and use of anion exchange membrane (AEM)-based miRNA sensor technology and a surface acoustic wave (SAW) exosome lysing technology address all of these concerns and provide us with an alternative method to detect miRNAs at picomolar concentrations in near real-time from fluid samples without requiring any sample preparation and without manual analyte transfer. [20,27] With this enhanced miRNA detection capability and improved accuracy compared to miRNA RT-qPCR by an integrated AEM-SAW biochip, both the discovery and utilization of novel biomarkers is increasingly feasible in a clinical environment.…”

“…[20,[24][25][26] Our recent development and use of anion exchange membrane (AEM)-based miRNA sensor technology and a surface acoustic wave (SAW) exosome lysing technology address all of these concerns and provide us with an alternative method to detect miRNAs at picomolar concentrations in near real-time from fluid samples without requiring any sample preparation and without manual analyte transfer. [20,27] With this enhanced miRNA detection capability and improved accuracy compared to miRNA RT-qPCR by an integrated AEM-SAW biochip, both the discovery and utilization of novel biomarkers is increasingly feasible in a clinical environment. [20] In addition to the detection limitations of current technologies, the inability to control the onset of ischemic/reperfusion events in studies with human subjects has proven a significant challenge in the use of miRNA measurement for clinical MI diagnosis, complicating attempts to temporally correlate miRNA expression with MI and modeling of biomarker expression dynamics.…”

“…[20,27] With this enhanced miRNA detection capability and improved accuracy compared to miRNA RT-qPCR by an integrated AEM-SAW biochip, both the discovery and utilization of novel biomarkers is increasingly feasible in a clinical environment. [20] In addition to the detection limitations of current technologies, the inability to control the onset of ischemic/reperfusion events in studies with human subjects has proven a significant challenge in the use of miRNA measurement for clinical MI diagnosis, complicating attempts to temporally correlate miRNA expression with MI and modeling of biomarker expression dynamics. [21] Additionally, animal studies so far have shown confounding results and often fail to predict responses in humans due to discordances between animal and human physiology, making animal models less than ideal.…”