The early diagnosis of acute myocardial infarction (AMI) is dependent on the combined feedback of multiple cardiac biomarkers. However, it remains challenging to precisely detect multicardiac biomarkers in complex blood early due to the lack of sensitive and specific diagnostic indicators and the low abundance and small size of associated biomarkers with high specificity (such as microRNAs). To make matters worse, spectral overlap significantly limits the multiplex analysis of cardiac biomarkers by fluorescent probes, leading to bias in the diagnosis of myocardial infarction. Herein, we developed a method for simultaneous detection of miRNAs and protein biomarkers using size- and color-coded microbeads that carry signature for target capture. We also constructed a microfluidic chip with different spacer arrays that segregate these microbeads in different chip regions according to their size to produce signature signals, indicating the level of different biomarkers. The signals on the microbeads were hugely amplified by catalytic hairpin assembly and rolling circle amplification. Notably, this strategy enables the simultaneous and in situ sensitive profiling of six kinds of biomarkers via adding two different fluorescent labels, removing the limitations of spectral overlap. We envision that the strategy has great potential for application in clinical diagnosis for AMI.

中文翻译：

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双编码亲和微珠特征组合分析用于急性心肌梗塞高灵敏度诊断

急性心肌梗死（AMI）的早期诊断依赖于多种心脏生物标志物的综合反馈。然而，由于缺乏敏感和特异的诊断指标，以及具有高特异性的相关生物标志物（如 microRNA）丰度低且尺寸小，早期精确检测复杂血液中的多心脏生物标志物仍然具有挑战性。更糟糕的是，光谱重叠显着限制了荧光探针对心脏生物标志物的多重分析，导致心肌梗死的诊断出现偏差。在此，我们开发了一种使用带有目标捕获特征的大小和颜色编码微珠同时检测 miRNA 和蛋白质生物标志物的方法。我们还构建了具有不同间隔阵列的微流控芯片，该阵列根据微珠的大小将这些微珠隔离在不同的芯片区域中，以产生特征信号，指示不同生物标志物的水平。通过催化发夹组装和滚环放大，微珠上的信号被极大地放大。值得注意的是，该策略通过添加两种不同的荧光标记，能够同时和原位敏感地分析六种生物标志物，消除了光谱重叠的限制。我们预计该策略在 AMI 的临床诊断中具有巨大的应用潜力。