Quantitative biomarker detection methods featured with rapidity, high accuracy, and label-free are demonstrated for the development of point-of-care (POC) technologies or “beside” diagnostics. Microbead aggregation via protein-specific linkage provides an effective approach for selective capture of biomarkers from the samples, and can directly readout the presence and amount of the targets. However, sensors or microfluidic analyzers that can accurately quantify the microbead aggregation are scared. In this work, we demonstrate a microwell-based microbeads analyzing system, by which online manipulations of microbeads including trapping, arraying, and rotations can be realized, providing a series of microfluidic approaches to layout the aggregated microbeads for further convenient characterizations. Prostate specific antigen is detected using the proposed system, demonstrating the limit of detection as low as 0.125 ng/mL (3.67 pM). A two-step reaction kinetics model is proposed for the first time to explain the dynamic process of microbeads aggregation. The developed microbeads aggregation analysis system has the advantages of label-free detection, high throughput, and low cost, showing great potential for portable biomarker detection.

中文翻译：

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基于手机的基于微孔的微珠聚集测定用于便携式生物标记物检测

具有快速，高精度和无标签功能的定量生物标志物检测方法已被证明可用于即时医疗（POC）技术或“旁边”诊断技术的开发。通过蛋白质特异性连接的微珠聚集提供了一种从样品中选择性捕获生物标志物的有效方法，并且可以直接读出靶标的存在和数量。然而，害怕能够精确地量化微珠聚集的传感器或微流体分析仪。在这项工作中，我们演示了一个基于微孔的微珠分析系统，通过该系统可以实现对微珠的在线操作，包括捕获，排列和旋转，从而提供了一系列微流控方法来布置聚集的微珠，以进一步方便地进行表征。使用提议的系统检测前列腺特异性抗原，证明检测限低至0.125 ng / mL（3.67 pM）。首次提出了两步反应动力学模型来解释微珠聚集的动力学过程。所开发的微珠聚集分析系统具有无标记检测，高通量和低成本的优点，显示出便携式生物标记检测的巨大潜力。