Surface-based Microfluidic Systems for Enhanced Biomarker Detection
Surface-based Microfluidic Systems for Enhanced Biomarker Detection
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DOI：
10.15102/1394.00001803
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发表时间：
2021-04
影响因子：
0.7
通讯作者：
S. Sathish
中科院分区：
文献类型：
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作者：
S. Sathish
用于增强生物标志物检测的基于表面的微流体系统世纪已经看到了与微流体生物测定设备集成的即时（POC）测试系统的发展激增，用于便携式、快速和用户友好的疾病诊断。这些系统从少量患者的血浆中检测诊断生物标志物，通过利用其与特定受体分子结合的先天性质。当可以在几分钟内检测到低生物标志物浓度（1 pM-1 nM）时，认为微流体生物测定装置具有“高效率”。本论文探讨了微尺度下表面化学、生物标记物传输和生物分子反应的集体影响，为开发快速、灵敏和用户友好的基于荧光的POC系统提出了设计原则。首先，我们利用射频空气等离子体共价拴在聚甲基丙烯酸甲酯微流控生物测定装置内的受体蛋白，在高通量。接下来，这些设备与手掌大小的模块化流体处理设备集成，该设备允许精确混合，过滤和输送流体，用于随后检测沙眼衣原体特异性抗体，在15分钟内检测限（LoD）为7 nM，用作“概念验证”POC测试设备。接下来，使用新型3D玻璃装置研究微流体生物测定系统中的生物标志物转运依赖性动力学增强，其中分析不同浓度的荧光标记受体和配体抗体之间的实时结合事件。结合实验测量和标度分析，提出了两个关键的控制无量纲参数，以实现“快速”和“灵敏”的配体检测：局部佩克莱数Peδ，表征局部对流和扩散驱动的配体运输之间的平衡;和动力学达姆科勒数（Dakinetic），表征受体-配体结合和对流驱动的配体补充之间的平衡。我们观察到均匀的配体结合可以通过减小耗尽层厚度（> 10.在Dakinetic > 10时，Dakinetic << 10−2。有了动力学常数的先验知识，这些设计原理可以应用于各种生物分子系统，为在不久的将来创建高效的POC测试系统铺平道路。
Surface-based Microfluidic Systems for Enhanced Biomarker Detection The 21st century has seen a surge in the development of point-of-care (POC) testing systems integrated with microfluidic bioassay devices, for portable, fast, and user-friendly disease diagnostics. These systems detect diagnostic biomarkers from a small quantity of the patient’s blood plasma, by exploiting their innate nature to bind to specific receptor molecules. A microfluidic bioassay device is considered to be of “high efficiency” when low biomarker concentrations (1 pM–1 nM) can be detected within a few minutes. This thesis explores the collective influence of surface chemistry, biomarker transport and biomolecular reactions at the microscale, to propose design principles for the development of rapid, sensitive and user-friendly fluorescence-based POC systems. First, we exploit radio-frequency air plasma to covalently tether receptor proteins within polymethyl methacrylate microfluidic bioassay devices, at high-throughput. Next, these devices are integrated with a palm-sized modular Fluid Handling Device that allows precise mixing, filtration, and delivery of fluids, for subsequent detection of Chlamydia trachomatis specific antibodies, with a limit of detection (LoD) of 7 nM within 15 mins, serving as a “proof-of-concept” POC testing device. Next, biomarker transport-dependent kinetic enhancements in microfluidic bioassay systems are investigated using novel 3D glass devices, where real-time binding events between varying concentrations of fluorescently-labelled receptor and ligand antibodies are analyzed. Combing experimental measurements with scaling analysis, two key control dimensionless parameters are proposed to achieve “rapid” and “sensitive” ligand detection: a local Peclet number Peδ that characterizes the balance between local convection and diffusion-driven transport of ligands; and a kinetic Damkohler number (Dakinetic) that characterizes the balance between the rates of receptor–ligand binding and convection-driven ligand replenishment. We observe that homogeneous ligand binding can be achieved by decreasing the depletion layer thickness (> 10. At Dakinetic > 10 for Dakinetic << 10−2. With prior knowledge of the kinetic constants, these design principles can be applied to various biomolecular systems, paving way to creating highly efficient POC testing systems in the near future.