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Design Optimization Of Microsphere-Based Immunoassay Sensors For Biodetection

机译：基于微球的生物检测免疫分析传感器的设计优化

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The performance of bioanalytic systems used for biowarfare agent detection, food or water toxin analysis relies on quantifiable and repeatable biomolecular interactions. Microsphere-based systems have come to be recognized as the platform of choice for next generation detection technologies. Microsphere-based immunoassay design is critically dependent on the complex interplay between buffer and bead properties as well as operational parameters. In previous work, we successfully developed physics-based computational tools for modeling sample detection using microspheres in microfluidic environments [1,2]. The models fully integrate Lagrangian transport of the beads, convective- diffusive transport of analyte and biomolecular surface binding reactions on the beads. Building of this multiphysics simulation framework, we present a methodology for optimization of microsphere-based assay design in this paper. The methodology is demonstrated via parameterization of a prototype sensor platform. The test assay platform is taken to be a simple Y- construct with serpentine loops for improved mixing and contacting between sample and beads. The automated parameterization methodology is applied to assess the impact of various geometric, protocol and property parameters on the overall signal as represented by mean surface coverage of the beads. Results from the present study suggest that for a given biological molecule of interest, the signal can be significantly improved by a judicious combination of these parameters. The current methodology provides a cost-effective alternative to traditional trial-and-error process for the optimization of immunoassay sensors for biodetection.
机译：用于生物战剂检测，食物或水毒素分析的生物分析系统的性能取决于可量化和可重复的生物分子相互作用。基于微球的系统已被公认为是下一代检测技术的首选平台。基于微球的免疫测定设计关键取决于缓冲液和微珠性能以及操作参数之间的复杂相互作用。在以前的工作中，我们成功开发了基于物理学的计算工具，用于在微流体环境中使用微球对样品检测进行建模[1,2]。这些模型完全整合了珠子的拉格朗日运输，分析物的对流扩散扩散和珠子上的生物分子表面结合反应。在建立这个多物理场仿真框架的基础上，我们在本文中提出了一种优化基于微球的分析设计的方法。通过原型传感器平台的参数化演示了该方法。测试测定平台被认为是具有蛇形环的简单Y-构建体，用于改善样品和珠之间的混合和接触。应用自动参数化方法来评估各种几何，协议和属性参数对总体信号的影响，以珠子的平均表面覆盖率表示。来自本研究的结果表明，对于给定的目标生物学分子，通过明智地组合这些参数可以显着改善信号。当前的方法为传统的试错法提供了一种经济高效的替代方案，可优化用于生物检测的免疫测定传感器。

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