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Design Optimization Of Microsphere-Based Immunoassay Sensors For Biodetection

机译：基于微球的免疫测定传感器设计优化

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摘要

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：用于生物巴鲁药剂检测，食品或水毒素分析的生物分析系统的性能依赖于可量化和可重复的生物分子相互作用。基于微球的系统已经被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批判性地取决于缓冲剂和珠子性能之间的复杂相位以及操作参数。在以前的工作中，我们成功开发了基于物理的计算工具，用于使用微流体环境中的微球进行模拟检测[1,2]。该模型完全集成了拉格朗日的珠子运输，对流 - 衍射分析物和生物分子表面对珠子的结合反应。本文提出了一种多种式仿真框架，我们提出了一种优化基于微球的测定设计的方法。通过原型传感器平台的参数化证明了方法。测试测定平台是用蛇形环的简单y构建体，用于改善样品和珠子之间的混合和接触。应用自动参数化方法来评估各种几何，协议和属性参数对珠子的平均表面覆盖所示的整体信号的影响。本研究结果表明，对于感兴趣的给定生物分子，通过这些参数的明智组合可以显着提高信号。目前的方法为传统的试验和误差过程提供了经济有效的替代方法，用于优化生物遗养免疫测定传感器。

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