SBIR Phase I: Development of Integrated Fluid/Solid/Bio-Kinetic Simulation Software for the Characterization of Microsphere-based Bio-analytic Systems

这一小型企业创新研究第一阶段(SBIR)项目将展示先进的模拟方法在预测用于生物传感应用的微球表面的生物分子结合方面的可行性和价值。目前使用的模型采用了许多特别的假设，特别是与对流质量传输有关的假设。在预测工作中，经常会遇到较大的系统误差。这里提出的新颖的高保真模拟有望提供对多相流、扩散和表面化学之间复杂相互作用的系统理解。在第一阶段，将开发一个以离散粒子模拟(适用于小珠)和嵌合体粒子模拟(适用于大珠)为特色的集成模拟环境。将开发详细的珠面化学模型(具有有限速率吸附、解吸和转变为不可逆态)，并完全耦合到流动模型。这项技术将使用犹他州州立大学开发的基于流态化的食品生物传感器免疫FLOW进行演示。流动和结合模拟结果都将与实验进行验证。在第二阶段，离散粒子技术和嵌合体粒子技术将进一步发展，以及更普遍的、用户指定的表面反应机理和生物分子特定结合现象的模型开发。该技术和本项目开发的软件在生物传感器领域的商业应用将向生物技术社区营销。该产品将能够快速创建下一代优化的生物传感器，同时增强对生化过程的基本理解。这项技术还将有利于传统化工和制药行业的研究。

This Small Business Innovation Research Phase I (SBIR) project will demonstrate the feasibility and value of advanced simulation methodology for the prediction of biomolecular binding on the surface of microspheres used in biosensing applications. Models in current use employ many ad-hoc assumptions, particularly related to convective mass transport. Large, systematic errors are commonly encountered in predictive efforts. Novel, high-fidelity simulations proposed here hold the promise of providing a systematic understanding of the complex interaction between multiphase flow, diffusion and surface chemistry. An integrated simulation environment featuring Discrete Particle Simulations (suited for small beads) and Chimera Particle Simulations (for larger beads) will be developed in Phase I. Detailed bead-surface chemistry models (featuring finite-rate adsorption, desorption and conversion to irreversible state) will be developed and fully coupled to the flow model. The technique will be demonstrated using Immunoflow , a food bio-sensor based on fluidization developed at Utah State University. Both flow and binding simulation results will be validated against experiments. In Phase II, both Discrete and Chimera particle techniques will be further developed along with more generalized, user specifiable surface reaction mechanisms and model development for bio-molecule specific binding phenomena.The commercial application of the technology and the software to be developed in this project is in the area of biosensors for marketing to the biotechnology community. The product will enable the rapid creation of the next generation of optimized biosensors while simultaneously enhancing the fundamental understanding of biochemical processes. The technology would also benefit research in the traditional chemical and pharmaceutical industries.