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

这个小企业创新研究第一阶段（SBIR）项目将展示先进的模拟方法的可行性和价值，用于预测生物传感应用中微球表面的生物分子结合。目前使用的模式采用了许多特别的假设，特别是与对流质量输送有关的假设。在预测工作中经常会遇到较大的系统性错误。本文提出的新颖、高保真的模拟有望为多相流、扩散和表面化学之间复杂的相互作用提供系统的理解。第一阶段将开发一个集成的模拟环境，包括离散粒子模拟（适用于小珠子）和嵌合体粒子模拟（适用于大珠子）。将开发详细的珠子表面化学模型（具有有限速率吸附、解吸和转化为不可逆状态），并与流动模型完全耦合。这项技术将使用免疫流来演示，这是一种由犹他州立大学开发的基于流化的食品生物传感器。流动和绑定的模拟结果将通过实验进行验证。在第二阶段，离散粒子和嵌合体粒子技术将进一步发展，同时更广泛，用户可指定的表面反应机制和生物分子特异性结合现象的模型开发。在这个项目中开发的技术和软件的商业应用是在生物传感器领域，向生物技术界推销。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。这项技术也将有利于传统化学和制药工业的研究。

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.