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

这个小型企业创新研究（SBIR）第二阶段项目将开发和定制先进的模拟软件，用于设计和优化微球和基于细胞的检测。目前的试验设计是缓慢的，不可靠的，昂贵的，多路复用，高通量分析的瓶颈。之前的I期研究已经成功地建立了有史以来第一个真正集成的（缓冲液流，解决微球运动和表面生物化学）测定设计和分析工具。第二阶段工作的目标是将第一阶段工作中演示的初始模型进一步开发成一个全面的通用设计环境。将开发并完全集成一套微珠表面生物化学模型（酶动力学、多步反应），包括用户可指定的表面反应机制。在寻求将应用扩展到基于细胞的测定中时，将创建用于可变形细胞的运动和捕获的模型，并且将进行跟踪微流体通道中的珠和细胞运动以及测定终点的详细流动可视化实验，以指导和验证这些模型。开发的模拟工具的价值将被证明在一个新的微流控，基于细胞的H-过滤器分析的红细胞为基础的氨基thiols.The商业应用的概念设计验证该项目将在生物技术和生物检测设计市场。小型化、多路复用、高通量、快速、高效和灵敏的测定是将来自人类基因组和组合文库的丰富数据转化为有效治疗的先决条件。开发的软件产品将使这些生物测定的合理的，基于计算机的设计。

This Small Business Innovation Research (SBIR) Phase II project will develop and customize advanced simulation software for the design and optimization of microsphere and cell-based assays. Current assay design by trial and error is slow, unreliable, expensive, and a bottleneck for multiplexed, high-throughput analysis. Prior Phase I research has successfully established a first-ever, truly integrated (buffer flow, resolved microsphere motion and surface biochemistry) assay design and analysis tool. The objective of the Phase II effort is to further develop the initial models demonstrated in the Phase I effort into a comprehensive, generalized design environment. A suite of bead-surface biochemistry models (enzyme kinetics, multi-step reactions) and including user specifiable surface reaction mechanisms will be developed and fully integrated. In seeking to expand the application to cell-based assays, models for the motion and capture of deformable cells will be created, and detailed flow visualization experiments tracking bead and cell motion as well as assay endpoints in microfluidic channels will be conducted to guide and validate these models. The value of the developed simulation tool will be demonstrated in the proof-of-concept design of a novel microfluidic, cell-based H-filter assay for red-blood cell based aminothiols.The commercial applications of this project will be in the biotechnology and bioassay design markets. Miniaturized, multiplexed, high-throughput, fast, efficient and sensitive assays are a pre-requisite to translating the wealth of data from the human genome and combinatorial libraries into effective therapeutics. The developed software product will enable rational, computer-based design of these bioassays.