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，以设计和优化微球和基于细胞的分析。目前通过试错法进行的分析设计缓慢、不可靠、昂贵，并且是多路分析、高通量分析的瓶颈。之前的第一阶段研究已经成功地建立了有史以来第一个真正集成的(缓冲流、可分辨微球运动和表面生物化学)分析设计和分析工具。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到一个全面的、通用的设计环境中。将开发一套珠面生物化学模型(酶动力学、多步骤反应)，并包括用户指定的表面反应机理，并完全集成。为了将应用扩展到基于细胞的分析，将创建可变形细胞的运动和捕获模型，并将进行跟踪微流控通道中的珠子和细胞运动以及分析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在一种新颖的微流控、基于细胞的H-Filter检测红细胞氨基硫醇的概念验证设计中得到证明，该项目的商业应用将在生物技术和生物检测设计市场上得到应用。小型化、多元化、高通量、快速、高效和灵敏的分析是将来自人类基因组和组合文库的丰富数据转化为有效疗法的先决条件。开发的软件产品将使这些生物检测的合理、基于计算机的设计成为可能。

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.