STTR Phase I: Development of a Computational Tool for Modeling, Simulation, and Design of Next Generation Discrete Droplet Microfluidic Systems

这个小型企业技术转移（STTR）第一阶段项目建议为基于液滴的微流体装置开发模拟和设计软件。设计用于生物和生物化学应用的微流控平台是一个费力的过程，涉及多次实验试验。将基本设计扩展到并行设备是另一个挑战。因此，能够加速发现过程的计算工具是必不可少的。提出的工作是开发一种合理的设计方法，该方法将全面访问开发大规模并行微流控架构的巨大设计空间。这项工作的智力优势涉及：(i)开发了一种结合线性代数和图论的方法，以一种可计算的方式模拟大规模基于液滴的微流控平台的行为，以及（ii）研究了一种专门的遗传算法（GA）方法，该方法将与仿真模块集成，以基于任何期望目标设计定制的基于液滴的微流控平台。该提案的第一阶段将侧重于开发和演示用于特定组合测序问题的微流控平台。此阶段的可交付产品是一个软件系统，它将接收来自用户的输入并交付CAD设备设计。如果成功，这个项目的更广泛的影响/商业潜力将是为微流控芯片实验室设备开发几个新的设计概念，这些设计概念提供了在分子水平上控制化学物质的能力。这将极大地增强我们对这些设备基本工作原理的理解。精确控制化学成分和浓度将有助于发现有助于蛋白质结晶和干细胞生长的物质。这将为制药公司（数十亿美元的产业）提供药物筛选和组合蛋白设计的宝贵资源。此外，这些平台还可以设计用于生物学应用，例如从健康细胞中优先分离癌细胞。该软件的最初客户将是大学和研究实验室。随着技术成功地通过验证周期，该软件要么可以直接授权给客户，要么可以在特定设计项目的行业中以设计咨询模式使用。该项目的宏伟愿景是开发一种自动化系统，该系统将从用户的设计概念开始，使用3D打印或Xurography合成基于液滴的微流控平台。

This Small Business Technology Transfer (STTR) Phase I project proposes to develop a simulation and design software for droplet-based microfluidic devices. Designing microfluidic platforms for biological and biochemistry applications is a laborious process involving several experimental trials. Scaling up a basic design to a parallelized device is another challenge. As a result, computational tools that can hasten the discovery process are essential. The proposed work is on the development of a rational design approach that will comprehensively access the vast design space for developing massively parallelized microfluidic architectures. The intellectual merits of the work are related to: (i) the development of a combined linear algebra and graph theory approach to simulate the behavior of large-scale droplet-based microfluidic platforms in a computationally tractable manner, and (ii) research on a specialized genetic algorithm (GA) approach, which will integrate with the simulation module for the design of customized droplet-based microfluidic platforms based on any desired objective. The first phase of the proposal will focus on the development and demonstration of a microfluidic platform for a specific combinatorial sequencing problem. A deliverable for this phase is a software system that would receive inputs from the user and deliver a CAD device design. The broader impact/commercial potential of this project, if successful, will be the development of several novel design concepts for microfluidic lab-on-a-chip devices that provide the ability to control chemicals at a molecular level. This will profoundly enhance our understanding of the fundamental workings of these devices. Precise control of chemical composition and concentration will lead to discovery of materials that help in protein crystallization and stem cell growth. This will be a valuable resource for pharmaceutical (multibillion dollar industry) companies for drug screening and combinatorial protein designs. Additionally, these platforms also can be designed for biological applications such as preferential separation of cancer cells from healthy cells. Initial customers for this software will be universities and research labs. As the technology successfully negotiates the validation cycle, the software either may be licensed directly to customers or used in a design consultancy mode with industries for specific design projects. The grand vision of the project is the development of an automated system that will synthesize droplet-based microfluidic platforms using either 3D printing or Xurography starting from just a design concept of a user.