PFI-TT: An Automated Platform for Production and Distribution of Engineered Tissue Microspheres

该创新合作伙伴关系 - 技术转化 (PFI-TT) 项目更广泛的影响/商业潜力是推进 3D 工程组织的发展，使其可在商业上用于癌症药物筛选。工程组织长期以来一直被认为是有前途的药物测试模型，因为它们比传统的 2D 细胞培养系统和自聚合 3D 模型更接近人体组织。这些系统还可以降低药物开发成本。问题在于无法快速、均匀地创建这些 3D 工程组织。该项目致力于弥合这些差距，从而提供更有效的药物筛选模型。这将推动早期消除无效候选药物的努力，加快抗癌药物的开发进程。开发更安全、更有效的抗癌药物可以改善临床结果。研究生、本科生和博士后研究人员将深入了解创新和创业精神，并为引领未来技术的商业化做好准备。拟议的项目将建立大规模生产工程组织微球并将其分配到多孔板中的能力，这是进一步验证疾病特异性工程组织微球在癌症药物筛选中的有效性的关键一步，并最终将预镀的工程组织微球作为可供客户分析的产品呈现。该提案的总体目标是生产和制备适用于结肠癌药物筛选目的的预铺板分析就绪工程组织微球。为了实现这一目标，我们将：（1）设计和制造低成本的光交联系统，以实现一致且可扩展的工程组织微球生产； (2) 设计并制造用于将工程组织微球分布到孔板中的原型； (3)一致且快速地制造一次性微流体装置盒的设计方法。该项目的成果将是我们的微流体封装平台的面包板原型和自动化分配系统，该系统可实现快速且可扩展的工程组织微球生产和分配。与当前的 2D 细胞模型和 3D 球状细胞聚集体相比，该项目将建立生产和使用更有效的 3D 组织模型进行药物筛选的能力。与竞争的3D细胞聚集技术相比，这种工程组织微球技术具有整合非聚集细胞和多种细胞类型并允许调节细胞微环境的优势。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is to advance 3D engineered tissues such that they can be used commercially for cancer drug screening. Engineered tissues have long been considered promising models for drug testing since they more closely approximate human tissue than traditional 2D cell culture systems and self-aggregated 3D models. These systems can also lower drug development costs. The problem lies in the inability to create these 3D engineered tissues rapidly and uniformly. This project works to bridge these gaps and thereby provide more effective drug screening models. This will advance efforts to eliminate ineffective drug candidates at an early stage, expediting the anti-cancer drug development process. Development of safer and more effective anticancer drugs can improve clinical outcomes. Graduate student, undergraduate student, and postdoctoral fellow researchers will gain insight into innovation and entrepreneurship and prepare to lead commercialization of future technologies.The proposed project will establish the ability to produce and distribute engineered tissue microspheres into multi-well plates on a large scale, which is a critical step for enabling the further validation of the effectiveness of disease-specific engineered tissue microspheres in cancer drug screening and eventually to present the pre-plated engineered tissue microspheres as assay-ready products for customers. The overarching goal of this proposal is to produce and prepare pre-plated assay-ready engineered tissue microspheres suitable for colon cancer drug screening purposes. To achieve this goal, we will: (1) design and fabricate a low-cost photocrosslinking system for consistent and scalable engineered tissue microspheres production; (2) design and fabricate a prototype for engineered tissue microspheres distribution into well plates; (3) design approaches for fabricating disposable microfluidic device cartridge consistently and rapidly. The outcome of this project will be a bread-board prototype of our microfluidic encapsulation platform and an automated dispensing system that enables rapid and scalable engineered tissue microspheres production and dispensing. This project will establish the ability to produce and employ more effective 3D tissue models for drug screening as compared to current 2D cell models and 3D spheroidal cell aggregates. Compared to competing 3D cell aggregate technology, this engineered tissue microspheres technology has the advantages of incorporating non-aggregating cells and multiple cell types and allowing modulation of cellular microenvironment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.