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

该创新-技术转化合作伙伴关系（PFI-TT）项目的更广泛影响/商业潜力是推进3D工程组织，使其可用于癌症药物筛选的商业用途。长期以来，工程组织一直被认为是药物测试的有前途的模型，因为它们比传统的2D细胞培养系统和自聚集的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。这将推动在早期阶段消除无效候选药物的努力，加快抗癌药物的开发过程。开发更安全、更有效的抗癌药物可以改善临床结局。研究生、本科生和博士后研究员将深入了解创新和创业，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和分配工程组织微球到多孔板中的能力，这是进一步验证疾病有效性的关键一步-我们的目标是在癌症药物筛选中提供特定的工程化组织微球，并最终将预涂板的工程化组织微球作为检测就绪产品提供给客户。本提案的首要目标是生产和制备适用于结肠癌药物筛选目的的预铺板的检测就绪的工程化组织微球。为了实现这一目标，我们将：（1）设计和制造一种低成本的光交联系统，用于一致和可扩展的工程化组织微球生产;（2）设计和制造一种原型，用于将工程化组织微球分布到孔板中;（3）设计方法，用于一致和快速地制造一次性微流控装置盒。该项目的成果将是我们的微流体封装平台的试验板原型和自动分配系统，该系统能够快速和可扩展的工程组织微球生产和分配。与目前的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细胞聚集体技术相比，这种工程组织微球技术具有整合非聚集性细胞和多种细胞类型以及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知识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.