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

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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.