EAGER: Collaborative Research: Biomanufacturing: Developing a Harvesting Approach for Spatially Targeted Cells from 3D Organoids and Tissues

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PI: LeDuc, Philip R.Proposal Number: 1547810PI: Davidson, Lance A. Proposal Number: 1547790Cellular biomanufacturing is significant for cell and tissue-based therapies and drug testing applications. Procuring the necessary types of cells from tissues as the starting material is critical for the success of cellular biomanufacturing operations. In this application, the investigators will study a new technology that has been developed for controlling fluid flow at the micrometer scale to extract live cells from living tissues, so they can be used as building blocks for the biomanufacturing industry.Cells most desired for biomanufacturing grow naturally within a complex heterogeneous three dimensional (3D) environment within human bodies, making their extraction very challenging. The goal of this proposal is to develop high throughput cell-harvesting approaches that allow for the controlled spatiotemporal application of reagents to 3D tissues for targeted cell extraction. To accomplish this, the investigators plan to develop a novel microfluidic harvesting approach to simultaneously image and etch phantom tissues layer-by-layer while recovering target cells downstream; and implement this microfluidics approach for use with laboratory grown organ-buds, i.e. organoids, to enable the extraction of stem cells with spatiotemporal control. The investigators will develop the ability to collect cells from defined locations within small complex 3D tissues such as organoids and use microfluidics to sort extracted cells and maintain their viability. If successful, this project will produce a significant advancement in the targeted harvesting of highly desired stem and progenitor cells from organoids and tissues with a high throughput technology that will then enable the use of recovered cells in cellular biomanufacturing as building blocks for diagnostic and therapeutic applications. The broader impacts of these studies include building an education and training pipeline for preparing future leaders in engineering and science.