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

PI：LeDuc，Philip R.提案编号：1547810 PI：Davidson，Lance A. 提案编号：1547790细胞生物制造对于基于细胞和组织的治疗和药物测试应用具有重要意义。 从组织中获得必要类型的细胞作为起始材料对于细胞生物制造操作的成功至关重要。在这项应用中，研究人员将研究一种新技术，该技术已被开发用于在微米尺度上控制流体流动，以从活组织中提取活细胞，因此它们可以用作生物制造行业的构建模块。生物制造最需要的细胞在人体内复杂的异质三维（3D）环境中自然生长，这使得它们的提取非常具有挑战性。 该提案的目标是开发高通量细胞收获方法，该方法允许将试剂控制时空应用于3D组织以进行靶向细胞提取。为了实现这一目标，研究人员计划开发一种新的微流体收获方法，以同时逐层成像和蚀刻体模组织，同时回收下游的靶细胞;并将这种微流体方法用于实验室生长的器官芽，即类器官，以实现时空控制的干细胞提取。研究人员将开发从小型复杂3D组织（如类器官）内的定义位置收集细胞的能力，并使用微流体技术对提取的细胞进行分类并保持其活力。如果成功，该项目将在利用高通量技术从类器官和组织中有针对性地收获高度期望的干细胞和祖细胞方面取得重大进展，然后将在细胞生物制造中使用回收的细胞作为诊断和治疗应用的构建模块。这些研究的更广泛的影响包括建立一个教育和培训管道，为未来的工程和科学领导者做好准备。

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.