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

PI: LeDuc, Philip r .提案号：1547810PI: Davidson， Lance A.提案号：1547790细胞生物制造对于细胞和组织为基础的治疗和药物测试应用具有重要意义。从组织中获取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，研究人员将研究一项新技术，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基础。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，这使得提取它们非常具有挑战性。本提案的目标是开发高通量细胞收集方法，允许试剂在三维组织中的受控时空应用，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集方法，在回收下游靶细胞的同时，一层一层地成像和蚀刻幻影组织；并将这种微流体方法应用于实验室培养的器官芽，即类器官，以实现具有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）的特定位置收集细胞的能力，并使用微流体对提取的细胞进行分类并保持其活力。如果获得成功，该项目将在从类器官和组织中以高通量技术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，然后将回收的细胞用于细胞生物制造，作为诊断和治疗应用的基石。这些研究的更广泛的影响包括建立教育和培训管道，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.