Microfluidics to explore ultrafast cell deformations to deliver large cargo via convective transport

微流体技术探索超快细胞变形，通过对流运输运送大件货物

• 批准号: 10522049
• 负责人: Todd Sulchek
• 金额: $ 30.1万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522049
• 关键词: Active Biological Transport; Affect; Biological; Biological Markers; Biomechanics; Biophysics; CRISPR/Cas technology; Cancer cell line; Carcinoma; Cell Separation; Cell Survival; Cell Volumes; Cell membrane; Cells; Charge; Contrast Media; Convection; Cytoplasm; Cytoskeleton; DNA Damage; DNA delivery; Device Designs; Devices; Diagnostic; Electroporation; Extracellular Fluid; Gene Delivery; Genetic; Goals; Gold; Grant; Health; Hematopoietic; Knowledge; Lab-On-A-Chips; Label; Liquid substance; Location; Mechanics; Mediating; Membrane; Mesenchymal Stem Cells; Messenger RNA; Methods; Microfluidic Microchips; Microfluidics; Modeling; Modification; Molecular; Nuclear Structure; Phenotype; Process; Property; Proteins; Reaction; Reagent; Relaxation; Route; Series; T-Lymphocyte; Testing; Therapeutic; Time; Transfection; Transgenes; Trauma; Viral; cancer cell; cell behavior; cell type; cellular engineering; design; extracellular; genome editing; in vivo imaging; induced pluripotent stem cell; innovation; iron oxide nanoparticle; lipofection; macromolecule; mechanical force; microfluidic technology; millisecond; nanoparticle; new technology; novel; novel strategies; particle; plasmid DNA; pressure; progenitor; programs; response; sensor; stem; stem cells; uptake

Project Summary The delivery of molecules and particles to cells is important for increased scientific understanding of molecular processes and networks, detecting intracellular biomarkers in diagnostic targets, and genetic modification of therapeutic cells. The challenges associated with current delivery approaches include limits to the size of molecules that can be delivered (especially plasmid DNA), damage or modification to target cells, and a limit to the cell processing throughput. In studies to develop new methods that can be used to deliver molecules and particles more broadly to many cell types, a novel cellular behavior was discovered that occurs as cells are rapidly compressed at timescales faster than a millisecond. As a result of fast compressions upon cells, cells respond by a temporary change of volume, which results in a pressure driven flow across the cell membrane to restore cell volume, and as a byproduct carries extracellular reagents into a cell through a convective phenomenon. The goal of this study is to understand how to optimize devices exploiting a new biophysical regime of cell compression in which fast timescales (<1 millisecond), high strain (>30%) to impact cells. These physical impacts of cells are increasingly important to understand due to applications in lab on a chip, cell sorting, and cell engineering. Secondly, the microfluidic technology will be optimized and tested for microfluidic delivery of probes and labels, as well as transfection of large transgenes for a variety of important cell types. The understanding of cell mechanical responses in an unexplored region of time and magnitude could enable new approaches to label and reprogram the cell that will be efficient to a broad range of cell types and reagents.

项目概要 将分子和颗粒递送至细胞对于增强对分子的科学理解非常重要 过程和网络，检测诊断目标中的细胞内生物标志物，以及基因改造 治疗细胞。与当前交付方法相关的挑战包括规模的限制 可以传递的分子（特别是质粒DNA），对靶细胞的损伤或修饰，以及限制 细胞处理吞吐量。研究开发可用于传递分子和 随着粒子更广泛地应用于许多细胞类型，人们发现了一种新的细胞行为，这种行为发生在细胞被 以快于一毫秒的时间尺度快速压缩。由于对细胞的快速压缩，细胞 通过暂时的体积变化做出响应，从而导致压力驱动的流穿过细胞膜 恢复细胞体积，并作为副产品通过对流将细胞外试剂带入细胞内 现象。这项研究的目的是了解如何利用新的生物物理学来优化设备 细胞压缩的机制，其中快速时间尺度（<1毫秒）、高应变（>30%）来影响细胞。这些 由于芯片、细胞实验室的应用，了解细胞的物理影响变得越来越重要 分选和细胞工程。其次，将针对微流控技术进行优化和测试 探针和标签的递送，以及对各种重要细胞类型的大转基因的转染。 在未探索的时间和幅度范围内了解细胞机械反应可以使 标记和重新编程细胞的新方法将对广泛的细胞类型有效 试剂。