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: 10707493
• 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/10707493
• 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; Cytoplasm; Cytoskeleton; DNA delivery; Device Designs; Devices; Diagnostic; Electroporation; Extracellular Fluid; Gene Delivery; Genetic; Goals; Grant; Health; Hematopoietic stem cells; Knowledge; Lab On A Chip; Label; Liquid substance; Location; Mechanics; Mediating; Membrane; Mesenchymal Stem Cells; Messenger RNA; Methods; Microfluidic Microchips; Microfluidics; Modeling; Modification; Molecular; Needles; 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; programs; response; sensor; 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.

项目摘要 分子和颗粒向细胞的递送对于增加对分子的科学理解很重要 过程和网络，检测诊断靶标的细胞内生物标志物以及遗传修饰 治疗细胞。与当前交付方法相关的挑战包括对大小的限制 可以输送的分子（尤其是质粒DNA），损伤或对靶细胞的修饰，以及限制 细胞处理吞吐量。在开发可用于传递分子和的新方法的研究中 颗粒更广泛地在许多细胞类型上，发现了一种新型的细胞行为，该行为发生时发生，因为细胞是 比毫秒更快地在时间尺度上压缩。由于细胞上的快速压缩，细胞 通过暂时变化的体积响应，从而导致横跨细胞膜的压力驱动流动到 恢复细胞体积，作为副产品，通过对流将细胞外试剂带入细胞 现象。这项研究的目的是了解如何优化利用新生物物理的设备 细胞压缩的状态，其中快速时标（<1毫秒），高应变（> 30％）撞击细胞。这些 由于在芯片上的实验室中应用，细胞对细胞的物理影响越来越重要 分类和细胞工程。其次，将对微流体进行优化和测试微流体技术 探针和标签的递送，以及针对各种重要细胞类型的大型转染的转染。 在未开发的时间和幅度中，对细胞机械响应的理解可以实现 标记和重新编程细胞的新方法，该细胞将有效到广泛的细胞类型和 试剂。

项目成果

Strain-dependent elastography of cancer cells reveals heterogeneity and stiffening due to attachment

癌细胞的应变依赖性弹性成像揭示了由于附着而产生的异质性和硬化

• DOI: 10.1016/j.jbiomech.2023.111479
• 发表时间: 2023
• 期刊: Journal of Biomechanics
• 影响因子: 2.4
• 作者: Xu, Wenwei;Kabariti, Saif;Young, Katherine M.;Swingle, Steven P.;Liu, Alan Y.;Sulchek, Todd
• 通讯作者: Sulchek, Todd