MEMS Acoustic Tweezers for Micromanipulation of Living Cells

用于活细胞显微操作的 MEMS 声学镊子

• 批准号: 9803092
• 负责人: EUN SOK KIM
• 金额: $ 33.8万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9803092
• 关键词: 3-Dimensional; Acoustics; Biochemical; Biological; Biological Assay; Biological Testing; Biology; Caliber; Cells; Cellular biology; Complex; Consultations; Development; Developmental Biology; Devices; Dimensions; Embryo; Embryonic Development; Environment; Feedback; Genes; Goals; Image; Lasers; Lipids; Liposomes; Liquid substance; Location; Malignant Neoplasms; Manuals; Measures; Mechanical Stress; Mechanics; Microfluidics; Micromanipulation; Microscopy; Microspheres; Molecular Biology; Movement; Optics; Organism; Organoids; Polystyrenes; Principal Investigator; Property; Proteins; Radiation; Research; Research Personnel; Sampling; Scanning; Series; Shapes; Signal Transduction; Solid; Specimen; Spottings; Stimulus; Stretching; Structure; Technology; Temperature; Testing; Time; Tissues; Transducers; Transfection; Transgenic Organisms; Tumor Biology; Ultrasonics; Work; Zebrafish; base; chemotherapy; density; design; embryo cell; experimental study; gene transplantation for gene therapy; grasp; imager; innovation; instrument; laser tweezer; lens; mechanical force; micromanipulator; optical imaging; particle; pressure; real-time images; response; success; technology development; tool; tumorigenic

Abstract This research is to develop Fresnel-lens-based ultrasonic tweezers that can capture and manipulate living tissue in three dimensional (3D) space on demand, very much like optical tweezers but with several orders of magnitude stronger mechanical trapping force for a given temperature rise. The lab led by the Principal Investigator (PI) recently demonstrated ultrasonic capture of microparticles (70 - 400 µm in diameter) in liquid with a single Multi-foci Fresnel Transducer (MFT). The captured microparticle was moved on demand by moving the MFT itself in 3D. Building on this success, this proposal will advance the transducer technology so that a single MFT can capture and move particles or cells in 3D on demand with an electrical signal without the need to move the transducer. This will benefit a wide range of biological researchers including those in molecular, developmental and cellular biology. Biological test experiments will be used to focus and validate the technology development. Our first specific application of the ultrasonic tweezers will be to trap and hold living specimens too large for laser-trapping (e.g., zebrafish embryos and cancer-derived spheroids) using a MFT. These trapped multi-cellular structures will be held free from mechanical contact for time-lapse microscopy, and will be distorted by the acoustic tweezers to test the effects of altered physical forces on embryo and organoid development. These experiments require trapping and tweezing forces large enough to change the shape of the embryo (far greater than the forces possible with optical tweezers). We will develop electrical controllability of the trapping location in 3D space so that the captured specimens may be: (1) moved from one location to another, (2) stretched or compressed for the characterization of the cell's elastic properties, (3) brought into contact with other cells or gene-containing liposomes. These will all be performed under electrical command without the need to move the ultrasonic tweezers mechanically. To optimize the development of ultrasonic tweezers as an enabling tool for biological experiments, two biological labs (led by the co-Investigators) will participate in the research from the start. They will receive successive versions of acoustic tweezers at the ends of the 6th, 18th, 30th, and 42nd month during the 4-year research period, and will use them to conduct the proposed experiments with transgenic embryos, cell spheroids and non-adherent circulating cells. The proposed biological experiments require manipulation of live cells in a liquid environment without any damage caused by the holding device. Such contact-free manipulation would be extremely difficult, if not impossible, without the proposed tweezers. The two biology labs will participate actively in a synergistic advancement of the tweezers, performing the biological experiments, and providing timely feedbacks, directing the PI's lab towards creating the most useful designs. Since MFT focuses acoustic energy on a very small spot and is capable of delivering acoustic energy through an intermediate solid, it can be incorporated into various microfluidic platforms for the management of cells, liquids, particles and proteins. The MFT's electrical controllability on the location and direction of the trapping force, combined with amenability of MFT being formed into an array, will allow the creation of complex biochemical assays and/or biomedical treatments at high throughput. The MFT's unprecedented capability of 3D capture and on-demand manipulation of microparticles/cells (of tens - hundreds of microns in diameter) will open up many new possibilities in cell study, gene transfection, juxtaposition and manipulation.

抽象的 这项研究旨在开发基于菲涅尔透镜的超声波镊子，可以捕获和操纵活体 按需在三维 (3D) 空间中组织，非常类似于光镊，但具有几个数量级 对于给定的温升，机械捕获力的强度更大 该实验室由校长领导。 研究者 (PI) 最近展示了超声波捕获液体中的微粒（直径 70 - 400 µm） 使用单个多焦点菲涅耳传感器 (MFT) 捕获的微粒根据需要移动。 在这一成功的基础上，将 MFT 本身移动到 3D 中，该提案将推动传感器技术的发展。 单个 MFT 可以根据需要通过电信号捕获和移动 3D 粒子或细胞，而无需 需要移动传感器，这将使广泛的生物研究人员受益，包括那些在 分子、发育和细胞生物学。 生物测试实验将用于集中和验证我们的第一个具体技术开发。 超声波镊子的应用将是捕获和固定对于激光捕获来说太大的活体样本（例如， 斑马鱼胚胎和癌症衍生的球体）将使用 MFT 来捕获这些被捕获的多细胞结构。 对于延时显微镜来说，不受机械接触的影响，并且会被声学镊子扭曲以 这些实验需要测试物理力对胚胎和类器官发育的影响。 捕获和镊子的力足够大以改变胚胎的形状（远远大于 可以使用光镊）。 我们将开发 3D 空间中捕获位置的电气可控性，以便捕获的样本 可能是：（1）从一个位置移动到另一个位置，（2）拉伸或压缩以表征 细胞的弹性特性，（3）与其他细胞或含有基因的脂质体接触这些都会受到影响。 在电气命令下执行，无需机械移动超声波镊子。 为了优化超声波镊子作为生物实验支持工具的开发，两个 生物实验室（由联合研究人员领导）将从一开始就参与研究。 4年内第6、18、30、42个月末的连续版本声学镊子 研究期间，并将利用它们进行转基因胚胎、细胞的拟议实验 所提出的生物实验需要操纵活体细胞。 这种非接触式操作不会对液体环境中的细胞造成任何损坏。 如果没有提议的镊子，这将是极其困难的，甚至是不可能的。 积极参与镊子的协同进步，进行生物实验，以及 提供及时的反馈，指导 PI 的实验室创建最有用的设计。 由于 MFT 将声能集中在一个非常小的点上，并且能够通过 一种中间固体，它可以合并到各种微流体平台中以管理细胞， MFT 对捕获位置和方向的电可控性。 力与形成阵列的 MFT 的适应性相结合，将允许创建复杂的 MFT 具有前所未有的高通量生化分析和/或生物医学治疗能力。 微粒/细胞（直径数十至数百微米）的 3D 捕获和按需操纵将 为细胞研究、基因转染、并置和操作开辟了许多新的可能性。