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: 10473728
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10473728
• 关键词: 3-Dimensional; Acoustics; Biochemical; Biological; Biological Assay; Biological Testing; Biology; Caliber; Cells; Cellular biology; Complex; Consultations; Development; Developmental Biology; Devices; 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; 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; mechanical stimulus; micromanipulator; optical imaging; particle; pressure; real-time images; response; success; technology development; tool; tumorigenic; 3-Dimensional; Acoustics; Biochemical; Biological; Biological Assay; Biological Testing; Biology; Caliber; Cells; Cellular biology; Complex; Consultations; Development; Developmental Biology; Devices; 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; 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; mechanical stimulus; 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 这项研究是为了开发基于菲涅耳镜头的超声镊子，可以捕获和操纵生活 按需三维（3D）空间的组织，非常类似于光学镊子 给定温度升高的机械捕获力更强。由校长领导的实验室 研究者（PI）最近证明了液体中微颗粒（直径70-400 µm）的超声捕获 带有单个多环球训练器换能器（MFT）。被捕获的微粒按需移动 以3D移动MFT。在这一成功的基础上，该提案将推进传感器技术，因此 单个MFT可以通过电信号捕获和移动3D中的颗粒或单元，而无需电信 需要移动传感器。这将受益于广泛的生物学研究人员，包括 分子，发育和细胞生物学。 生物测试实验将用于集中和验证技术开发。我们的第一个特定 超声镊子的应用将是捕获和固定太大的生物标本，无法激光捕获（例如， 斑马鱼胚胎和癌症衍生的球体使用MFT。这些被困的多细胞结构将是 没有机械接触以进行延时显微镜，并将被声学镊子扭曲为 测试改变物理力对胚胎和器官发育的影响。这些实验需要 捕获和扭曲力足以改变胚胎的形状（远大于力 使用光镊）。 我们将在3D空间中开发诱捕位置的电气可控性，以便捕获的标本 可能是：（1）从一个位置移到另一个位置，（2）拉伸或压缩以表征 细胞的弹性特性，（3）与其他细胞或含基因的脂质体接触。这些都是 在电命令下执行，无需机械移动超声波镊。 为了优化超声镊子的开发，作为生物实验的促成工具，两个 生物实验室（由共同投资者领导）将从一开始就参与研究。他们会收到的 在第4年，第6、18、30和42个月的末尾，声学镊子的成功版本的版本 研究期，并将使用它们进行转基因胚胎，细胞进行提出的实验 球体和非粘附循环细胞。拟议的生物学实验需要操纵现场 液体环境中的细胞，而没有固定装置造成的任何损坏。这样的无接触操作 没有提议的镊子，将是极其困难的，即使不是不可能的。两个生物学实验室将 积极参与镊子的协同进步，进行生物学实验，并 提供及时的反馈，将PI的实验室指导到创建最有用的设计。 由于MFT将声能聚焦在很小的位置上，并且能够通过 一种中间固体，可以将其纳入各种微流体平台中，以用于管理细胞， 液体，颗粒和蛋白质。 MFT在捕获的位置和方向上的电气可控性 力与MFT形成阵列的力性结合在一起，将允许创建复杂 高吞吐量的生化测定和/或生物医学治疗。 MFT的前所未有的能力 3D捕获和按需操纵微粒/细胞（数十个直径的微米）将 在细胞研究，基因翻译，并置和操纵中打开许多新的可能性。