Harmonic Acoustics for Neighboring cell Dynamic studies(HANDs)

用于邻近细胞动态研究的谐波声学 (HANDs)

• 批准号: 10640942
• 负责人: Luke P. Lee
• 金额: $ 42.9万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-10 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640942
• 关键词: Acoustics; Address; Advanced Development; Area; Atomic Force Microscopy; Autoimmune Diseases; Automation; Bacterial Infections; Benchmarking; Biological; Biological Models; Biological Process; Biology; Biomedical Research; Cancer Biology; Cardiovascular Diseases; Cell Communication; Cell Survival; Cells; Cellular biology; Consumption; Data; Development; Devices; Disease; Exposure to; Frequencies; Generations; Homeostasis; Hour; Immune; Immunooncology; Impairment; Industry Standard; Macrophage; Malignant Neoplasms; Methods; Microfluidics; Modeling; Monitor; Nature; Neurodegenerative Disorders; Optics; Pathology; Pattern; Performance; Phase; Phenotype; Physiological; Positioning Attribute; Procedures; Reporting; Research; Research Personnel; Resolution; Series; Signal Transduction; Solid; Specific qualifier value; Spectrum Analysis; Speed; Structure; T-Lymphocyte; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Transducers; Tumor-infiltrating immune cells; Virus Diseases; aspirate; behavioral study; biomaterial compatibility; cancer cell; cancer drug resistance; cell behavior; cell type; cellular pathology; cost; design; drug discovery; energy efficiency; improved; intercellular communication; interest; invention; laser tweezer; medical schools; next generation; novel therapeutic intervention; operation; optic tweezer; pressure; prevent; single cell analysis; stem cells; tool; transmission process; user-friendly; Acoustics; Address; Advanced Development; Area; Atomic Force Microscopy; Autoimmune Diseases; Automation; Bacterial Infections; Benchmarking; Biological; Biological Models; Biological Process; Biology; Biomedical Research; Cancer Biology; Cardiovascular Diseases; Cell Communication; Cell Survival; Cells; Cellular biology; Consumption; Data; Development; Devices; Disease; Exposure to; Frequencies; Generations; Homeostasis; Hour; Immune; Immunooncology; Impairment; Industry Standard; Macrophage; Malignant Neoplasms; Methods; Microfluidics; Modeling; Monitor; Nature; Neurodegenerative Disorders; Optics; Pathology; Pattern; Performance; Phase; Phenotype; Physiological; Positioning Attribute; Procedures; Reporting; Research; Research Personnel; Resolution; Series; Signal Transduction; Solid; Specific qualifier value; Spectrum Analysis; Speed; Structure; T-Lymphocyte; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Transducers; Tumor-infiltrating immune cells; Virus Diseases; aspirate; behavioral study; biomaterial compatibility; cancer cell; cancer drug resistance; cell behavior; cell type; cellular pathology; cost; design; drug discovery; energy efficiency; improved; intercellular communication; interest; invention; laser tweezer; medical schools; next generation; novel therapeutic intervention; operation; optic tweezer; pressure; prevent; single cell analysis; stem cells; tool; transmission process; user-friendly

PROJECT SUMMARY Dynamic cell-cell interactions are crucial for healthy cell behavior and proper intercellular communication. Impaired intercellular communication has been implicated in the pathologies of various diseases including cancer, neurodegenerative diseases, bacterial and viral infections, autoimmune diseases, and cardiovascular diseases. As a result, probing cell-cell interactions is essential to many areas of biomedical research. It can lead to a more detailed understanding of various diseases and the development of novel therapeutic strategies, such as personalized immuno-oncology. However, current single-cell analysis techniques are slow and require potentially harmful physical contact with cells of interest, hindering the progress in elucidating these phenomena. Recently, we invented Harmonic Acoustics for Neighboring cell Dynamic studies (HANDs), an acoustic- based, automated, contact-free, cell-cell-pairing technology, which overcomes the key obstacles associated with the existing technologies. In this R01 project, we will develop and validate the HANDs platform with the following features: (1) Contactless nature and high biocompatibility: Instead of requiring direct contact with solid substrates or beads, the proposed HANDs technology is a contactless method. In addition, rather than exposure to large shear forces, strong pressures, or powerful optics, which can cause physiological damage, the cells in our setup are manipulated gently with low-power acoustic waves. The proposed HANDs platform allows long- term (>24 hours) cell-cell interaction studies. This feat cannot easily be achieved using existing state-of-the-art technologies such as atomic force spectroscopy. (2) High-throughput reversible cell-cell interactions and precise quantitative analysis at the single-cell level: The multi-trapping nature of the HANDs technology enables the simultaneous and parallel study of numerous (>20,000) cell pairs with single-cell precision. Existing single-cell techniques are either limited to studying a single pair of cells at any given time or lack the precision needed to control cell pairing and separation, and precise quantitative analysis. (3) Automated operation: Unlike existing cell pairing technologies which require complicated procedures and tools to achieve operation, the proposed technology automatically aligns cell-cell pairs using acoustic traps. Additionally, once the control signal is specified, cells can be brought into contact and separated in whatever automated and prescribed contact pattern is desired for testing. (4) High resolution (~100 nm): Using single-phase unidirectional transducers and harmonic frequency modulation, we will improve the spatial resolution of our HANDs technology from ~1 μm to ~100 nm. We will validate the performance of our HANDs platform across two well-established models: interactions between T cells and cancer cells, and interactions between stem cells and macrophages. In this regard, we aim to demonstrate the far-reaching potential of HANDs to enable improved research in areas ranging from fundamental biology to personalized immuno-oncology and drug discovery.

项目摘要 动态细胞 - 细胞相互作用对于健康的细胞行为和适当的细胞间通信至关重要。 细胞间交流受损已与各种疾病的病理有关 癌症，神经退行性疾病，细菌和病毒感染，自身免疫性疾病和心血管疾病 疾病。结果，探测细胞 - 细胞相互作用对于生物医学研究的许多领域至关重要。它可以带领 更详细地了解各种疾病和新型治疗策略的发展，例如 作为个性化免疫肿瘤。但是，当前的单细胞分析技术很慢，需要 潜在的有害物理接触与感兴趣的细胞，阻碍了阐明这些现象的进展。 最近，我们发明了谐波声学，用于相邻的细胞动力学研究（Hand），一种声学 - 基于自动化，无接触式的，细胞纤维配对技术，它克服了与之相关的关键障碍 现有技术。在此R01项目中，我们将使用以下 特征：（1）非接触性质和高生物相容性：而不是需要直接与实心接触 底物或珠子，拟议的手技术是一种非接触式方法。另外，而不是曝光 大剪切力，强大的压力或强大的光学器件，可能造成物理损害，细胞中的细胞 我们的设置通过低功率声波轻轻地操纵。提议的手平台允许长期 术语（> 24小时）细胞 - 细胞相互作用研究。使用现有的最新技术无法轻易实现这一壮举 原子力光谱等技术。 （2）高通量可逆的细胞 - 细胞相互作用和 单细胞级别的精确定量分析：动手技术的多陷阱性质 实现具有单细胞精度的众多（> 20,000）细胞对的简单和平行研究。现存的 单细胞技术要么仅限于在任何给定时间研究一对单元，要么缺乏精度 需要控制细胞配对和分离，并精确的定量分析。 （3）自动化操作： 与现有的单元配对技术不同，这些技术需要复杂的程序和工具才能实现操作， 提出的技术会自动使用声学陷阱对齐细胞对。另外，一旦控制 指定信号，可以在任何自动和规定的接触中接触并分离单元 需要测试模式。 （4）高分辨率（〜100 nm）：使用单相单向传感器和 谐波频率调制，我们将把手技术的空间分辨率从〜1μm提高到 〜100 nm。我们将在两个公认的模型中验证双手平台的性能： T细胞与癌细胞之间的相互作用，以及干细胞与巨噬细胞之间的相互作用。在这个 令人担忧的是，我们旨在证明双手的深远潜力，以便在各个领域进行改进的研究 从基本生物学到个性化免疫肿瘤学和药物发现。