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

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.

项目概要 动态的细胞间相互作用对于健康的细胞行为和适当的细胞间通讯至关重要。 细胞间通讯受损与多种疾病的病理有关，包括 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。因此，探测细胞间相互作用对于生物医学研究的许多领域至关重要。它可以引导 更详细地了解各种疾病并开发新的治疗策略，例如 作为个性化免疫肿瘤学。然而，当前的单细胞分析技术速度缓慢并且需要 与感兴趣的细胞进行潜在有害的物理接触，阻碍了阐明这些现象的进展。 最近，我们发明了用于邻近细胞动态研究的谐波声学 (HANDs)，这是一种声学- 基于自动化、非接触式的细胞配对技术，克服了与细胞配对相关的关键障碍 现有技术。在这个 R01 项目中，我们将使用以下内容开发和验证 HANDs 平台 特点：（1）非接触性和高生物相容性：无需与固体直接接触 基板或珠子，所提出的 HANDs 技术是一种非接触式方法。另外，与其曝光 巨大的剪切力、强大的压力或强大的光学可能会导致生理损伤，细胞 我们的装置是用低功率声波轻轻操纵的。拟议的 HANDs 平台允许长期 术语（> 24 小时）细胞间相互作用研究。使用现有的最先进技术无法轻易实现这一壮举 原子力光谱等技术。 (2) 高通量可逆细胞间相互作用和 单细胞水平的精确定量分析：HANDs 技术的多重捕获性质 能够以单细胞精度同时并行研究大量（>20,000）细胞对。现存的 单细胞技术要么仅限于在任何给定时间研究一对细胞，要么缺乏精度 控制细胞配对和分离以及精确定量分析所需的。 (3)自动化操作： 与现有的细胞配对技术需要复杂的程序和工具来实现操作不同， 所提出的技术使用声学陷阱自动对齐细胞对。另外，一旦控制 指定信号后，可以以任何自动和规定的接触方式使细胞接触和分离 测试需要模式。 (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 HANDs 技术的空间分辨率从 ~1 μm 提高到 〜100纳米。我们将通过两个成熟的模型验证 HANDs 平台的性能： T 细胞和癌细胞之间的相互作用，以及干细胞和巨噬细胞之间的相互作用。在这个 在这方面，我们的目标是展示 HAND 的深远潜力，以改善以下领域的研究 从基础生物学到个性化免疫肿瘤学和药物发现。