Acoustic platform for separation, isolation, and enrichment in biomedical research

用于生物医学研究中分离、隔离和富集的声学平台

• 批准号: 10681223
• 负责人: John Mark Meacham
• 金额: $ 36.77万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10681223
• 关键词: Acceleration; Acoustics; Address; Affinity; Antibodies; Architecture; Area; Bacteria; Biocompatible Materials; Biological; Biological Markers; Biology; Biomedical Research; Biotechnology; Cell Line; Cell Separation; Cell Size; Cells; Chemicals; Computer Models; Custom; Detection; Devices; Diameter; Dimensions; Ensure; Exposure to; Fractionation; Gene Expression; Height; Hela Cells; Immunoassay; Individual; Investigation; Label; Lateral; Legal patent; Length; Location; MCF7 cell; Magnetism; Malignant Neoplasms; Mammalian Cell; Measurement; Medicine; Methods; Microbe; Microbial Biofilms; Microbiology; Microfluidic Microchips; Microfluidics; Mission; Modeling; Modification; Monitor; Motion; National Institute of General Medical Sciences; Operations Research; Outcome; Performance; Play; Porosity; Process; Property; Proteomics; Proxy; Reaction; Reagent; Records; Reproducibility of Results; Research; Research Methodology; Role; Sampling; Series; Shapes; Site-Directed Mutagenesis; Specific qualifier value; Specificity; Structure; System; Technology; Time; Translating; Translations; Validation; Width; antibody conjugate; biological systems; biomaterial compatibility; cancer cell; cell type; chemical synthesis; density; design; detection sensitivity; experimental study; fabrication; flexibility; high dimensionality; imaging agent; improved; medical specialties; meter; microfluidic technology; nanoscale; new technology; novel; particle; physical property; prototype; real time monitoring; screening; sound; success; technology development; technology platform; technology research and development; tool; transcriptomics; ultrasound

PROJECT ABSTRACT This focused technology research and development project will deliver a new class of acoustic separation/en- richment tools for multiple biomedical research applications. Acoustic microfluidics has emerged as a key ena- bling technology in biology and medicine, providing unmatched capability for non-contact, label-free object ma- nipulation and analysis. The proposed microfluidic platform is based on a novel concept: a longitudinal standing bulk acoustic wave (LSBAW) subunit that controls micro- to nanoscale objects for functional separation and/or confinement. The patented LSBAW subunits are highly configurable, which allows arrays of repeated subunits to meet varying capacity and throughput needs, from monitoring/detection in small-volume (sub-µL) reaction chambers to high-throughput enrichment of rare species. Outcomes of this project will include purpose-built prototype systems for: (i) high-throughput enrichment/fractionation, (ii) process control at high capacity, and (iii) multiplexed analyses with real-time monitoring. To establish the versatility and utility of the LSBAW platform, different configurations will be validated in research applications of value to, for example, cancer biologists (rare cell enrichment), synthetic biochemists (antibody conjugate synthesis on ultrasound-confined reaction sub- strates), and microbiologists (monitoring/measurement of biological mechanisms in bacterial cells). The technol- ogy outcomes of this project will be relevant not only to those applications, but will be broadly applicable to any field that relies on separation, isolation, and enrichment. The project includes three Aims: Aim 1: Demonstrate scalability of LSBAW subunits for high-volume, high-throughput enrichment of rare species. Aim 2: Validate series configurations of LSBAW subunit arrays for high-capacity cell modification/labeling or custom biomolecule synthesis. Aim 3: Validate multiplexed configurations of LSBAW subunit arrays for quantification and/or detection of a target species or biological mechanism. Validation experiments will be used to rigorously assess capabilities that are relevant to specific applications. Use of standard models (e.g., microparticles as proxies for biological cells) or well-characterized biological sys- tems (e.g., commercial antibodies; standard mammalian cell lines, mixtures of cells, and microbes) will ensure consistency and reproducibility of results. In each application, success will be defined using quantitative perfor- mance criteria (e.g., throughput, capacity, specificity, sensitivity) and comparison with appropriate existing tools and methods. The team merges expertise in microfluidics, synthesis and characterization of imaging agents, microbiology, and rare cell isolation/analysis, with strong track records of technology development and deploy- ment. Completion of these aims will translate a novel acoustic microfluidics concept to a suite of powerful and broadly accessible research tools that will accelerate research in a multitude of biomedical research fields.

项目摘要 这一重点技术研发项目将提供一种新型的声学分离/en- 声学微流控已成为多种生物医学研究应用的关键工具。 生物学和医学领域的 bling 技术，为非接触式、无标签物体制造提供无与伦比的能力 所提出的微流体平台基于一个新概念：纵向站立。 体声波 (LSBAW) 子单元控制微米级到纳米级物体以进行功能分离和/或 获得专利的 LSBAW 子单元具有高度可配置性，允许重复子单元阵列。 满足不同的容量和通量需求，从小体积（亚 µL）反应中进行监测/检测 该项目的成果将包括专门建造的实验室以高通量富集稀有物种。 原型系统用于：（i）高通量富集/分馏，（ii）高容量过程控制，以及（iii） 具有实时监控的多重分析为了建立 LSBAW 平台的多功能性和实用性， 不同的配置将在对癌症生物学家等有价值的研究应用中得到验证（罕见 细胞富集），合成生物化学家（超声限制反应子上的抗体结合物合成 策略）和微生物学家（监测/测量细菌细胞的生物机制）。 该项目的成果不仅与这些应用相关，而且广泛适用于任何 该项目包括三个目标： 目标 1：展示 LSBAW 亚基的可扩展性，用于大批量、高通量富集稀有物种。 目标 2：验证 LSBAW 亚基阵列的系列配置，以进行高容量细胞修饰/标记或 定制生物分子合成。 目标 3：验证 LSBAW 亚基阵列的多重配置，以定量和/或检测 目标物种或生物机制。 验证实验将用于严格评估与特定应用程序相关的功能。 使用标准模型（例如，微粒作为生物细胞的代表）或特征良好的生物系统 tems（例如，商业抗体；标准哺乳动物细胞系、细胞混合物和微生物）将确保 结果的一致性和可重复性在每个应用中，将使用定量性能来定义成功。 曼斯标准（例如吞吐量、容量、特异性、灵敏度）以及与适当的现有工具的比较 该团队融合了微流体、显像剂的合成和表征方面的专业知识， 微生物学和稀有细胞分离/分析，在技术开发和部署方面拥有良好的记录 这些目标的完成将把一种新颖的声学微流体概念转化为一套强大且有效的技术。 广泛使用的研究工具将加速众多生物医学研究领域的研究。