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/增强技术， 丰富的工具，用于多种生物医学研究应用。声学微流体技术已经成为一种关键的技术， 生物和医学领域的bling技术，为非接触、无标签的物体处理提供无与伦比的能力， 计算和分析。所提出的微流控平台是基于一个新的概念：纵向站立 体声波（LSBAW）子单元，其控制微米至纳米级物体以用于功能分离和/或 禁闭。获得专利的LSBAW子单元是高度可配置的，这允许重复子单元的阵列 以满足不同的容量和通量需求，从小体积（亚微升）反应中的监测/检测 高通量富集稀有物种。该项目的成果将包括专门建造的 原型系统：（i）高通量富集/分馏，（ii）高容量过程控制，和（iii） 实时监测的多重分析。为了建立LSBAW平台的通用性和实用性， 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（抗体偶联物的超声波限制反应亚 strates）和微生物学家（监测/测量细菌细胞中的生物机制）。技术- 该项目的ogy成果不仅与这些应用程序相关，而且将广泛适用于任何 依赖于分离、隔离和富集的领域。该项目包括三个目标： 目的1：证明LSBAW亚基用于稀有物种的高容量、高通量富集的可扩展性。 目的2：LSBAW亚基阵列的高容量细胞修饰/标记或 定制生物分子合成。 目的3：LSBAW亚基阵列的多重配置用于定量和/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相关的能力。 使用标准模型（例如，微粒作为生物细胞的替代物）或充分表征的生物系统， 项目（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 结果的一致性和再现性。在每个应用程序中，成功将被定义为使用定量性能- 管理标准（例如，通量、容量、特异性、灵敏度）并与适当的现有工具进行比较 和方法该团队融合了微流体、成像剂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，拥有强大的技术开发和部署记录， 我是说。这些目标的完成将把一个新的声学微流体概念转化为一套强大的， 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。