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 这个重点的技术研发项目将提供一类新的声学分离/ 多种生物医学研究应用的富裕工具。声学微流体已经作为关键ENA-出现 在生物学和医学领域的光彩技术，为非接触，无标签对象提供无与伦比的能力 滴答和分析。拟议的微流体平台基于一个新颖的概念：纵向站立 控制微观到纳米级对象进行功能分离和/或 监禁。获得专利的LSBAW亚基是高度可配置的，允许重复的亚基数组 为了满足各种容量和吞吐量的需求，从小体积（sub-µl）反应中的监测/检测 腔室，稀有物种的高通量富集。该项目的结果将包括专用 原型系统：（i）高通量富集/分级，（ii）高容量的过程控制和（iii） 通过实时监控进行多路复用分析。为了建立LSBAW平台的多功能性和效用， 在癌症生物学家等价值的研究应用中将验证不同的配置（罕见 细胞富集），合成生物化学家（超声限制反应下的抗体共轭合成 策略）和微生物学家（对细菌细胞中生物学机制的监测/测量）。技术 - 该项目的OGY结果不仅与这些申请有关，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： AIM 1：展示LSBAW亚基的可伸缩性，以占稀有物种的大量高通量富集。 AIM 2：验证LSBAW亚基阵列的串联配置，用于高容量的单元格修改/标签或 自定义生物分子合成。 AIM 3：验证LSBAW亚基阵列的多路复用配置，用于定量和/或检测 靶物种或生物学机制。 验证实验将用于严格评估与特定应用相关的功能。 使用标准模型（例如，微粒作为生物细胞的代理）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 管理标准（例如，吞吐量，容量，特异性，敏感性），并与适当的现有工具进行比较 和方法。团队合并了微流体学，成像剂的合成和表征的专业知识， 微生物学和罕见的细胞隔离/分析，具有技术开发和部署的良好记录 精神。这些目标的完成将使一种新颖的声学微流体概念转化为一套强大的和 广泛可访问的研究工具将在许多生物医学研究领域加速研究。