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

项目摘要 这一专注于技术研发的项目将提供一种新的声学分离/增强- 为多种生物医学研究应用提供丰富的工具。声学微流控技术已成为一种重要的技术手段。 生物和医学中的闪光技术，为非接触式、无标签的物体提供无与伦比的能力。 截断和分析。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)亚单元，用于控制微到纳米尺度的对象以进行功能分离和/或 禁闭。获得专利的LSBAW亚基是高度可配置的，这允许重复的亚基阵列 为满足不同的容量和吞吐量需求，从监测/检测到小体积(亚微米L)反应 小室对稀有物种的高通量浓缩。该项目的成果将包括专门建造的 用于以下方面的原型系统：(1)高通量浓缩/分馏；(2)高处理能力的过程控制；(3) 多路分析和实时监控。为了建立LSBAW平台的多功能性和实用性， 不同的配置将在研究应用中得到验证，例如，癌症生物学家(罕见 细胞浓缩)，合成生物化学家(超声限制反应子上的抗体偶联合成 以及微生物学家(监测/测量细菌细胞中的生物机制)。Technol- 该项目的结果不仅与这些应用有关，而且将广泛适用于任何 依靠分离、隔离和浓缩的油田。该项目包括三个目标： 目的1：展示LSBAW亚基的可扩展性，用于大量、高通量地浓缩稀有物种。 目标2：验证LSBAW亚单位阵列的系列配置，用于大容量细胞修饰/标记或 定制生物分子合成。 目标3：验证LSBAW亚单位阵列的多路复用配置，用于量化和/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功能。 使用标准模型(例如，作为生物细胞替代物的微粒)或表征良好的生物系统- TEM(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 结果的一致性和重复性。在每一项申请中，成功都将用定量的绩效来定义- Mance标准(例如，吞吐量、容量、特异性、敏感度)以及与现有适当工具的比较 和方法。该团队融合了微流体、显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，具有良好的技术开发和部署记录- 门槛。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和 广泛可用的研究工具，将加快在众多生物医学研究领域的研究。

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.