Development of a digital acoustofluidic system for automating liquid handling in biomedical research

开发用于生物医学研究中液体处理自动化的数字声流系统

• 批准号: 10795366
• 负责人: Tony Jun Huang
• 金额: $ 24.93万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10795366
• 关键词: Acoustics; Address; Adsorption; Area; Automation; Automobile Driving; Benchmarking; Biological Assay; Biology; Biomedical Research; Bite; Blood; Cell Line; Cell Survival; Chemistry; Clinical Chemistry; Complex; Crystallization; Development; Devices; Diffusion; Drug Screening; Electronics; Face; Industry Standard; Laboratories; Laboratory Research; Libraries; Liquid substance; Magnetism; Manuals; Medicine; Methods; Microfluidics; Miniaturization; Monitor; Organic solvent product; Performance; Pharmacologic Substance; Preparation; Property; Proteins; Reaction; Reagent; Reproducibility; Research; Research Personnel; Risk; Robotics; Route; Sampling; Scientist; Series; Solid; Speed; Sputum; Structure; Surface; System; Technology; Time; Transducers; United States National Institutes of Health; Universities; Viscosity; biological systems; biomaterial compatibility; chemical reaction; clinical diagnostics; comparative cost effectiveness; design; digital; electric field; high-throughput drug screening; improved; interest; invention; microsystems; model organism; pressure; prototype; screening; technology research and development; tool; voltage

PROJECT SUMMARY This R01 application is responsive to the NIH initiative PAR-19-253 “Focused Technology Research and Development”. Automated liquid handling technologies are valuable in many areas of biomedical research. For example, robotic pipetting systems have been extensively utilized to automate assays, thereby eliminating errors associated with manual pipetting and significantly improving reproducibility. However, the majority of automated liquid handling technologies suffer from a fundamental constraint: they rely on physical contact with a solid structure in order to manipulate liquid reagents. Therefore, traces of a reagent inevitably adsorb onto the contact surface and can possibly later dissolve into another liquid sample. Thus, the risk of cross-contamination due to this undesirable “fouling of the surface” limits the transport surfaces to a single type of working liquid plus reagent combination. Recently, we invented digital acoustofluidics (DAF), an acoustic-based, programmable, contact- free, liquid handling technology, which overcomes the key obstacles associated with the existing liquid handling methods. In this R01 project, we will develop and validate a DAF fluid processing system with the following features: (1) Rewritability, programmability, and ability to perform complex, cascade reactions: We will demonstrate the ability of DAF to transport and mix ‘fluidic bits’ (i.e., droplets) along prescribed, arbitrary routes without cross-contamination, leading to a 104-fold increase in the number of allowable combinations of reagent inputs on a single device (as compared with conventional platforms); (2) Biocompatibility: Instead of being directly subjected to strong acoustic pressure or high electric fields, the droplets are manipulated in a contactless, gentle manner. Our preliminary results show that the DAF platform has no significant effect on the viability of cells; (3) Versatility: DAF is not restricted to fluids with specific acoustic, electrical, hydrodynamic, or magnetic properties. This versatility makes DAF suitable for handling a wide range of liquids, even for challenging samples such as low-polarity fluids (e.g., organic solvents), sticky or viscous samples (e.g., blood and sputum), and solids (e.g., fecal samples and model organisms); (4) Miniaturization and convenient integration: Our DAF platform provides an unprecedented level of miniaturization and cost-effectiveness compared with existing robotic liquid handling systems. In addition, it is designed to be integrated with a variety of multi-well plates, enabling it to be seamlessly integrated into existing biomedical research laboratories. With the aforementioned advantages, the proposed DAF technology has the potential to exceed current industry standards, address unmet needs in the field, and provide a compelling platform for the development of a robust, rewritable, high- throughput, and digitally-programmable fluidic processor. We will validate its performance across two established biomedical applications: protein crystal chemistry, and high-throughput drug screening. In this regard, we aim to demonstrate the far-reaching potential of DAF to enable improved research in areas ranging from clinical chemistry to fundamental biology.

项目概要 该 R01 应用程序响应 NIH 计划 PAR-19-253“重点技术研究和 发展”。自动化液体处理技术在生物医学研究的许多领域都很有价值。 例如，机器人移液系统已被广泛用于自动化检测，从而消除错误 与手动移液相关并显着提高重现性。然而，大多数自动化 液体处理技术受到一个基本限制：它们依赖于与固体的物理接触 结构以操纵液体试剂。因此，微量试剂不可避免地会吸附在接触面上 表面，随后可能溶解到另一种液体样品中。因此，由于交叉污染的风险 这种不良的“表面污垢”将传输表面限制为单一类型的工作液体加试剂 组合。最近，我们发明了数字声流体 (DAF)，这是一种基于声学的、可编程的、接触式的 免费的液体处理技术，克服了现有液体处理的关键障碍 方法。在此 R01 项目中，我们将开发并验证 DAF 流体处理系统，其中包含以下内容 特点：（1）可重写性、可编程性以及执行复杂、级联反应的能力：我们将 展示 DAF 沿着规定的任意路线传输和混合“流体位”（即液滴）的能力 无交叉污染，使允许的试剂组合数量增加了 104 倍 单个设备上的输入（与传统平台相比）； (2)生物相容性：而不是 直接受到强声压或高电场的影响，液滴在 非接触式、温和的方式。我们的初步结果表明，DAF 平台对 细胞活力； (3) 多功能性：DAF 不限于具有特定声学、电学、流体动力学或 磁性。这种多功能性使得 DAF 适合处理各种液体，甚至是具有挑战性的液体 样品，例如低极性液体（例如有机溶剂）、粘性或粘性样品（例如血液和痰）， 和固体（例如粪便样本和模型生物）； (4)小型化、方便集成：我们的 与现有的 DAF 平台相比，DAF 平台提供了前所未有的小型化水平和成本效益 机器人液体处理系统。此外，它还设计用于与各种多孔板集成， 使其能够无缝集成到现有的生物医学研究实验室中。与前述 优势，所提出的 DAF 技术有可能超越当前的行业标准，解决 该领域未满足的需求，并为开发强大的、可重写的、高 吞吐量和数字可编程流体处理器。我们将在两个已建立的系统中验证其性能 生物医学应用：蛋白质晶体化学和高通量药物筛选。在这方面，我们的目标是 展示了 DAF 的深远潜力，可以改善临床等领域的研究 化学到基础生物学。

项目成果

Cellular immunity analysis by a modular acoustofluidic platform: CIAMAP.

• DOI: 10.1126/sciadv.adj9964
• 发表时间: 2023-12-22
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Zhong, Ruoyu;Sullivan, Matthew;Upreti, Neil;Chen, Roy;De Ganzo, Agustin;Yang, Kaichun;Yang, Shujie;Jin, Ke;He, Ye;Li, Ke;Xia, Jianping;Ma, Zhiteng;Lee, Luke P.;Konry, Tania;Huang, Tony Jun
• 通讯作者: Huang, Tony Jun

Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs.

• DOI: 10.1038/s41467-023-43239-6
• 发表时间: 2023-11-22
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: He, Ye;Yang, Shujie;Liu, Pengzhan;Li, Ke;Jin, Ke;Becker, Ryan;Zhang, Jinxin;Lin, Chuanchuan;Xia, Jianping;Ma, Zhehan;Ma, Zhiteng;Zhong, Ruoyu;Lee, Luke P.;Huang, Tony Jun
• 通讯作者: Huang, Tony Jun