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: 10175836
• 负责人: Tony Jun Huang
• 金额: $ 41.26万
• 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/10175836
• 关键词: Acoustics; Address; Adsorption; Animal Model; Area; Automation; Automobile Driving; Benchmarking; Biological Assay; Biology; Biomedical Research; Blood; Cell Line; Cell Survival; Chemistry; Clinical Chemistry; Complex; Crystallization; Custom; Development; Devices; Diffusion; Drug Screening; Electronics; Face; Industry Standard; Laboratories; Laboratory Research; Libraries; Liquid substance; Magnetism; Manuals; Medicine; Methods; 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; base; biological systems; biomaterial compatibility; chemical reaction; clinical diagnostics; comparative cost effectiveness; design; digital; electric field; high-throughput drug screening; improved; interest; microfluidic technology; microsystems; pressure; programs; 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.

项目摘要 该R01应用程序对NIH计划的响应是19-253 Pars pars'的“重点技术研究和 开发”。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，机器人移动系统已广泛用于自动化测定，从而消除了错误 与手动移液和显着提高可重复性相关。但是，大多数自动化 液体处理技术受到基本限制：它们依靠与固体的身体接触 结构以操纵液体试剂。因此，试剂的痕迹不可避免地会吸附到接触 表面，可能以后溶解到另一个液体样品中。那是由于 这种不良的“表面结垢”将传输表面限制为单一类型的工作液体加试剂 组合。最近，我们发明了数字声学（DAF），这是一种基于声学的，可编程的，接触的 - 免费的液体处理技术，它克服了与现有液体处理相关的关键障碍 方法。在此R01项目中，我们将开发和验证DAF流体处理系统 功能：（1）重写性，可编程性和执行复杂的能力，级联反应：我们将 证明DAF在规定的任意路线上运输和混合“流体钻头”（即液滴）的能力 没有交叉污染，导致试剂的允许组合数量增加104倍 单个设备上的输入（与常规平台相比）； （2）生物相容性：而不是 直接受到强声压或高电场的影响，将液滴操纵 非接触式，温柔的举止。我们的初步结果表明，DAF平台对 细胞的生存能力； （3）多功能性：DAF不限于具有特定声学，电气，流体动力或 磁性特性。这种多功能性使DAF适合处理各种液体，即使是为了挑战 诸如低极性流体（例如有机溶液），粘性或粘性样品（例如，血液和痰）之类的样品， 和固体（例如，粪便样品和模型生物）； （4）小型化和方便整合：我们的 DAF平台提供了前所未有的小型化和成本效益的水平 机器人液体处理系统。此外，它被设计为与多种多孔板集成 使其能够无缝整合到现有的生物医学研究实验室中。与近似 优势，拟议的DAF技术有可能超过当前的行业标准，地址 该领域未满足的需求，并为开发坚固，可重写，高级的发展提供了一个引人注目的平台 吞吐量和数字可编程的流体处理器。我们将验证其在两个已建立的 生物医学应用：蛋白质晶体化学和高通量药物筛查。在这方面，我们的目标是 证明DAF具有深远的潜力，可以改善临床领域的研究 基本生物学的化学。