Ultrasonic cell handling and manipulation for microfluidic detection and analysis systems.

用于微流体检测和分析系统的超声波细胞处理和操作。

• 批准号: EP/L025035/1
• 负责人: Peter Glynne-Jones
• 金额: $ 107.16万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL025035%2F1
• 关键词: Ultrasonic; cell; handling; manipulation; microfluidic

Miniaturisation of electronic devices has been matched in recent years by a drive to create miniature Lab-on-Chip systems that can handle and analyse chemical and biological materials in tiny volumes. Ultrasonic standing-wave fields are a promising technology that can potentially achieve many of the functions required for Lab-on-Chip systems, including: pumping, mixing, cell lysis, cell sorting, and sonoporation (opening pores in cell walls to allow drugs or genetic material to enter). Most importantly, by establishing and shaping the acoustic field bacteria and other biological cells can be manipulated and levitated within fluidic devices. In contrast to other technologies, it is possible to manipulate thousands of cells at once without harming them.However, controlling these various functions and preventing interactions in the confines of a microfluidic system is challenging and prevents wider uptake of these technologies. Research is required to better understand how secondary effects interfere with the primary functions. One example is the disruption of manipulation by acoustic streaming (a movement of the fluid itself induced by the ultrasound). Using novel techniques such as surface structuring I will enable the streaming flows to be controlled, and put to practical use (e.g. to enhance diffusion for cell perfusion, and analyte diffusion in sensor systems). Initial modelling suggests that this approach could enhance streaming by a factor of 10, leading to applications in other domains such as micro-cooling systems.I will be researching several other key areas: The mechanical stimulation of cells with acoustic forces to direct the development of mechanically responsive cells such as stem cells; the integration of ultrasonic arrays into microfluidic devices for enhanced flexibility of manipulation; and ways to integrate multiple acoustic functions within a single disposable device.The fundamental research will both enable and be driven by the second focus of the fellowship, applications. Two applications that each have the potential to transform existing technologies will be developed: 1) Bacterial detection in drinking water: My team has recently proven that bacteria (who typically experience forces 1000x smaller than human cells) can be successfully concentrated in flow-through ultrasonic devices. As part of a European project we have used this to concentrate the bacteria in samples of water to enhance the detection efficiency. However, I believe that we could deliver around a 100-fold increase in sensitivity by using the ultrasound to drive bacteria directly towards an antibody coated sensor surface where they will be captured and optically detected. Deploying such devices widely would be very beneficial for detecting contamination of drinking waters, rivers, and industrial waste streams. 2) Drug screening system: I will create a system that forms arrays of tiny clusters of human cells. Cells cultured in this 3D environment behave more naturally than those grown on a petri dish. The cells will be held in place by acoustic forces, both levitated away from contaminating surfaces, and also held against a steady flow of nutrients over a period of several days. Drugs will be introduced into the flow, and an integrated laser based detection system will monitor the resulting metabolites produced by the cells. The advantage of this is that large numbers of drugs can be tested in parallel, identifying those that could be further developed. A strong motivation for this application is that by providing a representative model of human tissues it could reduce the number of animal experiments required for drug testing.Given the huge potential impacts of these and other related systems I will work closely with industrial companies that have experience of creating detection and analytical systems to bring our technologies into widespread use.

近年来，电子设备的小型化与创建微型芯片实验室系统的动力相匹配，该系统可以处理和分析微小体积的化学和生物材料。超声驻波场是一种很有前途的技术，可以实现芯片实验室系统所需的许多功能，包括：泵送、混合、细胞裂解、细胞分选和声孔效应（打开细胞壁中的孔，允许药物或遗传物质进入）。最重要的是，通过建立和成形声场，细菌和其他生物细胞可以在流体装置内操纵和悬浮。与其他技术相比，它可以在不伤害细胞的情况下同时操纵数千个细胞。然而，在微流体系统的范围内控制这些不同的功能并防止相互作用是具有挑战性的，并且阻碍了这些技术的广泛应用。需要进行研究，以更好地了解次级效应如何干扰主要功能。一个例子是通过声流（由超声波引起的流体本身的运动）来中断操纵。使用诸如表面结构化I的新技术将使得能够控制流动流，并将其投入实际使用（例如，增强细胞灌注的扩散，以及传感器系统中的分析物扩散）。初步的模型表明，这种方法可以将流增强10倍，从而在其他领域，如微冷却系统的应用。我将研究其他几个关键领域：用声学力对细胞进行机械刺激，以指导干细胞等机械响应细胞的发育;将超声波阵列集成到微流体设备中，以增强操作的灵活性;以及如何在一个一次性设备中集成多种声学功能。基础研究将实现并受奖学金的第二个重点-应用的驱动。将开发两种有潜力改变现有技术的应用：1）饮用水中的细菌检测：我的团队最近证明，细菌（通常比人类细胞小1000倍）可以成功地集中在流通超声波设备中。作为一个欧洲项目的一部分，我们已经使用这种方法来浓缩水样中的细菌，以提高检测效率。然而，我相信我们可以通过使用超声波将细菌直接驱动到抗体涂覆的传感器表面，在那里它们将被捕获和光学检测，从而将灵敏度提高约100倍。广泛部署这种装置将非常有利于检测饮用沃茨、河流和工业废水流的污染。2)药物筛选系统：我将创建一个系统，形成微小的人类细胞簇阵列。在这种3D环境中培养的细胞比在培养皿中培养的细胞表现得更自然。这些细胞将通过声波力保持在适当的位置，既漂浮远离污染表面，也在几天的时间内保持对营养物质的稳定流动。药物将被引入流中，基于激光的集成检测系统将监测细胞产生的代谢产物。这样做的好处是，大量的药物可以同时进行测试，确定那些可以进一步开发。该应用的一个强烈动机是，通过提供人体组织的代表性模型，可以减少药物测试所需的动物实验数量。鉴于这些系统和其他相关系统的巨大潜在影响，我将与具有创建检测和分析系统经验的工业公司密切合作，将我们的技术广泛应用。

项目成果

Modal Rayleigh-like streaming in layered acoustofluidic devices

• DOI: 10.1063/1.4939590
• 发表时间: 2016-01-01
• 期刊: PHYSICS OF FLUIDS
• 影响因子: 4.6
• 作者: Lei, Junjun;Glynne-Jones, Peter;Hill, Martyn
• 通讯作者: Hill, Martyn

A Personal Respirator to Improve Protection for Healthcare Workers Treating COVID-19 (PeRSo).

• DOI: 10.3389/fmedt.2021.664259
• 发表时间: 2021
• 期刊: Frontiers in medical technology
• 作者: Elkington PT;Dickinson AS;Mavrogordato MN;Spencer DC;Gillams RJ;De Grazia A;Rosini S;Garay-Baquero DJ;Diment LE;Mahobia N;Mant A;Baynham T;Morgan H
• 通讯作者: Morgan H

Acoustic focussing for sedimentation-free high-throughput imaging of microalgae

• DOI: 10.1007/s10811-019-01907-5
• 发表时间: 2019-09
• 期刊: Journal of Applied Phycology
• 影响因子: 3.3
• 作者: B. Hammarström;M. Vassalli;P. Glynne-Jones

Transducer-Plane Streaming Patterns in Thin-Layer Acoustofluidic Devices

• DOI: 10.1103/physrevapplied.8.014018
• 发表时间: 2017-07-20
• 期刊: PHYSICAL REVIEW APPLIED
• 影响因子: 4.6
• 作者: Lei, Junjun;Hill, Martyn;Glynne-Jones, Peter
• 通讯作者: Glynne-Jones, Peter

Residual Stress, Thermomechanics & Infrared Imaging, Hybrid Techniques and Inverse Problems, Volume 9 - Proceedings of the 2015 Annual Conference on Experimental and Applied Mechanics

残余应力，热力学

• DOI: 10.1007/978-3-319-21765-9_11
• 发表时间: 2016
• 作者: Devivier C