Droplet-based microfluidics for single cell-omics

用于单细胞组学的基于液滴的微流体

• 批准号: BB/F005024/1
• 负责人: Jonathan Cooper
• 金额: $ 51万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF005024%2F1
• 关键词: Droplet; based; microfluidics; single; cell

Water will readily form droplets in oil, providing miniature enclosed environments, in which the aqueous (water phase) is separate from the oil phase. If these droplets are created in very small channels (the width of a human hair, for instance), then the size of the droplets can be comparable to that of individual single cells. By using the techniques of microfabrication, first established within the semi-conductor industry, we are able to create appropriate microchannel architectures that can create reproducible droplets that contain cells (the droplets behave like very small test tubes). However, to date, attempts to make such droplets have proved difficult. Currently they are unstable and will coalesce and disappear as rapidly as they form. Using a new technology, we propose to use the same two phase (oil and water) systems to create droplets with a structured coat, so that once the cells have been placed within the droplet, the micro-environment is stable and long lived. The techniques used for making such droplets will enable us to change the nature of the coating so that they can be considered 'intelligent'. In other words, by engineering the chemical composition of the coating, we can decide which molecules enter the micro-droplet. Intriguingly, we can also introduce nanometre scale sensors within the droplet wall that can report upon the metabolic state of the cell. Finally, we will create arrays of such structured droplets so that many single cells can be stored and analysed readily, and ultimately used in the process of finding and testing new medicines.

水将容易地在油中形成液滴，提供微型封闭环境，其中水（水相）与油相分离。如果这些液滴是在非常小的通道中产生的（例如人类头发的宽度），那么液滴的大小可以与单个细胞的大小相媲美。通过使用首先在半导体行业中建立的微制造技术，我们能够创建适当的微通道架构，该架构可以创建包含细胞的可再现液滴（液滴表现得像非常小的试管）。然而，迄今为止，制造这种液滴的尝试已被证明是困难的。目前，它们是不稳定的，并将合并和消失，因为它们的形成迅速。使用一种新技术，我们建议使用相同的两相（油和水）系统来创建具有结构化涂层的液滴，以便一旦细胞被放置在液滴中，微环境就稳定且寿命长。用于制造这种液滴的技术将使我们能够改变涂层的性质，使它们可以被认为是“智能”的。换句话说，通过设计涂层的化学成分，我们可以决定哪些分子进入微滴。有趣的是，我们还可以在液滴壁内引入纳米级传感器，可以报告细胞的代谢状态。最后，我们将创建这种结构化液滴的阵列，以便可以轻松存储和分析许多单细胞，并最终用于寻找和测试新药的过程。

项目成果

Hysteresis in multiphase microfluidics at a T-junction.

• DOI: 10.1021/la1004243
• 发表时间: 2010-05
• 期刊: Langmuir : the ACS journal of surfaces and colloids
• 作者: M. Zagnoni;Jamie E Anderson;J. Cooper

Electrically initiated upstream coalescence cascade of droplets in a microfluidic flow.

• DOI: 10.1103/physreve.80.046303
• 发表时间: 2009-10
• 期刊: Physical review. E, Statistical, nonlinear, and soft matter physics
• 作者: M. Zagnoni;C. Baroud;J. Cooper

Microfluidic single-cell array cytometry for the analysis of tumor apoptosis.

• DOI: 10.1021/ac9008463
• 发表时间: 2009-07-01
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Wlodkowic, Donald;Faley, Shannon;Zagnoni, Michele;Wikswo, John P.;Cooper, Jonathan M.
• 通讯作者: Cooper, Jonathan M.

Intracellular protein determination using droplet-based immunoassays.

使用基于液滴的免疫测定法测定细胞内蛋白质。

• DOI: 10.1021/ac200876q
• 发表时间: 2011
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Martino C