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微流控中皮升琼脂液滴破碎与微生物学应用:数值与实验方法

Picoliter agar droplet breakup in microfluidics meets microbiology application: numerical and experimental approaches.

作者信息

Khater Asmaa, Abdelrehim Osama, Mohammadi Mehdi, Azarmanesh Milad, Janmaleki Mohsen, Salahandish Razieh, Mohamad Abdulmajeed, Sanati-Nezhad Amir

机构信息

Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta T2N 1N4, Canada.

出版信息

Lab Chip. 2020 Jun 21;20(12):2175-2187. doi: 10.1039/d0lc00300j. Epub 2020 May 18.

DOI:10.1039/d0lc00300j
PMID:32420570
Abstract

Droplet microfluidics has provided lab-on-a-chip platforms with the capability of bacteria encapsulation in biomaterials, controlled culture environments, and live monitoring of growth and proliferation. The droplets are mainly generated from biomaterials with temperature dependent gelation behavior which necessitates stable and size-controlled droplet formation within microfluidics. Here, the biomaterial is agar hydrogel with a non-Newtonian response at operating temperatures below 40 °C, the upper-temperature threshold for cells and pathogens. The size of the produced droplets and the formation regimes are examined when the agar is injected at a constant temperature of 37 °C with agar concentrations of 0.5%, 1%, and 2% and different flow rate ratios of the dispersed phase to the continuous phase (φ: 0.1 to 1). The numerical simulations show that φ and the capillary number (Ca) are the key parameters controlling the agar droplet size and formation regime, from dripping to jetting. Also, increasing the agar concentration produces smaller droplets. The simulation data were validated against experimental agar droplet generation and transport in microfluidics. This work helps to understand the physics of droplet generation in droplet microfluidic systems operating with non-Newtonian fluids. Pathogenic bacteria were successfully cultured and monitored in high resolution in agar droplets for further research in antibiotic susceptibility testing in bacteremia and urinary tract infection.

摘要

微滴微流控技术为芯片实验室平台提供了在生物材料中封装细菌、控制培养环境以及实时监测细菌生长和增殖的能力。微滴主要由具有温度依赖性凝胶化行为的生物材料产生,这就需要在微流控装置中实现稳定且尺寸可控的微滴形成。在此,生物材料是琼脂水凝胶,在低于40℃的操作温度下呈现非牛顿响应,40℃是细胞和病原体的温度上限阈值。当在37℃恒温下注入浓度为0.5%、1%和2%的琼脂,并改变分散相和连续相的不同流速比(φ:0.1至1)时,研究了所产生微滴的尺寸和形成模式。数值模拟表明,φ和毛细管数(Ca)是控制琼脂微滴尺寸和形成模式(从滴状到射流状)的关键参数。此外,增加琼脂浓度会产生更小的微滴。模拟数据通过微流控装置中琼脂微滴的产生和传输实验得到了验证。这项工作有助于理解在使用非牛顿流体的微滴微流控系统中微滴产生的物理过程。致病性细菌已成功在琼脂微滴中进行高分辨率培养和监测,以便在菌血症和尿路感染的抗生素敏感性测试中开展进一步研究。

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