School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai 200030, China.
Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai 200433, China.
ACS Sens. 2022 Jul 22;7(7):1977-1984. doi: 10.1021/acssensors.2c00734. Epub 2022 Jul 11.
Flexible, robust, and user-friendly screening systems with a large dynamic range are highly desired in scientific research, industrial development, and clinical diagnostics. Droplet-based microfluidic systems with gradient concentrations of chemicals have been demonstrated as promising tools to provide confined microenvironments for screening tests with small reaction volumes. However, the generation and manipulation of gradient droplets, such as droplet merging, generally require sophisticated fluidic manipulation systems, potentially limiting their application in decentralized settings. We present a gradient-droplet SlipChip (gd-SlipChip) microfluidic device that enables instrument-free gradient droplet formation and parallel manipulation. The device can establish a gradient profile by free interfacial diffusion in a continuous fluidic channel. With a simple slipping step, gradient droplets can be generated by a surface tension-driven self-partitioning process. Additional reagents can be introduced in parallel to these gradient droplets with further slipping operations to initiate screening tests of the droplets over a large concentration range. To profile the concentration in the gradient droplets, we establish a numerical simulation model and verify it with hydrogen chloride (HCl) diffusion, as tested with a dual-color pH indicator (methyl orange and aniline blue). As a proof of concept, we tested this system with a gradient concentration of nitrofurantoin for the phenotypic antimicrobial susceptibility testing (AST) of . The results of our gd-SlipChip-based AST on both reference and clinical strains of can be indicated by the bacterial growth profile within 3 h and are consistent with the clinical culture-based AST.
在科学研究、工业发展和临床诊断中，人们非常希望拥有灵活、稳健且易于使用的、具有大动态范围的筛选系统。具有化学物质浓度梯度的液滴微流控系统已被证明是一种很有前途的工具，可以为具有小反应体积的筛选测试提供受限的微环境。然而，梯度液滴的产生和操纵，如液滴合并，通常需要复杂的流体操纵系统，这可能限制了它们在分散环境中的应用。我们提出了一种梯度液滴 SlipChip（gd-SlipChip）微流控装置，该装置能够实现无仪器的梯度液滴形成和并行操作。该装置可以通过在连续流道中的自由界面扩散来建立梯度分布。通过简单的滑移步骤，可以通过表面张力驱动的自分割过程产生梯度液滴。通过进一步的滑移操作，可以将额外的试剂引入这些梯度液滴中，以在大浓度范围内启动液滴的筛选测试。为了分析梯度液滴中的浓度，我们建立了一个数值模拟模型，并通过氯化氢（HCl）扩散进行了验证，并用双色调 pH 指示剂（甲基橙和苯胺蓝）进行了测试。作为概念验证，我们使用梯度浓度的呋喃妥因对 进行了基于 gd-SlipChip 的表型抗菌药敏测试（AST）。我们的 gd-SlipChip 基于 AST 的结果，无论是参考菌株还是临床菌株的，可以通过 3 小时内细菌生长情况来指示，并且与临床基于培养的 AST 一致。
