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基于蛋状多体积微腔的微流控平台的快速单测试中的抗菌药物敏感性测试。

Antimicrobial Susceptibility Testing in a Rapid Single Test via an Egg-like Multivolume Microchamber-Based Microfluidic Platform.

机构信息

Department of Food Science, College of Agricultural and Life Sciences, Cornell University, Stocking Hall, Ithaca, New York 14853, United States.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, 602 Tower Rd., Ithaca, New York 14853, United States.

出版信息

ACS Appl Mater Interfaces. 2021 May 5;13(17):19581-19592. doi: 10.1021/acsami.0c23096. Epub 2021 Apr 22.

Abstract

Fast determination of antimicrobial agents' effectiveness (susceptibility/resistance pattern) is an essential diagnostic step for treating bacterial infections and stopping world-wide outbreaks. Here, we report an egg-like multivolume microchamber-based microfluidic (EL-MVM) platform, which is used to produce a wide range of gradient-based antibiotic concentrations quickly (∼10 min). The EL-MVM platform works based upon testing a bacterial suspension in multivolume microchambers (microchamber sizes that range from a volume of 12.56 to 153.86 nL). Antibiotic molecules from a stock solution diffuse into the microchambers of various volumes at the same loading rate, leading to different concentrations among the microchambers. Therefore, we can quickly and easily produce a robust antibiotic gradient-based concentration profile. The EL-MVM platform's diffusion (loading) pattern was investigated for different antibiotic drugs using both computational fluid dynamics simulations and experimental approaches. With an easy-to-follow protocol for sample loading and operation, the EL-MVM platform was also found to be of high precision with respect to predicting the susceptibility/resistance outcome (>97%; surpassing the FDA-approval criterion for technology-based antimicrobial susceptibility testing instruments). These features indicate that the EL-MVM is an effective, time-saving, and precise alternative to conventional antibiotic susceptibility testing platforms currently being used in clinical diagnostics and point-of-care settings.

摘要

快速确定抗菌药物的有效性(敏感性/耐药模式)是治疗细菌感染和阻止全球爆发的重要诊断步骤。在这里,我们报告了一种基于卵状多体积微室的微流控(EL-MVM)平台,该平台可用于快速(约 10 分钟)产生广泛的基于梯度的抗生素浓度。EL-MVM 平台基于在多体积微室中测试细菌悬浮液来工作(微室大小范围从 12.56 到 153.86 nL 的体积)。来自储备溶液的抗生素分子以相同的加载速率扩散到不同体积的微室中,导致微室之间的浓度不同。因此,我们可以快速轻松地产生稳健的抗生素梯度浓度分布。使用计算流体动力学模拟和实验方法研究了 EL-MVM 平台的扩散(加载)模式对于不同的抗生素药物。EL-MVM 平台具有易于遵循的样本加载和操作协议,并且在预测敏感性/耐药性结果方面具有高精度(超过 97%;超过基于技术的抗生素药敏测试仪器的 FDA 批准标准)。这些特征表明,EL-MVM 是一种有效、节省时间且精确的替代传统抗生素药敏测试平台,目前正在临床诊断和即时护理环境中使用。

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