Antibiotic resistance is a major global challenge. Although microfluidic antibiotic susceptibility tests (AST) offer great potential for rapid and portable testing to inform correct antibiotic selection, the impact of miniaturisation on broth microdilution (BMD) is not fully understood. We developed a 10-plex microcapillary based broth microdilution using resazurin as a colorimetric indicator for bacterial growth. Each capillary had a 1 microlitre capillary volume, 100 times smaller than microplate broth microdilution. The microcapillary BMD was compared to an in-house standard microplate AST and commercial Vitek 2 system. When tested with 25 uropathogenic isolates (20 Escherichia coli and 5 Klebsiella pneumoniae) and 2 reference E. coli, these devices gave 96.1% (441/459 isolate/antibiotic combinations) categorical agreement, across 17 therapeutically beneficial antibiotics, compared to in-house microplate BMD with resazurin. A further 99 (50 E. coli and 49 K. pneumoniae) clinical isolates were tested against 10 antibiotics and showed 92.3% categorical agreement (914/990 isolate/antibiotic combinations) compared to the Vitek 2 measurements. These microcapillary tests showed excellent analytical agreement with existing AST methods. Furthermore, the small size and simple colour change can be recorded using a smartphone camera or it is feasible to follow growth kinetics using very simple, low-cost readers. The test strips used here are produced in large batches, allowing hundreds of multiplex tests to be made and tested rapidly. Demonstrating performance of miniaturised broth microdilution with clinical isolates paves the way for wider use of microfluidic AST.

中文翻译：

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使用微毛细管装置对革兰氏阴性临床分离株进行简化的抗生素敏感性测试的微型肉汤微量稀释

抗生素耐药性是一项重大的全球挑战。尽管微流控抗生素敏感性测试 (AST) 为快速和便携式测试以告知正确的抗生素选择提供了巨大的潜力，但小型化对肉汤微量稀释 (BMD) 的影响尚不完全清楚。我们开发了一种基于 10 重微毛细管的肉汤微量稀释液，使用刃天青作为细菌生长的比色指示剂。每个毛细管的毛细管体积为 1 微升，比微孔板肉汤微量稀释液小 100 倍。将微毛细管 BMD 与内部标准微孔板 AST 和商业 Vitek 2 系统进行比较。当使用 25 种泌尿道致病菌（20种大肠杆菌和 5种肺炎克雷伯菌）和 2 种参考大肠杆菌进行测试时，与内部微孔板 BMD 和刃天青相比，这些设备在 17 种治疗上有益的抗生素中给出了 96.1%（441/459 分离物/抗生素组合）的分类一致性。还有 99 个（50 个大肠杆菌和 49 个肺炎克雷伯菌）) 临床分离株针对 10 种抗生素进行了测试，与 Vitek 2 测量结果相比，显示出 92.3% 的分类一致性（914/990 分离株/抗生素组合）。这些微毛细管测试与现有的 AST 方法显示出极好的分析一致性。此外，可以使用智能手机相机记录小尺寸和简单的颜色变化，或者使用非常简单、低成本的阅读器跟踪生长动力学是可行的。这里使用的试纸是大批量生产的，可以快速制作和测试数百个多重测试。用临床分离株证明微型肉汤微稀释的性能为更广泛地使用微流控 AST 铺平了道路。