A 3D-printed microfluidic gradient generator with integrated photonic silicon sensors for rapid antimicrobial susceptibility testing,Lab on a Chip

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A 3D-printed microfluidic gradient generator with integrated photonic silicon sensors for rapid antimicrobial susceptibility testing
Lab on a Chip ( IF 6.1 ) Pub Date : 2022-11-22 , DOI: 10.1039/d2lc00640e
Christopher Heuer _{1,

2} , John-Alexander Preuss _{1,

3} , Marc Buttkewitz ₁ , Thomas Scheper ₁ , Ester Segal ₂ , Janina Bahnemann _{1,

3}

Affiliation

With antimicrobial resistance becoming a major threat to healthcare settings around the world, there is a paramount need for rapid point-of-care antimicrobial susceptibility testing (AST) diagnostics. Unfortunately, most currently available clinical AST tools are lengthy, laborious, or are simply inappropriate for point-of-care testing. Herein, we design a 3D-printed microfluidic gradient generator that automatically produces two-fold dilution series of clinically relevant antimicrobials. We first establish the compatibility of these generators for classical AST (i.e., broth microdilution) and then extend their application to include a complete on-chip label-free and phenotypic AST. This is accomplished by the integration of photonic silicon chips, which provide a preferential surface for microbial colonization and allow optical tracking of bacterial behavior and growth at a solid–liquid interface in real-time by phase shift reflectometric interference spectroscopic measurements (PRISM). Using Escherichia coli and ciprofloxacin as a model pathogen-drug combination, we successfully determine the minimum inhibitory concentration within less than 90 minutes. This gradient generator-based PRISM assay provides an integrated AST device that is viable for convenient point-of-care testing and offers a promising and most importantly, rapid alternative to current clinical practices, which extend to 8–24 h.

中文翻译：

具有集成光子硅传感器的 3D 打印微流体梯度发生器，用于快速抗菌敏感性测试

随着抗菌素耐药性成为全球医疗保健机构的主要威胁，对快速床旁抗菌素敏感性测试 (AST) 诊断的需求至关重要。不幸的是，大多数当前可用的临床 AST 工具冗长、费力，或者根本不适合即时检测。在此，我们设计了一种 3D 打印的微流体梯度发生器，可自动生成临床相关抗菌剂的两倍稀释系列。我们首先建立这些生成器对经典 AST 的兼容性（即, broth microdilution)，然后将其应用扩展到包括完整的片上无标签和表型 AST。这是通过光子硅芯片的集成实现的，它为微生物定植提供了一个优先表面，并允许通过相移反射干涉光谱测量 (PRISM) 实时光学跟踪固液界面上的细菌行为和生长。使用大肠杆菌和环丙沙星作为模型病原体-药物组合，我们在不到 90 分钟内成功确定了最低抑菌浓度。这种基于梯度发生器的 PRISM 测定提供了一种集成的 AST 设备，可用于方便的即时检测，并提供了一种有前途且最重要的是，可以快速替代当前的临床实践，后者可延长至 8-24 小时。

更新日期：2022-11-22

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