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High-throughput and automated diagnosis of antimicrobial resistance using a cost-effective cellphone-based micro-plate reader

机译：使用基于手机的高性价比微孔板读板器，高通量和自动诊断抗菌素

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Routine antimicrobial susceptibility testing (AST) can prevent deaths due to bacteria and reduce the spread of multi-drug-resistance, but cannot be regularly performed in resource-limited-settings due to technological challenges, high-costs, and lack of trained professionals. We demonstrate an automated and cost-effective cellphone-based 96-well microtiter-plate (MTP) reader, capable of performing AST without the need for trained diagnosticians. Our system includes a 3D-printed smartphone attachment that holds and illuminates the MTP using a light-emitting-diode array. An inexpensive optical fiber-array enables the capture of the transmitted light of each well through the smartphone camera. A custom-designed application sends the captured image to a server to automatically determine well-turbidity, with results returned to the smartphone in ~1?minute. We tested this mobile-reader using MTPs prepared with 17 antibiotics targeting Gram-negative bacteria on clinical isolates of Klebsiella pneumoniae, containing highly-resistant antimicrobial profiles. Using 78 patient isolate test-plates, we demonstrated that our mobile-reader meets the FDA-defined AST criteria, with a well-turbidity detection accuracy of 98.21%, minimum-inhibitory-concentration accuracy of 95.12%, and a drug-susceptibility interpretation accuracy of 99.23%, with no very major errors. This mobile-reader could eliminate the need for trained diagnosticians to perform AST, reduce the cost-barrier for routine testing, and assist in spatio-temporal tracking of bacterial resistance.
机译：常规抗菌药敏测试（AST）可以防止细菌死亡并减少多药耐药性的传播，但是由于技术挑战，成本高昂且缺乏经过培训的专业人员，因此无法在资源有限的环境中定期进行。我们演示了基于手机的自动且经济高效的96孔微量滴定板（MTP）读取器，该读取器能够执行AST而无需训练有素的诊断医生。我们的系统包括3D打印的智能手机附件，该附件可使用发光二极管阵列固定并照亮MTP。廉价的光纤阵列可以捕获通过智能手机相机传输的每个孔的光。定制设计的应用程序将捕获的图像发送到服务器以自动确定浊度，并在约1分钟内将结果返回至智能手机。我们使用含有17种针对革兰氏阴性细菌的抗生素制备的MTP，在含有高抗药性的肺炎克雷伯菌的临床分离株上测试了这种移动阅读器。使用78个患者隔离测试板，我们证明了我们的移动阅读器符合FDA定义的AST标准，浊度检测准确度为98.21％，最小抑菌浓度准确度为95.12％，并具有药物敏感性解释精度为99.23％，没有非常大的误差。这种移动阅读器可以消除对训练有素的诊断医生进行AST的需要，减少常规测试的成本障碍，并有助于对细菌抗性进行时空跟踪。

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