Electrical Engineering Department, University of California, Los Angeles, California 90095, United States.
Bioengineering Department, University of California, Los Angeles, California 90095, United States.
Sci Rep. 2016 Dec 15;6:39203. doi: 10.1038/srep39203.
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.
常规抗菌药敏试验(AST)可以预防细菌感染导致的死亡,并减少耐药菌的传播,但由于技术挑战、高成本和缺乏专业培训人员,在资源有限的环境中无法定期进行。我们展示了一种自动化且具有成本效益的基于手机的 96 孔微量滴定板(MTP)读取器,无需经过培训的诊断医生即可进行 AST。我们的系统包括一个 3D 打印的智能手机附件,该附件使用发光二极管(LED)阵列来保持和照亮 MTP。一个廉价的光纤阵列使智能手机摄像头能够捕获每个孔的透射光。一个定制设计的应用程序将捕获的图像发送到服务器,以自动确定孔的浊度,结果在大约 1 分钟内返回智能手机。我们使用针对革兰氏阴性菌的 17 种抗生素制备的 MTP 对含有高度耐药性抗菌谱的肺炎克雷伯菌临床分离株进行了这种移动读取器的测试。使用 78 个患者分离物测试板,我们证明我们的移动读取器符合 FDA 定义的 AST 标准,孔浊度检测准确率为 98.21%,最小抑菌浓度准确率为 95.12%,药物敏感性解释准确率为 99.23%,没有非常大的误差。这种移动读取器可以消除对经过培训的诊断医生进行 AST 的需求,降低常规测试的成本障碍,并有助于细菌耐药性的时空跟踪。