Division of Engineering in Medicine, Brigham and Women's Hospital-Harvard Medical School , 75 Francis Street, Boston, Massachusetts 02115, United States.
Department of Medicine, Harvard Medical School , 25 Shattuck Street, Boston, Massachusetts 02115, United States.
ACS Appl Mater Interfaces. 2017 Apr 12;9(14):12832-12840. doi: 10.1021/acsami.6b16571. Epub 2017 Mar 30.
Rapid antimicrobial susceptibility testing is important for efficient and timely therapeutic decision making. Due to globally spread bacterial resistance, the efficacy of antibiotics is increasingly being impeded. Conventional antibiotic tests rely on bacterial culture, which is time-consuming and can lead to potentially inappropriate antibiotic prescription and up-front broad range of antibiotic use. There is an urgent need to develop point-of-care platform technologies to rapidly detect pathogens, identify the right antibiotics, and monitor mutations to help adjust therapy. Here, we report a biosensor for rapid (<90 min), real time, and label-free bacteria isolation from whole blood and antibiotic susceptibility testing. Target bacteria are captured on flexible plastic-based microchips with printed electrodes using antibodies (30 min), and its electrical response is monitored in the presence and absence of antibiotics over an hour of incubation time. We evaluated the microchip with Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) as clinical models with ampicillin, ciprofloxacin, erythromycin, daptomycin, gentamicin, and methicillin antibiotics. The results are compared with the current standard methods, i.e. bacteria viability and conventional antibiogram assays. The technology presented here has the potential to provide precise and rapid bacteria screening and guidance in clinical therapies by identifying the correct antibiotics for pathogens.
快速的抗菌药敏测试对于高效和及时的治疗决策至关重要。由于全球范围内细菌耐药性的传播,抗生素的疗效正日益受到阻碍。传统的抗生素测试依赖于细菌培养,这既耗时又可能导致潜在的不适当的抗生素处方和广泛的抗生素前期使用。因此,迫切需要开发即时检测平台技术,以快速检测病原体、确定合适的抗生素,并监测突变,从而帮助调整治疗方案。在这里,我们报告了一种生物传感器,用于从全血中快速(<90 分钟)、实时和无需标记的细菌分离以及抗生素药敏测试。使用抗体(30 分钟)在带有印刷电极的柔性塑料基微芯片上捕获靶细菌,并在孵育 1 小时的过程中监测有无抗生素存在时的电响应。我们使用大肠杆菌和耐甲氧西林金黄色葡萄球菌(MRSA)作为临床模型,用氨苄西林、环丙沙星、红霉素、达托霉素、庆大霉素和甲氧西林抗生素评估了微芯片。结果与目前的标准方法(即细菌活力和常规药敏试验)进行了比较。该技术有可能通过识别针对病原体的正确抗生素,为临床治疗提供精确和快速的细菌筛选和指导。