基于创新微流控技术的快速低成本高通量细菌耐药性检测方法

项目名称： 基于创新微流控技术的快速低成本高通量细菌耐药性检测方法

项目编号： No.21505110

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 任康宁

作者单位： 香港浸会大学深圳研究院

项目金额： 21万元

中文摘要： 致病微生物的产生耐药性会使已有的药物失效，耐药性的产生因广谱抗生素滥用而加快。耐药性已成为世界重大危机，且形势在中国尤为严峻。利用可靠的药效筛选手段指导选用特异性抗生素，可显著减缓耐药性产生。然而，目前药效筛选基于细胞培养，费时且昂贵，无法指导用药。基于基因或纳米科技的新尝试尚有明显缺陷难以用于常规检测。本研究致力于建立一个基于创新的微流控技术的快速药效筛选方法。我们通过在特制芯片上进行细胞培养，并在单细胞尺度进行观测，更快地检测到致病微生物对药物的反应。此外，我们用具超强抗污性能的全氟化合物制作芯片，以解决通道沾污造成药物浓度不可控的难点问题；此设计支持高通量操作，且芯片的特殊设计具有浓缩功能，减少培养所需时间，进一步加快检测速度，且提高对体外难增殖细胞的响应。通过本项目，我们希望建立一套经济、便捷和可靠的方法，有助于有效控制微生物抗药性。除临床应用前景，这一平台还有望用于药物开发等。

中文关键词： 微流芯片；细菌耐药性；微加工；快速诊断；功能材料

英文摘要： Rapid, Low-cost, High-Throughput Test of Antimicrobial Susceptibility Based on Novel Microfluidic Technology..Antimicrobial resistance (AMR) is a natural phenomenon developed in microorganisms, and is accelerated by misuse of antibiotics. AMR makes the treatment difficult, costly, or even impossible, thus is causing major health threat as well as enormous financial loss worldwide. The issues of AMR in China are especially severe...Two strategies are effective in addressing AMR issues: (1) use narrow-spectrum antibiotics based on accurate diagnosis, preferentially, using antimicrobial susceptibility test (AST); (2) develop new antibiotics. However, both strategies are challenged by the lack of effective and affordable method to test the response of target microorganisms to drug administration. An AST involves a large number of tests, especially when the minimum inhibitory concentration (MIC) of each drug is desired. Current ASTs are based on observing cell-growth, which is costly and time-consuming. Similar challenge exists in the drug development which requires large-scale screening. Tremendous efforts have been made to improve AST technology; however, those new strategies, based on PCR, nanoparticles, or dielectrophoresis, are still impractical to be used for real specimens. ..Herein we propose a microfluidic platform which could have major contribution to addressing the aforementioned challenges. We are developing a new strategy to detect the response of microorganisms to drug treatment, using a microfluidic on-chip culture and counting platform which could detect the response of drug-affected bugs quicker than conventional methods. The device will be made of a new type of material, perfluoropolymers, which addresses major challenges associated with channel fouling in drug-loaded on-chip culture. Also, the system supports high-throughput operation without massive manipulation such as pipetting, thereby improving the reliability of the assay. Moreover, a special design of the microchannel will incorporate a concentration effect to further reduce the time need for incubation therefore accelerating the test. ..Through this project, we expect an inexpensive, user-friendly but quick and reliable method to benefit the control of AMR. As our method is designed to allow maximum accessibility, the broad range of clinics currently could not afford AST would be able to conduct routine test. At the mean time, the unique platform will allow us to obtain important new knowledge about the mechanism of AMR development. Finally, the platform could be implemented to drug discovery and other applications where similar tool is sought for.

英文关键词： microfluidic device;antimicrobial susceptibility;microfabrication;rapid diagnosis;functional material