Cell-on-hydrogel platform made of agar and alginate for rapid, low-cost, multidimensional test of antimicrobial susceptibility
Cell-on-hydrogel platform made of agar and alginate for rapid, low-cost, multidimensional test of antimicrobial susceptibility
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由琼脂和藻酸盐制成的细胞水凝胶平台，用于快速、低成本、多维抗菌敏感性测试
DOI：
10.1039/c6lc00417b
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发表时间：
2016
期刊：
影响因子：
6.1
通讯作者：
Ren Kangning
中科院分区：
文献类型：
--
作者：
Sun Han;Liu Zhengzhi;Hu Chong;Ren Kangning
抗生素耐药性（AMR）是全球传染病有效治疗的一个快速增长的威胁。两种主要补救措施包括：（1）使用基于快速诊断的窄谱抗生素;（2）开发新抗生素。这两种疗法的关键部分是抗菌药物敏感性试验（AST）。然而，目前的标准AST监测菌落形成是昂贵和耗时的，提出的新策略还没有实际的实施。在此，我们报告了一种策略，以制造全水凝胶微流控芯片使用藻酸盐掺杂琼脂。这种基于琼脂的微加工使得制备廉价的水凝胶装置成为可能，并允许微流体和传统的基于琼脂的细胞培养之间的无缝连接。与普通的微流控系统不同，在我们的系统中，细胞培养在装置的顶部，类似于正常的琼脂平板培养;另一方面，水凝胶内部的微流控通道允许精确产生药物的线性梯度，从而提供比传统的圆盘扩散方法更好的性能。该系统中的细胞不暴露于任何剪切流，这允许在2-3小时内获得单个细胞和AST结果的可靠跟踪。此外，我们的系统可以测试药物的协同作用，通过二维梯度生成。最后，该平台可以直接应用于新药发现和其他应用，其中用于研究微生物对药物施用的响应的快速、成本有效的方法是期望的。
Antimicrobial resistance (AMR) is a rapidly increasing threat to the effective treatment of infectious diseases worldwide. The two major remedies include: (1) using narrow-spectrum antibiotics based on rapid diagnosis; and (2) developing new antibiotics. A key part of both remedies is the antimicrobial susceptibility test (AST). However, the current standard ASTs that monitor colony formation are costly and time-consuming and the new strategies proposed are not yet practical to be implemented. Herein, we report a strategy to fabricate whole-hydrogel microfluidic chips using alginate-doped agar. This agar-based microfabrication makes it possible to prepare inexpensive hydrogel devices, and allows a seamless link between microfluidics and conventional agar-based cell culture. Different from common microfluidic systems, in our system the cells are cultured on top of the device, similar to normal agar plate culture; on the other hand, the microfluidic channels inside the hydrogel allow precise generation of linear gradient of drugs, thus giving a better performance than the conventional disk diffusion method. Cells in this system are not exposed to any shear flow, which allows the reliable tracking of individual cells and AST results to be obtained within 2–3 hours. Furthermore, our system could test the synergistic effect of drugs through two-dimensional gradient generation. Finally, the platform could be directly implemented to new drug discovery and other applications wherein a fast, cost-efficient method for studying the response of microorganisms upon drug administration is desirable.