title: Cell-on-hydrogel platform made of agar and alginate for rapid, low-cost, multidimensional test of antimicrobial susceptibility.
abstract: 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.
authors.affiliation: Department of Chemistry,, Hong Kong Baptist University, Waterloo Rd, Kowloon, Hong Kong, China. kangningren@hkbu.edu.hk.
authors.forename: Han
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Chemistry,, Hong Kong Baptist University, Waterloo Rd, Kowloon, Hong Kong, China. kangningren@hkbu.edu.hk.
authors.forename: Zhengzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Chemistry,, Hong Kong Baptist University, Waterloo Rd, Kowloon, Hong Kong, China. kangningren@hkbu.edu.hk.
authors.forename: Chong
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Chemistry,, Hong Kong Baptist University, Waterloo Rd, Kowloon, Hong Kong, China. kangningren@hkbu.edu.hk and State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Waterloo Rd, Kowloon, Hong Kong, China and HKBU Institute of Research and Continuing Education, Shenzhen, China.
authors.forename: Kangning
authors.initials: K
authors.lastname: Ren
mesh_terms: D000362:Agar / Q000737:chemistry; D000464:Alginates / Q000737:chemistry; D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002515:Cephradine / Q000494:pharmacology; D004058:Diffusion; D004867:Equipment Design; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry; D006358:Hot Temperature; D020100:Hydrogels / Q000737:chemistry*; D056656:Lab-On-A-Chip Devices; D008826:Microbial Sensitivity Tests / Q000295:instrumentation*; D008856:Microscopy, Fluorescence; D030781:Organisms, Genetically Modified
chemical_list: D000464:Alginates; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D006603:Hexuronic Acids; D020100:Hydrogels; D049452:Green Fluorescent Proteins; D000667:Ampicillin; D020723:Glucuronic Acid; D000362:Agar; D002515:Cephradine