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Bio-Design and Manufacturing  2022 Vol.5 No.1 P.210-219

http://doi.org/10.1007/s42242-021-00173-0


A 3D-printed microfluidic gradient concentration chip for rapid antibiotic-susceptibility testing


Author(s):  Huilin Zhang, Yuan Yao, Yue Hui, Lu Zhang, Nanjia Zhou & Feng Ju

Affiliation(s):  College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, 310058, China; more

Corresponding email(s):   zhounanjia@westlake.edu.cn, jufeng@westlake.edu.cn

Key Words:  Microfluidics, Gradient concentration chip, Digital light processing, Antibiotic-susceptibility test, Bacteria


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Huilin Zhang, Yuan Yao, Yue Hui, Lu Zhang, Nanjia Zhou & Feng Ju . A 3D-printed microfluidic gradient concentration chip for rapid antibiotic-susceptibility testing[J]. Journal of Zhejiang University Science D, 2022, 5(1): 210-219.

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Abstract: 
The rise of antibiotic resistance as one of the most serious global public health threats has necessitated the timely clinical diagnosis and precise treatment of deadly bacterial infections. To identify which types and doses of antibiotics remain effective for fighting against multi-drug-resistant pathogens, the development of rapid and accurate antibiotic-susceptibility testing (AST) is of primary importance. Conventional methods for AST in well-plate formats with disk diffusion or broth dilution are both labor-intensive and operationally tedious. The microfluidic chip provides a versatile tool for evaluating bacterial AST and resistant behaviors. In this paper, we develop an operationally simple, 3D-printed microfluidic chip for AST which automatically deploys antibiotic concentration gradients and fluorescence intensity-based reporting to ideally reduce the report time for AST to within 5 h. By harnessing a commercially available, digital light processing (DLP) 3D printing method that offers a rapid, high-precision microfluidic chip-manufacturing capability, we design and realize the accurate generation of on-chip antibiotic concentration gradients based on flow resistance and diffusion mechanisms. We further demonstrate the employment of the microfluidic chip for the AST of E. coli to representative clinical antibiotics of three classes: ampicillin, chloramphenicol, and kanamycin. The determined minimum inhibitory concentration values are comparable to those reported by conventional well-plate methods. Our proposed method demonstrates a promising approach for realizing robust, convenient, and automatable AST of clinical bacterial pathogens.

西湖大学鞠峰、周南嘉等 | 基于3D打印的浓度梯度微流控芯片用于微生物的快速药敏检测

本研究论文聚焦微生物的快速药敏检测研究。抗生素耐药是目前全球公共卫生安全面临的一项严峻挑战。病原菌的耐药性加速进化增加了临床治疗多重耐药感染的用药难度与病人死亡率。及时得到微生物的抗生素药物敏感性结果对于临床多重耐药感染的精准诊断与用药治疗具有重要意义。这项研究中设计了基于流阻的微液滴芯片,结合应用刃天青生物指示剂可在5 h内指示微生物在不同浓度抗生素下的生长。该芯片有若干独立的截留腔室,可自动产生抗生素浓度梯度并形成独立的微液滴用于检测细菌药敏性。该芯片简化了控制操作和设备集成,相较于传统方法缩短了药敏检测时间,具有良好的应用前景。

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