A microfluidic device for antimicrobial susceptibility testing based on a broth dilution method.
Bacterial resistance to antimicrobial compounds is increasing at a faster rate than the development of new antibiotics; this represents a critical challenge for clinicians worldwide. Normally, the minimum inhibitory concentration of an antibiotic, the dosage at which bacterial growth is thwarted, provides an effective quantitative measure for antimicrobial susceptibility testing, and determination of minimum inhibitory concentration is conventionally performed by either a serial broth dilution method or with the commercially available Etest®(Biomerieux, France) kit. However, these techniques are relatively labor-intensive and require a significant amount of training. In order to reduce human error and increase operation simplicity, a simple microfluidic device that can perform antimicrobial susceptibility testing automatically via a broth dilution method to accurately determine the minimum inhibitory concentration was developed herein. As a proof of concept, wild-type (ATCC 29212) and vancomycin-resistant Enterococcus cells were incubated at five different vancomycin concentrations on-chip, and the sample injection, transport, and mixing processes occurred within five reaction chambers and three reagent chambers via the chip's automatic dispensation and dilution functions within nine minutes. The minimum inhibitory concentration values measured after 24h of antibiotic incubation were similar to those calculated using Etest®. With its high flexibility, reliability, and portability, the developed microfluidic device provides a simple method for antimicrobial susceptibility testing in an automated format that could be implemented for clinical and point-of-care applications.
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, 30013 Taiwan.
Wen-Bin
WB
Lee
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, 30013 Taiwan.
Chien-Yu
CY
Fu
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, 30013 Taiwan.
Wen-Hsin
WH
Chang
Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, 83301 Taiwan.
Huey-Ling
HL
You
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, 30013 Taiwan.
Chih-Hung
CH
Wang
Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, 83301 Taiwan. Electronic address: mellee@cgmh.org.tw.
Mel S
MS
Lee
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, 30013 Taiwan; Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013 Taiwan; Institute of NanoEngineering and Microsystems, National Tsing Hua University, Hsinchu, 30013 Taiwan. Electronic address: gwobin@pme.nthu.edu.tw.
Gwo-Bin
GB
Lee
D000890:Anti-Infective Agents / Q000494:pharmacology*; D015374:Biosensing Techniques / Q000295:instrumentation; D024881:Drug Resistance, Bacterial; D016983:Enterococcus / Q000187:drug effects*; D004867:Equipment Design; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008826:Microbial Sensitivity Tests / Q000295:instrumentation*; D019095:Point-of-Care Systems; D014640:Vancomycin / Q000494:pharmacology*; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects*
D000890:Anti-Infective Agents; D014640:Vancomycin
Antibiotics; Antimicrobial resistance; Antimicrobial susceptibility testing; Broth dilution; Microfluidics; Minimum inhibitory concentration; Vancomycin-resistant Enterococcus