3D Microfluidic Concentration Gradient Generator for Combination Antimicrobial Susceptibility Testing


Microfluidic concentration gradient generators (µ-CGGs) have been utilized to identify optimal drug compositions through antimicrobial susceptibility testing (AST) for the treatment of antimicrobial-resistant (AMR) infections. Conventional µ-CGGs fabricated via photolithography-based micromachining processes, however, are fundamentally limited to two-dimensional fluidic routing, such that only two distinct antimicrobial drugs can be tested at once. This work addresses this limitation by employing Multijet-3D printed microchannel networks capable of fluidic routing in three dimensions to generate symmetric multi-drug concentration gradients. The three-fluid gradient generation characteristics of the fabricated 3D µ-CGG prototype were quantified through both theoretical simulations and experimental validations. Furthermore, the antimicrobial effects of three highly clinically-relevant classes of antibiotic drugs, tetracycline, ciprofloxacin, and amikacin, were evaluated via experimental single-antibiotic minimum inhibitory concentration (MIC), pair-wise and three-way antibiotic combination drug screening (CDS) studies against model antibiotic-resistant Escherichia coli bacteria. As such, this 3D µ-CGG platform has great potential to enable expedited combination AST screening for various biomedical and diagnostic applications.

Keywords: 3D printed, additive manufacturing, microfluidics, concentration gradient generator, minimum inhibitory concentration, combination drug screening, antibiotic, antimicrobial susceptibility testing

Eric Sweet
Brenda Yang
Joshua Chen
Reed Vickerman
Yujui Lin
Alison Long
Eric Jacobs
Tinglin Wu
Camille Mercier
Ryan Jew
Yash Attal
Siyang Liu
Andrew Chang
Publication date: 
November 2, 2020
Publication type: 
Journal Article
Sweet, E., Yang, B., Chen, J. et al. 3D microfluidic gradient generator for combination antimicrobial susceptibility testing. Microsyst Nanoeng 6, 92 (2020). https://doi.org/10.1038/s41378-020-00200-7

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