3D Microfluidic Concentration Gradient Generator for Combination Antimicrobial Susceptibility Testing

Abstract: 

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

Author: 
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
Citation: 
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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