3D microfluidic gradient generator for combination antimicrobial susceptibility testing

Autor: Camille Mercier, Ryan Jew, Yash Attal, Eric J. Jacobs, Tinglin Wu, Reed Vickerman, Liwei Lin, Joshua Chen, Andrew Chang, Alison T. Long, Eric Sweet, Siyang Liu, Brenda Yang, Yujui Lin
Rok vydání: 2020
Předmět:
Materials science
medicine.drug_class
Materials Science (miscellaneous)
Microfluidics
Antibiotics
02 engineering and technology
lcsh:Technology
Industrial and Manufacturing Engineering
03 medical and health sciences
Minimum inhibitory concentration
Engineering
medicine
Fluidics
Electrical and Electronic Engineering
030304 developmental biology
0303 health sciences
Microchannel
lcsh:T
Prevention
021001 nanoscience & nanotechnology
Condensed Matter Physics
Antimicrobial
Atomic and Molecular Physics
and Optics

Chemistry
Infectious Diseases
Emerging Infectious Diseases
Amikacin
lcsh:TA1-2040
5.1 Pharmaceuticals
Antimicrobial Resistance
Development of treatments and therapeutic interventions
0210 nano-technology
Biological system
lcsh:Engineering (General). Civil engineering (General)
Infection
medicine.drug
Combination drug
Zdroj: Microsystems & nanoengineering, vol 6, iss 1
Microsystems & Nanoengineering, Vol 6, Iss 1, Pp 1-14 (2020)
Popis: 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 multidrug 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 antibiotic drugs, tetracycline, ciprofloxacin, and amikacin, were evaluated via experimental single-antibiotic minimum inhibitory concentration (MIC) and pairwise 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.
Databáze: OpenAIRE