A high-throughput integrated biofilm-on-a-chip platform for the investigation of combinatory physicochemical responses to chemical and fluid shear stress

PLoS One. 2022 Aug 12;17(8):e0272294. doi: 10.1371/journal.pone.0272294. eCollection 2022.

Abstract

Physicochemical conditions play a key role in the development of biofilm removal strategies. This study presents an integrated, double-layer, high-throughput microfluidic chip for real-time screening of the combined effect of antibiotic concentration and fluid shear stress (FSS) on biofilms. Biofilms of Escherichia coli LF82 and Pseudomonas aeruginosa were tested against gentamicin and streptomycin to examine the time dependent effects of concentration and FSS on the integrity of the biofilm. A MatLab image analysis method was developed to measure the bacterial surface coverage and total fluorescent intensity of the biofilms before and after each treatment. The chip consists of two layers. The top layer contains the concentration gradient generator (CGG) capable of diluting the input drug linearly into four concentrations. The bottom layer contains four expanding FSS chambers imposing three different FSSs on cultured biofilms. As a result, 12 combinatorial states of concentration and FSS can be investigated on the biofilm simultaneously. Our proof-of-concept study revealed that the reduction of E. coli biofilms was directly dependent upon both antibacterial dose and shear intensity, whereas the P. aeruginosa biofilms were not impacted as significantly. This confirmed that the effectiveness of biofilm removal is dependent on bacterial species and the environment. Our experimental system could be used to investigate the physicochemical responses of other biofilms or to assess the effectiveness of biofilm removal methods.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antacids
  • Anti-Bacterial Agents / pharmacology
  • Biofilms
  • Escherichia coli*
  • Lab-On-A-Chip Devices*
  • Penicillins / pharmacology
  • Pseudomonas aeruginosa

Substances

  • Antacids
  • Anti-Bacterial Agents
  • Penicillins

Grants and funding

This work was supported in part by the United States Department of Agriculture’s National Institute of Food and Agriculture under award number 2019-38420-28975. This work was performed in part at the Cornell NanoScale Facility, a member of the National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation Grant NNCI-2025233. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.