A microfluidic platform for the characterisation of membrane active antimicrobials

Area of Science:

• Biochemistry
• Microfluidics
• Drug Discovery

Background:

• Bacterial resistance to antibiotics necessitates novel antimicrobial discovery.
• Polypeptide antibiotics show promise by targeting bacterial membranes.
• Efficient platforms for evaluating antimicrobial mechanisms are lacking.

Purpose of the Study:

• To develop and validate an integrated microfluidic platform for quantifying membranolytic antibiotic efficacy.
• To establish a high-throughput screening assay for novel antimicrobial agents.
• To investigate the dose-response of polypeptide antibiotics on biomimetic membranes.

Main Methods:

• An integrated lab-on-a-chip multilayer microfluidic device was engineered.
• Giant unilamellar vesicles (GUVs) were generated on demand in physiologically relevant buffers.
• Individual GUVs were immobilized in physical traps for controlled antibiotic delivery and monitoring of encapsulated dye leakage.

Main Results:

• The platform successfully quantified the membranolytic efficacy of antibiotics.
• Dose-response of cecropin B on bacterial membrane-mimicking GUVs was determined.
• The study demonstrated proof-of-principle for quantitative antibiotic screening.

Conclusions:

• The developed microfluidic platform provides a foundation for quantitative, high-throughput screening of antibiotics.
• This technology can accelerate the discovery of novel antimicrobial agents.
• The system enables systematic evaluation of antibiotic mechanisms of action.