Abstract

To combat the threat to public health of antimicrobial resistance, there is a need for faster, more portable diagnostic tools to aid in antibiotic selection. Current methods for determining antimicrobial resistance of pathogens in clinical samples take days to result and require high levels of user input. Microfluidics offers many potential benefits, reducing time to result, user input, and allowing point of care testing. This review focuses on the challenges of developing functional or phenotypic microfluidic antimicrobial susceptibility tests; such methods complement other vital tools such as nucleic acid detection. Some of the most important challenges identified here are not unique to microfluidics but apply to most antimicrobial susceptibility testing innovations and relate to the nature of the sample being tested. For many high priority samples, mixtures of bacteria, highly variable target cell density, and the sample matrix can all affect measurements, and miniaturization can create sensitivity problems if target bacteria are dilute. Recent advances including smartphone capability, new sensors, microscopy, and a resurgence in paper microfluidics offer important opportunities for microfluidic engineering to simplify functional and phenotypic antimicrobial susceptibility testing. But the complexity of most clinical samples remains one of the biggest barriers to rapid uptake of microfluidics for antimicrobial resistance testing.

Highlights

  • WHY ARE ANTIBIOTIC SUSCEPTIBILITY TESTS IMPORTANT AND WHAT ARE THE LIMITATIONS OF CURRENT METHODS?Many infectious diseases are caused by microorganisms that can be effectively treated using antibiotics

  • This review focuses on the challenges of developing functional or phenotypic microfluidic antimicrobial susceptibility tests; such methods complement other vital tools such as nucleic acid detection

  • Whilst aPOC phenotypic antimicrobial susceptibility tests (AST) is a long way off, significant improvements in the use of digital microscopy and smartphone imaging and novel sensors are likely to increase the use of single cell detection for rapid AST

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Summary

Introduction

WHY ARE ANTIBIOTIC SUSCEPTIBILITY TESTS IMPORTANT AND WHAT ARE THE LIMITATIONS OF CURRENT METHODS?Many infectious diseases are caused by microorganisms that can be effectively treated using antibiotics. Phenotypic AST methods are constrained fundamentally by the measurement of bacterial cell growth, with or without antibiotics. The initial inoculum cell density significantly affects MIC determination as higher cell densities of susceptible organisms may still show measurable growth in the presence of an inhibitory concentration of antibiotic (Postek et al, 2018; Smith and Kirby, 2018).

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