An integrated microfluidic chip-mass spectrometry system for rapid antimicrobial resistance analysis of bacteria producingβ-lactamases

Bacteria producingβ-lactamases have become a major issue in the global public health field.To restrain the development of drug resistance and reduce the abuse of antibiotics,it is very important to rapidly identify bacteria producingβ-lactamases and put forward a reasonable treatment plan.Here,an integrated microfluidic chip-mass spectrometry system was proposed for rapid screening ofβ-lactamaseproducing bacteria and optimization ofβ-lactamase inhibitor dosing concentration.The concentration gradient generator followed by an array of bacterial culture chambers,as well as micro-solid-phase extraction columns was designed for sample pretreatment before mass analysis.By using the combination system,the process of the hydrolysis of antibiotics byβ-lactamase-producing bacteria could be analyzed.To validate the feasibility,four antibiotics and two antibiotic inhibitors were investigated using three strains including negative control,SHV-1 and TEM-1 strains.SHV-1 and TEM-1 strains were successfully distinguished as theβ-lactamase producing strains.And the acquired optimal concentrations ofβ-lactamase inhibitors were in accordance with the results by that obtained from the traditional microdilution broth method.The total analysis time only needed around 2 h,which was faster than conventional methods that require a few days.The technique presented herein provides an easy and rapid protocol forβ-lactamase resistance related studies,which is important for the inhibition of antimicrobial resistance development and the reduction of antibiotics abuse.