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

Bacteria producing fi-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 producing fi-lactamases and put forward a reasonable treatment plan. Here, an inte-grated microfluidic chip-mass spectrometry system was proposed for rapid screening of fi-lactamase-producing bacteria and optimization of fi-lactamase inhibitor dosing concentration. The concentration gradient generator followed by an array of bacterial culture chambers, as well as micro-solid-phase ex-traction columns was designed for sample pretreatment before mass analysis. By using the combina-tion system, the process of the hydrolysis of antibiotics by fi-lactamase-producing bacteria could be an-alyzed. 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 suc-cessfully distinguished as the fi-lactamase producing strains. And the acquired optimal concentrations of fi-lactamase inhibitors were in accordance with the results by that obtained from the traditional microdi-lution 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 for fi-lactamase resistance related studies, which is important for the inhibition of antimicrobial resistance development and the reduction of antibiotics abuse.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.