DEPIS: A combined dielectrophoresis and impedance spectroscopy platform for rapid cell viability and antimicrobial susceptibility analysis

Abstract

Antimicrobial resistance (AMR) is caused by inappropriate or excessive antibiotic consumption. Early diagnosis of bacterial infections can greatly curb empirical treatment and thus AMR. Current diagnostic procedures are time-consuming as they rely on gene amplification and cell culture techniques that are inherently limited by the doubling rate of the involved species. Further, biochemical methods for species identification and antibiotic susceptibility testing for drug/dose effectiveness take several days and are non-scalable. We report a real-time, label-free approach called DEPIS that combines dielectrophoresis (DEP) for bacterial enrichment and impedance spectroscopy (IS) for cell viability analysis under 60 min. Target bacteria are captured on interdigitated electrodes using DEP (30 min) and their antibiotic-induced stress response is measured using IS (another 30 min). This principle is used to generate minimum bactericidal concentration (MBC) plots by measuring impedance change due to ionic release by dying bacteria in a low conductivity buffer. The results are rapid since they rely on cell death rather than cell growth which is an intrinsically slower process. The results are also highly specific and work across all bactericidal antibiotics studied, irrespective of their cellular target or drug action mechanism. More importantly, preliminary results with clinical isolates show that methicillin-susceptible Staphylococcus aureus (MSSA) can easily be differentiated from methicillin-resistant S. aureus (MRSA) under 1 h. This rapid cell analyses approach can aid in faster diagnosis of bacterial infections and benefit the clinical decision-making process for antibiotic treatment, addressing the critical issue of AMR.