Diagnostic system for rapid antimicrobial susceptibility testing of clinical samples

By the year 2050, antimicrobial resistance is predicted to cost over 100 trillion US$ cumulatively and claim 10 million lives per year. Thus, there is an urgent need to develop diagnostic methods that will help physicians to rapidly prescribe the correct antibiotics, namely antibiotic susceptibility testing (AST). Clinical microbiology laboratories employ various conventional methods of AST, taking approximately 18 hours for completion.

We aim to design an optical, label-free sensing platform using micro-structured silicon arrays for phenotypic AST of clinical samples within less than 2 hours. This will be achieved by unique silicon sensors, based on optical phase-shift reflectometric interference spectroscopic measurements (PRISM). The micro-structured Si sensors provide both a preferable solid-liquid interface for bacteria networking and a simultaneous transducing element that monitors the response of bacteria when exposed to antibiotics in real-time. By monitoring these optical changes, bacterial growth is observed in the presence of various antibiotics, enabling bacteria classification as susceptible or resistant.

The Si sensors are incorporated in disposable, inexpensive microfluidic devices, allowing for multiplexing the test in a safe and simple format. Using this system, we have studied a clinically-relevant Escherichia coli (E. coli) strain upon exposure to common antibiotics and was able to differentiate between susceptible and resistant categories. Using the latter values in PRISM studies of E. coli from clinical isolates of urinary tract infections allowed us to successfully differentiate between susceptible and resistant strains with high accuracy and within less than 90 min. Thus, PRISM platform is expected to be further validated in a clinical setting using a variety of bacterial pathogens found in bodily fluid samples, for potential clinical application.