Rapid diagnostics of heteroresistance

To efficiently combat antibiotic resistant bacteria, it is critical to have diagnostic methods that can detect all types of resistance.

Heteroresistance (HR) is a form of antibiotic resistance characterized by the presence of small resistant subpopulation(s), in a main population of susceptible cells.

During antibiotic exposure the resistant cells can rise to high frequency and cause treatment failure and recurrent infections.

Not only do many species of bacteria exhibit this form of resistance, but it has been reported against most antibiotic classes.

The resistant subpopulations are difficult to detect and study, and today clinicians are unable to reliably and rapidly detect the presence of HR phenotypes and adjust the choice of treatment accordingly.In this project, we will develop a new test to rapidly and correctly diagnose the presence of these rare antibiotic resistant cells.

Our solution is the development of a droplet-microfluidic based method to encapsulate cells in aqueous droplets for on-chip miniaturized cultures. As cells grow, a size change of the droplets occurs caused by the metabolic activity of the growing bacteria. We have demonstrated that a sensitivity on the order of 10^-7 can be achieved.

The method presents short analysis time and low limit of detection, with a user-friendly automatic yes/no read-out.

We foresee that this new technology could be implemented in established analysis workflows in clinical microbiology labs.