An Integrated Microsystem for Real-Time Detection and Threshold-Activated Treatment of Bacterial Biofilms

Abstract

Bacterial biofilms are the primary cause of infections in medical implants and catheters. Delayed detection of biofilm infections contributes to the widespread use of high doses of antibiotics, leading to the emergence of antibiotic-resistant bacterial strains. Accordingly, there is an urgent need for systems that can rapidly detect and treat biofilm infections in situ. As a step toward this goal, in this work we have developed for the first time a threshold-activated feedback-based impedance sensor-treatment system for combined real-time detection and treatment of biofilms. Specifically, we demonstrate the use of impedimetric sensing to accurately monitor the growth of Escherichia coli biofilms in microfluidic flow cells by measuring the fractional relative change (FRC) in absolute impedance. Furthermore, we demonstrate the use of growth measurements as a threshold-activated trigger mechanism to initiate successful treatment of biofilms using bioelectric effect (BE), applied through the same sensing electrode array. This was made possible through a custom program that (a) monitored the growth and removal of biofilms within the microfluidic channels in real-time and (b) enabled the threshold-based activation of BE treatment. Such BE treatment resulted in a ∼74.8 % reduction in average biofilm surface coverage as compared to the untreated negative control. We believe that this smart microsystem for integrated biofilm sensing and treatment will enable future development of autonomous biosensors optimized for accurate real-time detection of the onset of biofilms and their in situ treatment, directly on the surfaces of medical implants.

Options and Limitations in Clinical Investigation of Bacterial Biofilms

“…A novel impedimetric sensing system based on the interdigitated microelectrode microsystem envisions paving the way for the development of smart biosensors for rapid implant-associated biofilm identification and removal. In short, this microsystem allows label-free E. coli biofilm growth detection in microfluidic channels by evaluating the fractional relative change in real time as well as monitoring the threshold-activated bioelectric effect on the in situ treatment process (425). A custom-made surface plasmon resonance (SPR) biosensor was recently applied for E. coli biofilm formation investigation on gold-plated glass disks.…”

Depriving Bacterial Adhesion‐Related Molecule to Inhibit Biofilm Formation Using CeO2‐Decorated Metal‐Organic Frameworks

“…[10] The treatment of biofilm infections prior to the formation of a thick EPS would need only small doses of antibacterial agents for a shorter duration of time. [11] Therefore, inhibition of the biofilm formation is one of the promising avenues to confront drug resistance of bacteria. [7a,12] For example, Swartjes et al employed a DNase I enzyme coating to polymethylmethacrylate for the reductions of initial bacterial adhesion.…”

“…At this stage, the bacterial resistance is weaker due to the lack of protection of mature bacterial biofilm . The treatment of biofilm infections prior to the formation of a thick EPS would need only small doses of antibacterial agents for a shorter duration of time . Therefore, inhibition of the biofilm formation is one of the promising avenues to confront drug resistance of bacteria 7a,12.…”

Innovations in indwelling urethral catheterisation

“…Pushing liquid through the four channels strains the catheter surface, which has been shown in vitro to mechanically dislodge 90% of biofilm from the drainage lumen . Another exciting innovation under development is a flexible impedance sensor that integrates biofilm detection and treatment . The sensor can be rolled and inserted inside a urinary catheter, where it then conforms with the catheter surface.…”