Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage

Abstract

Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average "early warning" of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method.

Theranostic Infection‐Responsive Coating to In Situ Detect and Prevent Urinary Catheter Blockage

“…Therefore, at the specific time point, the released vesicles in urine solution exhibited different chromatic colors at different pH values, which would predict the potential pH range of the infected urine solution, and give an indication of initial infection and potential blockage by different chromatic colors collected in bladder chamber and drainage bag. The advanced color warning can alert patients or carers to the different stages of infection and thus providing more accurate signal of blockage for them, compared to existed coating sensor developed by others . However, the results in our study were quite different from results conducted by other groups such as time from sensing color change to catheter blockage .…”

“…The advanced color warning can alert patients or carers to the different stages of infection and thus providing more accurate signal of blockage for them, compared to existed coating sensor developed by others . However, the results in our study were quite different from results conducted by other groups such as time from sensing color change to catheter blockage . This was mainly due to the different experimental conditions including different infected urine model or different experimental setup.…”

“…The results showed that the coated sensor exhibited yellow to dark blue transition from pH 6 to pH 8. Jenkins et al designed a two‐layered hydrogel coated either on the top of catheter surface above the retention balloon or directly in the drainage bag. The sensing coating comprised two‐layered hydrogel coating: inner layer of poly (vinyl alcohol) hydrogel with fluorescent dye embedding inside and an outer layer of commercially available hydrogel EUDRAGITS100.…”

Bacterial biofilm formation on indwelling urethral catheters

“…A variation on this approach has also recently reported by Milo and colleagues who developed pH responsive drainage bag sensors and coatings for catheters (Milo et al . , ). These were based on incorporation of the dye carboxyfluorescein within a hydrogel matrix encapsulated by the pH responsive Eudragit polymer (Milo et al .…”

“…These were based on incorporation of the dye carboxyfluorescein within a hydrogel matrix encapsulated by the pH responsive Eudragit polymer (Milo et al . , ). In this system dissolution of the Eudragit polymer at elevated pH allows diffusion of the carboxyfluorescein indicator out of the hydrogel layer and into the urine, where it imparts a distinctive bright green coloration that signals the potential for blockage (Milo et al .…”