Researchers from Skoltech and the University of Texas at Austin have presented a proof of concept for a wearable sensor that can track healing of chronic skin wounds, even without the need to remove the bandages.
The team used a simulated wound environment to test the sensitivity of their sensor to three critical biomarkers: pyocyanin, produced by Pseudomonas aeruginosa, a bacterium typically colonizing chronic wounds; nitric oxide (NO-) secreted in response to bacterial infections by cells of the immune system; and uric acid, a metabolite which strongly correlates with the severity of a wound. All these compounds are electroactive: that is, they respond to electrical activity and thus can be detected by an electroanalytical sensor.
Experiments showed that both the sensor’s limits of detection and linear dynamic ranges, which represent the ranges of concentrations where a sensor produces meaningful quantitative results, were within the biologically relevant concentrations—that means a device based on these sensors could be used for wound monitoring in a clinical setting. The researchers also tested their sensor in cell cultures, where it successfully detected pyocyanin from P. aeruginosa and NO- from macrophages (immune cells that destroy bacteria and other ‘invaders’). Finally, the sensor was also able to detect the influence of Ag+ silver ions, a known antimicrobial agent, that suppressed pyocyanin production by the bacteria.
Electrochemical Detection of Multianalyte Biomarkers in Wound Healing Efficacy
The targeted diagnosis and effective treatments of chronic skin wounds remain a healthcare burden, requiring the development of sensors for real-time monitoring of wound healing activity. Herein, we describe an adaptable method for the fabrication of carbon ultramicroelectrode arrays (CUAs) on flexible substrates with the goal to utilize this sensor as a wearable device to monitor chronic wounds. As a proof-of-concept study, we demonstrate the electrochemical detection of three electroactive analytes as biomarkers for wound healing state in simulated wound media on flexible CUAs.
Notably, to follow pathogenic responses, we characterize analytical figures of merit for identification and monitoring of bacterial warfare toxin pyocyanin (PYO) secreted by the opportunistic human pathogen Pseudomonas aeruginosa. We also demonstrate the detection of uric acid (UA) and nitric oxide (NO•), which are signaling molecules indicative of wound healing and immune responses, respectively. The electrochemically determined limit of detection (LOD) and linear dynamic range (LDR) for PYO, UA, and NO• fall within the clinically relevant concentrations. Additionally, we demonstrate the successful use of flexible CUAs for quantitative, electrochemical detection of PYO from P. aeruginosa strains and cellular NO• from immune cells in the wound matrix. Moreover, we present an electrochemical examination of the interaction between PYO and NO•, providing insight into pathogen–host responses. Finally, the effects of the antimicrobial agent, silver (Ag+), on P. aeruginosa PYO production rates are investigated on flexible CUAs. Our electrochemical results show that the addition of Ag+ to P. aeruginosa in wound simulant decreases PYO secretion rates.