Scientists have developed a wearable DNA hydrogel-based sensor that detects bacterial infections in wounds even before visible signs are present, according to a new study in the November 19 issue of Science Advances.
The wireless infection detection on wounds (WINDOW) sensor, which was tested on wound swabs from 18 patients, can be embedded in wound dressings and sends a signal to a user's smartphone when its hydrogel degrades in response to bacterial DNA, alerting her to the presence of dangerous bacteria such as Staphylococcus aureus.
By overcoming barriers to continuous wound monitoring, including factors that have prevented the integration of multiple complex sensors into wearable devices, this technology could enable more rapid detection and treatment of wound infections.
"We were surprised that the DNA hydrogel could detect wound infection in the animal studies before any visible signs were obvious," said Ze Xiong, a researcher in the department of electrical and computer engineering at the National University of Singapore and the first author of the study. "We envision that the sensor may be placed under wound dressing after surgery after the patient has been discharged from the hospital. In the event that wound infection is detected, the patient can seek prompt medical care."
Insidious Infections
Surgical site infections are the most common type of infections people acquire during hospital visits, costing the U.S. healthcare system alone an estimated $3.5 billion to $10 billion each year. Diabetic foot ulcers — open sores that occur in about 15% of people with diabetes — also frequently develop infections that land patients in the hospital. In extreme cases, failure to manage these sores ends with foot amputation.
While it is critical to detect infected wounds fast so they can be treated before they worsen, current detection methods rely on either examinations by healthcare workers or time-consuming lab tests, leading to delays in critical treatments such as antibiotics.
To overcome these costly delays through continuous wound monitoring, Xiong and colleagues developed a customized DNA hydrogel or DNAgel — an approach that marked a significant departure from previous wound monitoring studies.
"There has been prior work on wound sensors that can continuously measure temperature, pH, and electrical impedance," said Xiong. "Our work differs from these approaches in that it senses a biomarker, DNase, that is directly associated with infection, and does so using a material, DNA hydrogel, that selectively responds to it."
"During wound infection, the amount of bacteria increases, along with the amount of DNase enzyme secreted by the bacteria," explained Xiong. The DNase then cleaves the DNA strands that make up the hydrogel, causing it to dissolve. This allows the monitoring to be performed in a continuous manner without having the sensor saturate."
Xiong and colleagues crafted the DNAgel using a chemical strategy that allowed them to form a polymer designed to remain stable in humid environments, like skin. To test how quickly the material dehydrates, they placed a small hydrogel sample in an open centrifuge tube and exposed it to a 37°C environment for 24 hours. The novel DNAgel maintained more than 80% of its weight at 70% relative humidity, while other common hydrogels have been previously show to retain only 30% weight under similar conditions.
However, the novel hydrogel still won't stay hydrated indefinitely. "A limitation is that the DNA hydrogel will dry out over time, which limits the length of time that the sensor can work," said Xiong. "We are exploring ways to extend its lifetime."
The researchers evaluated the DNAgel's ability to detect S. aureus infection in wound swabs collected from 18 patients with diabetic foot ulcers, three of whom were known to be positive for the bacteria. They found a 52% decrease in the fluorescence intensity of stained DNAgel that was exposed to the infected samples, but no more than a 27% decrease in the fluorescence intensity of DNAgel exposed to controls. Fluorescence intensity is a measure of how much DNAgel remains after bacterial contact, indicating that the gel degrades in the presence of S. aureus with minimal interference from harmless microbes.
Putting WINDOW to the Test
Xiong and colleagues integrated the DNAgel sensor with a circuit and communication module similar to technology used by most smartphones to develop the WINDOW sensor. To test WINDOW's ability to detect early-stage infections, they attached strips of gauze coated with either live S. aureus suspensions or a sterile broth to 6-milimeter wounds in mice, then attached the sensor to the wounds to monitor for infections. After 24 hours, the infected wounds looked identical to the uninfected controls, but WINDOW detected a 0.4-volt signal change in the infected wounds, indicating that pathogenic bacteria had broken down the DNAgel and that an infection was present. In response, the sensor sent an alert to a custom smartphone app.
While the current study only explored WINDOW's ability to detect stealthy S. aureus infections, Xiong noted that several other types of pathogenic bacteria that commonly cause wound infections secrete DNase, too.
"We expect that the DNA hydrogel can also detect these bacteria, although this will need to be verified in future work," he said.
"We think that the sensor can be expanded to detect additional parameters to further improve sensitivity and specificity," Xiong added. "We now are working with doctors to clinically validate the sensor in a larger group of patients, and discussing with companies to commercialize the technology."