The approach bypasses traditional reliance on electrical or optical proxies, revealing a chemically grounded method for plasma monitoring that could inform a wide range of gas analysis and process-control applications.
Cold atmospheric plasma is increasingly used in medicine, particularly for wound healing, decontamination, and oncology. Its therapeutic effects arise largely from reactive oxygen and nitrogen species (RONS), including hydrogen peroxide (H2O2), which play key roles in inflammation control, antimicrobial action, and tissue repair.
But dose control has remained a major challenge. Too little plasma can be ineffective, while too much can trigger oxidative damage and delay healing.
Traditional plasma diagnostics, such as electrical signals or optical emission spectroscopy, are effective in industrial settings but provide limited insight into biological outcomes and are impractical for clinical use.
The authors argue that the most clinically relevant way to control plasma dose is to monitor the chemical species that actually interact with tissue, in real time, at the treatment site.
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Sensors Inside the Treatment Zone
To do this, the team used commercially available, non-enzymatic wire sensors small enough to operate directly in liquids, cell cultures, and living tissue.
The sensors measure two complementary indicators: hydrogen peroxide concentration and oxidation-reduction potential (ORP), a voltage-based readout that reflects the overall redox state created by multiple oxidants and antioxidants.
Both sensors rely on a platinum-iridium working electrode designed to withstand exposure to highly reactive plasma species. The hydrogen peroxide sensor features a Nafion membrane to enhance selectivity, while the ORP sensor remains uncoated to capture the net oxidative environment.
Sensor signals were read using either commercial potentiostats or a custom microcontroller, allowing the system to be integrated into a compact, portable setup.
Linking Chemistry to Biology
Using a combination of in vitro scratch assays and in vivo mouse wound models, the researchers correlated real-time sensor measurements with biological outcomes measured hours to weeks later.
These included wound closure rates, cell proliferation, oxidative stress responses, and scar formation.
The results revealed a clear dose-response pattern. Intermediate plasma exposures promoted faster healing and reduced scarring, while higher doses increased oxidative stress and caused temporary delays in recovery.
Rather than identifying a single causal molecule, the study emphasizes correlations between measured RONS levels and downstream biological effects - a practical approach given the complexity of plasma-tissue interactions.
ORP measurements proved particularly useful in capturing the cumulative redox environment, complementing hydrogen peroxide readings and highlighting how different tissues exhibit distinct baseline oxidative states.
Control in Living Tissue
The most significant advance came from integrating the sensors into a closed-loop control system. During treatment, hydrogen peroxide was monitored continuously using pulsed chronoamperometry, a technique that reduces signal artifacts caused by plasma ignition.
Instead of applying plasma for a fixed duration, the system automatically shut off treatment once hydrogen peroxide levels increased by 25 micromolar above baseline. This conservative threshold was deliberate, based on lower-quartile responses across animals, to minimize the risk of overexposure.
In live mouse wounds, the controller consistently terminated treatment at different times depending on baseline conditions, wound environment, and biological variability, demonstrating dose-based control rather than time-based delivery.
A Future of Adaptive Plasma Medicine
While the system is not yet designed for patient-specific personalization, the study establishes a practical framework for adaptive plasma therapies that respond to real biological conditions in real time. By accounting for baseline variability across tissues and environments, sensor-driven feedback offers a more reliable alternative to fixed treatment protocols.
The authors note that further work will be needed to address sensor durability, sterilization, and regulatory requirements before clinical deployment.
Still, the findings suggest that integrating electrochemical sensing into plasma devices could significantly improve safety, reproducibility, and therapeutic effectiveness.
Although the experiments focused on wound healing, the approach could extend to other plasma-based treatments, including cancer therapy and infection control. More broadly, the study illustrates how embedding real-time chemical sensing into medical devices can bridge the gap between physical dose delivery and biological response.
Journal Reference
Thomas J.E., et al. (2025). Electrochemical sensors for in situ monitoring of reactive species during cold atmospheric plasma-based therapies. Communications Engineering. DOI: 10.1038/s44172-025-00560-w