Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO₂ Detection

Monitoring of carbon dioxide (CO₂) body levels is crucial under several clinical conditions (e.g., human intensive care and acid-base disorders). To date, painful and risky arterial blood punctures have been performed to obtain discrete CO₂ measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO₂, these are currently limited to benchtop devices, requiring trained personnel, being tedious, and providing punctual information, among other disadvantages. To the best of our knowledge, the literature and market lack a wearable device for real-time, on-body monitoring of CO₂. Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO₂-MN, comprising a combination of potentiometric pH- and carbonate (CO₃^2-)-selective electrodes together with the reference electrode. The CO₂-MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO₃^2- concentrations directly into the interstitial fluid (ISF). The levels for the pH-CO₃^2- tandem are then used to estimate the PCO₂ in the ISF. Assessing the response of each individual MN, we found adequate response time (t₉₅ < 5s), sensitivity (50.4 and -24.6 mV dec^-1 for pH and CO₃^2-, respectively), and stability (1.6 mV h^-1 for pH and 2.1 mV h^-1 for CO₃^2-). We validated the intradermal measurements of CO₂ at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO₂-MN wearable device for on-body measurements. A good correlation between ISF and blood CO₂ concentrations was observed, demonstrating the high potential of the developed MN sensing technology as an alternative to blood-based analysis in the near future. Moreover, these results open new horizons in the noninvasive, real-time monitoring of CO₂ as well as other clinically relevant gases.