Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO 2 Detection.

Monitoring of carbon dioxide (CO 2 ) 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 CO 2 measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO 2 , 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 CO 2 . Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO 2 -MN, comprising a combination of potentiometric pH- and carbonate (CO 3 2- )-selective electrodes together with the reference electrode. The CO 2 -MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO 3 2- concentrations directly into the interstitial fluid (ISF). The levels for the pH-CO 3 2- tandem are then used to estimate the P CO 2 in the ISF. Assessing the response of each individual MN, we found adequate response time ( t 95 < 5s), sensitivity (50.4 and -24.6 mV dec -1 for pH and CO 3 2- , respectively), and stability (1.6 mV h -1 for pH and 2.1 mV h -1 for CO 3 2- ). We validated the intradermal measurements of CO 2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO 2 -MN wearable device for on-body measurements. A good correlation between ISF and blood CO 2 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 CO 2 as well as other clinically relevant gases.