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

Abstract

Monitoring of carbon dioxide (CO2) body levels is crucial underseveral clinical conditions (e.g., human intensive care and acid−base disorders).To date, painful and risky arterial blood punctures have been performed to obtaindiscrete CO2 measurements needed in clinical setups. Although noninvasivealternatives have been proposed to assess CO2, these are currently limited tobenchtop devices, requiring trained personnel, being tedious, and providingpunctual information, among other disadvantages. To the best of our knowledge,the literature and market lack a wearable device for real-time, on-body monitoringof CO2. Accordingly, we have developed a microneedle (MN)-based sensor array,labeled as CO2−MN, comprising a combination of potentiometric pH- andcarbonate (CO32−)-selective electrodes together with the reference electrode. TheCO2−MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO32−concentrations directly into the interstitial fluid (ISF). The levels for the pH−CO32− tandem are then used to estimate the PCO2 inthe ISF. Assessing the response of each individual MN, we found adequate response time (t95 < 5s), sensitivity (50.4 and −24.6 mVdec−1 for pH and CO32−, respectively), and stability (1.6 mV h−1 for pH and 2.1 mV h−1 for CO32−). We validated the intradermalmeasurements of CO2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing thesuitability of the CO2−MN wearable device for on-body measurements. A good correlation between ISF and blood CO2concentrations 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 wellas other clinically relevant gases.