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

Abstract

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 PCO 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 bloodbased 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.

Unlocking the Potential of Wearable Sensors in Healthcare and Beyond

“…This microneedle array features conductive recessed microcavities, with electropolymerized polyaniline boronic acid that served as an enzyme immobilization and detection layer for ammonia produced in a reaction with the urease enzyme; a Nafion membrane coating is used to protect it from the potential leaching of the urease enzyme. Sensor design of microneedles can also extend to potentiometric sensors, as demonstrated by the team of Crespo and Cuartero, who developed all solid-state ion selective microneedles to detect pH and carbonate, as indicators of dissolved CO 2 . One unique feature of microneedle-based patches is that they are well poised for closed-loop systems of monitoring and managing drug delivery.…”