在几种临床条件下,监测二氧化碳(CO2)身体水平是至关重要的(例如,人类重症监护和酸碱紊乱)。迄今为止,已经进行了痛苦和危险的动脉血液穿刺,以获得临床设置中所需的离散CO2测量值。尽管已经提出了非侵入性替代方法来评估CO2,但这些方法目前仅限于台式设备,需要训练有素的人员,乏味,提供准时的信息,在其他缺点中。据我们所知,文献和市场缺乏实时的可穿戴设备,二氧化碳的身体监测。因此,我们开发了一种基于微针(MN)的传感器阵列,标记为CO2-MN,包括电位pH-和碳酸盐(CO32-)-选择性电极的组合以及参比电极。CO2-MN建立在表皮贴片上,使其能够到达皮肤的角质层,测量pH和CO32-浓度直接进入间质液(ISF)。然后使用pH-CO32-串联的水平来估计ISF中的PCO2。评估每个MN的反应,我们发现了足够的响应时间(t95<5s),灵敏度(对于pH和CO32-,50.4和-24.6mVdec-1,分别),和稳定性(pH为1.6mVh-1,CO32-为2.1mVh-1)。我们在离体水平验证了二氧化碳的皮内测量,用老鼠的皮肤碎片,然后,在麻醉的大鼠体内检测,显示CO2-MN可穿戴设备用于身体测量的适用性。观察到ISF和血液CO2浓度之间的良好相关性,证明了在不久的将来,已开发的MN传感技术作为基于血液的分析的替代方案的巨大潜力。此外,这些结果为非侵入性,实时监测CO2以及其他临床相关气体。
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 (CO32-)-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 CO32- concentrations directly into the interstitial fluid (ISF). The levels for the pH-CO32- 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 CO32-, respectively), and stability (1.6 mV h-1 for pH and 2.1 mV h-1 for CO32-). 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.