García-Guzmán Juan José, Pérez-Ràfols Clara, Cuartero María, Crespo Gastón A
Department of Chemistry, School of Engineering Science in Chemistry, Biochemistry and Health, Royal Institute of Technology, KTH, Teknikringen 30, SE-100 44 Stockholm, Sweden.
ACS Sens. 2021 Mar 26;6(3):1129-1137. doi: 10.1021/acssensors.0c02397. Epub 2021 Feb 10.
We present herein the most complete characterization of microneedle (MN) potentiometric sensors for pH transdermal measurements for the time being. Initial assessment demonstrated suitable analytical performances (e.g., Nernstian slope, linear range of response from 8.5 to 5.0, and fast response time) in both buffer media and artificial interstitial fluid (ISF). Excellent repeatability and reproducibility together with adequate selectivity and resiliency facilitate the appropriateness of the new pH MN sensor for transdermal ISF analysis in healthcare. The ability to resist skin insertions was evaluated in several setups using three different animal skins (i.e., chicken, pork, and rat). The developed pH MN sensor was able to withstand from 5 to 10 repetitive insertions in all the skins considered with a minimal change in the calibration graph (<3% variation in both slope and intercept after the insertions). pH measurements were validated by determining the pH with the MN sensor and a commercial pH electrode in chicken skin portions previously conditioned at several pH values, obtaining excellent results with an accuracy of <1% and a precision of <2% in all cases. Finally, pH MN sensors were applied for the very first time to transdermal measurements in rats together with two innovative validation procedures: (i) measuring subcutaneous pH directly with a commercial pH microelectrode and (ii) collecting ISF using hollow MNs and then the pH measurement of the sample with the pH microelectrode. The pH values obtained with pH MN sensors were statistically more similar to subcutaneous measurements, as inferred by a paired sample -test at 95% of confidence level. Conveniently, the validation approaches could be translated to other analytes that are transdermally measured with MN sensors.
我们在此展示了目前用于经皮pH测量的微针（MN）电位传感器的最完整特性。初步评估表明，在缓冲介质和人工组织间液（ISF）中，该传感器均具有合适的分析性能（例如，能斯特斜率、8.5至5.0的线性响应范围以及快速响应时间）。出色的重复性和再现性，以及足够的选择性和弹性，使得新型pH MN传感器适用于医疗保健中的经皮ISF分析。我们使用三种不同的动物皮肤（即鸡皮、猪皮和大鼠皮）在多种设置下评估了该传感器抵抗皮肤穿刺的能力。所开发的pH MN传感器能够在所有测试的皮肤中经受5至10次重复穿刺，校准曲线变化极小（穿刺后斜率和截距的变化均小于3%）。通过使用MN传感器和商业pH电极测定预先调节至几个pH值的鸡皮部分的pH，对pH测量进行了验证，在所有情况下均获得了优异的结果，准确度<1%，精密度<2%。最后，pH MN传感器首次与两种创新的验证程序一起应用于大鼠的经皮测量：（i）使用商业pH微电极直接测量皮下pH；（ii）使用空心MN收集ISF，然后用pH微电极测量样品的pH。通过95%置信水平的配对样本检验推断，pH MN传感器获得的pH值在统计学上与皮下测量值更相似。方便的是，这些验证方法可以推广到其他用MN传感器进行经皮测量的分析物。
