Abstract
We present herein the most complete characterization of microneedle (MN) potentiometric sensors for pH transdermal measurements for the time being. Initial in vitro 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 ex vivo 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). Ex vivo 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 t-test at 95% of confidence level. Conveniently, the validation approaches could be translated to other analytes that are transdermally measured with MN sensors.
Highlights
We present the most complete characterization of microneedle (MN) potentiometric sensors for pH transdermal measurements for the time being
While the interest of measuring glucose to manage diabetes is undeniable, it has been proved that acid/base disorders are closely related to many diseases such as renal failure, ischemia, multiple sclerosis, and psychiatric disorders
While a great number of pH MN sensors can be found in the literature, with electrochemical readout and others,[2,17,18] to the best of our knowledge, only few works reported on real applications involving the in vivo determination of pH and transdermal measurements in interstitial fluid (ISF) totally lack
Summary
The fabrication process for the pH WE was adapted from a recipe previously reported by our group.[26]. Ex vivo evaluation of the MN patch for transdermal pH detection in the ISF of different types of animal skins was accomplished to investigate two key aspects: (i) the response of the developed MN sensors is not altered and/or the external modification detached from the MN with the skin insertion; and (ii) appropriate accuracy of the measurements by means of a carefully designed validation protocol. The second part of the ex vivo assays focused on the validation of transdermal pH measurements with the developed MN patch once inserted in animal skin and demonstrating the suitability of an external calibration of the sensor for the pH quantification in further on-body studies We designed these tests on the basis of skin pieces that were conditioned 24 h at different pH. It should be noted that this method requires surgery, and future efforts should be devoted to the development of noninvasive and reliable validation protocols toward an adequate validation of pure in vivo measurements in animals and humans
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