Toward In Vivo Transdermal pH Sensing with a Validated Microneedle Membrane Electrode

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.

Potentiometric pH Nanosensor for Intracellular Measurements: Real-Time and Continuous Assessment of Local Gradients

“…For these cations, the pH nanosensor displayed an almost negligible response, and thus, very low apparent selectivity coefficients were calculated using the separate solution method for X = Na + , K + , Mg 2+ , and Ca 2+ , respectively. These results confirmed the excellent selectivity already reported for membrane-based ion-selective electrodes based on hydrogen ionophore I (Sigma) for pH detection …”

“…These results confirmed the excellent selectivity already reported for membrane-based ion-selective electrodes based on hydrogen ionophore I (Sigma) for pH detection. 46 …”

“…These results confirmed the excellent selectivity already reported for membrane-based ion-selective electrodes based on hydrogen ionophore I (Sigma) for pH detection. 46 Investigation of the Positioning of the Reference Electrode in Cell-Based Experiments. For the sensing architecture to provide accurate potentiometric intracellular measurements, both the indicator (pH nanosensor) and the RE should be in principle placed inside the same cell.…”

Green MIP-202(Zr) Catalyst: Degradation and Thermally Robust Biomimetic Sensing of Nerve Agents

“…Additionally, owing to the exceptional proton conductive properties of MIP-202(Zr) based on the protonated amine functionalities (NH 3 + Cl − ) of its aspartate linkers at nearneutral pH, 45 we also demonstrated a complementary DFP detection capability by developing a MIP-202/pH-ISE catalytic sensor based on a recently reported solid-contact pH-ISE transducer. 74 The corresponding dynamic sensing response for the solid-contact potentiometric pH-sensing transducer displays a nearly Nernstian response of 56.7 mV/dec over the 5.0−8.9 pH range (with an RSD = 2.12%, n = 3) (Supporting Information Figure S17). Accordingly, the potentiometric DFP sensing mechanism is based on detecting the decreased pH associated with increasing concentration of the HF byproduct upon catalytic hydrolysis of DFP.…”

Microneedle-Based Potentiometric Sensing System for Continuous Monitoring of Multiple Electrolytes in Skin Interstitial Fluids

“…The phantom gels are conditioned with a known concentration of Na + or K + overnight. We first collect the ISF in phantom gels using a custom-made hollow microneedle system 60 and then measure the Na + and K + concentrations in these conditioned gels by using commercial sodium and potassium testers (HORIBA Ltd., Japan). In the meantime, a pre-calibrated microneedle-based potentiometric sensor is manually inserted into the skin-mimicking phantom gel and the OCP is recorded in triplicate.…”