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

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Sensor Technology

Background:

• Transdermal monitoring of physiological parameters like pH is crucial for healthcare.
• Existing methods for interstitial fluid (ISF) pH measurement can be invasive or lack real-time capabilities.
• Microneedle (MN) technology offers a minimally invasive approach for transdermal analyte detection.

Purpose of the Study:

• To fully characterize microneedle (MN) potentiometric sensors for transdermal pH measurements.
• To evaluate the analytical performance and skin insertion resilience of the developed pH MN sensor.
• To validate the sensor's accuracy and precision for *in vivo* transdermal pH monitoring in rats.

Main Methods:

• Characterization of pH MN sensor performance *in vitro* using buffer solutions and artificial ISF.
• Evaluation of sensor durability through multiple skin insertions (*ex vivo*) on chicken, pork, and rat skin.
• *Ex vivo* validation against a commercial pH electrode and *in vivo* validation in rats using direct subcutaneous measurements and ISF collection.

Main Results:

• The pH MN sensor exhibited Nernstian response, a linear range from 8.5 to 5.0, and fast response times *in vitro*.
• Sensors demonstrated excellent repeatability, reproducibility, selectivity, and resiliency, withstanding 5-10 skin insertions with minimal calibration drift (<3%).
• *Ex vivo* measurements showed <1% accuracy and <2% precision compared to commercial electrodes; *in vivo* measurements correlated well with subcutaneous pH.

Conclusions:

• The developed pH MN sensor is suitable for transdermal ISF analysis in healthcare due to its analytical performance and robustness.
• The sensor's ability to withstand repeated skin insertions and its validated accuracy make it a promising tool for continuous pH monitoring.
• The study presents novel validation strategies for transdermal MN sensors, applicable to other analytes.