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

Abstract

Electrolytes play a pivotal role in regulating cardiovascular functions, hydration, and muscle activation. The current standards for monitoring electrolytes involve periodic sampling of blood and measurements using laboratory techniques, which are often uncomfortable/inconvenient to the subjects and add considerable expense to the management of their underlying disease conditions. The wide range of electrolytes in skin interstitial fluids (ISFs) and their correlations with those in plasma create exciting opportunities for applications such as electrolyte and circadian metabolism monitoring. However, it has been challenging to monitor these electrolytes in the skin ISFs. In this study, we report a minimally invasive microneedle-based potentiometric sensing system for multiplexed and continuous monitoring of Na+ and K+ in the skin ISFs. The potentiometric sensing system consists of a miniaturized stainless-steel hollow microneedle to prevent sensor delamination and a set of modified microneedle electrodes for multiplex monitoring. We demonstrate the measurement of Na+ and K+ in artificial ISFs with a fast response time, excellent reversibility and repeatability, adequate selectivity, and negligible potential interferences upon the addition of a physiologically relevant concentration of metabolites, dietary biomarkers, and nutrients. In addition, the sensor maintains the sensitivity after multiple insertions into the chicken skin model. Furthermore, the measurements in artificial ISFs using calibrated sensors confirm the accurate measurements of physiological electrolytes in artificial ISFs. Finally, the skin-mimicking phantom gel and chicken skin model experiments demonstrate the sensor’s potential for minimally invasive monitoring of electrolytes in skin ISFs. The developed sensor platform can be adapted for a wide range of other applications, including real-time monitoring of nutrients, metabolites, and proteins.

Microneedle‐Based Technology: Toward Minimally Invasive Disease Diagnostics

“…The concentration of these target biomarkers in ISF is consistent with those in the blood. [78] Li et al [79] designed an MNs sensing system that could monitor the electrolytes in the ISF. The biosensing system could selectively analyze Na + and K + in ISF and had the advantages of short detection time, high accuracy and repeatability.…”

“…a) The picture on the left was a schematic diagram of the MN sensor inserted into the skin, and the picture on the right was a potential sensing system composed of Na + selective electrode, K + selective electrode and Ag/AgCl reference electrode; b) optical image and SEM image of microneedle-based potential sensing system; c) modified Na + selective electrode, K + selective electrode and reference electrode; d) the optics image of MNs potential sensing system acting on chicken skin. Reproduced with permission [79]. Copyright 2021, American Chemical Society.…”

Point-of-care and self-testing for potassium: recent advances

“…Li et al (2021) demonstrated a stainless-steel hollow microneedle-based potentiometric sensing system for continuous monitoring of multiple electrolytes in skin interstitial fluids. 55 These authors demonstrated monitoring of potassium and sodium ions by testing on phantom gel and chicken skin. Fig.…”

Advances and challenges in developing smart, multifunctional microneedles for biomedical applications

“…(iii) Schematic illustration of steps for the functionalization of electrodes. Reproduced with permission from Li et al (2021). Copyright 2021 American Chemical Society.…”