In Vivo Transdermal Multi-Ion Monitoring with a Potentiometric Microneedle-Based Sensor Patch

Abstract

Microneedle sensor technology offers exciting opportunities for decentralized clinical analyses. A novel issue puts forward herein is to demonstrate the uniqueness of membrane-based microneedles to accomplish real-time, on-body monitoring of multiple ions simultaneously. The use of multi-ion detection is clinically relevant since it is expected to provide a more complete and reliable assessment of the clinical status of a subject concerning electrolyte disorders and others. We present a microneedle system for transdermal multiplexed tracing of pH, Na + , K + , Ca 2+ , Li + , and Cl − . The device consists of an array of seven solid microneedles externally modified to provide six indicator electrodes, each selective for a different ion, and a common reference electrode, all integrated into a wearable patch read in a potentiometric mode. We show in vitro measurements at the expected clinical levels, resulting in a fast response time, excellent reversibility and repeatability, and adequate selectivity. Closeto-Nernstian sensitivity, sufficient stability and resiliency to skin penetration guarantee the sensor's success in transdermal measurements, which we demonstrate through ex vivo (with pieces of rat skin) and in vivo (on-body measurements in rats) tests. Accuracy is evaluated by comparison with gold standard techniques to characterize collected dermal fluid, blood, and serum. In the past, interstitial fluid (ISF) analysis has been challenging due to difficult sample collection and analysis. For ions, this has resulted in extrapolations from blood concentrations (invasive tests) rather than pure measurements in ISF. The developed microneedle patch is a relevant analytical tool to address this information gap.

Porous Microneedle-Based Potentiometric Sensor for Intradermal Electrolyte Monitoring

“…Microneedle-based electrochemical sensors are suitable for monitoring ISF biomarkers because they could penetrate through the stratum corneum without touching the blood vessels or nerves; they have been used for measuring alcohol, glucose, and ions in ISF. [13][14][15][16][17] Parrilla et al have developed a wearable biochemical patch that used solid microneedles for the detection of intradermal K + in ISF and showed a fast response time, selectivity, and reproducibility. 16 Recently, the porous microneedle (PMN), 18 which has a network of micro/nanochannels throughout the needle, have been reported to be useful for minimally invasive measurements of the TEP 19 and reactive oxygen species in the skin 20 as well as the transdermal drug delivery.…”

“…The unique feature of the present sensor system is the simple single-needle configuration, which could allow lower invasive transdermal analysis than the conventional MN-based sensing with multiple needle electrodes. 16,17 In addition, the electrolyte-filled porous structure acts as a salt bridge, which could eliminate external influences, including the TEP. ACCEPTED MANUSCRIPT 14 Fig.…”

Selective Deionization of Thin-Layer Samples Using Tandem Carbon Nanotubes–Polymeric Membranes

“…Moreover, the molar ratio of the two ionophores in the membrane could also be investigated for a more efficient uptake of the two respective ions, which will be necessary to explore when meeting applications of the CNT-ISM actuators in real samples. Overall, both one or two ionophore-based ISMs for selective deionization of thin-layer samples are foreseen to be implemented in multiple analytical devices, including the detection of Li + in biofluids (with Na + and K + as the main interferents) 33 and Mg 2+ in biofluids or environmental water (with H + and Ca 2+ as the main interferents), 34 among other cases.…”

Ultrasonic Plasticization Microinjection Precision Molding of Polypropylene Microneedle Arrays

“…The percutaneous drug administration technology means that the drug enters human body via the skin to keep the drug activity and drug property and improve patients’ medication compliance. − The outermost layer of the skin is coated with a layer of cuticle, with a thickness of 10–20 μm, and its specific chemical property and physical structure make it difficult for the biomacromolecular drugs to surmount the cuticle. , At the end of the last century, Henry and Allen proposed the percutaneous drug administration via microneedle . The microneedle, a kind of minimally invasive, painless, and effective percutaneous drug administration method, can pierce into the cuticle and form a channel to effectively address the low transdermal efficiency of macromolecular drug and has harvested good application value in the field of biological monitoring, − beauty, − body fluid/blood collection, − etc.…”