Self-calibrated ionophore-based ion-selective electrodes for at-home measurements of blood electrolytes

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SUMMARY Measurements of electrolytes in body fluids are essential for diagnosing and managing many chronic heart, kidney, parathyroid, and nerve disorders. Ion-selective electrodes have been routinely used for electrolyte measurements in clinical chemistry analyzers and blood analyzers in hospitals since the 1980s. However, patients with conditions such as hypoparathyroidism, heart failure, bipolar disorder, and end-stage renal disease often need to monitor their electrolytes much more frequently than allowed by hospital visits. It is an even bigger problem for disabled, elderly, and low-income patients as well as patients living in rural and underserved areas. The past decade has witnessed a surge of interest in accessible and affordable electrolyte monitoring based on home-use sensors, wearable sensors, transdermal sensors, and implantable sensors. However, ion-selective electrodes are only accurate when calibrated with a standard solution at the point of use. All centralized, benchtop, and handheld instruments with ion-selective electrodes use pumps or actuators to handle calibration solutions and samples via complicated fluidic systems. Because this technically demanding calibration procedure cannot be implemented in the low-cost and compact sensors on the body or at home, these emerging sensors cannot generate reliable data for medical decisions. Therefore, calibration has been a fundamental bottleneck for translating new electrolyte monitoring modalities into healthcare practice. This project aims to develop a completely new calibration strategy for ion-selective electrodes without using any moving parts or fluidics. A narrow calibration phase is built in between the working and reference electrodes to provide a baseline potential that serves as a one-point calibration. Surprisingly, the calibration bridge does not need to be removed for the sample testing because the sample dominates the interfacial charge transfer and the potentiometric signal. This highly unique built-in calibration method does not increase the complexity, footprint, cost, and sample volume of the electrolyte sensors and, therefore, enables their use for low-volume samples in decentralized settings. This R21 grant will focus on home-use Ca2+ and K+ selective sensors because of the urgent and overlooked need for at-home monitoring of these electrolytes from capillary blood. In Aim 1, we will use 3D printing and microfabrication techniques to prepare all-solid-state self-calibrating sensors that are portable, transportable, stable, and mass-producible. In Aim 2, we will determine the analytical performance characteristics of these sensors and validate their accuracy and precision in human blood samples against a commercial blood analyzer. This exploratory grant will allow us to confirm the feasibility of the self-calibration concept in home-use sensors using Ca2+ and K+ as the example analytes. In future work, we will adopt this concept in sensors toward more and multiple electrolytes in various decentralized settings. The ultimate goal is to empower patients to monitor electrolyte concentrations in a frequent and minimally invasive manner for their self-management of chronic diseases.