Abstract Background Point-of-care (POC) diagnostic platforms require electrochemical sensors that are not only accurate and stable but also affordable and scalable for widespread adoption. Reference electrode selection plays a crucial role in ensuring sensor reliability while balancing cost-effectiveness and manufacturability. This study explores the optimization of reference electrode designs with a focus on minimizing drift, improving stability, and enabling scalable, cost-efficient production. Additionally, the dynamic range and variability of sodium (Na?) and potassium (K?) sensors were evaluated against an FDA-cleared benchtop reference system. Methods A range of reference electrode materials and configurations were assessed based on key performance indicators, including stability, drift over time, potential shift, and manufacturability. Electrochemical testing was conducted to evaluate signal consistency under controlled conditions. Separately, Na? and K? sensor performance was characterized by measuring contrived whole blood samples across physiologically relevant concentrations. Sensor readings were compared to a reference analyzer to assess correlation and dynamic range. To evaluate manufacturing reproducibility, multiple batches of sensors were tested to assess batch-to-batch variability, ensuring consistency in sensor performance across different production lots. Variability was quantified by analyzing intra-batch and inter-batch precision across multiple test runs. Results Optimization of the reference electrode led to improved stability and reduced drift, with key materials demonstrating enhanced low-cost manufacturability. The Na? and K? sensors exhibited strong correlation with the reference system across the tested concentration range, with minimal variability observed between replicates. Most samples tested met the CLIA accuracy requirements for both Na+ and K+ sensors (+/- 4 and 5 mmol/L, respectively) demonstrating the sensors accuracy and precision as well as the reliability of the manufatcuring processes. Conclusion The findings support the feasibility of an optimized, low-cost reference electrode design suitable for scalable POC sensor manufacturing. Additionally, Na? and K? sensor performance demonstrated strong agreement with an established reference system, reinforcing the viability of an affordable, high-performance POC platform for rapid metabolic panel testing. These advancements highlight the potential of cost-effective electrochemical sensor technology to expand access to rapid diagnostics.
Eric Charrault (2025) studied this question.