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Abstract:We developed a minimally invasive glucose monitoring system that uses a microneedle to permeate the skin surface and a small hydrogel to accumulate interstitial fluid glucose. The measurement of glucose and sodium ion levels in the hydrogel is required for estimating glucose levels in blood; therefore, we developed a small, enzyme-fixed glucose sensor with a high-selectivity, all-solid-state, sodium ion-selective electrode (ISE) integrated into its design. The glucose sensor immobilized glucose oxidase showed a good correlation between the glucose levels in the hydrogels and the reference glucose levels (r > 0.99), and exhibited a good precision (coefficient of variation = 2.9%, 0.6 mg/dL). In the design of the sodium ISEs, we used the insertion material Na0.33MnO2 as the inner contact layer and DD16C5 exhibiting high Na + /K + selectivity as the ionophore. The developed sodium ISE exhibited high selectivity (logk Na,K pot = −2.8) and good potential stability. The sodium ISE could measure 0.4 mM (10 −3.4 M) sodium ion levels in the hydrogels containing 268 mM (10 −0.57 M) KCl. The small integrated sensor (ϕ < 10 mm) detected glucose and sodium ions in hydrogels simultaneously within 1 min, and it exhibited sufficient performance for use as a minimally invasive glucose monitoring system.