Clinical Evaluation of Microneedle Biosensors for Continuous Lactate Monitoring in Critically Ill Patients

Continuous lactate monitoring is critical for early detection and management of sepsis, shock, and metabolic stress, yet current serum assays remain invasive, intermittent, and resource-intensive. We present a clinical evaluation of a minimally invasive microneedle-based electrochemical biosensor for real-time interstitial fluid (ISF) lactate monitoring. The microneedle biosensor features a platinum working electrode modified with a lactate oxidase reagent layer and a polyvinyl chloride anti-fouling membrane for H₂O₂-mediated amperometry, toward highly selective and stable ISF lactate detection. In a pilot study of twenty-one participants across an intensive care unit, emergency department, cardiopulmonary exercise testing, and controlled laboratory settings, two enzyme-based microneedle sensors placed on the forearm and thigh continuously tracked lactate for 4 h. Sensor performance demonstrated strong agreement with blood lactate assays (r = 0.94), high diagnostic accuracy for hyperlactatemia (>4 mmol/L; receiver operating characteristic analysis, area under the curve = 0.95), and minimal bias (-0.028 mmol/L) over a wide dynamic range (0.7-22.9 mmol/L) with high selectivity against interferents. No significant ISF-blood differences (p > 0.05) or adverse events were observed. These findings establish microneedle biosensors as a promising platform for precision medicine, with considerable potential to transform sepsis care, guide resuscitation, and improve assessment of exertional dyspnea.