Fenestrated Microneedle Biosensor for Continuous In Vivo Lactate Monitoring in Interstitial Fluid.

Lactate is a key biomarker of tissue metabolism and oxygenation, yet clinical assessment still relies on intermittent blood tests that overlook rapid metabolic dynamics and disrupt clinical workflows. Continuous transdermal monitoring of lactate in interstitial fluid (ISF) offers a minimally invasive approach for real-time monitoring of metabolic status, particularly in conditions associated with metabolic syndrome such as obesity and diabetes. Here we report a proof-of-concept transdermal lactate biosensor based on a fenestrated microneedle array (F-MNA), consisting of a polymeric MNA enclosed within a fenestrated polymeric shell that protects the biosensing layer while retaining access to ISF. Under controlled anesthetized conditions, the biosensor differentiated ISF lactate profiles between healthy and diabetic-obese (db/db) mice, with the db/db group exhibiting higher baseline lactate concentrations. In fasted healthy mice subjected to subcutaneous glucose challenge, the biosensor captured transient increases in ISF lactate followed by partial recovery over the 2 h monitoring period. Biosensor-derived ISF lactate showed strong temporal association with paired blood lactate measurements while exhibiting a systematic positive ISF-to-blood concentration offset. These findings establish proof-of-concept continuous transdermal ISF lactate monitoring under controlled in vivo conditions.