In vivo real-time monitoring of tissue perfusion via L-lactate levels in interstitial fluid: an innovative and portable microfluidic device trial using a pig model

BACKGROUND: The postoperative assessment of the tissue is a major challenge in reconstructive flap surgery. Lactate serves as a key indicator of metabolic dysfunction, providing essential insights into tissue oxygenation and perfusion, cellular stress, and identifying potential pathological conditions. Consequently, continuous monitoring of lactate levels is vital for postoperative tissue analysis in patients undergoing microvascular tissue transfer to prevent serious complications. However, methodologies for the time-resolved sensing of metabolic biomarkers across various body fluids still pose a major challenge and are currently out of reach. MATERIALS AND METHODS: To address the need for time-resolved detection, we developed an innovative portable device relying on droplet-based microfluidics technology for monitoring lactate levels in interstitial fluids (ISFs) in an enzyme-based fluorometric manner. This device was evaluated on individual animal samples and during in vivo trials, with results benchmarked against a standard clinical blood gas analyzer. RESULTS: System demonstrates high accuracy and sensitivity (limit of detection of ca . 2 µM versus 100 µM for the clinical method), coupled with a short response time ( ca. 0.5 minutes) and reagent-saving process (reducing 90% reagent usage in traditional methods). Using a microdialysis probe, we enabled continuous and minimally invasive collection of ISF dialysate. The lactate measurements in ISF closely correlate with those obtained from the blood gas analyzer and exhibited long-term stability, delivering high temporal resolution (0.5 seconds intervals) over an 8-hour animal trial. Comparative analysis revealed that lactate levels in ISF were consistently higher and exhibited a slight lag compared to blood lactate levels. CONCLUSION: This approach demonstrated highly selective, sensitive, and robust detection of lactate in a clinical environment, with a microfluidics-powered instrument. We expect that this strategy can be used in the future as a tool for time-resolved biomarkers monitoring for bedside postoperative care.

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