Quantification of pyruvate in-vitro using mid-infrared spectroscopy: Developing a system for microdialysis monitoring in traumatic brain injury patients.

Introduction: Complex metabolic disruption is a major aspect of the pathophysiology of traumatic brain injury (TBI). Pyruvate is an intermediate in glucose metabolism and considered one of the most clinically informative metabolites during neurocritical care of TBI patients, especially in deducing the lactate/pyruvate ratio (LPR) - a widely-used metric for probing the brain's metabolic redox state. LPR is conventionally measured offline on a bedside analyzer, on hourly accumulations of brain microdialysate. However, there is increasing interest within the field to quantify microdialysate pyruvate and LPR continuously in near-real-time within its pathophysiological range. We have previously measured pure standard pyruvate in-vitro using mid-infrared transmission, employing a commercially available external cavity-quantum cascade laser (EC-QCL) and a microfluidic flow cell and reported a limit of detection (LOD) of 0.1 mM. Research question: The present study was to test whether the current commercially available state-of-the-art mid-infrared transmission system, can detect pyruvate levels lower than previously reported. Materials and methods: We measured pyruvate in perfusion fluid on the mid-infrared transmission system also equipped with an EC-QCL and microfluidic flow cells, tested at three pathlengths. Results: We characterised the system to extract its relevant figures-of-merit and report the LOD of 0.07 mM. Discussion and conclusion: The reported LOD of 0.07 mM represents a clinically recognised threshold and is the lowest value reported in the field for a sensor that can be coupled to microdialysis. While work is ongoing for a definitive evaluation of the system to measuring pyruvate, these preliminary results set a good benchmark and reference against which future developments can be examined.