Parametric study of a microdialysis probe and study of depletion effect using ethanol as a test analyte

Although microdialysis is a common in vivo sampling technique, a detailed characterization of the performance of a microdialysis probe used for sampling ethanol molecules has not been conducted. In this work, experimental and computational investigations were carried out to quantitatively study ethanol diffusion characteristics for home-made and commercially available probes. Probe efficiency, i.e. recovery rate (defined as the ethanol concentration in the dialysate to that in the external medium surrounding the probe) was used to characterize the performance. The recovery rate was measured at different perfusion flow rates (0.1, 0.2, 0.5, 1, 1.5, 2 μL/min) and external ethanol concentrations (1, 2.5, 5, 10, 20 mM) with controlled environmental conditions. Effect of temperature was also investigated at 19, 37 and 47 °C. The results show that reducing the flow rate from 2 to 0.1 μL/min at least triples the recovery rate for the home-made probes, and it remains nearly unchanged when varying external ethanol concentration. The performance for two commercial microdialysis probes with different membrane materials and configurations were also determined and have similar recovery rates. Through computational modeling, the diffusion coefficient of ethanol in the semipermeable membrane of the home-made probe was determined by fitting the experimental data, and it was found to be 9 × 10¹¹ m²/s (R² > 0.99). In addition, the depletion effect over time at different flow rates along with estimated in vivo ethanol clearance were simulated numerically, showing that the depletion region shrinks significantly when the flow rate is below 1 μL/min. The results provide better understanding of the diffusion characteristics of the microdialysis probe when used for sampling ethanol which can be used for better interpretation of in vivo measurements and for microdialysis probe optimization.