Generalizing the Theory of Microdialysis

The efficiency of sampling or delivering solutes (analytes) by in vivo microdialysis is influenced by the diffusive permeabilities of the probe and the tissue in which the probe is implanted. In tissue, processes removing the analyte from the extracellular space are as important as diffusion in determining permeability. In addition to diffusion, analyte permeation through these media may be augmented or diminished by bulk fluid movement (transmembrane and interstitial convection). Within the perfusate, the dominant process is axial convection. Both diffusive and convective determinants of probe efficiency may be influenced by probe geometry (Figure 1; longitudinal cross-sectional view). The main geometric parameters are the probe membrane length and radii, but inner cannula geometry can also be an appreciable factor. The objective of this study is to generalize the mathematical description of microdialysis. The treatment extends in several ways previous mathematical models (Bungay et al. [1]; Morrison et al. [2]; Morrison et al. [3]; Wallgren et al. [4]). In addition to removing some simplifications and approximations and adding convective transport, the revised theory is applicable to low-molecular-weight lipophilic, as well as hydrophilic solutes. This is achieved by incorporating transcellular solute movement as a pathway paralleling interstitial diffusion. This change accompanies employing the combined intracellular and extracellular volumes, rather than the interstitial volume, as the basis for solute mass balances.