Microdialysis is a well-developed membrane-based tool relying on diffusion to sample diffusible constituents of complex media, such as biological tissue. The objective of this research is to expand the utility of microdialysis by combining transmembrane convection with diffusion to enhance solute exchange between microdialysis probes and the surrounding medium. We have developed a mathematical model to describe probe performance and performed validation experiments utilizing tracer solutes and commercially available probes with 100-kDa molecular weight cutoff membranes. Diffusive and fluid permeabilities of the probe membranes are evaluated for probes immersed in well-stirred bathing media in vitro. Transmembrane convection alters the solute extraction fraction, i.e., the fractional loss of a solute from the probe perfusate during delivery and the fractional gain by the perfusate during sampling. The extraction fraction change depends upon the magnitude and direction (inward or outward) of fluid movement across the membrane. However, for solutes with zero reflection coefficients, equality is maintained between these delivery and sampling extraction fractions. This equality is a prerequisite for probe calibration approaches that rely on analyte delivery from the perfusate. Thus, we have provided the theoretical and experimental basis for exploiting convection in a quantitative manner to enhance solute delivery and sampling in microdialysis applications.
Bibliographical noteFunding Information:
This research was supported [in part] by the Intramural Research Programs of the NIH, including the National Institute of Biomedical Imaging and Bioengineering. The authors are grateful to Dr. Robert L. Dedrick for his critical assistance in preparation of the manuscript and to Professor Rueben A. Gonzales for establishing that backpressure from effluent flow can produce transmembrane fluid loss in probes constructed from low-fluid-permeability cellulosic membranes. The latter observation was the initial stimulus for the present analysis.
- Mathematical modeling