Microdialysis is used to introduce or withdraw a constant amount of a biologically active substance into or from the extracellular cerebro-spinal fluid in living animals. The microdialysis probe is designed to mimic a "capillary" system in which the substrate has to cross a semi-permeable membrane. The direction of flow depends primarily on concentration gradients. The gradient built up by the substance in question is not exclusively dependent on the differences in concentration between sample and extracellular fluid, but depends also on the velocity of flow inside the microdialysis chamber. For instance, when a physiological salt solution is dialyzed from inside the chamber, the solution equilibrates with the extracellular fluid, i.e. solutes diffuse from the cerebro-spinal fluid across the membrane into the probe. After a period of time, the chamber contains the substance (and other solutes) in an amount representative of that dissolved in the extracellular cerebral fluid. On the basis of in vitro calibration data, the chamber is estimated to recover 10-20% of the actual extracellular moities. Thus, micro-dialysis can also be used to collect molecules from the cerebral fluids. The rate of diffusion is a function of the area of the membrane, the flow rate and the diffusion coefficient of the substances. Since the microdialysate is applied continuously, the amount of substrate which is exchanged also depends on the duration of microdialysis. By using microdialysis as a diffusion trap, femtomolar concentrations of molecules in the extracellular fluid can be captured.
Microdialysis is applicable to living animals. The major disadvantages are that only small amounts of substance(s) can be collected and that the surgical insertion of the chamber causes lesioning or irritation of brain tissue; and this may change the physiological composition of the extracellular fluid.
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