Microdialysis

Microdialysis is a minimally-invasive sampling technique that is used for continuous measurement of free, unbound analyte concentrations in the extracellular fluid of virtually any tissue. Analytes may include endogenous molecules (e.g. neurotransmitter, hormones, glucose, etc.) to assess their biochemical functions in the body, or exogenous compounds (e.g. pharmaceuticals) to determine their distribution within the body. The microdialysis technique requires the insertion of a small microdialysis catheter (also referred to as microdialysis probe) into the tissue of interest. The microdialysis probe is designed to mimic a blood capillary and consists of a shaft with a semipermeable hollow fiber membrane at its tip, which is connected to inlet and outlet tubing. The probe is continuously perfused with an aqueous solution (perfusate) that closely resembles the (ionic) composition of the surrounding tissue fluid at a low flow rate of approximately 0.1-5μL/min. Once inserted into the tissue or (body)fluid of interest, small solutes can cross the semipermeable membrane by passive diffusion. The direction of the analyte flow is determined by the respective concentration gradient and allows the usage of microdialysis probes as sampling as well as delivery tools. The solution leaving the probe (dialysate) is collected at certain time intervals for analysis.

The microdialysis principle was first employed in the early 1960s, when push-pull canulas and dialysis sacs were implanted into animal tissues, especially into rodent brains, to directly study the tissues' biochemistry. While these techniques had a number of experimental drawbacks, such as the number of samples per animal or no/limited time resolution, the invention of continuously perfused dialytrodes in 1972 helped to overcome some of these limitations. Further improvement of the dialytrode concept resulted in the invention of the "hollow fiber", a tubular semipermeable membrane with a diameter of ~200-300μm, in 1974. Today's most prevalent shape, the needle probe, consists of a shaft with a hollow fiber at its tip and can be inserted by means of a guide cannula into the brain and other tissues.

There are a variety of probes with different membrane and shaft length combinations available. The molecular weight cutoff of commercially available microdialysis probes covers a wide range of approximately 6-100kD, but also 1MD is available. While water-soluble compounds generally diffuse freely across the microdialysis membrane, the situation is not as clear for highly lipophilic analytes, where both successful (e.g. corticosteroids) and unsuccessful microdialysis experiments (e.g. estradiol, fusidic acid) have been reported. However, the recovery of water-soluble compounds usually decreases rapidly if the molecular weight of the analyte exceeds 25% of the membrane’s molecular weight cutoff.

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