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.
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 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.
[5] 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.
In order to correlate concentrations measured in the dialysate with those present at the distant sampling site, a calibration factor (recovery) is needed.
The extraction efficiency is defined as the ratio between the loss/gain of analyte during its passage through the probe (Cin−Cout) and the difference in concentration between perfusate and distant sampling site (Cin−Csample).
The strength of this method is that, at steady-state, no assumptions about the behaviour of the compound in the vicinity of the probe have to be made, since equilibrium exists at a specific time and place.
[15] However, under transient conditions (e.g. after drug challenge), the probe recovery may be altered resulting in biased estimates of the concentrations at the sampling site.
The design of the DNNF calibration method has proven very useful for studies that evaluate the response of endogenous compounds, such as neurotransmitters, to drug challenge.
[21] When employed in brain research, microdialysis is commonly used to measure neurotransmitters (e.g. dopamine, serotonin, norepinephrine, acetylcholine,[22] glutamate, GABA) and their metabolites, as well as small neuromodulators (e.g. cAMP, cGMP, NO), amino acids (e.g. glycine, cysteine, tyrosine), and energy substrates (e.g. glucose, lactate, pyruvate).
[23][24][25] Applications in other organs include the skin (assessment of bioavailability and bioequivalence of topically applied dermatological drug products),[26] and monitoring of glucose concentrations in patients with diabetes (intravascular or subcutaneous probe placement).
Microdialysis has also found increasing application in environmental research,[27] sampling a diversity of compounds from waste-water and soil solution, including saccharides,[28] metal ions,[29] micronutrients,[30] organic acids,[31] and low molecular weight nitrogen.
