Microdialysis is a sampling technique that is used to measure the concentration of the unbound fraction of endogenous substances – such as neurotransmitters, hormones, metabolites or glucose – or exogenous substances in the extracellular space of different tissues. At CTC, we have successfully performed microdialysis of the synovial fluid of the knee, and evaluated whether it could be applied for investigating local effects on biomarker levels (for example lactate, glucose and pyruvate) in the interstitial fluid of the knee joint.
The microdialysis method can also be used for application of drugs in the perfusate (the solution entering the microdialysis probe). Simultaneous evaluation of biomarkers in the dialysate (the solution leaving the probe) then provides the possibility to study local physiological and pharmacodynamic effects of the drug. Microdialysis combined with microdosing of potential medicinal products can be utilised for early proof-of-principle-studies and hence accelerate the development of new medicinal products, especially within rheumatology and autoimmune diseases.
The basic principle of microdialysis is to mimic the function of a capillary blood vessel by perfusing a thin dialysis probe with physiological fluid, after it has been inserted in the knee joint using a guide cannula. A semi-permeable membrane covering the probe allows water-soluble substances that are smaller than the molecular weight cut-off to pass through the pores of the membrane. Molecules in the interstitial space diffuse along a concentration gradient through the microdialysis membrane into the perfusate. Substances which have been added to the perfusate will diffuse in the opposite direction to reach the interstitial space, where effects may be exerted on the cells lining it. Collection of the dialysate in micro vials designed for low evaporation and minute volumes at certain time intervals enables monitoring of concentrations of compounds in the interstitial space.
Microdialysis of the synovial fluid of the knee is minimally invasive, and no general anaesthesia is needed. Depending on the study, the subjects can be discharged from the clinic as early as a few hours after the assessment.