Microdialysis is a minimally-invasive sampling technique that is used for continuous measurement of free, unbound analyte concentrations in extracellular fluid and was initially developed for CNS research. It can be performed in any tissue type to assess the physiological or pharmacological functions of biochemicals (e.g., neurotransmitters, hormones, glucose) or determine the distribution of new chemical entities within the body.
The technique involves the implantation of a semi-permeable membrane in the target issue. The hollow fiber membrane is connected to inlet and outlet tubing, and the probe is continuously perfused with a solution that resembles the sampled tissue of interest (e.g., artificial CSF). Molecules that are small enough to diffuse across the pores of the membrane will diffuse from the in vivo sampling site to the inside of the membrane across a diffusion gradient and will be collected at time points for analysis.
Apart from conventional microdialysis that sample small molecular weight analytes, Charles River offers a push-pull method to sample high molecular weight analytes (peptides, proteins, tau, and interleukins). The push-pull probes have a higher membrane cut-off and due to the bigger pores, a “pull” flow in the outlet is needed to ensure that the perfusion liquid is not lost along with the “push” flow in the inlet tube.
The MetaQuant method is a proprietary microdialysis method that uses customizable probes developed by Brainlink. This method is used in various tissues including the GI tract, heart, liver, bone, kidney, lung, eye, and skin tissue and is a modified regular microdialysis probe combining measurement of absolute levels in the tissue of interest with sampled volume collection equal to the regular microdialysis technique. Ultraslow flows are applied in this technique.
Client-developed compound showed clear behavioral phenotype, but mechanism of action was unclear.
A study was designed to combine conventional microdialysis with MetaQuant, plasma, and CSF sampling to monitor a range of neurotransmitters, potential biomarkers, and free-drug concentrations in different compartments simultaneously.
One particular biomarker was elevated in a dose-related manner and increased in-brain CSF and plasma as peak drug concentrations were achieved. Based on this study, the compound was taken forward into development. Later, the marker was subsequently used as a clinical biomarker in later-stage trials.