Microdialysis Technique

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 perform metabolite ID/metabolite profiling, or determine the distribution of new chemical entities within the body. Microdialysis sampling is an excellent way to model the pharmacokinetics of a given therapeutic compound.

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The microdialysis 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. While microdialysis was originally developed as a method to sample the CNS, it has been used in oncology tumor models.


Figures 1 & 2: Measurement of Glutamine in the CSF or spinal cord of rodents via CSF sampling Norepinephrine

Bar graph showing levels of glutamine in the cerebrospinal fluid and spinal cord of either immobilized or freely moving animals.
Bar graph showing levels of norepinephrine in the cerebrospinal fluid and spinal cord of either immobilized or freely moving animals.

Measurement of neurotransmitters (glutamine and norepinephrine) in the CSF and spinal cord of anaesthetized or freely moving rodents is shown.


Figure 3: Measurement of Norepinephrine in Gut Tissues

Line graph showing levels of norepinephrine in the gut of a rodent model measured over time (20 minute intervals over 3 hours).

Measurement of norepinephrine in gut tissues sampled using microdialysis is shown.


Apart from conventional microdialysis that sample small molecular weight analytes and support metabolite profiling, Charles River offers a push-pull method to sample high molecular weight analytes (peptides, proteins including tau and alpha-synuclein and interleukins 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.


Figure 4: Measurement of Abeta in APP Transgenic Rodent Models

Line graphs showing the levels of beta-amyloid peptides measured using either conventional microdialysis (green line) or the more effective method, push pull microdialysis (blue line).

Conventional and push-pull microdialysis for Abeta peptides is compared. ELN 44989 is a nonselective gamma-secretase inhibitor.


The MetaQuant method is a proprietary microdialysis method that uses customizable probes to perform metabolite profiling and identification. 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.


Case Study: Customized Microdialysis

  • Situation

    Client-developed compound showed clear behavioral phenotype, but mechanism of action was unclear.

  • Approach

    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.

  • Result

    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.


Frequently Asked Questions (FAQs) About Microdialysis Services