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Cerebral Microdialysis or Cerebral Open Flow Microperfusion? Which is the right technique for your sampling experiment?
Posted on 10/11/2021 by Starlette Douglass
Choosing the appropriate technique for in vivo cerebral fluid sampling is essential for maximizing analyte recovery. Traditionally, microdialysis has been used exclusively for this purpose, but the development of an alternative approach called open flow microperfusion has expanded the number of options for real-time measurement of analytes. Understanding the key similarities and differences between cerebral microdialysis (cMD) and open flow microperfusion (cOFM) will minimize interfering variables and increase awareness of tissue conditions and sample quality, thus increasing successful outcomes of your studies.
Equipment Required
- Stereotaxic Equipment
- Surgical Instruments
- Infusion Pump
- Probe
- Collection Method
- Tubing
- Other Accessories*
Fundamentally, both cMD and cOFM techniques enable measurement of analytes in specific brain regions. Both techniques are invasive in that they require implantation of a sampling probe into the brain region of interest. While the specifics may be different, the overall process and equipment required for each technique are very similar.
Despite their similarities, key differences in the probe construction lead to unique experimental considerations when deploying either technique
In a traditional microdialysis experiments, a guide/probe pairing is implanted into the brain. The guide is inserted first and, after the implant has had time to heal, a cMD probe is inserted. The cMD probe is designed with a membrane positioned at the distal end of the probe that extends beyond the length of the guide and into the brain region of interest. The probe insertion retraumatizes the tissue at the time of sampling, which needs to be accounted for in some experimental designs.
The membrane consists of pore openings, the size of which determines the molecules can pass through. This is referred to as the molecular weight cut off (MWCO) of the membrane. Limiting the size of the collected solutes increases specificity of the sample and protects vulnerable solutes from enzymatic breakdown during collection periods.
- Looking at the filter function of the membrane from a different angle, the disadvantage is that it complicates the ability to obtain an absolute concentration of the analyte in the fluid. Another potential pitfall of using a probe with a membrane is that it can become clogged in a process known as biofouling, where proteins and tissue plug the pores of the membrane and reduce or eliminate flow. The combination of biofouling and the potential for scar tissue formation at the site of implant mean that cMD has a limited study duration; typically, these studies can be run for 7-10 days after implant.
Figure 1. Traditional design of microdialysis guide (left) and probe (right).
Alternatively, the design of the cOFM guide/probe does not have a membrane. Components of the cOFM guide/probe are shown in the schematic to the below.
Figure 2. cOFM probes are made of four components: healing dummy, guide, locking wedge and sampling insert.
The guide/probe design allows for open exchange of fluids between the perfusate and interstitial fluid.
The guide/probe design for cOFM permits an open exchange of fluids between the perfusate and interstitial fluid. In this novel technique, perfusate is introduced directly into the interstitial fluid before being sampled. The mixing of the interstitial fluid occurs at openings in the cannula rather than outside of it, eliminating additional trauma to the surrounding tissue and producing a more representative sampling environment. The sample is unfiltered and is not limited in terms of the size of molecule that can be collected. Even more, the smaller diameter of the cOFM cannulae results in less trauma from the implant procedure. But one of the most appealing features of the cOFM probe is that the materials used to construct the probes minimize glial scarring around the cannula and sampling area; this makes it possible to use cOFM for weeks at a time, including some studies that have continued for up to 6 months.
Figure 3. Positioning of the guide/probe differs between microdialysis and OFM. In microdialysis (left), the probe’s membrane extends past the guide and into the target tissue. In cOFM, the guide is positioned directly in the target tissue (right).
Each technique fills a niche within the field, with their own strengths and weaknesses. In addition to the information above which primarily addresses probe construction, the chart below highlights some additional similarities and differences.
BASi offers products that will allow for successful exploration of both techniques. cMD and cOFM samples
are available and allow for recovery comparison testing prior to purchase. To request samples, or for more information about cMD or cOFM, visit our website at www.basinc.com or reach out to us at basi@basinc.com.
*For guidance on selecting appropriate tubing or tubing connectors, click here.
Disclaimer: The information contained in this post represents the views and opinion of the author and does not necessarily represent the views or opinions SUNY University at Albany or the Research Foundation of SUNY.
Starlette Douglass on LinkedIn https://www.linkedin.com/in/starlette-douglass-84b2b894/
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