Content deleted Content added
m →Applications: Task 17: replace to-be-deprecated: |name-list-format= (2× replaced; usage: 2 of 4); |
Citation bot (talk | contribs) Altered last2. Add: bibcode, authors 1-1. Removed parameters. Some additions/deletions were parameter name changes. | Use this bot. Report bugs. | Suggested by Abductive | Category:Membrane technology | #UCB_Category 62/79 |
||
| (22 intermediate revisions by 15 users not shown) | |||
Line 1:
{{Short description|Biological fluid sampling technique}}
{{More citations needed|article|date=August 2010}}
[[File:CMA Microdialysis probes.jpg|thumbnail|Microdialysis probes manufactured by CMA Microdialysis AB, Kista, Sweden]]
'''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. Analytes may include endogenous molecules (e.g. [[neurotransmitter]], [[hormones]], [[glucose]], etc.) to assess their biochemical functions in the body, or exogenous compounds (e.g. [[pharmaceuticals]]) to determine their distribution within the body. The microdialysis technique requires the insertion of a small microdialysis catheter (also referred to as microdialysis probe) into the tissue of interest. 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 probe is continuously [[Perfusion|perfused]] with an aqueous solution (perfusate) that closely resembles the (ionic) composition of the surrounding tissue fluid at a low flow rate of approximately 0.1-5μL/min.<ref name="chaurasia">{{
== History ==
The microdialysis principle was first employed in the early 1960s, when [[Push-pull perfusion|push-pull canulas]]<ref>{{
== Microdialysis probes ==
[[File:Schematic illustration of a microdialysis probe.png|thumb|right|upright=1.8|Schematic illustration of a ''microdialysis probe'']]
There are a variety of probes with different membrane and shaft length combinations available. The molecular weight cutoff of commercially available microdialysis probes covers a wide range of approximately 6-100kD, but also 1MD is available. While water-soluble compounds generally diffuse freely across the microdialysis membrane, the situation is not as clear for highly lipophilic analytes, where both successful (e.g. corticosteroids) and unsuccessful microdialysis experiments (e.g. estradiol, fusidic acid) have been reported.<ref name
== Recovery and calibration methods ==
Due to the constant [[perfusion]] of the microdialysis probe with fresh perfusate, a total equilibrium cannot be established.<ref name="chaurasia" /> This results in dialysate concentrations that are lower than those measured at the distant sampling site. In order to correlate concentrations measured in the dialysate with those present at the distant sampling site, a calibration factor (recovery) is needed.<ref>{{Cite journal |last1=Bouw |first1=M. René |last2=Hammarlund-Udenaes |first2=Margareta |year=1998 |title=Methodological aspects of the use of a calibrator in in vivo microdialysis-further development of the retrodialysis method |url=https://link.springer.com/article/10.1023/A:1011992125204 |journal=Pharmaceutical Research |volume=15 |issue=11 |pages=1673–1679 |doi=10.1023/A:1011992125204 |pmid=9833986 |s2cid=11177946}}</ref> The recovery can be determined at steady-state using the constant rate of analyte exchange across the microdialysis membrane. The rate at which an analyte is exchanged across the semipermeable membrane is generally expressed as the analyte’s extraction efficiency. The extraction efficiency is defined as the ratio between the loss/gain of analyte during its passage through the probe (C<sub>in</sub>−C<sub>out</sub>) and the difference in concentration between perfusate and distant sampling site (C<sub>in</sub>−C<sub>sample</sub>).
In theory, the extraction efficiency of a microdialysis probe can be determined by: 1) changing the drug concentrations while keeping the flow rate constant or 2) changing the flow rate while keeping the respective drug concentrations constant. At steady-state, the same extraction efficiency value is obtained, no matter if the analyte is enriched or depleted in the perfusate.<ref name="chaurasia" /> Microdialysis probes can consequently be calibrated by either measuring the loss of analyte using drug-containing perfusate or the gain of analyte using drug-containing sample solutions. To date, the most frequently used calibration methods are the low-flow-rate method, the no-net-flux method,<ref name
=== Low-flow-rate method ===
Line 34 ⟶ 35:
== Applications ==
The microdialysis technique has undergone much development since its first use in 1972,<ref name="Delgado" /> when it was first employed to monitor concentrations of endogenous biomolecules in the brain.<ref name="Benveniste">{{
When employed in brain research, microdialysis is commonly used to measure neurotransmitters (e.g. [[dopamine]], [[serotonin]], [[norepinephrine]], [[acetylcholine]],<ref>{{Cite journal |last=Yoshikawa, M., Kawaguchi, M. |date=April 2021 |title=In Vivo Monitoring of Acetylcholine Release from Nerve Endings in Salivary Gland |journal=Biology |volume=10 |issue=5 |page=351 |doi=10.3390/biology10050351 |pmc=8143079 |pmid=33919193 |doi-access=free}}</ref> [[glutamate]], [[GABA]]) and their metabolites, as well as small neuromodulators (e.g. [[cyclic adenosine monophosphate|cAMP]], [[cyclic guanosine monophosphate|cGMP]], [[nitric oxide|NO]]), [[amino acids]] (e.g. [[glycine]], [[cysteine]], [[tyrosine]]), and energy substrates (e.g. [[glucose]], [[lactic acid|lactate]], [[pyruvate]]). Exogenous drugs to be analyzed by microdialysis include new [[antidepressants]], [[antipsychotics]], as well as [[antibiotics]] and many other drugs that have their pharmacological effect site in the brain. The first non-metabolite to be analyzed by microdialysis in vivo in the human brain was [[rifampicin]].<ref>{{
Applications in other organs include the skin (assessment of [[bioavailability]] and [[bioequivalence]] of topically applied dermatological drug products),<ref name="Schmidt">{{
Microdialysis has also found increasing application in environmental research,<ref>{{
== Critical analysis ==
Line 53 ⟶ 54:
=== Limitations ===
# Despite scientific advances in making microdialysis probes smaller and more efficient, the invasive nature of this technique still poses some practical and ethical limitations. For example, it has been shown that implantation of a microdialysis probe can alter tissue [[morphology (biology)|morphology]] resulting in disturbed microcirculation, rate of metabolism or integrity of physiological barriers, such as the [[blood–brain barrier]].<ref>{{
# Microdialysis has a relatively low temporal and spatial resolution compared to, for example, electrochemical [[biosensors]]. While the temporal resolution is determined by the length of the sampling intervals (usually a few minutes), the spatial resolution is determined by the dimensions of the probe. The probe size can vary between different areas of application and covers a range of a few millimeters (intracerebral application) up to a few centimeters ([[Subcutaneous tissue|subcutaneous]] application) in length and a few hundred micrometers in diameter.{{citation needed|date=August 2018}}
# Application of the microdialysis technique is often limited by the determination of the probe’s recovery, especially for [[in vivo]] experiments. Determination of the recovery may be time-consuming and may require additional subjects or pilot experiments. The recovery is largely dependent on the flow rate: the lower the flow rate, the higher the recovery. However, in practice the flow rate cannot be decreased too much since either the sample volume obtained for analysis will be insufficient or the temporal resolution of the experiment will be lost. It is therefore important to optimize the relationship between flow rate and the sensitivity of the analytical assay. The situation may be more complex for lipophilic compounds as they can stick to the tubing or other probe components, resulting in a low or no analyte recovery.{{citation needed|date=August 2018}}
| |||