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Cerebral microdialysis for protein biomarker monitoring in the neurointensive care setting - a technical approach
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
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2014 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, 245- p.Article in journal (Refereed) Published
Abstract [en]

Cerebral microdialysis (MD) was introduced as a neurochemical monitoring method in the early 1990s and is currently widely used for the sampling of low molecular weight molecules, signaling energy crisis, and cellular distress in the neurointensive care (NIC) setting. There is a growing interest in MD for harvesting of intracerebral protein biomarkers of secondary injury mechanisms in acute traumatic and neurovascular brain injury in the NIC community. The initial enthusiasm over the opportunity to sample protein biomarkers with high molecular weight cut-off MD catheters has dampened somewhat with the emerging realization of inherent methodological problems including protein-protein interaction, protein adhesion, and biofouling, causing an unstable in vivo performance (i.e., fluid recovery and extraction efficiency) of the MD catheter. This review will focus on the results of a multidisciplinary collaborative effort, within the Uppsala Berzelii Centre for Neurodiagnostics during the past several years, to study the features of the complex process of high molecular weight cut-off MD for protein biomarkers. This research has led to new methodology showing robust in vivo performance with optimized fluid recovery and improved extraction efficiency, allowing for more accurate biomarker monitoring. In combination with evolving analytical methodology allowing for multiplex biomarker analysis in ultra-small MD samples, a new opportunity opens up for high-resolution temporal mapping of secondary injury cascades, such as neuroinflammation and other cell injury reactions directly in the injured human brain. Such data may provide an important basis for improved characterization of complex injuries, e.g., traumatic and neurovascular brain injury, and help in defining targets and treatment windows for neuroprotective drug development.

Place, publisher, year, edition, pages
2014. Vol. 5, 245- p.
National Category
Neurology Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-239227DOI: 10.3389/fneur.2014.00245PubMedID: 25520696OAI: oai:DiVA.org:uu-239227DiVA: diva2:773842
Available from: 2014-12-19 Created: 2014-12-19 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Microdialysis Sampling of Macro Molecules: Fluid Characteristics, Extraction Efficiency and Enhanced Performance
Open this publication in new window or tab >>Microdialysis Sampling of Macro Molecules: Fluid Characteristics, Extraction Efficiency and Enhanced Performance
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, fluid characteristics and sampling efficiency of high molecular weight cut-off microdialysis are presented, with the aim of improving the understanding of microdialysis sampling mechanisms and its performance regarding extraction efficiency of biological fluid and biomarkers.

Microdialysis is a well-established clinical sampling tool for monitoring small biomarkers such as lactate and glucose. In recent years, interest has raised in using high molecular weight cut-off microdialysis to sample macro molecules such as neuropeptides, cytokines and proteins. However, with the increase of the membrane pore size, high molecular weight cut-off microdialysis exhibits drawbacks such like unstable catheter performance, imbalanced fluid recovery, low and unstable molecule extraction efficiency, etc. But still, the fluid characteristics of high molecular weight cut-off microdialysis is rarely studied, and the clinical or in vitro molecule sampling efficiency from recent studies vary from each other and are difficult to compare.  

Therefore, in this thesis three aspects of high molecular weight cut-off microdialysis have been explored. The first, the fluid characteristics of large pore microdialysis has been investigated, theoretically and experimentally. The results suggest that the experimental fluid recovery is in consistency with its theoretical formula. The second, the macromolecule transport behaviour has been visualized and semi-quantified, using an in vitro test system and fluorescence imaging. The third, two in vitro tests have been done to mimic in vivo cerebrospinal fluid sampling under pressurization, using native and differently surface modified catheters. As results, individual protein/peptide extraction efficiencies were achieved, using targeted mass spectrometry analysis.

In summary, a theory system of the fluid characteristics of high molecular weight cut-off microdialysis has been built and testified; Macromolecular transport of microdialysis catheter has been visualized; In vivo biomolecules sampling has been simulated by well-defined in vitro studies; Individual biomolecular extraction efficiency has been shown; Different surface modifications of microdialysis catheter have been investigated. It was found that, improved sampling performance can be achieved, in terms of balanced fluid recovery and controlled protein extraction efficiency.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 52 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1278
Keyword
microdialysis, high molecular weight cut-off, fluid characteristics, fluid recovery, extraction efficiency, biomarker, microporous membrane, macromolecule transport, transmembrane, large pore, surface modification, pluronic, dextran, in vitro, microdialysis catheter
National Category
Manufacturing, Surface and Joining Technology Nano Technology
Research subject
Engineering Science with specialization in Microsystems Technology; Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-261068 (URN)978-91-554-9315-8 (ISBN)
Public defence
2015-10-16, Polhem Salen, Angstrom Laboratory, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Berzelii Centre EXSELENT
Available from: 2015-09-25 Created: 2015-08-28 Last updated: 2015-10-01

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