uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Refined microdialysis method for protein biomarker sampling in acute brain injury in the neurointensive care setting
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 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.
Show others and affiliations
2014 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 17, 8671-8679 p.Article in journal (Refereed) Published
Abstract [en]

There is growing interest in cerebral microdialysis (MD) for sampling of protein biomarkers in neurointensive care (NIC) patients. Published data point to inherent problems with this methodology including protein interaction and biofouling leading to unstable catheter performance. This study tested the in vivo performance of a refined MD method including catheter surface modification, for protein biomarker sampling in a clinically relevant porcine brain injury model. Seven pigs of both sexes (10-12 weeks old; 22.2-27.3 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure (ICP) and cerebral perfusion pressure was recorded during the stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 min) until brain death. One naïve MD catheter and one surface modified with Pluronic F-127 (10 mm membrane, 100 kDa molecular weight cutoff MD catheter) were inserted into the right frontal cortex and perfused with mock CSF with 3% Dextran 500 at a flow rate of 1.0 μL/min and 20 min sample collection. Naïve catheters showed unstable fluid recovery, sensitive to ICP changes, which was significantly stabilized by surface modification. Three of seven naïve catheters failed to deliver a stable fluid recovery. MD levels of glucose, lactate, pyruvate, glutamate, glycerol and urea measured enzymatically showed an expected gradual ischemic and cellular distress response to the intervention without differences between naïve and surface modified catheters. The 17 most common proteins quantified by iTRAQ and nanoflow LC-MS/MS were used as biomarker models. These proteins showed a significantly more homogeneous response to the ICP intervention in surface modified compared to naïve MD catheters with improved extraction efficiency for most of the proteins. The refined MD method appears to improve the accuracy and precision of protein biomarker sampling in the NIC setting.

Place, publisher, year, edition, pages
2014. Vol. 86, no 17, 8671-8679 p.
National Category
Analytical Chemistry Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
URN: urn:nbn:se:uu:diva-232026DOI: 10.1021/ac501880uISI: 000341229200025PubMedID: 25075428OAI: oai:DiVA.org:uu-232026DiVA: diva2:746264
Available from: 2014-09-12 Created: 2014-09-12 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

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Dahlin, Andreas PPurins, KarlisClausen, FredrikChu, JiangtaoSedigh, AmirLorant, TomasEnblad, PerLewén, AndersHillered, Lars

Search in DiVA

By author/editor
Dahlin, Andreas PPurins, KarlisClausen, FredrikChu, JiangtaoSedigh, AmirLorant, TomasEnblad, PerLewén, AndersHillered, Lars
By organisation
Microsystems TechnologyNeurosurgeryTransplantation Surgery
In the same journal
Analytical Chemistry
Analytical ChemistryEngineering and Technology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 1450 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf