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Impact of static pressure on transmembrane fluid exchange in high molecular weight cut off microdialysis
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
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 Medical Sciences, Biochemial structure and function. (Klinisk kemi)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. (Dahlin)
2014 (English)In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 16, no 2, 301-310 p.Article in journal (Refereed) Published
Abstract [en]

With the interest of studying larger biomolecules by microdialysis (MD), this sampling technique has reached into the ultrafiltration region of fluid exchange, where fluid recovery (FR)  has a strong dependence on pressure. Hence in this study, we focus on the fluid exchange across the high molecular weight cut off MD membrane under the influence of the static pressure in the sampling environment. A theoretical model is presented for MD with such membranes, where FR has a linear dependence upon the static pressure of the sample. Transmembrane (TM) osmotic pressure difference and MD perfusion rate decide how fast FR increases with increased static pressure.

A test chamber for in vitro MD under static pressure was constructed and validated. It can hold four MD probes under controlled pressurized conditions. Comparison showed good agreement between experiment and theory. Moreover, test results showed that the fluid recovery of the test chamber MD can be set accurately via the chamber pressure, which is controlled by sample injection into the chamber at precise rate. This in vitro system is designed for modelling in vivo MD in cerebrospinal fluid and studies with biological samples in this system may be good models for in vivo MD. 

Place, publisher, year, edition, pages
2014. Vol. 16, no 2, 301-310 p.
National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
URN: urn:nbn:se:uu:diva-212726DOI: 10.1007/s10544-013-9833-1ISI: 000334362000013OAI: oai:DiVA.org:uu-212726DiVA: diva2:679122
Funder
Swedish Research Council, P29797-1
Available from: 2013-12-13 Created: 2013-12-13 Last updated: 2017-12-06Bibliographically 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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Chu, JiangtaoHjort, KlasLarsson, AndersDahlin, Andreas P

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