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  • 1.
    Bergström, Sara K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Ramström, Margareta
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Andersson, Marit
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    A simplified multidimensional approach for analysis of complex biological samples: on-line LC-CE-MS2006In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 131, no 7, 791-798 p.Article in journal (Refereed)
    Abstract [en]

    Information on protein expression, disease biomarkers or surrogate markers and genetic disorders can nowadays be achieved from analysis of complex biological samples by liquid separation coupled to mass spectrometric (MS) detection. This paper describes fast multidimensional separation by on-line liquid chromatography (LC) and capillary electrophoresis (CE), followed by electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) MS detection. This detector provides ultrahigh resolution of the detected ions, mass accuracy at the ppm-level and high sensitivity. Most of the challenge of this system lies in the development of a new interface for the on-line coupling of LC to CE. The interface developed in poly(dimethylsiloxane) provides a RSD for injection repeatability of <3.5% and surface control for unspecific binding by deactivation with a cationic polymer, PolyE-323. We have evaluated the interface, as well as the overall system, with respect to robustness and deconvolution ability. Sequence coverage for bovine serum albumin (BSA) of 93% showed a high recovery of sample in the different transfer steps through the system. The detection limit for identification is 277 ng mL−1 (or 280 nM) on average for peptides. In the future, we expect LC-CE-MS to be a novel strategy for elucidating the chemistry of biological matrices.

  • 2.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Impact of static pressure on transmembrane fluid exchange in high molecular weight cut off microdialysis2014In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 16, no 2, 301-310 p.Article in journal (Refereed)
    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. 

  • 3.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Consequence of static pressure on transmembrane exchanges during in vitro microdialysis sampling of proteins2012In: Monitoring Molecules in Neuroscience: 14th International Conference, September 16 – 20, London, U.K., 2012Conference paper (Refereed)
  • 4.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Koudriavtsev, Vitali
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Fluorescence imaging of macromolecule transport in high molecular weight cut-off microdialysis2014In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, no 29, 7601-7609 p.Article in journal (Refereed)
    Abstract [en]

    When microdialysis (MD) membrane exceeds molecular weight cut-off (MWCO) of 100 kDa, the fluid mechanics are in the ultrafiltration regime. Consequently, fluidic mass transport of macromolecules in the perfusate over the membrane may reduce the biological relevance of the sampling and cause an inflammatory response in the test subject. Therefore, a method to investigate the molecular transport of high MWCO MD is presented. An in vitro test chamber was fabricated to facilitate the fluorescent imaging of the MD sampling process, using fluoresceinylisothiocyanate (FITC) dextran and fluorescence microscopy. Qualitative studies on dextran behavior inside and outside the membrane were performed. Semiquantitative results showed clear dextran leakage from both 40 and 250 kDa dextran when 100 kDa MWCO membranes were used. Dextran 40 kDa leaked out with an order of magnitude higher concentration and the leakage pattern resembled more of a convective flow pattern compared with dextran 250 kDa, where the leakage pattern was more diffusion based. No leakage was observed when dextran 500 kDa was used as a colloid osmotic agent. The results in this study suggest that fluorescence imaging could be used as a method for qualitative and semiquantitative molecular transport and fluid dynamics studies of MD membranes and other hollow fiber catheter membranes.

  • 5.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Koudriavtsev, Vitali
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Flourescence imaging of molecule transport in high molecular weight cut-off microdialysis2014Conference paper (Refereed)
  • 6.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Koudriavtsev, Vitali
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Analysis of Dextran Leakage across large pore Microdialysis probe by Fluorescent Imaging2013Conference paper (Refereed)
  • 7.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Undin, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergström Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Influence of surface modification and static pressure on microdialysis protein extraction efficiency2015In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 17, no 5, UNSP 96Article in journal (Refereed)
    Abstract [en]

    There is growing interest in using microdialysis (MD) for monitoring larger and more complexmolecules such as neuropeptides and proteins. This promotes the use of MD membranes withmolecular weight cut off (MWCO) of 100 kDa or above. The hydrodynamic property of themembrane goes to ultrafiltration or beyond, making the MD catheters more sensitive to pressure.In the meantime, despite the large pore size, studies have shown that membrane biofouling stilllead to unstable catheter performance. The objective is to study in vitro how 500 kDa dextranand Poloxamer 407 surface modification affect the fluid recovery (FR) and extraction efficiency(EE) of 100 kDa MWCO MD catheters. A pressure chamber was designed to facilitate the tests,using as MD sample a protein standard with similar concentrations as in human cerebral spinalfluid, comparing native and Poloxamer 407 modified MD catheters. The collected dialysatefractions were examined for FR and protein EE, employing Dot-it Spot-it Protein Assay for totalprotein EE and targeted mass spectrometry (MS) for EE of individual proteins and peptides. TheFR results suggested that the surface modified catheters were less sensitive to the pressure andprovide higher precision, and provided a FR closer to 100%. The surface modification did notshow a significant effect on the protein EE. The average total protein EE of surface modifiedcatheters was slightly higher than that of the native ones. The MS EE data of individual proteinsshowed a clear trend of complex response in EE with pressure.

  • 8.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Undin, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Wang, Cong
    Park, Jungyul
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Protein Desalination Chip for Mass Spectrometry Sample Preparation2015Conference paper (Refereed)
    Abstract [en]

    This work focuses on desalination of a protein sample in a lab-on-chip device using the ion concentration polarization (ICP) technique. It was demonstrated with a salt containing buffer with four proteins and two peptides of concentrations typical to cerebrospinal fluid (CSF). Not only was the output desalinated but its protein concentration with large molecular weight (MW) was as much as 3 times higher for the largest protein compared to the original. We conclude that ICP based microfluidic chips have great potential for desalination and protein concentration in microdialysis sampling coupled to mass spectroscopy (MS).

  • 9.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Undin, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Influence of different pluronic surface modifications and pressure on microdialysis protein extraction efficiency2015In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781Article in journal (Refereed)
    Abstract [en]

    There is growing interest in using microdialysis (MD) for monitoring larger and more complexmolecules such as neuropeptides and proteins. This promotes the use of MD membranes withmolecular weight cut off (MWCO) of 100 kDa. Hence, the hydrodynamic property of themembrane goes to ultrafiltration, making the sampling more sensitive to pressure changes. Also,despite the large membrane pore size, studies have shown that membrane biofouling still leads tounstable catheter performance. Our objective is to study in vitro how four kinds of surfacemodifications (Pluronic L31, L44, F87 and F127+L31) affect the fluid recovery (FR) andextraction efficiency (EE) of 100 kDa MWCO MD catheters, under controlled pressure. Apressure chamber was employed to facilitate the tests, using as MD sample a protein standardwith proteins of similar concentrations as in human cerebral spinal fluid. The collected dialysatefractions were examined for FR and EE. Targeted mass spectrometry analysed the EE ofindividual proteins and peptides. The thicker the pluronic adsorption layer, the less thehydrodynamic diameter of the membrane pores, leading to lower and more stable FR. The foursurface modifications had three different behaviours: Pluronic F127 + L31 showed similarbehavior to the Pluronic F127 and the native original membrane; Pluronic F87 showed acontinuous EE increase with pressure; Pluronic L31 and L44 showed similar EE values, whichwere stable with pressure. Different surface modifications are clearly selective to differentproteins and peptides. We conclude that a pluronic surface modification could provide MDsampling with more stable FR, and more stable or enhanced EE with high FR, depending on theobjective of the sampling.

  • 10.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Chu, Jiangtao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Kaller, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    During, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Novel Microdialysis Method to Study The Acute Cytokine Response to Diffuse Traumatic Brain Injury in the Rat2014In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, no 5, A19-A19 p.Article in journal (Refereed)
  • 11.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Microscale Tools for Sample Preparation, Separation and Detection of Neuropeptides2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The analysis of low abundant biological molecules is often challenging due to their chemical properties, low concentration and limited sample volumes. Neuropeptides are one group of molecules that fits these criteria. Neuropeptides also play an important role in biological functions, which makes them extra interesting to analyze. A classic chemical analysis involves sampling, sample preparation, separation and detection. In this thesis, an enhanced solid supported microdialysis method was developed and used as a combined sampling- and preparation technique. In general, significantly increased extraction efficiency was obtained for all studied peptides. To be able to control the small sample volumes and to minimize the loss of neuropeptides because of unwanted adsorption onto surfaces, the subsequent analysis steps were miniaturized to a micro total analysis system (µ-TAS), which allowed sample pre-treatment, injection, separation, manipulation and detection.

    In order to incorporate these analysis functions to a microchip, a novel microfabrication protocol was developed. This method facilitated three-dimensional structures to be fabricated without the need of clean room facilities.

    The sample pre-treatment step was carried out by solid phase extraction from beads packed in the microchip. Femtomole levels of neuropeptides were detected from samples possessing the same properties as microdialysates. The developed injection system made it possible to conduct injections from a liquid chromatographic separation into a capillary electrophoresis channel, which facilitated for advanced multidimensional separations. An electrochemical sample manipulation system was also developed. In the last part, different electrospray emitter tip designs made directly from the edge of the microchip substrate were developed and evaluated. The emitters were proven to be comparable with conventional, capillary based emitters in stability, durability and dynamic flow range. Although additional developments remain, the analysis steps described in this thesis open a door to an integrated, on-line µ-TAS for neuropeptides analysis in complex biological samples.

    List of papers
    1. A feasibility study of solid supported enhanced microdialysis
    Open this publication in new window or tab >>A feasibility study of solid supported enhanced microdialysis
    Show others...
    2004 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 6, 1678-1682 p.Article in journal (Refereed) Published
    Abstract [en]

    For the first time, a solid supported enhanced microdialysis methodology for analysis of neuropeptides is described. The microdialysis samples were, in this study, subsequently collected in fractions, dissolved from the solid particles, dried, and resolved in a formic acid buffer in order to make them suitable for capillary liquid chromatography-mass spectrometry. Different microdialysis flow profiles were evaluated where air-gapped continuous flow was considered most suitable for the solid supported microdialysis mode. Six endogenous neuropeptides were initially used to investigate the feasibility of this enhanced microdialysis methodology. The improved relative recovery obtained from the solid supported enhanced microdialysis was varying from no effect to 10 times higher as compared to ordinary microdialysis. The most efficient enrichment was obtained for luteinizing hormone releasing hormone, which was the largest but also the most hydrophilic of the peptides. In contrast, no significant difference in recovery was observed for Leu-enkephalin being the smallest and the most hydrophobic peptide tested. These results indicate an increased flux and selective uptake of hydrophilic peptides across the membrane and enrichment on the particles in solid supported microdialysis.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-93181 (URN)10.1021/ac035305l (DOI)15018567 (PubMedID)
    Available from: 2005-05-10 Created: 2005-05-10 Last updated: 2013-06-14Bibliographically approved
    2. Poly(dimethylsiloxane)-Based Microchip for Two-Dimensional Solid-Phase Extraction-Capillary Electrophoresis with an Integrated Electrospray Emitter Tip
    Open this publication in new window or tab >>Poly(dimethylsiloxane)-Based Microchip for Two-Dimensional Solid-Phase Extraction-Capillary Electrophoresis with an Integrated Electrospray Emitter Tip
    Show others...
    2005 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 77, no 16, 5356-5363 p.Article in journal (Refereed) Published
    Abstract [en]

    A microchip in poly(dimethylsiloxane) (PDMS) for in-line solid-phase extraction-capillary electrophoresis-electrospray ionization-time-of-flight mass spectrometry (SPE-CE-ESI-TOF-MS) has been developed and evaluated. The chip was fabricated in a novel one-step procedure where mixed PDMS was cast over steel wires in a mold. The removed wires defined 50-um cylindrical channels. Fused-silica capillaries were inserted into the structure in a tight fit connection. The inner walls of the inserted fused-silica capillaries and the PDMS microchip channels were modified with a positively charged polymer, PolyE-323. The chip was fabricated in a two-level cross design. The channel at the lower level was packed with 5-um hyper-cross-linked polystyrene beads acting as a SPE medium used for desalting. The upper level channel acted as a CE channel and ended in an integrated emitter tip coated with conducting graphite powder to facilitate the electrical contact for sheathless ESI. An overpressure continuously provided fresh CE electrolyte independently of the flows in the different levels. Further studies were carried out in order to investigate the electrophoretic and flow rate properties of the chip. Finally, six-peptide mixtures, in different concentrations, dissolved in physiological salt solution was injected, desalted, separated, and sprayed into the mass spectrometer for analysis with a limit of detection in femtomole levels.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-74074 (URN)10.1021/ac050495g (DOI)16097780 (PubMedID)
    Available from: 2005-08-26 Created: 2005-08-26 Last updated: 2011-12-07Bibliographically approved
    3. A simplified multidimensional approach for analysis of complex biological samples: on-line LC-CE-MS
    Open this publication in new window or tab >>A simplified multidimensional approach for analysis of complex biological samples: on-line LC-CE-MS
    Show others...
    2006 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 131, no 7, 791-798 p.Article in journal (Refereed) Published
    Abstract [en]

    Information on protein expression, disease biomarkers or surrogate markers and genetic disorders can nowadays be achieved from analysis of complex biological samples by liquid separation coupled to mass spectrometric (MS) detection. This paper describes fast multidimensional separation by on-line liquid chromatography (LC) and capillary electrophoresis (CE), followed by electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) MS detection. This detector provides ultrahigh resolution of the detected ions, mass accuracy at the ppm-level and high sensitivity. Most of the challenge of this system lies in the development of a new interface for the on-line coupling of LC to CE. The interface developed in poly(dimethylsiloxane) provides a RSD for injection repeatability of <3.5% and surface control for unspecific binding by deactivation with a cationic polymer, PolyE-323. We have evaluated the interface, as well as the overall system, with respect to robustness and deconvolution ability. Sequence coverage for bovine serum albumin (BSA) of 93% showed a high recovery of sample in the different transfer steps through the system. The detection limit for identification is 277 ng mL−1 (or 280 nM) on average for peptides. In the future, we expect LC-CE-MS to be a novel strategy for elucidating the chemistry of biological matrices.

    National Category
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-80932 (URN)10.1039/b601660j (DOI)
    Available from: 2006-06-29 Created: 2006-06-29 Last updated: 2012-03-23Bibliographically approved
    4. On-line coupling of a microelectrode array equipped poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip to electrospray mass spectrometry
    Open this publication in new window or tab >>On-line coupling of a microelectrode array equipped poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip to electrospray mass spectrometry
    Show others...
    In: Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-93184 (URN)
    Available from: 2005-05-10 Created: 2005-05-10 Last updated: 2011-03-21
    5. Sheathless electrospray from polymer microchips
    Open this publication in new window or tab >>Sheathless electrospray from polymer microchips
    Show others...
    2003 In: Analytical Chemistry, Vol. 75, no 15, 3934-3940 p.Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93185 (URN)
    Available from: 2005-05-10 Created: 2005-05-10 Last updated: 2011-03-21
    6. Capillary electrophoresis coupled to mass spectrometry from a polymer modified poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip
    Open this publication in new window or tab >>Capillary electrophoresis coupled to mass spectrometry from a polymer modified poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip
    Show others...
    2005 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 130, no 2, 193-199 p.Article in journal (Refereed) Published
    Abstract [en]

    Hybrid capillary-poly(dimethysiloxane) (PDMS) microchips with integrated electrospray ionization (ESI) tips were directly fabricated by casting PDMS in a mould. The shapes of the emitter tips were drilled into the mould, which produced highly reproducible three-dimensional tips. Due to the fabrication method of the microfluidic devices, no sealing was necessary and it was possible to produce a perfect channel modified by PolyE-323, an aliphatic polyamine coating agent. A variety of different coating procedures were also evaluated for the outside of the emitter tip. Dusting graphite on a thin unpolymerised PDMS layer followed by polymerisation was proven to be the most suitable procedure. The emitter tips showed excellent electrochemical properties and durabilities. The coating of the emitter was eventually passivated, but not lost, and could be regenerated by electrochemical means. The excellent electrochemical stability was further confirmed in long term electrospray experiments, in which the emitter sprayed continuously for more than 180 h. The PolyE-323 was found suitable for systems that integrate rigid fused silica and soft PDMS technology, since it simply could be applied successfully to both materials. The spray stability was confirmed from the recording of a total ion chromatogram in which the electrospray current exhibited a relative standard deviation of 3.9% for a 30 min run. CE-ESI-MS separations of peptides were carried out within 2 min using the hybrid PDMS chip resulting in similar efficiencies as for fused silica capillaries of the same length and thus with no measurable band broadening effects, originating from the PDMS emitter.

    National Category
    Analytical Chemistry Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-93084 (URN)10.1039/b414592e (DOI)15665973 (PubMedID)
    Available from: 2005-05-03 Created: 2005-05-03 Last updated: 2011-12-08Bibliographically approved
    7. Sample pretreatment on a microchip with an integrated electrospray emitter
    Open this publication in new window or tab >>Sample pretreatment on a microchip with an integrated electrospray emitter
    Show others...
    2006 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 27, no 11, 2075-2082 p.Article in journal (Refereed) Published
    Keyword
    Electrospray emitter, Microchip, PDMS, Sample pretreatment
    National Category
    Chemical Sciences Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-95129 (URN)10.1002/elps.200500763 (DOI)
    Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2016-06-22Bibliographically approved
  • 12.
    Dahlin, Andreas P.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Protein digestion, like you never seen it before. Identification and quantification of femtomole amounts of proteins adsorbed onto microdialysis membranes using on surface enzymatic digestion (oSED) in conjunction with isobaric tagging, nanoliquid chromatography and tandem mass spectrometry2012Other (Other (popular science, discussion, etc.))
  • 13.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Microdialysis sampling of proteins in vitro and in vivo2013Conference paper (Refereed)
  • 14.
    Dahlin, Andreas P.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bergström, Sara K.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
    Markides, Karin E.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Poly(dimethylsiloxane)-Based Microchip for Two-Dimensional Solid-Phase Extraction-Capillary Electrophoresis with an Integrated Electrospray Emitter Tip2005In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 77, no 16, 5356-5363 p.Article in journal (Refereed)
    Abstract [en]

    A microchip in poly(dimethylsiloxane) (PDMS) for in-line solid-phase extraction-capillary electrophoresis-electrospray ionization-time-of-flight mass spectrometry (SPE-CE-ESI-TOF-MS) has been developed and evaluated. The chip was fabricated in a novel one-step procedure where mixed PDMS was cast over steel wires in a mold. The removed wires defined 50-um cylindrical channels. Fused-silica capillaries were inserted into the structure in a tight fit connection. The inner walls of the inserted fused-silica capillaries and the PDMS microchip channels were modified with a positively charged polymer, PolyE-323. The chip was fabricated in a two-level cross design. The channel at the lower level was packed with 5-um hyper-cross-linked polystyrene beads acting as a SPE medium used for desalting. The upper level channel acted as a CE channel and ended in an integrated emitter tip coated with conducting graphite powder to facilitate the electrical contact for sheathless ESI. An overpressure continuously provided fresh CE electrolyte independently of the flows in the different levels. Further studies were carried out in order to investigate the electrophoretic and flow rate properties of the chip. Finally, six-peptide mixtures, in different concentrations, dissolved in physiological salt solution was injected, desalted, separated, and sprayed into the mass spectrometer for analysis with a limit of detection in femtomole levels.

  • 15.
    Dahlin, Andreas P
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Sjödin, Marcus O D
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Quantification of Proteins Adsorbed to Surface Modified and Non-Modified Microdialysis Membranes using on-Surface Enzymatic Digestion (oSED) iTRAQ-MALDI-TOF/TOF MS2012In: 60th ASMS Conference on Mass Spectrometry and Allied Topics, May 20 - 24, Vancouver, Canada, 2012Conference paper (Refereed)
  • 16.
    Dahlin, Andreas P
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Sjödin, Marcus O.D.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Multiplexed quantification of proteins adsorbed to surface-modified and non-modified microdialysis membranes2012In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 402, no 6, 2057-2067 p.Article in journal (Refereed)
    Abstract [en]

    A simple and straightforward method for discovery and quantification of proteins adsorbed onto delicate and sensitive membrane surfaces is presented. The adsorbed proteins were enzymatically cleaved while still adsorbed onto the membranes using an on-surface enzymatic digestion (oSED). This was followed by isobaric tagging, nanoliquid chromatography, and tandem mass spectrometry. Protein adsorption on tri-block copolymer Poloxamer 407 surface-modified microdialysis (MD) membranes were compared with protein adsorption on unmodified MD membranes. Ventricular cerebrospinal fluid (vCSF) kept at 37 °C was used as sample matrix. In total, 19 proteins were quantified in two biological replicates. The surface-modified membranes adsorbed 33% less proteins than control membranes and the most abundant proteins were subunits of hemoglobin and clusterin. The adsorption of clusterin on the modified membranes was on average 36% compared to control membranes. The most common protein in vCSF, Albumin, was not identified adsorbed to the surface at all. It was also experimentally verified that oSED, in conjunction with tandem mass spectrometry can be used to quantify femtomole amounts of proteins adsorbed on limited and delicate surfaces, such as MD membranes. The method has great potential and can be used to study much more complex protein adsorption systems than previously reported.

  • 17.
    Dahlin, Andreas P
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Purins, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Chu, Jiangtao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Refined microdialysis method for protein biomarker sampling in acute brain injury in the neurointensive care setting2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 17, 8671-8679 p.Article in journal (Refereed)
    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.

  • 18.
    Dahlin, Andreas P
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Purins, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Improved Microdialysis Sampling of Proteins using Surface Modified Catheters: An in vivo Study in Standardized Pig Brain Death Model2013Conference paper (Refereed)
  • 19.
    Dahlin, Andreas P.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Caldwell, Karin D.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Methodological aspects on microdialysis protein sampling and quantification in biological fluids: an in vitro study on human ventricular CSF.2010In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 11, 4376-4385 p.Article in journal (Refereed)
    Abstract [en]

    There is growing interest in sampling of protein biomarkers from the interstitial compartment of the brain and other organs using high molecular cutoff membrane microdialysis (MD) catheters. However, recent data suggest that protein sampling across such MD membranes is a highly complex process that needs to be further studied. Here, we report three major improvements for microdialysis sampling of proteins in complex biological matrixes. The improvements in this in vitro study using human ventricular cerebrospinal fluid as the sample matrix include increased fluid recovery control, decreased protein adsorption on the microdialysis membrane and materials, and novel quantitative mass spectrometry analysis. Dextrans in different concentrations and sizes were added to the perfusion fluid. It was found that dextrans with molecular mass 250 and 500 kDa provided a fluid recovery close to 100%. An improved fluid recovery precision could be obtained by self-assembly triblock polymer surface modification of the MD catheters. The modified catheters also delivered a significantly increased extraction efficiency for some of the investigated proteins. The final improvement was to analyze the dialysates with isobaric tagged (iTRAQ) proteomics, followed by tandem mass spectrometric analysis. By using this technique, 48 proteins could be quantified and analyzed with respect to their extraction efficiencies. The novel aspects of microdialysis protein sampling, detection, and quantification in biological fluids presented in this study should be considered as a first step toward better understanding and handling of the challenges associated with microdialysis sampling of proteins. The next step is to optimize the developed methodology in vivo.

  • 20.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Chu, Jiangtao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebral microdialysis for protein biomarker monitoring in the neurointensive care setting - a technical approach2014In: Frontiers in Neurology, ISSN 1664-2295, Vol. 5, 245- p.Article in journal (Refereed)
    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.

  • 21.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Purins, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    New Microdialysis Method for Protein Biomarker Sampling in the Neurointensive Care Setting2014In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, no 5, A22-A22 p.Article in journal (Refereed)
  • 22.
    Lindberg, Peter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Signal Processing.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Bergström, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Thorslund, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Andrén, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nikolajeff, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Sample pretreatment on a microchip with an integrated electrospray emitter2006In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 27, no 11, 2075-2082 p.Article in journal (Refereed)
  • 23.
    Ogden, Sam
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Knaust, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Bodén, Roger
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    On-chip pump system for high-pressure microfluidic applications2013Conference paper (Refereed)
    Abstract [en]

    This paper presents a micropump system with four integrated paraffin actuated pumps: Two mobile phase pumps and two sample injector pumps. The mobile phase pumps are evaluated by their ability to deliver a stable, low-ripple flow to be used in chip-based high performance liquid chromatography. It is shown that the two mobile phase pumps can be driven in combined operation with an induced offset to significantly lower flow fluctuations.

  • 24.
    Undin, Torgny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Competitive Protein Adsorption as Observed and Quantified by - Surface Enzymatic Digestion (oSED) and Mass Spectrometry2012In: 60th ASMS Conference on Mass Spectrometry and Allied Topics, May 20 - 24, Vancouver, Canada, 2012Conference paper (Refereed)
  • 25.
    Undin, Torgny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergström Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström.
    Mass spectrometric determination of the effect of surface deactivation on membranes used for the sampling of cerebrospinal fluid (CSF)Manuscript (preprint) (Other academic)
  • 26.
    Undin, Torgny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergström Lind, Sara
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    A mass spectrometry based method for investigating time dependent protein adsorption on surfaces in contact with complex biological samplesArticle in journal (Other academic)
  • 27.
    Undin, Torgny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergström Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    MS for investigation of time-dependent protein adsorption on surfaces in complex biological samples2015In: Future Science OA, ISSN 2056-5623, 32Article in journal (Refereed)
    Abstract [en]

    Aim: This study aims at developing a nondestructive way for investigating proteinadsorption on surfaces such as biomaterials using mass spectrometry. Methods: Ventricular cerebrospinal fluid in contact with poly carbonate membranes were usedas adsorption templates and on-surface enzymatic digestion was applied to desorbproteins and cleave them into peptides. Mass spectrometric analysis provided bothprotein identification and determination of protein specific adsorption behavior. Results: In general, the adsorption increased with incubation time but also proteinspecifictime-resolved adsorption patterns from the complex protein solutionwere discovered. Conclusion: The method developed is a promising tool for thecharacterization of biofouling, which sometimes causes rejection and encapsulationof implants and can be used as complement to other surface analytical techniques.

    One problem associated with artificial materials in the body is that proteins in thebody interact with the surface, which sometimes causes rejection of the implant.In this study, a method for investigating the time-dependent protein adsorptionon a surface originating from a complex biological protein solution was developed.Compared with other surface analyses, this method can identify what proteins thatadsorbs on the surface. In addition, determination of protein-specific adsorptionbehavior in relation to incubation was possible

  • 28.
    Undin, Torgny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Investigation of Time Dependent Competitive Protein Adsorption to Surfaces Using Mass Spectrometry2013Conference paper (Refereed)
    Abstract [en]

    Introduction

    Surfaces in a complex protein solution will adsorb proteins. This event is fast and dynamic and triggers a biological response against the inserted/implanted biomaterial that eventually will lead to biofouling and encapsulation. This affects the properties of the inserted devices, such as hampered membrane functions of microdialysis (MD) probes or distortion in response of biosensors.

    Methods

    Untreated and coated filtration membranes were used as adsorption templates for human ventricular cerebrospinal fluid (vCSF). After adsorption in an incubation chamber, the membranes were washed, dried and the proteins were reduced, alkylated and digested. The sample preparation procedure was conducted according to an on-surface enzymatic digestion (oSED) protocol previously described by our group. The oSED digests were analyzed by nanoLC ESI-MS/MS using a 7T hybrid LTQ FT and Velos pro orbitrap mass spectrometer.

    Preliminary Data

    In this study, we present a time resolved map of protein adsorption. Non-coated and tri-block polymer coated, polycarbonate membranes was used as templates. As expected, a time and surface property dependent protein adsorption relationship was observed. It is not surprising that the degree of protein binding onto modified and non-modified surfaces was dependent on the properties of the protein as well as the properties of the surface. The process of biofouling for in vivo inserted materials can be postponed and thereby increasing the lifetime and use of e.g. microdialysis probes for patient monitoring. The preliminary data are very promising making it possible to identify a spectra of adsorbed proteins on different surfaces in a time dependent way

  • 29.
    Undin, Torgny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hörnaeus, Katarina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergström Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mechanistic investigation of the on surface enzymatic digestion (oSED) protein adsorption detection method using targeted mass spectrometry2016In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, no 5, 1714-1720 p.Article in journal (Refereed)
    Abstract [en]

    This study describes our efforts to study some of the mechanistic aspects of the earlier established onsurface enzymatic digestion (oSED) method. In a multitude of application areas, it has become important to be able to fully characterize and understand selective protein adsorption to biomaterial surfaces for various applications, including biomedicine (implants), nanotechnology (microchip surfaces and sensors) and materials sciences. Herein, the investigation of the mechanistic aspects was based on microdialysis catheter tubes that were flushed with controlled protein solutions mimicking the extracellular fluid of the brain. The protein adsorption properties were monitored using high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) with a targeted method. The temporally resolved results show that most proteins stay adsorbed onto the surface during the entire digestion process and are only cut away piece by piece, whereas smaller proteins and peptides seem to desorb rather easily from the surface. This information will simplify the interpretation of data generated using the oSED method and can also be used for the characterization of the physicochemical properties controlling the adsorption of individual proteins to specific surfaces.

  • 30.
    Wetterhall, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Identification of human cerebrospinal fluid proteins and their distribution in an in vitro microdialysis sampling system2014In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 57, no SI, 34-40 p.Article in journal (Refereed)
    Abstract [en]

    A qualitative study is presented on how proteins from a complex biological sample are distributed in a microdialysis sample system. A comparison between proteins identified in the human ventricular cerebrospinal fluid (CSF) sample, the collected dialysate and the proteins adsorbed onto the membrane was conducted. The microdialysis experiment was performed in vitro at 37 °C for the duration of 24h. Thereafter, the membranes were removed from the catheter and the adsorbed proteins were tryptically digested using the on-surface enzymatic digestion (oSED) protocol. The CSF samples and the dialysates were digested using a standard in-solution trypsin digestion protocol.  In the final phase, the samples were analysed using nano-liquid chromatography in combination with tandem mass spectrometry. In the four sample compartments analysed (CSF start, Membrane, Dialysate, CSF end) a total of 134 different proteins were found. However, most of the identified proteins(n=87) were uniquely found in one sample compartment only. Common CSF proteins such as albumin, apolipoproteins and cystatin C together with plasma proteins such as hemoglobin and fibrinogen were among the 11 proteins that were found in all samples. These proteins are present in high concentrations in CSF, which means that they effectively block out the detection signal of less abundant proteins.  Therefore, only 25 % of the proteins adsorbed onto the membrane were detected in the CSF compared with the dialysate that shared 44% of its proteins with the CSF. The proteins adsorbed onto the membrane were significantly more hydrophobic, had a lower instability index and more thermostable compared to the proteins in the CSF and the dialysate. The results suggest that proteins adsorbed onto the microdialysis membranes may escape detection because they are prevented from passing the membrane into the dialysate. Thus, the membrane needs to be examined after sample collection in order to better verify the protein content in the original sample. This is particularly important when searching for new protein biomarkers for neurodegenerative diseases.

  • 31.
    Wetterhall, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Sjödin, Marcus O D
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mapping the protein distribution within a microdialysis sampling system by on-surface enzymatic digestion in combination with mass spectrometry2012In: Monitoring Molecules in Neuroscience: 14th International Conference, September 16 – 20, London, U.K., 2012Conference paper (Refereed)
1 - 31 of 31
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