uu.seUppsala University Publications
Change search
Refine search result
123 51 - 100 of 103
CiteExportLink to result list
Permanent 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
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51. Lanekoff, Ingela
    et al.
    Thomas, Mathew
    Laskin, Julia
    Shotgun approach for quantitative imaging of phospholipids using nanospray desorption electrospray ionization mass spectrometry2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 3, p. 1872-80Article in journal (Refereed)
    Abstract [en]

    Mass spectrometry imaging (MSI) has been extensively used for determining spatial distributions of molecules in biological samples, and there is increasing interest in using MSI for quantification. Nanospray desorption electrospray ionization (nano-DESI) is an ambient MSI technique where a solvent is used for localized extraction of molecules followed by nanoelectrospray ionization. Doping the nano-DESI solvent with carefully selected standards enables online quantification during MSI experiments. In this proof-of-principle study, we demonstrate that this quantification approach can be extended to provide shotgun-like quantification of phospholipids in thin brain tissue sections. Specifically, two phosphatidylcholine (PC) standards were added to the nano-DESI solvent for simultaneous imaging and quantification of 22 endogenous PC species observed in nano-DESI MSI. Furthermore, by combining the quantitative data obtained in the individual pixels, we demonstrate quantification of these PC species in seven different regions of a rat brain tissue section.

  • 52.
    Laskin, Julia
    et al.
    Pacific Northwest National Laboratory.
    Andersson, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 1, p. 52-73Article, review/survey (Refereed)
  • 53.
    Lavén, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Wallenborg, Susanne
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Bergström, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Djodjic, Majda
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Ljung, Jenny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Berglund, Oskar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Edenwall, Niklas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Markides, Karin E.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Radionuclide Imaging of Miniaturized Chemical Analysis Systems2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 23, p. 7102-7108Article in journal (Refereed)
    Abstract [en]

    We propose radionuclide imaging as a valuable tool for the study of molecular interactions in miniaturized systems for chemical analysis. Sensitive and quantitative imaging can be performed with compounds labeled with short-lived positron-emitting radionuclides, such as C-11 and Ga-68, within selected parts of the system. Radionuclide imaging is not restricted to transparent materials since the relatively energetic positrons can penetrate high optical density materials. Experimentally, a radiotracer is introduced into the object of study, which is subsequently placed on a phosphor storage plate. After exposure, the plate is scanned with a laser and a digital, quantitative image can be reconstituted. To demonstrate the concept, three types of microstructures suited for integration in chemical analysis systems were imaged with C-11- and Ga-68-labeled tracers. The influence of factors such as geometry of the object and type of radionuclide on resolution and sensitivity was investigated. The resolution ranged from 0.9 to 2.7 mm (fwhm). Measuring low amounts of radioactivity in the three structures, 2-20 Bq could be detected, which corresponded to 2.3-500 amol or 2.4-110 pM tracer. The imaging approach was applied to study analyte concentration and sample dilution effects on the performance of a capillary extraction column integrated in an automated LC-ESI-MS system. The utility of the technique was further illustrated by imaging of microchannels in a zeonor plastic compact disk and in a poly(dimethylsiloxane) material for the study of nonspecific peptide adsorption.

  • 54.
    Lee, Jae Kyoo
    et al.
    Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA..
    Jansson, Erik T.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA..
    Nam, Hong Gil
    Inst Basic Sci, Ctr Plant Aging Res, Daegu 42988, South Korea.;DGIST, Dept New Biol, Daegu 42988, South Korea..
    Zare, Richard N.
    Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA..
    High-Resolution Live-Cell Imaging and Analysis by Laser Desorption/Ionization Droplet Delivery Mass Spectrometry2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 10, p. 5453-5461Article in journal (Refereed)
    Abstract [en]

    We have developed a new ambient-ionization mass spectrometric technique named laser desorption/ionization droplet delivery mass spectrometry (LDIDD-MS). LDIDD-MS permits high-resolution, high-sensitivity imaging of tissue samples as well as measurements of both single-cell apoptosis and live-cell exocytosis. A pulsed Hz) UV laser beam (266 nm) is focused on a surface covered with target analytes to trigger their desorption and ionization. A spray of liquid droplets is simultaneously directed onto the laser-focused surface region to capture the ionized analytes and deliver them to a mass spectrometer. The approach of rapid and effective capturing of molecules after laser desorption/ionization allows the limit of detection for the amino acid lysine to be as low as 2 amol under ambient ionization conditions. Two-dimensional maps of the desorbed/ionized species are recorded by moving the sample on an XY translational stage. The spatial resolution for imaging with LDIDD-MS was determined to be 2.4 mu m far an ink-printed pattern and 3 mu m for mouse brain tissue. We applied LDIDD-MS to single-cell analysis of apoptotic HEK cells. Differences were observed in the profiles of fatty acids and lipids between healthy HEK cells and those undergoing apoptosis. We observed upregulation of phosphatidylcholine (PC) with a relatively shorter carbon chain length and downregulation of PC with a relatively longer carbon chain length. We also applied LDIDD-MS for a real-time direct measurements of live-cell exocytosis. The catecholamine dopamine and trace amines (phenethylamine and tyramine) were detected from live PC12 cells without damaging them.

  • 55.
    Lindholm, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Forssén, Patrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Numerical Analysis.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Validation of the Accuracy of the Perturbation Peak Method for Determination of Multicomponent Adsorption Isotherm Parameters in LC2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, p. 5472-5478Article in journal (Refereed)
  • 56.
    Lindholm, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Forssén, Patrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Numerical Analysis.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Validation of the Accuracy of the Perturbation Peak Method for Determination of Single and Binary Adsorption Isotherm Parameters in LC2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, p. 4856-4865Article in journal (Refereed)
  • 57. Lipponen, Katriina
    et al.
    Stege, Patricia W.
    Cilpa, Geraldine
    Samuelsson, Jorgen
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Riekkola, Marja-Liisa
    Three Different Approaches for the Clarification of the Interactions between Lipoproteins and Chondroitin-6-sulfate2011In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 15, p. 6040-6046Article in journal (Refereed)
    Abstract [en]

    Two different experimental approaches were used for obtaining a comprehensive view and understanding of the interactions between apolipoprotein B-100 (ApoB-100) of low-density lipoprotein and apolipoprotein E (ApoE) of high-density lipoprotein and chondroitin-6-sulfate (C6S) of arterial proteoglycan. The techniques employed were partial filling affinity capillary electrophoresis (PF-ACE) and continuous flow quartz crystal inicrobalance (QCM). In addition, molecular dynamic (MD) simulations were used to provide a supportive visual insight into the interaction mechanism. A new tool for analysis of QCM-data was utilized, i.e., adsorption energy distribution calculations, which allowed a deeper understanding of the interactions, especially at different temperatures. The PF-ACE technique probed mainly the strong adsorption interactions whereas in the MD calculations short:- and long-range interactions could be distinguished. Although there are differences in the techniques, a pretty good agreement was achieved between the three approaches for the interaction of 19 amino acid peptide of ApoB with C6S giving log affinity constants of 4.66 by QCM, 5.02 by PP-ACE, and 7.39 by MD, and for 15 amino acid peptide of ApoE with C6S 5.34 by QCM, 5.28 by PT-ACE, and 4.60 by MD at physiological temperature 37.0 degrees C.

  • 58. Liu, Pengyuan
    et al.
    Lanekoff, Ingela T
    Laskin, Julia
    Dewald, Howard D
    Chen, Hao
    Study of electrochemical reactions using nanospray desorption electrospray ionization mass spectrometry2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 13, p. 5737-5743Article in journal (Refereed)
    Abstract [en]

    The combination of electrochemistry (EC) and mass spectrometry (MS) is a powerful analytical tool for studying mechanisms of redox reactions, identification of products and intermediates, and online derivatization/recognition of analytes. This work reports a new coupling interface for EC/MS by employing nanospray desorption electrospray ionization, a recently developed ambient ionization method. We demonstrate online coupling of nanospray desorption electrospray ionization MS with a traditional electrochemical flow cell, in which the electrolyzed solution emanating from the cell is ionized by nanospray desorption electrospray ionization for MS analysis. Furthermore, we show first coupling of nanospray desorption electrospray ionization MS with an interdigitated array (IDA) electrode enabling chemical analysis of electrolyzed samples directly from electrode surfaces. Because of its inherent sensitivity, nanospray desorption electrospray ionization enables chemical analysis of small volumes and concentrations of sample solution. Specifically, good-quality signal of dopamine and its oxidized form, dopamine o-quinone, was obtained using 10 μL of 1 μM solution of dopamine on the IDA. Oxidation of dopamine, reduction of benzodiazepines, and electrochemical derivatization of thiol groups were used to demonstrate the performance of the technique. Our results show the potential of nanospray desorption electrospray ionization as a novel interface for electrochemical mass spectrometry research.

  • 59. Mahmoudian, Laili
    et al.
    Kaji, Noritada
    Tokeshi, Manabu
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Baba, Yoshinobu
    Rolling circle amplification and circle-to-circle amplification of a specific gene integrated with electrophoretic analysis on a single chip2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 7, p. 2483-2490Article in journal (Refereed)
    Abstract [en]

    We have developed an integrated platform for rolling circle amplification (RCA) and circle-to-circle amplification (C2CA) of circular probe (padlock probe) and subsequent microchip electrophoretic detection of a specific gene on a poly(methyl methacrylate) microchip. RCA and C2CA were successfully carried out at a steady temperature of 37 degrees C in the sample well of the microchip, and their respective product was detected on the same channel of the microchip, which was prefilled with a polymer separation matrix and fluorescent dye. Using a species-specific padlock probe for bacterial pathogen V. cholerae, a 25-ng bacterial genomic DNA could be detected in less than 65 min (including RCA and microchip electrophoresis) by this platform. Stable dsDNA C2CA product of genomic DNA for V. cholerae can be detected with the introduced integrated platform. Furthermore, the usefulness of this technique for the monitoring of RCA was demonstrated. This integrated platform provides a sensitive, fast, high-throughput, and reproducible method for signal amplification and detection of the padlock probes in the same microchip and is a promising tool for highly specific gene detection strategies.

  • 60. Marty, Michael T
    et al.
    Baldwin, Andrew J
    Marklund, Erik G
    Hochberg, Georg K A
    Benesch, Justin L P
    Robinson, Carol V
    Bayesian deconvolution of mass and ion mobility spectra: from binary interactions to polydisperse ensembles.2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 8Article in journal (Refereed)
    Abstract [en]

    Interpretation of mass spectra is challenging because they report a ratio of two physical quantities, mass and charge, which may each have multiple components that overlap in m/z. Previous approaches to disentangling the two have focused on peak assignment or fitting. However, the former struggle with complex spectra, and the latter are generally computationally intensive and may require substantial manual intervention. We propose a new data analysis approach that employs a Bayesian framework to separate the mass and charge dimensions. On the basis of this approach, we developed UniDec (Universal Deconvolution), software that provides a rapid, robust, and flexible deconvolution of mass spectra and ion mobility-mass spectra with minimal user intervention. Incorporation of the charge-state distribution in the Bayesian prior probabilities provides separation of the m/z spectrum into its physical mass and charge components. We have evaluated our approach using systems of increasing complexity, enabling us to deduce lipid binding to membrane proteins, to probe the dynamics of subunit exchange reactions, and to characterize polydispersity in both protein assemblies and lipoprotein Nanodiscs. The general utility of our approach will greatly facilitate analysis of ion mobility and mass spectra.

  • 61.
    Melin, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Johansson, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nikolajeff, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Jarvius, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Thermoplastic microfluidic platform for single-molecule detection, cell culture and actuation2005In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 77, no 22, p. 7122-30Article in journal (Refereed)
    Abstract [en]

    We have developed a multipurpose microfluidic platform that allows for sensitive fluorescence detection on inexpensive disposable chips. The fabrication scheme involves rapid injection molding of thermoplastics, followed by silica deposition and covalent attachment of an unstructured flexible lid. This combines the virtues of elastomer technology with high-throughput compact disk injection molding. Using this technique, the time to produce 100 chips using a single master can be lowered from more than 1 week by standard PDMS technologies to only a couple hours. The optical properties of the fabricated chips were evaluated by studying individual fluorescence-labeled DNA molecules in a microchannel. Concatemeric DNA molecules were generated through rolling circle replication of circular DNA molecules, which were labeled by hybridization of fluorescence-tagged oligonucleotides. Rolling circle products (RCPs) were detected after as little as 5 min of DNA polymerization, and the RCPs in solution showed no tendency for aggregation. To illustrate the versatility of the platform, we demonstrate two additional applications: The flexible property of the lid was used to create a peristaltic pump generating a flow rate of 9 nL/s. Biocompatibility of the platform was illustrated by culturing Chinese hamster ovary cells for 7 days in the microfluidic channels.

  • 62.
    Moberg, My
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Nilsson, Eva M.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Holmström, Sara J. M.
    Lundström, Ulla S.
    Pettersson, Jean
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Markides, Karin E.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Fingerprinting metal-containing biomolecules after reductive displacement of iron by gallium and subsequent column-switched LC-ICPMS analysis applied on siderophores2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 9, p. 2618-2622Article in journal (Refereed)
    Abstract [en]

    Column-switching liquid chromatography followed by low-resolution ICPMS was evaluated as a tool for speciation analysis of metal-containing biomolecules. The strategy was applied on siderophores, strong iron chelators of low molecular weight (M(w) < 1500). Prior to the LC-ICPMS analysis, reductive displacement of iron by gallium was performed using ascorbate as the reducing agent to increase the sensitivity. Different experimental conditions during the exchange reaction were tested using ferrichrysin and ferrichrome for evaluation. A reaction time of 30 min and a pH of 3.9 gave an exchange yield of 27 and 83% for ferrichrysin and ferrichrome, respectively. A gradient elution profile was also developed to separate gallium-chelated siderophores on a PGC column. Detection limits for standard solutions of ferrichrysin and ferrichrome in the low-nanomolar range were obtained by monitoring the gallium-69 isotope. The combined use of LC-ICPMS and LC-ESI-MS/MS was also evaluated as a tool to identify unknown metal complexes, here siderophores, in field soil solution samples.

  • 63.
    Nielsen, Michael L.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Savitski, Mikhail M.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Kjeldsen, Frank
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Zubarev, Roman A.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Physicochemical properties determining the detection probability of tryptic peptides in Fourier transform mass spectrometry. A correlation study2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 19, p. 5872-5877Article in journal (Refereed)
    Abstract [en]

    Sequence verification and mapping of posttranslational modifications require nearly 100% sequence coverage in the "bottom-up" protein analysis. Even in favorable cases, routine liquid chromatography-mass spectrometry detects from protein digests peptides covering 50-90% of the sequence. Here we investigated the reasons for limited peptide detection, considering various physicochemical aspects of peptide behavior in liquid chromatography-Fourier transform mass spectrometry (LC-FTMS). No overall correlation was found between the detection probability and peptide mass. In agreement with literature data, the signal increased with peptide hydrophobicity. Surprisingly, the pI values exhibited an opposite trend, with more acidic tryptic peptides detected with higher probability. A mixture of synthesized peptides of similar masses confirmed the hydrophobicity dependence but showed strong positive correlation between pI and signal response. An explanation of this paradoxal behavior was found through the observation that more acidic tryptic peptide lengths tend to be longer. Longer peptides tend to acquire higher average charge state in positive mode electrospray ionization than more basic but shorter counterparts. The induced-current detection in FTMS favors ions in higher charge states, thus providing the observed pI-FTMS signal anticorrelation.

  • 64.
    Nilsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Goodwin, Richard J. A.
    Shariatgorji, Mohammadreza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Vallianatou, Theodosia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Webborn, Peter J. H.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mass Spectrometry Imaging in Drug Development2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 3, p. 1437-1455Article, review/survey (Refereed)
  • 65. Ordeig, Olga
    et al.
    Godino, Neus
    del Campo, Javier
    Muñoz, Francesc Xavier
    Nikolajeff, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Micro Structural Technology.
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Inorganic Chemistry.
    On-Chip Electric Field Driven Electrochemical Detection Using a Poly(dimethylsiloxane) Microchannel with Gold Microband Electrodes2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 10, p. 3622-3632Article in journal (Refereed)
    Abstract [en]

    An external electric field driven in-channel detection technique for on-chip electrochemical detection in micro fabricated devices is described based on a microfluidic system containing an array of 20 microband electrodes. It is shown that an external electric field induces a potential difference between two gold microband electrodes in a poly(dimethylsiloxane) (PDMS) microchannel, and that this enables the electrochemical detection of electroactive species such as ascorbic acid and Fe(CN)64−. The results, which are supported by simulations of the behavior of the microband electrodes in the microfluidic system, show that the induced potential difference between the electrodes can be controlled by altering the external electric field or by using different microbands in the microband array. As the obtained currents depend on the concentrations of electroactive species in the flowing solution and the detection can be carried out anywhere within the channel without interference of the external electric field, the present approach significantly facilitates electrochemical detection in capillary electrophoresis. This approach consequently holds great promise for application in inexpensive portable chip-based capillary electrophoresis (CE) devices.

  • 66.
    Palmblad, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Ramström, Margareta
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Markides, Karin E
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Håkansson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Prediction of chromatographic retention and protein identification in liquid chromatography/mass spectrometry2002In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 74, no 22, p. 5826-5830Article in journal (Refereed)
    Abstract [en]

    Liquid chromatography coupled on- or off-line with mass spectrometry is rapidly advancing as a tool in proteomics capable of dealing with the inherent complexity in biology and complementing conventional approaches based on two-dimensional gel electrophoresis. Proteins can be identified by proteolytic digestion and peptide mass fingerprinting or by searching databases using short-sequence tags generated by tandem mass spectrometry. This paper shows that information on the chromatographic behavior of peptides can assist protein identification by peptide mass fingerprinting in liquid chromatography/mass spectrometry. This additional information is significant and already available at no extra experimental cost.

  • 67.
    Paraskova, Julia V.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Jorgensen, Charlotte
    Reitzel, Kasper
    Pettersson, Jean
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Rydin, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Speciation of Inositol Phosphates in Lake Sediments by Ion-Exchange Chromatography Coupled with Mass Spectrometry, Inductively Coupled Plasma Atomic Emission Spectroscopy, and P-31 NMR Spectroscopy2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 5, p. 2672-2677Article in journal (Refereed)
    Abstract [en]

    A method for the detection and speciation of inositol phosphates (InsP(n)) in sediment samples was tested, utilizing oxalateoxalic acid extraction followed by determination by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLCMS/MS) using electrospray ionization (ESI) in negative mode. The chromatographic separation was carried out using water and ammonium bicarbonate as mobile phase in gradient mode. Data acquisition under MS/MS was attained by multiple reaction monitoring. The technique provided a sensitive and selective detection of InsP(n) in sediment samples. Several forms of InsPn in the oxalateoxalic acid extracted sediment were identified. InsP(6) was the dominating form constituting 0.250 mg P/g DW (dry weight); InsP(5) and InsP(4) constituted 0.045 and 0.014 mg P/g DW, respectively. The detection limit of the LCESI-MS/MS method was 0.03 mu M InsPn, which is superior to the currently used method for the identification of InsPn, P-31 nuclear magnetic resonance spectroscopy (P-31 NMR). Additionally sample handling time was significantly reduced.

  • 68.
    Pavankumar, Asalapuram R.
    et al.
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden..
    Engström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden.;Res Ctr Borstel, Mol & Expt Mycobacteriol, Borstel, Germany..
    Liu, Jie
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden.;Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China..
    Herthnek, David
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden..
    Nilsson, Mats
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden..
    Proficient Detection of Multi-Drug-Resistant Mycobacterium tuberculosis by Padlock Probes and Lateral Flow Nucleic Acid Biosensors2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 8, p. 4277-4284Article in journal (Refereed)
    Abstract [en]

    Tuberculosis is a major communicable disease. Its causative agent, Mycobacterium tuberculosis, becomes resistant to antibiotics by acquisition of point mutations in the chromosome. Multi-drug-resistant tuberculosis (MDR-TB) is an increasing public health threat, and prompt detection of such strains is of critical importance. As rolling circle amplification of padlock probes can be used to robustly distinguish single-nucleotide variants, we combined this technique with a sensitive lateral flow nucleic acid biosensor to develop a rapid molecular diagnostic test for MDR-TB, A proof-of-concept test was established for detection of the most common mutations [rpoB 531 (TCG/TTG) and katG 315 (AGC/ACC)] causing MDR-TB and verification of loss of the respective wild type. The molecular diagnostic test produces visual signals corresponding to the respective genotypes on lateral flow strips in approximately 75 min. By detecting only two mutations, the test can detect about 60% of all MDR-TB cases. The padlock probe-lateral flow (PLP-LF) test is the first of its kind and can ideally be performed at resource-limited clinical laboratories. Rapid information about the drug-susceptibility pattern can assist clinicians to choose suitable treatment regimens and take appropriate infection control actions rather than prescribing empirical treatment, thereby helping to control the spread of MDR-TB in the community.

  • 69.
    Persson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Eilers, Gerriet
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Ryderfors, Linus
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Mukhtar, Emad
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Possnert, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Salehpour, Mehran
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Evaluation of Intracavity Optogalvanic Spectroscopy for Radiocarbon Measurements2013In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 85ASAP, no 14, p. 6790-6798Article in journal (Refereed)
    Abstract [en]

    Ever since the first publication of intracavity optogalvanic spectroscopy (ICOGS) in 2008, this novel technique for measuring the 14C/12C ratio in carbon dioxide has rendered considerable attention. As a result, there are currently at least five different research groups pursuing research on ICOGS. With a claimed limit of detection of 10–15 (14C/12C), i.e., in the same order as accelerator mass spectroscopy, achieved with a relatively inexpensive and uncomplicated table-top system, ICOGS has major scientific and commercial implications. However, during the past 5 years, no research group has been able to reproduce these results or present additional proof for ICOGS’s capability of unambiguous 14C detection, including the authors of the original publication. Starting in 2010, our group has set up a state-of-the-art ICOGS laboratory and has investigated the basic methodology of ICOGS in general and tried to reproduce the reported experiments in particular. We have not been able to reproduce the reported results concerning the optogalvanic signals dependence on14C concentration and wavelength and, ultimately, not seen any evidence of the capability of ICOGS to unambiguously detect 14C at all. Instead, we have found indications that the reported results can be products of measurement uncertainties and mistakes. Furthermore, our results strongly indicate that the reported limit of detection is likely to be overestimated by at least 2 orders of magnitude, based on the results presented in the original publication. Hence, we conclude that the original reports on ICOGS cannot be confirmed and therefore must be in error.

  • 70.
    Persson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Salehpour, Mehran
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Comment on “Intracavity OptoGalvanic Spectroscopy Not Suitable for Ambient Level Radiocarbon Detection"2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 8, p. 4578-4579Article in journal (Refereed)
    Abstract [en]

    Every new discovery must undergo thorough scientific scrutiny before being recognized. One important step in the process is confirmation by independent experiments. The case at hand is intracavity optogalvanic spectroscopy (ICOGS), which was first published by Murnick et al. in 2008, and claimed to have the potential to revolutionize rare-isotope measurements in general and those of radiocarbon in particular. Since then, no data has been reported in any shape or form to support it. On the contrary, in spite of extensive efforts at five different sites around the world – apart from Murnick’s group at Rutgers University, Professor Meijer’s group at the Energy and Sustainability Research Institute Groningen at University of Groningen, Professor Lackner’s group at the Department of Earth and Environmental Engineering at Columbia University, our group at the Department of Physics and Astronomy at Uppsala University, and the company Planetary Emission Management Inc. – the original data still remains unconfirmed, and a number of publications have seriously questioned the scientific validity of the original report.

  • 71.
    Pettersson, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Amirkhani, Ardeshir
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Arvidsson, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    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.
    A feasibility study of solid supported enhanced microdialysis2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 6, p. 1678-1682Article in journal (Refereed)
    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.

  • 72.
    Resendez, Angel
    et al.
    Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
    Panescu, Priera
    Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
    Zuniga, Ruth
    Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
    Banda, Isaac
    Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
    Joseph, Jorly
    Mahatma Gandhi Univ, IIRBS, Kottayam 686560, Kerala, India.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
    Singaram, Bakthan
    Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
    Multiwell Assay for the Analysis of Sugar Gut Permeability Markers: Discrimination of Sugar Alcohols with a Fluorescent Probe Array Based on Boronic Acid Appended Viologens2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 10, p. 5444-5452Article in journal (Refereed)
    Abstract [en]

    With the aim of discerning between different sugar and sugar alcohols of biomedical relevance, such as gut permeability, arrays of 2-component probes were assembled with up to six boronic acid-appended viologens (BBVs): 4,4'-o-BBV, 3,3'-o-BBV, 3,4'-o-BBV, 4,4'-o,m-BBV, 4,7'-o-PBBV, and pBoB, each coupled to the fluorophore 8-hydroxypyrene, 1,3,6-trisulfonic acid trisodium salt (HPTS). These probes were screened for their ability to discriminate between lactulose, l-rhamnose, 3-O-methyl-d-glucose, and xylose. Binding studies of sugar alcohols mannitol, sorbitol, erythritol, adonitol, arabitol, galactitol, and xylitol revealed that diols containing threo-1,2-diol units have higher affinity for BBVs relative diols containing erythro-1,2 units. Those containing both threo-1,2- and 1,3-syn diol motifs showed high affinity for boronic acid binding. Fluorescence from the arrays were examined by principle component analysis (PCA) and linear discriminant analysis (LDA). Arrays with only three BBVs sufficed to discriminate between sugars (e.g., lactulose) and sugar alcohols (e.g., mannitol), establishing a differential probe. Compared with 4,4'-o-BBV, 2-fold reductions in lower limits of detection (LOD) and quantification (LOQ) were achieved for lactulose with 4,7-o-PBBV (LOD 41 μM, LOQ 72 μM). Using a combination of 4,4'-o-BBV, 4,7-o-PBBV, and pBoB, LDA statistically segregated lactulose/mannitol (L/M) ratios from 0.1 to 0.5, consistent with values encountered in small intestinal permeability tests. Another triad containing 3,3'-o-BBV, 4,4'-o-BBV, and 4,7-o-PBBV also discerned similar L/M ratios. This proof-of-concept demonstrates the potential for BBV arrays as an attractive alternate to HPLC to analyze mixtures of sugars and sugar alcohols in biomedical applications and sheds light on structural motifs that make this possible.

  • 73.
    Russell, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Roy, Subhadeep
    Ganguly, Saheli
    Qian, Xiaoyan
    Caruthers, Marvin H.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Formation of Silver Nanostructures by Rolling Circle Amplification Using Boranephosphonate-Modified Nucleotides2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 13, p. 6660-6666Article in journal (Refereed)
    Abstract [en]

    We investigate the efficiency of incorporation of boranephosphonate-modified nucleotides by phi29 DNA poly, merase and present a simple method for forming large defined silver nanostructures by rolling circle amplification (RCA) using boranephosphonate internudeotide linkages. RCA is a linear DNA amplification technique that can use specifically circularized DNA probes for detection of target nucleic acids and proteins. The resulting product is a collapsed single-stranded DNA molecule with tandem repeats of the DNA probe. By substituting each of the natural nucleotides with the corresponding 5'-(alpha-P-borano)-deoxynudeosidetriphosphate, only a small reduction in amplification rate is observed. Also, by substituting all four natural nucleotides, it is possible to enzymatically synthesize a micrometensized, single-stranded DNA molecule with only boranephosphonate internucleotide linkages. Well-defined silver particles are then readily formed along the rolling circle product.

  • 74.
    Salehpour, Mehran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Possnert, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Bryhni, Heige
    Subattomole sensitivity in biological accelerator mass spectrometry2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 10, p. 3515-3521Article in journal (Refereed)
    Abstract [en]

    The Uppsala University 5 MV Pelletron tandem accelerator has been used to study C-14-labeled biological samples utilizing accelerator mass spectrometry (ANIS) technology. We have adapted a sample preparation method for small biological samples down to a few tens of micrograms of carbon, involving among others, miniaturizing of the graphitization reactor. Standard AMS requires about 1 mg of carbon with a limit of quantitation of about 10 amol. Results are presented for a range of small sample sizes with concentrations down to below 1 pM of a pharmaceutical substance in human blood. It is shown that C-14-labeled molecular markers can be routinely measured from the femtomole range down to a few hundred zepto-mole (10(-21) mol), without the use of any additional separation methods.

  • 75.
    Samuelsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Arnell, Robert
    Diesen, Jarle
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Tibbelin, Julius
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Paptchikhine, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Development of the Tracer-Pulse method for adsorption studies of analyte mixures in liquid chromatography utilizing mass spectrometric detection2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 6, p. 2105-2112Article in journal (Refereed)
    Abstract [en]

    The tracer-pulse method provides the real adsorption data points directly from simple, straightforward calculations and is therefore a superior method for multicomponent adsorption isotherm determination in HPLC. Only one important problem has restricted its use so far: the tracer peaks are invisible using any conventional detection principle. We present a solution to this problem with an approach with a firm base in analytical chemistry, utilizing stable isotopes and mass spectrometric detection. The new approach was used for the determination of binary adsorption isotherms, and a systematic investigation was made of its main sources of error. With this modification, the tracer method can be a prime choice for future characterizations of multicomponent separation systems and of competitive drug binding studies.

  • 76.
    Samuelsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Injection technique for generating accurate adsorption isotherm data using the elution by characteristic points method2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 20, p. 7887-7893Article in journal (Refereed)
    Abstract [en]

    With the use of the elution by characteristic points (ECP) method, the adsorption isotherms are rapidly determined from the diffusive part of an overloaded elution profile. However, very large injection volumes are required, which lead to extremely tailed rears of the injection profiles. The ECP method is based on a theory assuming rectangular injection profiles and can therefore not account for such profiles. Consequently, the use of the ECP method in the traditional way, with classical full-loop injections, results in serious errors on the determined adsorption isotherm parameters which has not been demonstrated until this study. Therefore, we developed and validated a new experimental injection method, here denoted the "cut-injection" technique where instead nearly rectangular injection profiles are generated. The result convincingly shows that adsorption isotherms acquired by using the new cut-injection technique nearly totally coincide with adsorption isotherms determined using the accurate reference methods.

  • 77.
    Samuelsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Forssén, Patrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing.
    Stefansson, Morgan
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Surface Biotechnology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Experimental Proof of a Chromatographic Paradox: Are the injected molecules in the peak?2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, p. 953-958Article in journal (Refereed)
  • 78.
    Sandblad, Peter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Arnell, Robert
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Samuelsson, Jörgen
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Approach for reliable evaluation of drug proteins interactions using surface plasmon resonance technology2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 9, p. 3551-3559Article in journal (Refereed)
    Abstract [en]

    The surface plasmon resonance (SPR) biosensor was recently introduced to the analytical biochemical society for measuring small drug-protein interactions. However, the technique has many times been used without specifying the type of enantiomeric form of the chiral drug measured and/or with using a too narrow drug concentration range resulting in biased values of binding coefficients and sometimes even assumptions about single-site bindings although the binding in reality comprises a multisite interaction. In this study we will give guidelines for reliable experimental and methodological approaches to avoid these pitfalls. For this purpose, we also introduce a new tool, based on physical chemistry, to the sensor community; the calculation of the adsorption energy distribution (AED). The AED-calculations reveal the degree of heterogeneity directly from the SPR raw data and thus guide us into a narrower selection of probable models before the rival model fitting procedure. We demonstrate how to measure reliable equilibrium data for the two typically different cases: drug binding to (i) transport (plasma) proteins and to (ii) a target protein. Both the binding of the chiral beta-blocker propranolol to alpha(1)-acid glycoprotein (AGP) and that of the anticoagulant warfarin to human serum albumin were heterogeneous, with a few strong enantioselective sites and many weak nonselective sites. We also demonstrate how the multisite binding rapidly falsely turns to single-site as the concentration range is narrowed and how adding dimethyl sulfoxide to the buffer affects multisite drug-protein data. The binding of the enantiomers of the thrombin inhibitor melagatran was investigated on both thrombin and the transport proteins, revealing clear enantioselectivity for thrombin in favor of the active enantiomer, but almost similar binding properties for both enantiomers to the transport protein AGP. The AED-calculations verified that both these system has a unimodal energy distribution and are best described with a homogeneous adsorption model.

  • 79.
    Santos-Neto, Alvaro J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Sjöberg, Per
    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.
    Lancas, Fernando M.
    Capillary Column Switching Restricted-Access Media-Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry System for Simultaneous and Direct Analysis of Drugs in Biofluids2007In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 79, no 16, p. 6359-6367Article in journal (Refereed)
    Abstract [en]

    Capillary online restricted-access media-liquid chromatography-electrospray ionization-tandem mass spectrometry (RAM-LC-ESI-MS/MS) for direct analysis of drugs and metabolites spiked in biological fluids was developed. Using a column switching setup it was possible to perform effective sample preparation and analysis of raw biological fluids (plasma and urine) without matrix effects in the electrospray mass spectrometric detection step. The peak focusing efficiency of the extraction column was more effective in backflush compared to foreflush mode. The system was able to concentrate diminished samples of polar drugs and their metabolites reaching quantifiable results as low as 1 ng/mL utilizing a sample volume of only 333 nL of biofluids. New column hardware was developed to circumvent clogging problems experienced with plasma injections. The glass fiber filter frit, which is commonly used, was replaced with a short piece of 20 μm i.d. fused silica capillary. The extraction columns were able to handle up to 60 injections and showed a high loading capacity, making the saturation of the MS detector the limiting factor on the linear dynamic range. The simultaneous separation and detection of 10 drugs and metabolites was obtained in 8 min of analysis, including the online sample preparation and enrichment step.

  • 80.
    Savitski, Mikhail M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
    Nielsen, Michael L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
    Zubarev, Roman A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
    Side-chain losses in electron capture dissociation to improve peptide identification2007In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 79, no 6, p. 2296-2302Article in journal (Refereed)
    Abstract [en]

    Analysis of a database of some 20 000 conventional electron-capture dissociation (ECD) mass spectra of doubly charged ions belonging to tryptic peptides revealed widespread appearance of w ions and related u ions that are due to partial side chain losses from radical z. ions. Half of all z. ions that begin with Leu or Ile produce w ions in conventional one-scan ECD mass spectra, which differentiates these isomeric residues with >97% reliability. Other residues exhibiting equally frequent side chain losses are Gln, Glu, Asp, and Met (cysteine was not included in this work). Unexpectedly, Asp lost not a radical group like other amino acids but a molecule CO2, thus giving rise to a radical w. ion with the possibility of a radical cascade. Losses from amino acids as distant as seven residues away from the cleavage site were detected. The mechanism of such losses seems to be related to radical migration from the original site at the αCn atom in a Zn. ion to other αC and βC atoms. The side chain losses confirm sequence assignment, improve the database matching score, and can be useful in de novo sequencing.

  • 81.
    Shariatgorji, Mohammadreza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Källback, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gustavsson, Lena
    Schintu, Nicoletta
    Svenningsson, Per
    Goodwin, Richard J. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Controlled-pH Tissue Cleanup Protocol for Signal Enhancement of Small Molecule Drugs Analyzed by MALDI-MS Imaging2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 10, p. 4603-4607Article in journal (Refereed)
    Abstract [en]

    The limit of detection of low-molecular weight compounds in tissue sections, analyzed by matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), was significantly improved by employing sample washing using a pH-controlled buffer solution. The pH of the washing solutions were set at values whereby the target analytes would have low solubility. Washing the tissue sections in the buffered solution resulted in removal of endogenous soluble ionization-suppressing compounds and salts, while the target compound remained in situ with minor or no delocalization during the buffered washing procedure. Two pharmaceutical compounds (cimetidine and imipramine) and one new protease inhibitor compound were successfully used to evaluate the feasibility of the pH-controlled tissue washing protocol for MALDI-MSI. Enhancement in signal-to-noise ratio was achieved by a factor of up to 10.

  • 82.
    Shariatgorji, Mohammadreza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Goodwin, Richard J. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Svenningsson, Per
    Schintu, Nicoletta
    Banka, Zoltan
    Kladni, Laszlo
    Hasko, Tibor
    Szabo, Andras
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Deuterated Matrix-Assisted Laser Desorption Ionization Matrix Uncovers Masked Mass Spectrometry Imaging Signals of Small Molecules2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 16, p. 7152-7157Article in journal (Refereed)
    Abstract [en]

    D-4-alpha-Cyano-4-hydroxycinnamic acid (D-4-CHCA) has been synthesized for use as a matrix for matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) and MALDI-MS imaging (MSI) of small molecule drugs and endogenous compounds. MALDI-MS analysis of small molecules has historically been hindered by interference from matrix ion clusters and fragment peaks that mask signals of low molecular weight compounds of interest. By using D-4-CHCA, the cluster and fragment peaks of CHCA, the most common matrix for analysis of small molecules, are shifted by + 4, + 8 and + 12 Da, which expose signals across areas of the previously concealed low mass range. Here, obscured MALDI-MS signals of a synthetic small molecule pharmaceutical, a naturally occurring isoquinoline alkaloid, and endogenous compounds including the neurotransmitter acetylcholine have been unmasked and imaged directly from biological tissue sections.

  • 83. Sjövall, Peter
    et al.
    Lausmaa, Jukka
    Johansson, Bo-Lennart
    Andersson, Mikael
    Surface Chemical Analysis of Carbohydrate Materials Used for Chromatography Media by Time-of-Flight Secondary Ion Mass Spectrometry2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 7, p. 1857-1864Article in journal (Refereed)
    Abstract [en]

    The surface chemical structure of two raw materials (agarose and dextran) and four base matrixes used in the manufacture of chromatography media were analyzed using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The results show that the small differences in molecular structure between these materials result in significant differences in the TOF-SIMS spectra and that these differences can be identified and quantified using either of two different approaches. In a novel approach, fragment ion distributions were extracted from the TOF-SIMS spectra for each material, providing an immediate and systematic overview of the spectral features. Difference fragment distributions were used to highlight spectral differences between the materials. The results of the fragment ion distribution analysis, in terms of identification and quantification of spectral variations between different materials, were found to be in agreement with the results from a principal component analysis using the same set of data. Both methods were found capable of (i) distinguishing between agarose and dextran and (ii) detecting and quantifying the degree of cross-linking present in the four base matrix materials. In addition, using a deuterated chemical cross-linker, it was possible to identify spectral features specifically connected to the cross-link molecular structure.

  • 84.
    Stolt, Ragnar
    et al.
    Department of Analytical Chemistry, BioSysteMetrics Group, Stockholm University.
    Torgrip, Ralf J. O.
    Lindberg, Johan
    Csenki, Leonard
    Kolmert, Johan
    Schuppe-Koistinen, Ina
    Jacobsson, Sven P.
    Second-Order Peak Detection for Multicomponent High-Resolution LC/MS Data2006In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 78, no 4, p. 975-83Article in journal (Refereed)
    Abstract [en]

    The first step when analyzing multicomponent LC/MS data from complex samples such as biofluid metabolic profiles is to separate the data into information and noise via, for example, peak detection. Due to the complex nature of this type of data, with problems such as alternating backgrounds and differing peak shapes, this can be a very complex task. This paper presents and evaluates a two-dimensional peak detection algorithm based on raw vector-represented LC/MS data. The algorithm exploits the fact that in high-resolution centroid data chromatographic peaks emerge flanked with data voids in the corresponding mass axis. According to the proposed method, only 4‰ of the total amount of data from a urine sample is defined as chromatographic peaks; however, 94% of the raw data variance is captured within these peaks. Compared to bucketed data, results show that essentially the same features that an experienced analyst would define as peaks can automatically be extracted with a minimum of noise and background. The method is simple and requires a priori knowledge of only the minimum chromatographic peak widtha system-dependent parameter that is easily assessed. Additional meta parameters are estimated from the data themselves. The result is well-defined chromatographic peaks that are consistently arranged in a matrix at their corresponding m/z values. In the context of automated analysis, the method thus provides an alternative to the traditional approach of bucketing the data followed by denoising and/or one-dimensional peak detection. The software implementation of the proposed algorithm is available at http://www.anchem.su.se/peakd as compiled code for Matlab.

  • 85.
    Strömberg, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zardán Gómez de la Torre, Teresa
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Göransson, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gunnarsson, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Svedlindh, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Multiplex Detection of DNA Sequences Using the Volume-Amplified Magnetic Nanobead Detection Assay2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 9, p. 3398-3406Article in journal (Refereed)
    Abstract [en]

    The possibility for conducting multiplex detection of DNA-sequences using the volume-amplified magnetic nanobead detection assay[Stromberg, M.; Goransson, J.; Gunnarsson, K; Nilsson, M.; Svedlindh, P.; Stromme, M. Nano Lett. 2008, 8, 816-821] was investigated. In this methodology, a batch consisting of a mixture of several sizes of probe-tagged magnetic beads was used for detection of several types of  targets in the same compartment Furthermore, a nonlinear least-squares deconvolution procedure of the composite imaginary part of complex   magnetization vs frequency spectra based on the Cole-Cole model was   applied to analyze the data. The results of a quantitative biplex analysis experiment were compared with the corresponding separate   single-target assays. Finally, triplex analysis was briefly demonstrated qualitatively. Biplex and triplex detection were found to perform well qualitatively. Biplex detection was found to enable a rough target quantification. Multiplex detection may become a  complement to performing multiple separate single-target assays for, e.g., parallel detection of multiple infectious pathogens. Multiplex detection also permits robust relative quantification and inclusion of an internal control to improve quantification accuracy.

  • 86. Suits, Frank
    et al.
    Hoekman, Berend
    Rosenling, Therese
    Bischoff, Rainer
    Horvatovich, Peter
    Threshold-avoiding proteomics pipeline.2011In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 20, p. 7786-94Article in journal (Refereed)
    Abstract [en]

    We present a new proteomics analysis pipeline focused on maximizing the dynamic range of detected molecules in liquid chromatography-mass spectrometry (LC-MS) data and accurately quantifying low-abundance peaks to identify those with biological relevance. Although there has been much work to improve the quality of data derived from LC-MS instruments, the goal of this study was to extend the dynamic range of analyzed compounds by making full use of the information available within each data set and across multiple related chromatograms in an experiment. Our aim was to distinguish low-abundance signal peaks from noise by noting their coherent behavior across multiple data sets, and central to this is the need to delay the culling of noise peaks until the final peak-matching stage of the pipeline, when peaks from a single sample appear in the context of all others. The application of thresholds that might discard signal peaks early is thereby avoided, hence the name TAPP: threshold-avoiding proteomics pipeline. TAPP focuses on quantitative low-level processing of raw LC-MS data and includes novel preprocessing, peak detection, time alignment, and cluster-based matching. We demonstrate the performance of TAPP on biologically relevant sample data consisting of porcine cerebrospinal fluid spiked over a wide range of concentrations with horse heart cytochrome c.

  • 87.
    Svedberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Pettersson, A.
    Nilsson, S.
    Bergquist, J.
    Nyholm, L.
    Nikolajeff, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Markides, K.E.
    Sheathless electrospray from polymer microchips2003In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 75, no 15, p. 3934-3940Article in journal (Refereed)
  • 88.
    Svedberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Pettersson, Andreas
    Nilsson, Stefan
    Bergquist, Jonas
    Nyholm, Leif
    Nikolajeff, Fredrik
    Markides, Karin
    Sheathless Electrospary from a Polymer Microchip2003In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 75, no 15, p. 3934-3940Article in journal (Refereed)
  • 89.
    Svensson, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sköld, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Fälth, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nydahl, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Svenningsson, Per
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
    Neuropeptidomics: MS applied to the discovery of novel peptides from the brain2007In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 79, no 1, p. 14-21Article in journal (Refereed)
    Abstract [en]

    Peptidomics involves the comprehensive analysis of the peptide content of a certain cell, organ, body fluid, or organism. Per E. Andrén and colleagues at Uppsala University and the Karolinska Institutet (both in Sweden) describe neuropeptidomics approaches in brain lysates and tissue sections to study peptide expression in disease models and to identify potentially biologically active neuropeptides.

  • 90.
    Swales, John G.
    et al.
    AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England;Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 1WB, S Yorkshire, England.
    Dexter, Alex
    Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England.
    Hamm, Gregory
    AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strittmatter, Nicole
    AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England.
    Michopoulos, Filippos
    AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England.
    Hardy, Christopher
    AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England.
    Morentin-Gutierrez, Pablo
    AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England.
    Mellor, Martine
    AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Clench, Malcolm R.
    Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 1WB, S Yorkshire, England.
    Bunch, Josephine
    Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England.
    Critchlow, Susan E.
    AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England.
    Goodwin, Richard J. A.
    AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England.
    Quantitation of Endogenous Metabolites in Mouse Tumors Using Mass-Spectrometry Imaging2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 10, p. 6051-6058Article in journal (Refereed)
    Abstract [en]

    Described is a quantitative-mass-spectrometry-imaging (qMSI) methodology for the analysis of lactate and glutamate distributions in order to delineate heterogeneity among mouse tumor models used to support drug-discovery efficacy testing. We evaluate and report on preanalysis-stabilization methods aimed at improving the reproducibility and efficiency of quantitative assessments of endogenous molecules in tissues. Stability experiments demonstrate that optimum stabilization protocols consist of frozen-tissue embedding, post-tissue-sectioning desiccation, and storage at -80 degrees C of tissue sections sealed in vacuum-tight containers. Optimized stabilization protocols are used in combination with qMSI methodology for the absolute quantitation of lactate and glutamate in tumors, incorporating the use of two different stable-isotope-labeled versions of each analyte and spectral-clustering performed on each tissue section using k-means clustering to allow region-specific, pixel-by-pixel quantitation. Region-specific qMSI was used to screen different tumor models and identify a phenotype that has low lactate heterogeneity, which will enable accurate measurements of lactate modulation in future drug-discovery studies. We conclude that using optimized qMSI protocols, it is possible to quantify endogenous metabolites within tumors, and region-specific quantitation can provide valuable insight into tissue heterogeneity and the tumor microenvironment.

  • 91. Swales, John G.
    et al.
    Tucker, James W.
    Strittmatter, Nicole
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Cobice, Diego
    Clench, Malcolm R.
    Mackay, C. Logan
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Takats, Zoltan
    Webborn, Peter J. H.
    Goodwin, Richard J. A.
    Mass Spectrometry Imaging of Cassette-Dosed Drugs for Higher Throughput Pharmacokinetic and Biodistribution Analysis2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 16, p. 8473-8480Article in journal (Refereed)
    Abstract [en]

    Cassette dosing of compounds for preclinical drug plasma pharmacokinetic analysis has been shown to be a powerful strategy within the pharmaceutical industry for increasing throughput while decreasing the number of animals used. Presented here for the first time is data on the application of a cassette dosing strategy for label-free tissue distribution studies. The aim of the study was to image the spatial distribution of eight nonproprietary drugs (haloperidol, bufuralol, midazolam, clozapine, terfenadine, erlotinib, olanzapine, and moxifloxacin) in multiple tissues after oral and intravenous cassette dosing (four compounds per dose route). An array of mass spectrometry imaging technologies, including matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), liquid extraction surface analysis tandem mass spectrometry (LESA-MS/MS), and desorption electrospray ionization mass spectrometry (DESI-MS) was used. Tissue analysis following intravenous and oral administration of discretely and cassette-dosed compounds demonstrated similar relative abundances across a range of tissues indicating that a cassette dosing approach was applicable. MALDI MSI was unsuccessful in detecting all of the target compounds; therefore, DESI MSL a complementary mass spectrometry imaging technique, was used to detect additional target compounds. In addition, by adapting technology used for tissue profiling (LESA-MS/MS) low spatial resolution mass spectrometry imaging (similar to 1 mm) was possible for all targets across all tissues. This study exemplifies the power of multiplatform MSI analysis within a pharmaceutical research and development (R&D) environment. Furthermore, we have illustrated that the cassette dosing approach can be readily applied to provide combined, label-free pharmacokinetic and drug distribution data at an early stage of the drug discovery/development process while minimizing animal usage.

  • 92. Tanaka, Yo
    et al.
    Xi, Hui
    Sato, Kae
    Mawatari, Kazuma
    Renberg, Björn
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kitamori, Takehiko
    Single-Molecule DNA Patterning and Detection by Padlock Probing and Rolling Circle Amplification in Microchannels for Analysis of Small Sample Volumes2011In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 9, p. 3352-3357Article in journal (Refereed)
    Abstract [en]

    The rolling circle amplification (RCA) is a versatile DNA amplification method in which a DNA molecule is amplified using a single DNA primer, allowing the product to be counted as a single dot. Circular templates for RCA can arise from padlock probes in highly specific DNA target-mediated ligation reactions. However, improvement of detection efficiency represents an important challenge. In homogeneous assays, the detection efficiency is generally only under 0.1%, mainly because the sample volume is too large compared with the detection volume. Here, we used microchannel surfaces in a glass microchip for DNA detection in small volume samples. First, DNA patterning on glass surfaces in microchannels was demonstrated using chemical surface patterning by UV light. By using a photochemical reaction, we realized DNA patterning in a closed space. Second, RCA was demonstrated using dilutions of target molecules, and a calibration curve was obtained. The highest detection efficiency was 22.5% by virtue of the reduced sample volumes from several hundred microliters to 5.0 nL. Accordingly, a countable number of DNA molecules was successfully detected. This method is suitable for analysis of very small volume samples such as single cells, especially by using extended-nanochannels with dimensions of 10-1000 nm.

  • 93.
    Tenje, Maria
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Lund University, Department of Biomedical Engineering.
    Fornell, Anna
    Lund University, Department of Biomedical Engineering.
    Ohlin, Mathias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Nilsson, Johan
    Lund University, Department of Biomedical Engineering.
    Particle Manipulation Methods in Droplet Microfluidics2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 3, p. 1434-1443Article in journal (Refereed)
    Abstract [en]

    This Feature article describes the different particle manipulation techniques available in the droplet microfluidics tool-box to handle particles encapsulated inside droplets and to manipulate whole droplets. We address the advantages and disadvantages of the different techniques to guide new users.  

  • 94. Ulrich, Christian
    et al.
    Andersson, Olof
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Inorganic Chemistry.
    Björefors, Fredrik
    Potential and Current Distributions at Electrodes intended for Bipolar Patterning2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 1, p. 453-459Article in journal (Refereed)
    Abstract [en]

    This paper deals with the use of reaction gradients on bipolar electrodes for the patterning of electrode surfaces. More specifically, the potential and current density distributions in two setups containing bipolar electrodes were investigated to optimize and design specific gradient geometries. Comparisons with simulations based on simple conductivity models showed a good qualitative agreement, demonstrating that these models could be used to predict bipolar behavior in more complex setups. In conjunction with imaging surface plasmon resonance (iSPR) experiments, the reaction gradients on bipolar electrodes could further be visualized. It was, for example, found that the gradient in potential difference was approximately linearly distributed in the center of the bipolar electrode and that these potential differences could be determined using an ordinary Ag/AgCl reference electrode. The present results thus provide a better understanding of the processes relevant for bipolar patterning. This approach was finally used to generate a circular gradient region in a self-assembled monolayer, thereby showing the possibilities to create interesting substrates for biosensors and microarray applications.

  • 95.
    Wang, Xiaofeng
    et al.
    Institute of Analytical and Bioanalytical Chemistry, University of Ulm.
    Karlsson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Forsberg, Pontus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Sieger, Markus
    Institute of Analytical and Bioanalytical Chemistry, University of Ulm.
    Nikolajeff, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Österlund, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Mizaikoff, Boris
    Institute of Analytical and Bioanalytical Chemistry, University of Ulm.
    Diamonds are a Spectroscopist’s Best Friend: Thin Film Diamond Mid-Infrared Waveguides for Advanced Chem/Bio Sensors2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 16, p. 8136-8141Article in journal (Refereed)
    Abstract [en]

    The first combination of mid-infrared (MIR) tunable quantum cascade lasers (tQCLs) with thin film diamond strip waveguides (DSWG) suitable for advanced chem/bio sensing is demonstrated. The sensing system comprises thin diamond films grown on surface- passivated Si wafers via chemical vapor deposition (CVD) and microstructured using inductively coupled plasma (ICP) etching, serving as photonic waveguide for radiation emitted by a broadly tunable quantum cascade laser (tQCL) in the spectral regime of 5.78-6.35 µm (1570-1730 cm-1). The characterization of the freestanding diamond waveguides reveals excellent transmission properties across a broad MIR band. As a proof of concept, the detection of acetone in D2O via evanescent field absorption is demonstrated achieving a limit of detection (LOD) as low as 200 pL, which indicates a significant sensitivity improvement compared to conventional MIR slab/strip waveguides reported to date. Providing characteristic absorption features within the tuning range of the tQCL, studies using anisaldehyde as analyte further corroborate the potential of tQCL-DSWG-based chem/bio sensors.

  • 96.
    Wen, Chenyu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Zeng, Shuangshuang
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Zhang, Zhen
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Zhang, Shi-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Group behavior of nanoparticles translocating multiple nanopores2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, p. 13483-13490Article in journal (Refereed)
    Abstract [en]

    Nanopores have been implemented as nanosensors for DNA sequencing, biomolecule inspection, chemical analysis, nanoparticle detection, etc. For high-throughput and parallelized measurement using nanopore arrays, individual addressability has been a crucial technological solution in order to enable scrutiny of signals generated at each and every nanopore. Here, an alternative pathway of employing arrayed nanopores to perform sensor functions is investigated by examining the group behavior of nanoparticles translocating multiple nanopores. As no individual addressability is required, fabrication of nanopore devices along with microfluidic cells and readout circuits can be greatly simplified. Experimentally, arrays of less than 10 pores are shown to be capable of analyzing translocating nanoparticles with a good signal-to-noise margin. According to theoretical predictions, more pores (than 10) per array can perform high-fidelity analysis if the noise level of the measurement system can be better controlled. More pores per array would also allow for faster measurement at lower concentration because of larger capture cross sections for target nanoparticles. By experimentally varying the number of pores, the concentration of nanoparticles, or the applied bias voltage across the nanopores, we have identified the basic characteristics of this multievent process. By characterizing average pore current and associated standard deviation during translocation and by performing physical modeling and extensive numerical simulations, we have shown the possibility of determining the size and concentration of two kinds of translocating nanoparticles over 4 orders of magnitude in concentration. Hence, we have demonstrated the potential and versatility of the multiple-nanopore approach for high-throughput nanoparticle detection.

    The full text will be freely available from 2019-10-29 15:50
  • 97.
    Wetterhall, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Nilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Markides, Karin
    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.
    A conductive polymeric material used for nanospray needle and low-flow sheathless electrospray ionization applications2002In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 74, no 1, p. 239-245Article in journal (Refereed)
    Abstract [en]

    A conductive polypropylene/graphite mixture is used for the production of polymeric nanospray needle emitters and as a coating on fused-silica capillaries that are used for sheathless electrospray ionization (ESI). The described production of these polymeric nanospray needle emitters and sheathless ESI contacts is exceptionally easy and at a very low cost. The described polymeric nanospray emitters have shown excellent features regarding their chemical inertness and spray performance. The long-term stability of the nanospray needles exceeds 24 h of continuous use. Furthermore, the resistance to electrical discharges, which is one of the factors that often limits the lifetime of metal coated tips, has proven to be outstanding. A voltage of up to 5 kV could be applied without loss of spray performance. The use of polypropylene emitters offers a number of desirable features, as compared to silica based emitters. Among these features are mechanical flexibility and simplified regeneration of the nanospray needle. Continuous nanospray of peptides and proteins in conjunction with orthogonal time-of-flight mass spectrometry are shown with signal relative standard deviations of 5%. In addition, the polypropylene/graphite mixture has also been applied as the conductive contact for sheathless ESI in fast capillary electrophoresis separations.

  • 98. Wisniewski, Jacek R.
    et al.
    Gaugaz, Fabienne Z.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fast and Sensitive Total Protein and Peptide Assays for Proteomic Analysis2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 8, p. 4110-4116Article in journal (Refereed)
    Abstract [en]

    The determination of total protein content is one of the most frequent analytical tasks in biochemistry and molecular biology. Here we evaluate measurements of tryptophan fluorescence (WF) for total protein determination in whole tissue lysates and for peptide quantification in protein digests. We demonstrate that the fluorescence spectrometry of tryptophan offers a simple, sensitive, and direct method for protein and peptide assays. The WF assay is fully compatible with SDS and other solutes that are commonly used for lysis of tissue and cells. We found that the content of tryptophan varies only a little between mouse tissues (1.16 +/- 0.08% of total amino acids) and is similar in human cells (1.19 +/- 0.06%). Therefore, free tryptophan can be used as a universal standard. We show that the assay can be carried out on a standard fluorescence spectrometer with cuvettes as well as in a 96-well format using a plate reader. The method is particularly suitable for determination of peptide content in diluted samples. Notably, the whole sample can be recovered after the measurement.

  • 99.
    Zettersten, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Co, Michelle
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Wende, Sandra
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Turner, Charlotta
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Identification and Characterization of Polyphenolic Antioxidants Using On-Line Liquid Chromatography, Electrochemistry, and Electrospray Ionization Tandem Mass Spectrometry2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 21, p. 8968-8977Article in journal (Refereed)
    Abstract [en]

    It is demonstrated that electrochemistry (EC) coupled to liquid chromatography (LC) and electrospray ionization tandem mass spectrometry (LC/EC/ESI-MS/MS) can be used to rapidly obtain information about the antioxidant activity (i.e., oxidation potential) and capacity (i.e., amount) of polyphenolic compounds, including catechin, kaempferol, resveratrol, quercetin, and quercetin glucosides. The described on-line LC/EC/ESI-MS/MS method facilitates the detection and characterization of individual antioxidants based on a combination of the obtained m/z values for the antioxidants and their oxidation products, the potential dependences for the ion intensities, and correlations between the retention times in the LC, EC, and MS chromatograms. As these results provide patterns that can be used in rapid screening for antioxidants in complex samples, the method should be a valuable complement to chemical assays commonly used to determine the total antioxidant capacity of samples. It is shown that the antioxidant capacity for a mixture of polyphenolic compounds depends on the redox potential employed in the evaluation, and this should consequently be taken into account when comparing results from different total antioxidant capacity assays. It is also demonstrated that the inherent antioxidant capacities of phenolic compounds increase with an increasing number of hydroxyl groups and that the potential needed to oxidize the remaining hydroxyl groups increases successively upon oxidation of the compound. Unlike chemical assays, which generally do not provide any information about the identities of the compounds on the molecular level, the present screening method can be used to identify individual antioxidants, rank compounds with respect to their ease of oxidation, and to study the antioxidant capacity at any redox potential of interest.

  • 100.
    Zettersten, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    Oxidation of 4-chloroaniline studied by on-line electrochemistry electrospray ionization mass spectrometry2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 13, p. 5180-5187Article in journal (Refereed)
    Abstract [en]

    The oxidation of 4-chloroaniline (4-CA) has been studied by electrochemistry (EC) coupled on-line with electrospray ionization mass spectrometry (ESI-MS) using two electrochemical flow cells of different design. The experimental results, which generally verify previously suggested oxidation pathways for 4-CA, also indicate the presence of a so far unrecognized comproportionation reaction. The oxidation of 4-CA (m/z 128.2) was found to give rise to the formation of both an oxidized dimer, 4-[(4-chlorophenyl)imino]-2,5-cyclohexadien-1-imine (m/z 217.2) and a reduced dimer, 4-amino-4’-chlorodiphenylamine (m/z 219.2), in addition to a dimer intermediate (m/z 253.2). This unexpected formation of the reduced dimer is shown to stem from a comproportionation reaction involving 4-CA and the oxidized dimer. The presence of the latter reaction was clearly seen by comparing results obtained with two thin-layer flow cells, both with conversion efficiencies of 50% but of different design, with respect to the influence of the counter electrode reaction on the reaction at the working electrode. The experimental results demonstrate that the formation of the reduced dimer is favored by a decrease in the local pH in the flow cell and the influence of the pH on the oxidation of 4-CA was also investigated in the pH range between 2.0 and 6.0 using off-line voltammetry. It is concluded that EC/ESI-MS is a powerful tool for the study of the present type of reactions and that studies on reaction pathways are best carried out with thin-layer flow cells having conversion efficiencies smaller than 100% as this facilitates the detection of reaction intermediates. Comproportionation reactions, similar to the reaction present in the 4-CA system, can also be expected to be present during the formation of conducting polymers such as polyaniline and polypyrrole.

123 51 - 100 of 103
CiteExportLink to result list
Permanent 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