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  • 1. Adler, Belinda
    et al.
    Boström, Tove
    KTH, School of Biotechnology (BIO), Proteomics.
    Ekström, Simon
    Hober, Sophia
    KTH, School of Biotechnology (BIO), Proteomics.
    Laurell, Thomas
    Miniaturized and Automated High-Throughput Verification of Proteins in the ISET Platform with MALDI MS2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 20, p. 8663-8669Article in journal (Refereed)
    Abstract [en]

    A major bottleneck in high-throughput protein production is the validation step, which is why parallel and automated sample processing methods are highly desirable. Also, a miniaturized sample preparation format is preferred, as the reduction of reagent volumes significantly decreases the analysis cost per sample. We have developed an automated and miniaturized protein sequence verification protocol for recombinant proteins utilizing peptide mass fingerprinting and MS/MS analysis. The integrated selective enrichment target (ISET) platform, previously developed in our group, with its dual functionality, being both a sample preparation platform and a MALDI target plate, is employed. All steps including immobilized metal ion affinity chromatography of protein on cobalt-loaded beads, tryptic digestion, and MALDI MS analysis are performed in an array format, without any sample transfers, on the same ISET chip. The automated configuration reduced the sample preparation time significantly. Starting with crude lysate, a full plate of 48 purified, digested samples prepared for MALDI-MS can be generated in 4 h, with only 30 min of operator involvement. This paper demonstrates the utility of the method by parallel analysis of 45 His-tagged human recombinant proteins.

  • 2. Akter, Farhima
    et al.
    Mie, Masayasu
    Grimm, Sebastian
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Nygren, Per-Åke
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Kobatake, Eiry
    Detection of Antigens Using a Protein-DNA Chimera Developed by Enzymatic Covalent Bonding with phiX Gene A2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 11, p. 5040-5046Article in journal (Refereed)
    Abstract [en]

    The chemical reactions used to make antibody DNA conjugates in many immunoassays diminish antigen-binding activity and yield heterogeneous products. Here, we address these issues by developing an antibody-based rolling circle amplification (RCA) strategy using a fusion of phi X174 gene A* protein and Z(mab2s) (A*-Zmab). The phi X174 gene A* protein is an enzyme that can covalently link with DNA, while the Z(mab2s) protein moiety can bind to specific species of antibodies. The DNA in an A*-Zmab conjugate was attached to the A* protein at a site chosen to not interfere with protein function, as determined by enzyme-linked immunosorbent assay (ELISA) and gel mobility shift analysis. The novel A*-Zmab-DNA conjugate retained its binding capabilities to a specific class of murine immunoglobulin gamma 1 (IgG1) but not to rabbit IgG. This indicates the generality of the A*-Zmab-based immuno-RCA assay that can be used in-sandwich ELISA format. Moreover, the enzymatic covalent method dramatically increased the yields of A*-Zmab-DNA conjugates up to 80% after a 15 min reaction. Finally, sensitive detection of human interferon-gamma (IFN-gamma) was achieved by immuno-RCA using our fusion protein in sandwich ELISA format. This new approach of the use of site-specific enzymatic DNA conjugation to proteins should be applicable to fabrication of novel immunoassays for biosensing.

  • 3.
    Aldaeus, Fredrik
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    New Concepts for Dielectrophoretic Separations and Dielectric Measurements of Bioparticles2006Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    This thesis presents two new concepts for separation of micro particles using dielectrophoresis, demonstrated by calculated examples, as well as a new method for obtaining dielectric data on living cells. The thesis is based on four papers.

    Paper I describes how the trapping efficiency of micro particles may be significantly increased when superpositioned electric fields are employed in a high conductivity medium. Avoiding low conductivity media is important when working with living cells. Calculations were performed to predict trajectories of Escherichia coli bacteria in the system with superpositioned electric fields, and a model was developed which employed two arrays of interdigitated electrodes in a micro channel.

    Paper II proposes a new concept for separation of micro particles, based on repetitive dielectrophoretic trapping and release in a flow system. Calculations show that the resolution increases as a direct function of the number of trap and release steps, and that a difference in size will have a larger influence on the separation than a difference in dielectrophoretic properties. Polystyrene beads in deionized water were used as a model, and calculations were performed to predict the particle behavior and the separation efficiency. It should be possible to separate particles with a size difference of 0.2 % by performing 200 trap-and-release steps. The enhanced separation power of multi step dielectrophoresis could have significant applications, not only for fractionation of particles with small differences in size, but also for measuring changes in surface conductivity.

    Paper III presents a new calculation method for predicting dielectrophoretic motion of micro particles. The method is based on a soft sphere method often used in molecular dynamics. Results from the calculations are in good agreement with theoretical predictions as well as initial experimental results, showing that the method provides good efficiency and accuracy.

    Paper IV describes a new method for measurements of conductivity of living bacteria. To obtain reliable conductivity values, it is important to handle the cells as gently as possible during the measurement process. A standard conductivity meter was used in combination with cross-flow filtration. In this way, repeated centrifugation and resuspension is avoided which otherwise may cause damage to the bacteria. The conductivity of Bacillus subtilis was determined to be 7000 μS/cm by means of the cross-flow filtration method, and the values differ from earlier published values by almost an order of a magnitude.

    In addition to the work presented in the papers, some experimental dielectrophoresis work in chip-based systems was performed. The behavior of Escherichia coli and polystyrene beads at different voltages and frequencies were studied. Separation of beads with different sizes was achieved on an array of interdigitated electrodes. Using electrodes with a pointed shape, alignment in different directions, pearl-chain formation, rotation, and other dielectrophoretic motion of E. coli were observed.

  • 4.
    Aminlashgari, Nina
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    SALDI-MS Method Development for Analysis of Pharmaceuticals and Polymer Degradation Products2012Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Surface assisted laser desorption ionization-mass spectrometry (SALDI-MS) was evaluated as a new tool for analysis of polymer degradation products. A SALDI method was developed enabling rapid analysis of low molecular mass polyesters and their degradation products. In addition, the possibility to utilize nanocomposite films as easy-to-handle surfaces for analysis of pharmaceutical compounds was investigated.

    Poly(ε-caprolactone) was used as a model compound for SALDI-MS method development. The signal-to-noise values obtained by SALDI-MS were 20 times higher compared to traditional matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) of the same samples with 2,5-dihydroxybenzoic acid as a matrix. Halloysite nanoclay and magnesium oxide showed best potential as surfaces and clean backgrounds in the low mass range were observed. The SALDI-MS method for the analysis of polyester degradation products was also verified by electrospray ionization-mass spectrometry (ESI-MS). An advantage over ESI-MS is the possibility to directly analyze degradation products in buffer solutions. Compared to gas chromatography-mass spectrometry (GC-MS) it is possible to analyze polar compounds and larger molecular mass ranges at the same time as  complicated extraction steps are avoided.

    The possibility to use nanocomposite films as surfaces instead of free nanoparticles was evaluated by solution casting of poly(lactide) (PLA) films with eight inorganic nanoparticles. The S/N values of the pharmaceutical compounds, acebutolol, propranolol and carbamazepine, analyzed on the nanocomposite surfaces were higher than the values obtained on the surface of plain PLA showing that the nanoparticles participated in the ionization/desorption process even when they are immobilized. Beside the ease of handling, the risk for instrument contamination is reduced when nanocomposites are used instead of free nanoparticles. The signal intensities depended on the type of drug, type and concentration of nanoparticle. PLA with 10 % titanium oxide or 10 % silicon nitride functioned best as SALDI-MS surfaces.

  • 5.
    Aminlashgari, Nina
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Hakkarainen, Minna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Surface Assisted Laser Desorption Ionization-Mass Spectrometry (SALDI-MS) for Analysis of Polyester Degradation Products2012In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 23, no 6, p. 1071-1076Article in journal (Refereed)
    Abstract [en]

    Novel surface assisted laser desorption ionization-mass spectrometry (SALDI-MS) method was developed for rapid analysis of low molecular mass polyesters and their degradation products by laser desorption ionization-mass spectrometry. Three polycaprolactone materials were analyzed by the developed method before and after hydrolytic degradation. The signal-to-noise values obtained by SALDI-MS were 20-100 times higher compared with the ones obtained by using traditional MALDI-MS matrices. A clean background at low mass range and higher resolution was obtained by SALDI-MS. Different nanoparticle, cationizing agent, and solvent combinations were evaluated. Halloysite nanoclay and magnesium hydroxide showed the best potential as SALDI surfaces. The SALDI-MS spectrum of the polyester hydrolysis products was verified by ESI-MS. The developed SALDI-MS method possesses several advantages over existing methods for similar analyses.

  • 6.
    Aminlashgari, Nina
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Shariatgorji, Mohammadreza
    Department of Analytical Chemistry, Stockholm University, Stockholm, Sweden.
    Ilag, Leopold L.
    Department of Analytical Chemistry, Stockholm University, Stockholm, Sweden.
    Hakkarainen, Minna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Nanocomposites as novel surfaces for laser desorption ionization mass spectrometry2011In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 3, no 1, p. 192-197Article in journal (Refereed)
    Abstract [en]

    The possibility to utilize nanocomposite films as easy-to-handle surfaces for surface assisted laser desorption ionization-mass spectrometry (SALDI-MS) of small molecules, such as pharmaceutical compounds, was evaluated. The signal-to-noise values of acebutolol, propranolol and carbamazepine obtained on the nanocomposite surfaces were higher than the values obtained on plain PLA surface showing that the nanoparticles participate in the ionization/desorption process even when they are immobilized in the polymer matrix. The advantages of nanocomposite films compared to the free nanoparticles used in earlier studies are the ease of handling and reduction of instrument contamination since the particles are immobilized into the polymer matrix. Eight inorganic nanoparticles, titanium dioxide, silicon dioxide, magnesium oxide, hydroxyapatite, montmorillonite nanoclay, halloysite nanoclay, silicon nitride and graphitized carbon black at different concentrations were solution casted to films with polylactide (PLA). There were large differences in signal intensities depending on the type of drug, type of nanoparticle and the concentration of nanoparticles. Polylactide with 10% titanium oxide or 10% silicon nitride functioned best as SALDI-MS surfaces. The limit of detection (LOD) for the study was ranging from 1.7 ppm up to 56.3 ppm and the signal to noise relative standard deviations for the surface containing 10% silicon nitride was approximately 20-30%. Scanning electron microscopy demonstrated in most cases a good distribution of the nanoparticles in the polymer matrix and contact angle measurements showed increasing hydrophobicity when the nanoparticle concentration was increased, which could influence the desorption and ionization. Overall, the results show that nanocomposite films have potential as surfaces for SALDI-MS analysis of small molecules.

  • 7.
    Araújo, Ana Catarina
    et al.
    KTH, School of Biotechnology (BIO), Glycoscience.
    Song, Yajing
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ståhl, Patrik L.
    Brumer, Harry, III
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Activated Paper Surfaces for the Rapid Hybridization of DNA through Capillary Transport2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 7, p. 3311-3317Article in journal (Refereed)
    Abstract [en]

    The development of low-cost, accurate, and equipment-free diagnostic tests is crucial to many clinical, laboratory, and field applications, including forensics and medical diagnostics. Cellulose fiber-based paper is an inexpensive, biodegradable, and renewable resource, the use of which as a biomolecule detection matrix and support confers several advantages compared to traditional materials such as glass. In this context, a new, facile method for the preparation of surface functionalized papers bearing single-stranded probe DNA (ssDNA) for rapid target hybridization via capillary transport is presented. Optimized reaction conditions were developed that allowed the direct, one-step activation of standard laboratory filters by the inexpensive and readily available bifunctional linking reagent, 1,4-phenylenediisothiocyanate. Such papers were thus amenable to subsequent coupling of amine-labeled ssDNA under standard conditions widely used for glass-based supports. The intrinsic wicking ability of the paper matrix facilitated rapid sample elution through arrays of probe DNA, leading to significant, detectable hybridization in the time required for the sample liquid to transit the vertical length of the strip (less than 2 min). The broad applicability of these paper test strips as rapid and specific diagnostics in "real-life" situations was exemplified by the discrimination of amplicons generated from canine and human mitochondrial and genomic DNA in mock forensic samples.

  • 8.
    Axelsson, Karolin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Chemical signals in interactions between Hylobius abietis and associated bacteria2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pine weevil (Hylobius abietis L.) is one of the two topmost economically important insect pests in Swedish conifer forests. The damage increase in areas were the silvicultural practice is to use clear cuttings were the insects gather and breed. During egglaying the female protects her offspring by creating a cave in roots and stumps were she puts her egg and covers it with frass, a mixture of weevil feces and chewed bark. Adult pine weevils have been observed to feed on the other side of the egg laying site and antifeedant substance has been discovered in the feces of the pine weevil. We think it is possible that microorganisms present in the frass contribute with antifeedant/repellent substances. Little is known about the pine weevils associated bacteria community and their symbiotic functions. In this thesis the bacterial community is characterized in gut and frass both from pine weevils in different populations across Europe as well as after a 28 day long diet regime on Scots pine, silver birch or bilberry. Volatile substances produced by isolated bacteria as well as from a consortium of microorganisms were collected with solid phase micro extraction (SPME) and analyzed with GC-MS. The main volatiles were tested against pine weevils using a two-choice test. Wolbachia, Rahnella aquatilis, Serratia and Pseudomonas syringae was commonly associated with the pine weevil. 2-Methoxyphenol, 2-phenylethanol, 3-methyl-1-butanol were found in the headspace from Rahnella aquatilis when grown in substrate containing pine bark. 2-Methoxyphenol and 3-methyl-1-butanol, phenol and methyl salicylate were found in pine feces. Birch and bilberry feces emitted mainly linalool oxides and bilberry emitted also small amounts of 2-phenylethanol.

    A second part of the thesis discusses the role of fungi in forest insect interactions and the production of oxygenated monoterpenes as possible antifeedants. Spruce bark beetles (Ips typhographus L.) aggregate with the help of pheromones and with collected forces they kill weakened adult trees as a result of associated fungi growth and larval development. A fungi associated with the bark beetle, Grosmannia europhoides, was shown to produce de novo 2-methyl-3-buten-2-ol, the major component of the spruce bark beetle aggregation pheromone. Chemical defense responses against Endoconidiophora polonica and Heterobasidion parviporum were investigated using four clones of Norway spruce with different susceptibility to Heterobasidion sp. Clone specific differences were found in induced mono-, sesqui and diterpenes. A number of oxygenated monoterpenes which are known antifeedants for the pine weevil were produced in the infested areas.

  • 9. Badia, J. D.
    et al.
    Strömberg, E.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Ribes-Greus, A.
    Karlsson, S.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    A statistical design of experiments for optimizing the MALDI-TOF-MS sample preparation of polymers. An application in the assessment of the thermo-mechanical degradation mechanisms of poly (ethylene terephthalate)2011In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 692, no 1-2, p. 85-95Article in journal (Refereed)
    Abstract [en]

    The sample preparation procedure for MALDI-TOF MS of polymers is addressed in this study by the application of a statistical Design of Experiments (DoE). Industrial poly (ethylene terephthalate) (PET) was chosen as model polymer. Different experimental settings (levels) for matrixes, analyte/matrix proportions and concentrations of cationization agent were considered. The quality parameters used for the analysis were signal-to-noise ratio and resolution. A closer inspection of the statistical results provided the study not only with the best combination of factors for the MALDI sample preparation, but also with a better understanding of the influence of the different factors, individually or in combination, to the signal. The application of DoE for the improvement of the MALDI measure of PET stated that the best combination of factors and levels was the following: matrix (dithranol), proportion analyte/matrix/cationization agent (1/15/1, V/V/V), and concentration of cationization agent (2 g L-1). In a second part, multiple processing by means of successive injection cycles was used to simulate the thermo-mechanical degradation effects on the oligomeric distribution of PET under mechanical recycling. The application of MALDI-TOF-MS showed that thermo-mechanical degradation primarily affected initially predominant cyclic species. Several degradation mechanisms were proposed, remarking intramolecular transesterification and hydrolysis. The ether links of the glycol unit in PET were shown to act as potential reaction sites, driving the main reactions of degradation.

  • 10.
    Banerjee, Indradumna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Salih, Tagrid
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Erlandsson, Johan
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Fibre Technology.
    Pettersson, Torbjörn
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science. KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Fibre Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center. KTH, School of Engineering Sciences (SCI), Centres, VinnExcellence Center BiMaC Innovation. KTH, Superseded Departments (pre-2005), Chemistry.
    Araújo, A. C.
    Karlsson, M.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Slipdisc: A versatile sample preparation platform for point of care diagnostics2017In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 56, p. 35048-35054Article in journal (Refereed)
    Abstract [en]

    We report a microfluidic sample preparation platform called "Slipdisc" based on slipchip technology. Slipdisc is a rotational slipchip that uses a unique hand-wound clockwork mechanism for precise movement of specially fabricated polycarbonate discs. In operation, the microchannels and microchambers carved on the closely aligned microfluidic discs convert from continuous filled paths to defined compartments using the slip movement. The clockwork mechanism introduced here is characterised by a food dye experiment and a conventional HRP TMB reaction before measuring lactate dehydrogenase (LDH) enzyme levels, which is a crucial biomarker for neonatal diagnostics. The colorimetry based detection of LDH was performed with an unmodified camera and an image analysis procedure based on normalising images and observing changes in red channel intensity. The analysis showed a close to unity coefficient of determination (R2 = 0.96) in detecting the LDH concentration when compared with a standard Chemical Analyser, demonstrating the excellent performance of the slipdisc platform with colorimetric detection. The versatile point of care sample preparation platform should ideally be suited for a multitude of applications at resource-limited settings.

  • 11. Beck, O.
    et al.
    Kenan Modén, N.
    Seferaj, S.
    Lenk, Gabriel
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Helander, A.
    Study of measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spot (DBS) samples and application of a volumetric DBS device2018In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 479, p. 38-42Article in journal (Refereed)
    Abstract [en]

    Phosphatidylethanol (PEth) is a group of phospholipids formed in cell membranes following alcohol consumption. PEth measurement in whole blood samples is established as a specific alcohol biomarker with clinical and medico-legal applications. This study further evaluated the usefulness of dried blood spot (DBS) samples collected on filter paper for PEth measurement. Specimens used were surplus volumes of venous whole blood sent for routine LC–MS/MS quantification of PEth 16:0/18:1, the major PEth homolog. DBS samples were prepared by pipetting blood on Whatman 903 Protein Saver Cards and onto a volumetric DBS device (Capitainer). The imprecision (CV) of the DBS sample amount based on area and weight measurements of spot punches were 23–28%. Investigation of the relationship between blood hematocrit and PEth concentration yielded a linear, positive correlation, and at around 1.0–1.5 μmol/L PEth 16:0/18:1, the PEth concentration increased by ~ 0.1 μmol/L for every 5% increase in hematocrit. There was a close agreement between the PEth concentrations obtained with whole blood samples and the corresponding results using Whatman 903 (PEthDBS = 1.026 PEthWB + 0.013) and volumetric device (PEthDBS = 1.045 PEthWB + 0.016) DBS samples. The CV of PEth quantification in DBS samples at concentrations ≥ 0.05 μmol/L were ≤ 15%. The present results further confirmed the usefulness of DBS samples for PEth measurement.

  • 12.
    Benkestock, Kurt
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Electrospray Ionization Mass Spectrometry for Determination of Noncovalent Interactions in Drug Discovery2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Noncovalent interactions are involved in many biological processes in which biomolecules bind specifically and reversibly to a partner. Often, proteins do not have a biological activity without the presence of a partner, a ligand. Biological signals are produced when proteins interact with other proteins, peptides, oligonucleotides, nucleic acids, lipids, metal ions, polysaccharides or small organic molecules. Some key steps in the drug discovery process are based on noncovalent interactions. We have focused our research on the steps involving ligand screening, competitive binding and ‘off-target’ binding. The first paper in this thesis investigated the complicated electrospray ionization process with regards to noncovalent complexes. We have proposed a model that may explain how the equilibrium between a protein and ligand changes during the droplet evaporation/ionization process.

    The second paper describes an evaluation of an automated chip-based nano-ESI platform for ligand screening. The technique was compared with a previously reported method based on nuclear magnetic resonance (NMR), and excellent correlation was obtained between the results obtained with the two methods. As a general conclusion we believe that the automated nano-ESI/MS should have a great potential to serve as a complementary screening method to conventional HTS. Alternatively, it could be used as a first screening method in an early phase of drug development programs when only small amounts of purified targets are available.

    In the third article, the advantage of using on-line microdialysis as a tool for enhanced resolution and sensitivity during detection of noncovalent interactions and competitive binding studies by ESI-MS was demonstrated. The microdialysis device was improved and a new approach for competitive binding studies was developed.

    The last article in the thesis reports studies of noncovalent interactions by means of nanoelectrospray ionization mass spectrometry (nanoESI-MS) for determination of the specific binding of selected drug candidates to HSA. Two drug candidates and two known binders to HSA were analyzed using a competitive approach. The drugs were incubated with the target protein followed by addition of site-specific probes, one at a time. The drug candidates showed predominant affinity to site I (warfarin site). Naproxen and glyburide showed affinity to both sites I and II.

  • 13.
    Benkestock, Kurt
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Edlund, Per Olof
    Biovitrum AB, Dept Analyt Sci.
    Roeraade, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Electrospray ionization mass spectrometry as a tool for determination of drug binding sites to human serum albumin by noncovalent interaction2005In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 19, no 12, p. 1637-1643Article in journal (Refereed)
    Abstract [en]

    Most proteins in blood plasma bind ligands. Human serum albumin (HSA) is the main transport protein with a very high capacity for binding of endogenous and exogenous compounds in plasma. Many pharmacokinetic properties of a drug depend on the level of binding to plasma proteins. This work reports studies of noncovalent interactions by means of nanoelectrospray ionization mass spectrometry (nanoESI-MS) for determination of the specific binding of selected drug candidates to HSA. Warfarin, iopanoic acid and digitoxin were chosen as site-specific probes that bind to the main sites of HSA. Two drug candidates and two known binders to HSA were analyzed using a competitive approach. The drugs were incubated with the target protein followed by addition of site-specific probes, one at a time. The drug candidates showed predominant affinity to site I (warfarin site). Naproxen and glyburide showed affinity to both sites I and II. The advantages of nanoE-SI-MS for these studies are the sensitivity, the absence of labeled molecules and the short method development time.

  • 14.
    Benkestock, Kurt
    et al.
    KTH, Superseded Departments, Chemistry.
    Edlund, Per Olof
    Biovitrum AB, Analyt Sci.
    Roeraade, Johan
    KTH, Superseded Departments, Chemistry.
    On-line microdialysis for enhanced resolution and sensitivity during electrospray mass spectrometry of non-covalent complexes and competitive binding studies2002In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 16, no 21, p. 2054-2059Article in journal (Refereed)
    Abstract [en]

    Many proteins and macromolecules easily form metal adduct ions which impairs their analysis by mass spectrometry. The present study describes how the formation of undesired adducts can be minimized by on-line microdialysis for non-covalent binding studies of macromolecules with low molecular mass ligands with electrospray ionization mass spectrometry (ESI-MS). The technique was indispensable for protein-ligand studies due to reduction of unwanted adduct ions, and thus gave excellent resolution and a sensitivity improvement of at least 5 times. The core of the analytical system was a modified microdialysis device, which was operated in countercurrent mode. A novel technique based on microdialysis for competitive binding studies is also presented. The noncovalent complex between a protein and a ligand was formed in the sample vial prior to analysis. The complex was injected into an on-line microdialysis system where a competitive ligand was administered in the dialysis buffer outside of the fiber. The second ligand competitively displaced the first ligand through transport via the wall of the dialysis fiber, and the intact complexes were detected by ESI-MS.

  • 15.
    Benkestock, Kurt
    et al.
    KTH, Superseded Departments, Chemistry.
    Sundqvist, Gustav
    KTH, Superseded Departments, Chemistry.
    Edlund, Per Olof
    Biovitrum AB, Dept Analyt Sci.
    Roeraade, Johan
    KTH, Superseded Departments, Chemistry.
    Influence of droplet size, capillary-cone distance and selected instrumental parameters for the analysis of noncovalent protein-ligand complexes by nano-electrospray ionization mass spectrometry2004In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 39, no 9, p. 1059-1067Article in journal (Refereed)
    Abstract [en]

    It has been suggested in the literature that nano-electrospray ionization (nano-ESI) mass spectrometry better reflects the equilibrium between complex and free protein in solution than pneumatically assisted electrospray ionization (ESI) in noncovalent interaction studies. However, no systematic studies of the effects of ionization conditions have been performed to support this statement. In the present work, different instrumental and sample-derived parameters affecting the stability of noncovalent complexes during analysis by nano-ESI were investigated. In general, increased values of parameters such as drying gas flow-rate, ion-source temperature, capillary tip voltage and buffer concentration lead to a dissociation of ribonuclease A (RNAse)-cytidine 2'-monophosphate (CMP) and cytidine 5'-triphosphate (CTP) complexes. The size of the electrosprayed droplets was shown to be an important issue. Increasing the capillary to cone distance yielded an increased complex to free protein ratio when a hydrophilic ligand was present and the reverse effect was obtained with a hydrophobic ligand. Important in this regard is the degree of sampling of ions originating from late-generation residue droplets, that is, ions present in the droplet bulk. Sampling of these ions increases with longer capillary-cone distance (flight time). Furthermore, when the sample flow-rate was increased by increasing the capillary internal tip i.d. from 4 to 30 mum, a decreased complex to free protein ratio for the RNAse-CTP system was observed. This behavior was consistent with the change in surface to volume ratio for flow-rates between 2 and 100 nl min(-1). Finally, polarity switching between positive and negative ion modes gave a higher complex to free protein ratio when the ligand and the protein had the same polarity.

  • 16.
    Benkestock, Kurt
    et al.
    KTH, Superseded Departments, Chemistry.
    Van Pelt, C. K.
    Advion BioSci Inc, Ithaca, NY USA.
    Åkerud, T.
    Lund Univ, Dept Biophys Chem.
    Sterling, A.
    Advion BioSci Ltd, Norwich, Norfolk England.
    Edlund, Per Olof
    Biovitrum AB, Analyt Sci.
    Roeraade, Johan
    KTH, Superseded Departments, Chemistry.
    Automated Nano-Electrospray Mass Spectrometry for Protein-Ligand Screening by Noncovalent Interaction Applied to Human H-FABP and A-FABP2003In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 8, no 3, p. 247-256Article in journal (Refereed)
    Abstract [en]

    A method for ligand screening by automated nano-electrospray ionization mass spectrometry (nano-ESI/MS) is described. The core of the system consisted of a chip-based platform for automated sample delivery from a 96-well plate and subsequent analysis based on noncovalent interactions. Human fatty acid binding protein, H-FABP (heart) and A-FABP (adipose), with small potential ligands was analyzed. The technique has been compared with a previously reported method based on nuclear magnetic resonance (NMR), and excellent correlation with the found hits was obtained. In the current MS screening method, the cycle time per sample was 1.1 min, which is approximately 50 times faster than NMR for single compounds and approximately 5 times faster for compound mixtures. High reproducibility was achieved, and the protein consumption was in the range of 88 to 100 picomoles per sample. Furthermore, a novel protocol for preparation of A-FABP without the natural ligand is presented. The described screening approach is suitable for ligand screening very early in the drug discovery process before conventional high-throughput screens (HTS) are developed and/or used as a secondary screening for ligands identified by HTS.

  • 17.
    Björk, Anders
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    Chemometric and signal processing methods for real time monitoring and modeling: applications in the pulp and paper industry2007Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    In the production of paper, the quality of the pulp is an important factor both for the productivity and for the final quality. Reliable real-time measurements of pulp quality are therefore needed. One way is to use acoustic or vibration sensors that give information-rich signals and place the sensors at suitable locations in a pulp production line. However, these sensors are not selective for the pulp properties of interest. Therefore, advanced signal processing and multivariate calibration are essential tools. The current work has been focused on the development of calibration routes for extraction of information from acoustic sensors and on signal processing algorithms for enhancing the information-selectivity for a specific pulp property or class of properties. Multivariate analysis methods like Principal Components Analysis (PCA), Partial Least Squares (PLS) and Orthogonal Signal Correction (OSC) have been used for visualization and calibration. Signal processing methods like Fast Fourier Transform (FFT), Fast Wavelet Transform (FWT) and Continuous Wavelet Transform (CWT) have been used in the development of novel signal processing algorithms for extraction of information from vibrationacoustic sensors.

    It is shown that use of OSC combined with PLS for prediction of Canadian Standard Freeness (CSF) using FFT-spectra produced from vibration data on a Thermo Mechanical Pulping (TMP) process gives lower prediction errors and a more parsimonious model than PLS alone. The combination of FFT and PLS was also used for monitoring of beating of kraft pulp and for screen monitoring. When using regular FFT-spectra on process acoustic data the obtained information tend to overlap. To circumvent this two new signal processing methods were developed: Wavelet Transform Multi Resolution Spectra (WT-MRS) and Continuous Wavelet Transform Fibre Length Extraction (CWT-FLE). Applying WT-MRS gave PLS-models that were more parsimonious with lower prediction error for CSF than using regular FFT-Spectra. For a Medium Consistency (MC) pulp stream WT-MRS gave predictions errors comparable to the reference methods for CSF and Brightness. The CWT-FLE method was validated against a commercial fibre length analyzer and good agreement was obtained. The CWT-FLE-curves could therefore be used instead of other fibre distribution curves for process control. Further, the CWT-FLE curves were used for PLS modelling of tensile strength and optical parameters with good results.

    In addition to the mentioned results a comprehensive overview of technologies used with acoustic sensors and related applications has been performed.

  • 18.
    Björk, Anders
    et al.
    KTH, Superseded Departments, Chemistry.
    Danielsson, Lars-Göran
    KTH, Superseded Departments, Chemistry.
    Extraction of Distribution Curves from Process Acoustic Measurements on a TMP-process2004In: Pulp & paper Canada, ISSN 0316-4004, Vol. 105, no 11, p. 42-46Article in journal (Refereed)
    Abstract [en]

    We have developed a method to extract fibre length distributions from acoustic data recorded on pulp streaming from a TMP refiner. The method is based on the use of a Continuous Wavelet Transform, CWT. Measurements were performed using an accelerometer on the refiner blow-line during a full-scale trial with a double disc refiner. During trials conditions were varied over a wide range. The agreement is good between results from our method, CWT-FLE and from FiberMaster.

  • 19.
    Björk, Anders
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry (closed 20110630).
    Danielsson, Lars-Göran
    AstraZeneca.
    Modeling of pulp quality parameters from distribution curves extracted from process acoustic measurements on a thermo mechanical pulp (TMP) process2007In: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 85, no 1, p. 63-69Article in journal (Refereed)
    Abstract [en]

    In this paper the feasibility of modeling strength and optical pulp properties from length distribution curves extracted from acoustic data using continuous wavelet transform-fiber length extraction, CWT-FLE (A Björk and L-G Danielsson, 'Extraction of Distribution Curves from Process Acoustic Measurements on a TMP-Process', Pulp and Paper Canada 105 No. 11 (2004), T260-T264) by use of Partial Least Squares (PLS) have been tested. The curves used have earlier been validated against length distribution curves obtained by analyzing pulp samples with a commercial analyzer (FiberMaster). The curves were extracted from acoustic data without any "calibration" against fiber length analyses. The acoustic measurements were performed using an accelerometer affixed to the refiner blow-line during a full-scale trial with a Sunds Defibrator double disc refiner at SCA Ortviken, Sweden. Pulp samples were collected concurrently with the acoustic measurements and extensive physical testing has been made on these samples. For each trial point three pulp samples were collected. PLS1 and PLS2 models were successfully made linking the distribution curves obtained using CWT-FLE to pulp tensile strength properties as well as optical properties. The resulting Root Mean Square Error of Prediction (RMSEP) for all parameters is comparable to what can be obtained by pooling the standard deviations of reference measurements from the different trial points. The results obtained are compared to FiberMaster data modeled in the same fashion, yielding lower prediction errors than the CWT-FLE data. However, this can be partly due to the five-year storage of pulp samples between pulp sampling/acoustic measurement and FiberMaster analyses/sheet testing. The acoustic method is fast and produces results without dead time and could constitute a new tool for improving process control and optimizing the fiber characteristics in a specific process and for a specific purpose. The technique could be implemented in a PC-environment at a fairly low cost.

  • 20.
    Björk, Anders
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Danielsson, Lars-Göran
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Predicting Pulp Quality from Process Acoustic Measurements on a Medium Concistency Pulp Stream2006In: JPAC, Journal of Process Analytical Chemistry., ISSN 1077-419X, Vol. 10, no 1, p. 1-5Article in journal (Refereed)
  • 21.
    Björk, Anders
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Danielsson, Lars-Göran
    Pulp Quality And Performance Indicators For Pressure Screens Based On Process Acoustic MeasurementsManuscript (Other academic)
  • 22.
    Björk, Anders
    et al.
    KTH, Superseded Departments, Chemistry.
    Danielsson, Lars-Göran
    KTH, Superseded Departments, Chemistry.
    Spectra of wavelet scale coefficients from process Acoustic Measurements as input for PLS modelling of pulp quality2002In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 16, no 8-10, p. 521-528Article in journal (Refereed)
    Abstract [en]

    Acoustic and vibration signals are captured by simple standard accelerometers. These can often be mounted directly on operative process equipment, creating a completely non-invasive measurement system. The signals from the accelerometer are then amplified, digitized by an analogue-to-digital converter and stored in some suitable format in a PC. The method most often used for signal processing of acoustic data has been to apply variants of fast Fourier transform (FFT) on sampled data to produce a frequency domain representation. An alternative way tried here is to use the fast wavelet transform (FWT) in combination with FFT. The FWT has the advantage that it produces time-resolved representations and, on each time scale, different features can be extracted. However, in this case, time resolution has no meaning, since the starting points for data acquisitions were not fixed. The wavelet step can be seen as a series of pre-filters and it is here followed by FFT on coefficients at each wavelet scale. The results are compared to those obtained after FFT on the complete time series. We have used spectra of wavelet scale coefficients in an attempt to model pulp quality with PLS. In this case the number of points in the resulting wavelet multiresolution spectrum (WT-MRS) can be limited to a low number, e.g. 255 compared to 1025 with direct FFT on the time series. In the PLS modelling step the advantage is that the first two components describe Y much better than when using the conventional approach, e.g. 72% explained Y variance compared to 40%. A second advantage is that the model requires fewer coefficients.

  • 23.
    Björk, Anders
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    Danielsson, Lars-Göran
    AstraZeneca.
    Gannå, Anders
    SCA Graphic Sundsvall AB.
    Applied Real-Time Acoustic Chemometrics for Measurements of Canadian Standard Freeness2005In: Paperi ja puu, ISSN 0031-1243, Vol. 87, no 7, p. 452-457Article in journal (Refereed)
    Abstract [en]

    In this paper we present a method for measuring Canadian Standard Freeness (CSF) on-line in real-time using acoustic measurements. The method can be used to present a new CSF value every second. The higher measurement rate and the reduced time-delay compared to conventional pulp sensors make it a suitable tool for improved refiner control.

    The method was developed during full-scale trials on two separate Sunds Defibrator double disc refiners at SCA Ortviken, Sweden. Acoustic measurements were performed using an accelerometer affixed to the refiner blow line. Trial conditions have been varied over a wide range of pulp quality and disturbances in the vibration signal. CSF was for example varied in the range 62-453 ml and refiner-housing pressure was varied from 0,35 to 0,39 MPa.

    The vibration signals collected during I second were treated to yield power spectra that were used for all further work. A median spectrum was calculated for each experimental point and these spectra were combined with reference values for freeness to make up the calibration matrices. The spectra were pre-treated using Orthogonal Signal Correction (OSC) and Subsequently Partial Least Squares Regression (PLSR) was used to build models between spectra and freeness. For model validation leave-one-out cross validation has been used.

    Over the range 90-250 ml we can predict CSF from median power spectra with a Root Mean Square Error of Prediction (RMSEP) of 23 ml. Over the larger CSF range of 62-453 mt the RMSEP deteriorates to 39 mt. Data from two separate trials on different refiners and from different seasons were included in these models.

  • 24.
    Björkholm, Eva
    et al.
    Arbetsmiljöinstitutet.
    Hultman, Annika
    Arbetsmiljöinstitutet.
    Rudling, Jan
    Arbetsmiljöinstitutet.
    Determination of chlorine and chlorine dioxide in workplace air by impinger collection and ion-chromatographic analysis1988In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, no 457, p. 409-414Article in journal (Refereed)
  • 25.
    Björkholm, Eva
    et al.
    Arbetsmiljöinstitutet.
    Hultman, Annika
    Arbetsmiljöinstitutet.
    Rudling, Jan
    Arbetsmiljöinstitutet.
    Evaluation of two diffusive samplers for monitoring chlorine and chlorine dioxide in workplace air1990In: Applied Occupational and Environmental Hygiene, Vol. 5, no 11, p. 767-770Article in journal (Refereed)
  • 26.
    Bonn, Jonas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Improved Techniques for Sampling and Sample Introduction in Gas Chromatography2008Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Sampling and sample introduction are two key steps in quantitative gas chromatography. In this thesis, a development of a previously described sampling technique as well as a novel concept for sample introduction in gas chromatography are presented. The thesis is based on two papers.

    Paper I describes a method for preparing physically mixed polymers for use as sorbent phases in open tubular trapping of gaseous analytes. The concept is based on mechanical disintegration and mixing of solid or liquid poly(ethylene glycol), PEG, into poly(dimethylsiloxane), PDMS, in a straightforward manner. The resulting mixture exhibits a higher affinity towards polar analytes, as compared to pure PDMS.

    Paper II describes a novel approach to liquid sample introduction with the split/splitless inlet, used in gas chromatography. Classical injection techniques struggle with discrimination of high boiling analytes and poor repeatability of the injected amount of analytes. The presented injection technique utilizes high voltage to obtain a spraying effect of the injected liquid. The spraying effect can be achieved with a cold needle, which is unprecedented for gas chromatographic injections. The cold needle spraying results in highly repeatable injections, free from discrimination of high boiling analytes.

  • 27.
    Bonn, Jonas
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Redeby, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Roeraade, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    A novel injection technique for the split/splitless gas chromatography inletManuscript (Other academic)
  • 28.
    Brodin, Ida
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Chemical Properties and Thermal Behaviour of Kraft Lignins2009Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Research concerning lignin has increased during the last years due to its renewability and ready availability in black liquor at pulp mills. Today, the kraft lignin found in black liquor is used as a fuel to gain energy in the recovery boiler at the mill. However, a new isolation concept, LignoBoost®, has enabled isolation of part of the lignin while allowing the use of black liquor as a fuel. This isolated lignin can be utilised as a fuel in, for example, thermal power stations or further upgraded to more value-added products. In this context, the most interesting value-added product is carbon fibre. The demand for carbon fibre has increased, but the biggest obstacle for a more extended use is the high production cost. About half of the production cost is related to the raw material.

    In this work, the possibility of using kraft lignin as a precursor for carbon fibre production has been investigated through fundamental studies. Kraft lignins originating from birch, Eucalyptus globulus, softwoods and softwoods from liner production have been studied. By separating the lignin while still in solution in the black liquor, unwanted large particles such as carbohydrates can easily be removed. After isolation according to the LignoBoost process and purification with the use of an ion-exchanger, the lignins have been both chemically and thermally characterised. Identification of the released compounds at different temperatures has been performed because only 40% of carbon relative to original lignin remains, down from theoretical 60% after thermal treatment up to 1000°C. The main released compounds were phenols, as revealed by pyrolysis-GC/MS. Additionally, a pre-oxidation was done in order to try to stabilise the lignins. It was shown that an oxidation prior to the thermal treatment increases the yield by more than 10% and that the main release of compounds takes place between 400°C and 600°C. Fractionated lignin is better qualified as raw material for carbon fibre production because it is purer and its softening temperature can be detected. Fractionated kraft lignins from all investigated wood sources have high possibilities to act as precursors for the manufacture of carbon fibre.

  • 29. Brun, Matthias A
    et al.
    Griss, Rudolf
    Reymond, Luc
    Tan, Kui-Thong
    Piguet, Joachim
    National Centre of Competence in Research Chemical Biology, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
    Peters, Ruud J R W
    Vogel, Horst
    Johnsson, Kai
    Semisynthesis of fluorescent metabolite sensors on cell surfaces.2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 40Article in journal (Refereed)
    Abstract [en]

    Progress in understanding signal transduction and metabolic pathways is hampered by a shortage of suitable sensors for tracking metabolites, second messengers, and neurotransmitters in living cells. Here we introduce a class of rationally designed semisynthetic fluorescent sensor proteins, called Snifits, for measuring metabolite concentrations on the cell surface of mammalian cells. Functional Snifits are assembled on living cells through two selective chemical labeling reactions of a genetically encoded protein scaffold. Our best Snifit displayed fluorescence intensity ratio changes on living cells significantly higher than any previously reported cell-surface-targeted fluorescent sensor protein. This work establishes a generally applicable and rational strategy for the generation of cell-surface-targeted fluorescent sensor proteins for metabolites of interest.

  • 30.
    Brändén, Magnus
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Sandén, Tor
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Brzezinski, Peter
    Widengren, Jerker
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Localized Proton Microcircuits at the Biological Membrane-Water Interface2006In: PNAS, ISSN 0027-8424, Vol. 103, no 52, p. 19677-19770Article in journal (Refereed)
    Abstract [en]

    Cellular processes such as nerve conduction, energy metabolism, and import of nutrients into cells all depend on transport of ions across biological membranes through specialized membrane-spanning proteins. Understanding these processes at a molecular level requires mechanistic insights into the interaction between these proteins and the membrane itself. To explore the role of the membrane in ion translocation we used an approach based on fluorescence correlation spectroscopy. Specifically, we investigated exchange of protons between the water phase and the membrane surface, as well as diffusion of protons along membrane surfaces, at a single-molecule level. We show that the lipid head groups collectively act as a proton-collecting antenna, dramatically accelerating proton uptake from water to a membrane-anchored proton acceptor. Furthermore, the results show that proton transfer along the surface can be significantly faster than that between the lipid head groups and the surrounding water phase. Thus, ion translocation across membranes and between the different membrane protein components is a complex interplay between the proteins and the membrane itself, where the membrane acts as a proton-conducting link between membrane-spanning proton transporters

  • 31. Carniato, Stéphane
    et al.
    Taïeb, Richard
    Journel, Loïc
    Guillemin, Renaud
    Stolte, Wayne C.
    Lindle, Dennis W.
    Gel'mukhanov, Faris
    KTH, School of Biotechnology (BIO), Theoretical Chemistry.
    Simon, Marc
    Resonant X-ray Raman scattering on molecules: A benchmark study on HCl2010In: Journal of Electron Spectroscopy and Related Phenomena, ISSN 0368-2048, E-ISSN 1873-2526, Vol. 181, no 2-3, p. 116-120Article in journal (Refereed)
    Abstract [en]

    Resonant X-ray Raman scattering is a powerful tool to study molecular dynamics and subtle chemical effects like the molecular field beyond vibrational and lifetime limitations. Using this technique in the tender X-ray region, gas phase HCl is studied as a benchmark molecule for other compounds like freons, which play an important role in physical-chemical properties of the ozone layer of atmosphere.

  • 32.
    Chmyrov, Volodymyr
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Spielmann, Thiemo
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Hevekerl, Heike
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Widengren, Jerker
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Trans-Cis isomerization of lipophilic dyes probing membrane microviscosity in biological membranes and in live cells2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 11, p. 5690-5697Article in journal (Refereed)
    Abstract [en]

    Membrane environment and fluidity can modulate the dynamics and interactions of membrane proteins and can thereby strongly influence the function of cells and organisms in general. In this work, we demonstrate that trans-cis isomerization of lipophilic dyes is a useful parameter to monitor packaging and fluidity of biomembranes. Fluorescence fluctuations, generated by trans-cis isomerization of the thiocarbocyanine dye Merocyanine 540 (MC540), were first analyzed by fluorescence correlation spectroscopy (FCS) in different alcohol solutions. Similar isomerization kinetics of MC540 in lipid vesicles could then also be monitored, and the influence of lipid polarity, membrane curvature, and cholesterol content was investigated. While no influence of membrane curvature and lipid polarity could be observed, a clear decrease in the isomerization rates could be observed with increasing cholesterol contents in the vesicle membranes. Finally, procedures to spatially map photoinduced and thermal isomerization rates on live cells by transient state (TRAST) imaging were established. On the basis of these procedures, MC540 isomerization was studied on live MCF7 cells, and TRAST images of the cells at different temperatures were found to reliably detect differences in the isomerization parameters. Our studies indicate that trans-cis isomerization is a useful parameter for probing membrane dynamics and that the TRAST imaging technique can provide spatial maps of photoinduced isomerization as well as both photoinduced and thermal back-isomerization, resolving differences in local membrane microviscosity in live cells.

  • 33. Csenki, Leonard
    et al.
    Alm, Erik
    Torgrip, Ralf
    Aeberg, Magnus
    Zamani, Leila
    Dept. of Analytical Chemistry Stockholm University.
    Shuppe-Koistinen, Ina
    Lindberg, Johan
    Hyphenated chromatography and chemometrics: breaking new grounds in the analysis of complex samples2007In: G.I.T. Laboratory Journal Europe, ISSN 1611-6038, Vol. 11, no 1-2, p. 39-40Article in journal (Refereed)
    Abstract [en]

    The task of analyzing complex samples has always been the challenge for the analytical sciences. Today more effort is put into characterizing a greater number of sample constituents, at lower levels and with higher speed and accuracy, all in one analytical run. Present challenges consist of, for example, the analysis of samples with biological/environmental origin measuring as many constituents in the sample as possible. By hyphenating chromatography (GC or (UP)LC) with mass spectrometry (MS) several hundreds of different molecules can be screened in one analysis - now we are faced with the problem of analyzing the large amounts of generated data, trying to extract the relevant information. This is where the fields of chemometrics and data processing, and hyphenated chromatography are successfully married. Here we outline some of the data requirements and new algorithms making exploratory analytical chemistry possible.

  • 34. Cuartero, Maria
    et al.
    Pankratova, Nadezda
    Cherubini, Thomas
    Crespo, Gaston A.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Massa, Francesco
    Confalonieri, Fabio
    Bakker, Eric
    In Situ Detection of Species Relevant to the Carbon Cycle in Seawater with Submersible Potentiometric Probes2017In: ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS, ISSN 2328-8930, Vol. 4, no 10, p. 410-415Article in journal (Refereed)
    Abstract [en]

    We report on the development of a submersible probe for the simultaneous potentiometric detection of carbonate, calcium, and pH in seawater. All-solid-state electrodes incorporating nanomaterials provide an adequate response time (<10 s), stability (drifts of <0.9 mV h(-1)), reproducibility (calibration parameter deviation of <0.7%), and accuracy (deviation of <8% compared to reference techniques) for real-time monitoring of seawater using a flow system. The functioning of the deployable prototype was checked in an outdoor mesocosm and via long-term monitoring in Genoa Harbor. The electrodes worked properly for 3 weeks, and the system demonstrated the capability to autonomously operate with routines for repetitive measurements, data storage, and management. In situ profiles observed in Genoa Harbor and Arcachon Bay were validated using on site and ex situ techniques. The validation of in situ-detected carbonate is a challenge because both re-equilibration of the sample with atmospheric CO2 and the use of apparent thermodynamic constants for speciation calculations lead to some differences (<20% deviation). The submersible probe is a promising tool for obtaining rapid and trustworthy information about chemical levels in marine systems. Moreover, the fluidic approach allows for the integration of other ion sensors that may require sample pretreatment.

  • 35.
    Danielsson, Marie
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Borg-Karlson, Anna-Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Tracing induced stress sites in conifers by single needle analysesManuscript (preprint) (Other academic)
  • 36. De Prins, Jurate
    et al.
    Mozuraitis, Raimondas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Lopez-Vaamonde, Carlos
    Rougerie, Rodolphe
    Sex attractant, distribution and DNA barcodes for the Afrotropical leaf-mining moth Phyllonorycter melanosparta (Lepidoptera: Gracillariidae))2009In: Zootaxa, ISSN 1175-5326, E-ISSN 1175-5334, no 2281, p. 53-67Article in journal (Refereed)
    Abstract [en]

    The sex attractant for Phyllonorycter melanosparta (Meyrick, 1912) has been determined as (10E)-dodec-10-en-1-yl acetate and (10E)-dodec-10-en-1-ol combined in a ratio 10:1. The distribution of this species in Eastern Africa is updated and its presence in Kenya is recorded for the first time. We discuss the taxonomic status of P. melanosparta with reference to three character sets: semiochemicals, morphological and molecular characters (DNA barcodes). This combination of characters is also proposed as a new approach to study the diversity and phylogeny of Phyllonorycter in the Afrotropical region.

  • 37.
    Dias, Jorge T
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Svedberg, Gustav
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Nystrand, Mats
    Andersson-Svahn, Helene
    Gantelius, Jesper
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Rapid signal enhancement method for nanoprobe-based biosensing2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6837Article in journal (Refereed)
    Abstract [en]

    The introduction of nanomaterials as detection reagents has enabled improved sensitivity and facilitated detection in a variety of bioanalytical assays. However, high nanoprobe densities are typically needed for colorimetric detection and to circumvent this limitation several enhancement protocols have been reported. Nevertheless, there is currently a lack of universal, enzyme-free and versatile methods that can be readily applied to existing as well as new biosensing strategies. The novel method presented here is shown to enhance the signal of gold nanoparticles enabling visual detection of a spot containing < 10 nanoparticles. Detection of Protein G on paper arrays was improved by a 100-fold amplification factor in under five minutes of assay time, using IgG-labelled gold, silver, silica and iron oxide nanoprobes. Furthermore, we show that the presented protocol can be applied to a commercial allergen microarray assay, ImmunoCAP ISAC sIgE 112, attaining a good agreement with fluorescent detection when analysing human clinical samples.

  • 38.
    Edlund, Ulrica
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Yu, Yang
    Ryberg, Yingzhi Zhu
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Krause-Rehberg, Reinhard
    Albertsson, Ann-Christine
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Positron Lifetime Reveals the Nano Level Packing in Complex Polysaccharide-Rich Hydrolysate Matrixes2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 8, p. 3676-3681Article in journal (Refereed)
    Abstract [en]

    Positron annihilation lifetime spectroscopy (PALS) was used to quantify the free volume and molecular packing in hydrolysate and hemicellulose-based barriers films, derived from process streams during wood processing operations. These hydrolysate films, comprising a fair share of lignin coexisting with poly- and oligo-saccharides, have very low but variable oxygen permeability but differ among themselves with respect to barrier performance as well as molecular weight, degree of branching, and monosaccharide residue main chain composition. From PALS measurements on hydrolysates, the free volume hole radius (r(h)), radius distributions (n(r(h))), volume-weighted hole sizes (<v(h)>(v)), and hole volume distributions (g(v(h))) were calculated showing that the hydrolysate matrixes are very densely packed with small holes. The results show a clear relationship between hydrolysate molecular architecture and composition, the nanolevel molecular packing, and the ability of suppressing the diffusion of oxygen through the film.

  • 39.
    Ek, Patrik
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Mass Spectrometry with Electrospray Ionization from an Adjustable Gap2008Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    In this thesis the fabrication and analytical evaluation of two new electrospray emitters utilized for mass spectrometry analysis is presented. The emitters are based on a new concept, where the spray orifice can be varied in size. The thesis is based on two papers.

    All present-day nanoelectrospray emitters have fixed dimensions. The range of the applicable flow rate for such an emitter is therefore rather limited and exchange of emitters may be necessary from one experiment to another. Optimization of the signal of the analyte ions is also limited to adjustments of the applied voltage or the distance between the emitter and the mass spectrometer inlet. Furthermore, clogging can occur in emitters with fixed dimensions of narrow orifice sizes. In this thesis, electrospray emitters with a variable size of the spray orifice are proposed. An open gap between two thin substrates is filled with sample solution via a liquid bridge from a capillary. Electrospray is generated at the end point of the gap, which can be varied in width.

    In Paper I, electrospray emitters fabricated in polyethylene terephthalate have been evaluated. Triangular tips are manually cut from the polymer film. The tips are mounted to form a gap between the edges of the tips. The gap wall surfaces are subjected to a hydrophilic surface treatment to increase the wetting of the gap walls.

    In Paper II, silicon electrospray chips with high precision are fabricated and evaluated. A thin beam, elevated from the bulk silicon chip is fabricated by means of deep reactive ion etching. The top surfaces of the beams of two chips act as a sample conduit when mounted in the electrospray setup. An anisotropic etching step with KOH of the intersecting <100> crystal planes results in a very sharp spray point. The emitters were given a hydrophobic surface treatment except for the hydrophilic gap walls.

    For both emitter designs, the gap width has been adjusted during the experiments without any interruption of the electrospray. For a continuously applied peptide mixture, a shift towards higher charge states and increased signal to noise ratios could be observed when decreasing the gap width. The limit of detection has been investigated and the silicon chips have been interfaced with capillary electrophoresis.

  • 40.
    Ek, Patrik
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    New methods for sensitive analysis with nanoelectrospray ionization mass spectrometry2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, new methods that address some current limitations in nanoelectrospray mass spectrometry (nESI-MS) analysis are presented. One of the major objectives is the potential gain in sensitivity that can be obtained when employing the proposed techniques.

    In the first part of this thesis, a new emitter, based on the generation of electrospray from a spray orifice with variable size, is presented. Electrospray is generated from an open gap between the edges of two individually mounted, pointed tips. The fabrication and evaluation of two different types of such emitters is presented; an ESI emitter fabricated from polyethylene terephtalate (Paper I), and a high-precision silicon device (Paper II). Both emitters were surface-treated in a selective way for an improved wetting of the gap and to confine the sample solution into the gap.

    In the second part of this thesis, different methods for improved sensitivity of nESI-MS analysis have been developed. In Paper III, a method for nESI-MS analysis from discrete sample volumes down to 1.5 nL is presented, using commercially available nESI needles. When analyzing attomole amounts of analyte in such a small volume of sample, an increased sensitivity was obtained, compared to when analyzing equal amounts in conventional nESI-MS analysis. To be able to analyze smaller sample volumes, needles with a narrower orifice and a higher flow resistance were needed. This triggered the development of a new method for fabrication of fused silica nESI needles (Paper IV). The fabrication is based on melting of a fused silica capillary by means of a rotating plasma, prior to pulling the capillary into a fine tip. Using the described technique, needles with sub-micrometer orifices could be fabricated. Such needles enabled the analysis of sample volumes down to 275 pL, and a further improvement of the sensitivity was obtained. In a final project (Paper V), nESI-MS was used to study the aggregation behavior of Aβ peptides, related to Alzheimer’s disease. An immunoprecipitation followed by nESI-MS was employed. This technique was also utilized to study the selectivity of the antibodies utilized.

  • 41.
    Ek, Patrik
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Roeraade, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    New Method for Fabrication of Fused Silica Emitters with Submicrometer Orifices for Nanoelectrospray Mass Spectrometry2011In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 20, p. 7771-7777Article in journal (Refereed)
    Abstract [en]

    In this paper, we describe a new method for fabrication of nanoelectrospray emitters. The needles were pulled from fused silica capillary tubing, which was melted by means of a plasma, formed by electrical discharges between two pointed platinum electrodes. A key feature of the pulling device is a rotating configuration of the electrodes, which results in an even radial heating of the capillary. The construction of the setup is straightforward, and needles with a variety of shapes can be fabricated, including orifices of submicrometer dimensions. Pulled needles with long tapered tips and an orifice of 0.5 mu m were utilized for electrospray ionization mass spectrometry (ESI-MS) of discrete sample volumes down to 275 pL. The picoliter-sized samples were transferred into the tip of the needle from a silicon microchip by aspiration. To avoid a rapid evaporation of the sample, all manipulations were performed under a cover of a fluorocarbon liquid. The limit of detection was measured to be ca. 20 attomole for insulin (chain B, oxidized).

  • 42.
    Ek, Patrik
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Schönberg, Tommy
    Sjödahl, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Jacksén, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Vieider, Christian
    Emmer, Åsa
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Roeraade, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Electrospray Ionization from an Adjustable Gap between two Silicon Chips2009In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 44, no 2, p. 171-181Article in journal (Refereed)
    Abstract [en]

    In this paper, a silicon chip - based electrospray emitter with a variable orifice size is presented. The device consists of two chips, with a thin beam elevating from the center of each of the chips. The chips are individually mounted to form an open gap of a narrow, uniform width between the top areas of the beams. The electrospray is generated at the endpoint of the gap, where the spray point is formed by the very sharp intersection between the crystal planes of the < 100 > silicon chips. Sample solution is applied to the rear end of the gap from a capillary via a liquid bridge, and capillary forces ensure a spontaneous imbibition of the gap. The sample solution is confined to the gap by means of a hydrophobic treatment of the surfaces surrounding the gap, as well as the geometrical boundaries formed by the edges of the gap walls. The gap width could be adjusted between 1 and 25 μm during electrospray experiments without suffering from any interruption of the electrospray process. Using a peptide sample solution, a shift toward higher charge states and increased signal-to-noise ratios was observed when the gap width was decreased. The limit of detection for the peptide insulin (chain B, oxidized) was approximately 4 nM. We also show a successful interfacing of the electrospray setup with capillary electrophoresis.

  • 43.
    Ek, Patrik
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Sjödahl, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Roeraade, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Electrospray Ionization from a Gap with Adjustable Width2006In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 20, no 21, p. 3176-3182Article in journal (Refereed)
    Abstract [en]

    In this paper, we present a new concept for electrospray ionization mass spectrometry, where the sample is applied in a gap which is formed between the edges of two triangular-shaped tips. The size of the spray orifice can be changed by varying the gap width. The tips were fabricated from polyethylene terephthalate film with a thickness of 36 μm. To improve the wetting of the gap and sample confinement, the edges of the tips forming the gap were hydrophilized by means of silicon dioxide deposition. Electrospray was performed with gap widths between 1 and 36 μm and flow rates down to 75 nL/min. The gap width could be adjusted in situ during the mass spectrometry experiments and nozzle clogging could be managed by simply widening the gap. Using angiotensin I as analyte, the signal-to-noise ratio increased as the gap width was decreased, and a shift towards higher charge states was observed. The detection limit for angiotensin I was in the low nM range.

  • 44.
    Ek, Patrik
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry (closed 20110630).
    Stjernström, Mårten
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry (closed 20110630).
    Emmer, Åsa
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry (closed 20110630).
    Roeraade, Johan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry (closed 20110630).
    Electrospray ionization mass spectrometry from discrete nanoliter-sized sample volumes2010In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 24, no 17, p. 2561-2568Article in journal (Refereed)
    Abstract [en]

    We describe a method for nanoelectrospray ionization mass spectrometry (nESI-MS) of very small sample volumes. Nanoliter-sized sample droplets were taken up by suction into a nanoelectrospray needle from a silicon microchip prior to ESI. To avoid a rapid evaporation of the small sample volumes, all manipulation steps were performed under a cover of fluorocarbon liquid. Sample volumes down to 1.5 nL were successfully analyzed, and an absolute limit of detection of 105 attomole of insulin (chain B, oxidized) was obtained. The open access to the sample droplets on the silicon chip provides the possibility to add reagents to the sample droplets and perform chemical reactions under an extended period of time. This was demonstrated in an example where we performed a tryptic digestion of cytochrome C in a nanoliter-sized sample volume for 2.5h, followed by monitoring the outcome of the reaction with nESI-MS. The technology was also utilized for tandem mass spectrometry (MS/MS) sequencing analysis of a 2 nL solution of angiotensin I.

  • 45. Eller, J.
    et al.
    Rosén, Tomas
    Electrochemistry Laboratory.
    Marone, F.
    Stampanoni, M.
    Wokaun, A.
    Bchi, F. N.
    Progress in in situ X-ray tomographic microscopy of liquid water in gas diffusion layers of PEFC2011In: Journal of the Electrochemical Society, ISSN 0013-4651, Vol. 158, no 8, p. B963-B970Article in journal (Refereed)
    Abstract [en]

    Water management is an important factor for optimizing polymer electrolyte fuel cells (PEFC) under high current density conditions as required for the automotive application. The characteristics of the local liquid saturation of the gas diffusion layer (GDL) is of particular interest. Here we report on the development of in-situ X-ray tomographic microscopy (XTM) with a pixel sizes in the order of 2 μm and sensitivity for carbon and liquid water for the quantitative analysis of liquid water in GDLs. In-situ XTM of PEFC is a major experimental challenge. A complete cell needs to be operated under realistic conditions in the constraint space of the small field of view on the beamline sample stage. Further phase segmentation of the images is required to successfully analyze the quantitative properties of the different phases. For this a workflow, applying differential images between dry and wet structures has been developed. Cells with Toray TGP-H-060 GDLs were analyzed in-situ. Droplets that appear on the GDL surface are connected to a significant water structure inside the GDL. Further the water cluster size distribution in the GDL shows that while small droplets (<100 pl) are numerous, most of the water is contained in few larger clusters.

  • 46. Emmer, Åsa
    et al.
    JANSSON, M
    ROERAADE, J
    A NEW APPROACH TO DYNAMIC DEACTIVATION IN CAPILLARY ZONE ELECTROPHORESIS1991In: HRC Journal of High Resolution Chromatography, ISSN 0935-6304, E-ISSN 1521-4168, Vol. 14, no 11, p. 738-740Article in journal (Refereed)
  • 47. EMMER, Åsa
    et al.
    JANSSON, M
    ROERAADE, J
    IMPROVED CAPILLARY ZONE ELECTROPHORETIC SEPARATION OF BASIC-PROTEINS, USING A FLUOROSURFACTANT BUFFER ADDITIVE1991In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 547, no 1-2, p. 544-550Article in journal (Refereed)
  • 48. Emmer, Åsa
    et al.
    JANSSON, M
    ROERAADE, J
    SEPARATION OF PIG-LIVER ESTERASE ISOENZYMES AND SUBUNITS BY CAPILLARY ZONE ELECTROPHORESIS IN THE PRESENCE OF FLUORINATED SURFACTANTS1994In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 672, no 1-2, p. 231-236Article in journal (Refereed)
  • 49. Emmer, Åsa
    et al.
    JANSSON, M
    ROERAADE, J
    LINDBERG, U
    HOK, B
    FABRICATION AND CHARACTERIZATION OF A SILICON MICROVALVE1992In: Journal of Microcolumn Separations, ISSN 1040-7685, E-ISSN 1520-667X, Vol. 4, no 1, p. 13-15Article in journal (Refereed)
  • 50. Emmer, Åsa
    et al.
    ROERAADE, J
    CAPILLARY ELECTROPHORESIS, COMBINED WITH AN ONLINE MICRO POSTCOLUMN ENZYME ASSAY1994In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 662, no 2, p. 375-381Article in journal (Refereed)
1234 1 - 50 of 175
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