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  • 1.
    Amini, Nahid
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Shariatgorji, Mohammadreza
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Crescenzi, Carlo
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Screening and Quantification of Pesticides in Water Using a Dual-Function Graphitized Carbon Black Disk2010In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 1, p. 290-296Article in journal (Refereed)
    Abstract [en]

    A simple platform for combining solid phase extraction (SPE) and surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) of extracted analytes, using disks prepared by embedding graphitized carbon black (GCB-4) particles in a network of polytetrafluoroethylene (PTFE), is presented. The system provides a convenient approach for rapid SALDI-MS screening of substances in aqueous samples, which can be followed by robust quantitative and/or structural analyses by liquid chromatography (LC)/MS/MS of positive samples. The extraction discs are easily transferred between gaskets where the sample extraction and desorption of selected samples is performed and the mass spectrometer. The SPE and SALDI properties of the new GCB-4 disc have been characterized for 15 pesticides with varying chemical properties, and the screening strategy has been applied to the analysis of pesticides in agricultural drainage water. Atrazine and atrazine-desethyl-2-hydroxy were detected in the sampled water by SALDI-MS screening and subsequently confirmed and quantified using LC/MS/MS.

  • 2.
    Amini, Nahid
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Shariatgorji, Mohammadreza
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    SALDI-MS Signal Enhancement Using Oxidized Graphitized Carbon Black Nanoparticles2009In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 20, no 6, p. 1207-1213Article in journal (Refereed)
    Abstract [en]

    The signal intensity of low-molecular-weight compounds analyzed using surface-assisted laserdesorption/ionization time-of-flight mass spectrometry (SALDI-TOF-MS) was significantlyenhanced when oxidized graphitized carbon black (GCB) particles were used as the desorption/ionization surface. The surface of oxidized GCB contains more carboxylic acid groupsthan non-oxidized GCB. Carboxylic acid groups enhance the efficiency of the ionizationprocess and the desorption of more hydrophobic compounds. A common pharmaceuticalcompound, propranolol, was successfully extracted from Baltic Sea blue mussels and quantifiedusing oxidized GCB as the SALDI surface, whereas deuterated propranolol was used asthe internal standard. The calibration curve showed a wide linear dynamic range of response(0.1–20 g/mL) and good reproducibility (RSD 10%). It was not possible to detectpropranolol in Baltic Sea blue mussels when non-oxidized GCB was used as the SALDI surface.

  • 3. Andersson, P
    et al.
    Jesson, G
    Kylberg, G
    Ekstrand, G
    Thorsén, G
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Parallel nanoliter microfluidic analysis system2007In: Anal Chem, Vol. 79, p. 4022-4030Article in journal (Refereed)
  • 4.
    Avagyan, Rozanna
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Luongo, Giovanna
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Östman, Conny
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Benzothiazole, benzotriazole, and their derivates in clothing textiles - a potential source of environmental pollutants and human exposure2015In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 22, no 8, p. 5842-5849Article in journal (Refereed)
    Abstract [en]

    Textiles play an important role in our daily life, and textile production is one of the oldest industries. In the manufacturing chain from natural and/or synthetic fibers to the final clothing products, the use of many different chemicals is ubiquitous. A lot of research has focused on chemicals in textile wastewater, but the knowledge of the actual content of harmful chemicals in clothes sold on the retail market is limited. In this paper, we have focused on eight benzothiazole and benzotriazole derivatives, compounds rated as high production volume chemicals. Twenty-six clothing samples of various textile materials and colors manufactured in 14 different countries were analyzed in textile clothing using liquid chromatography tandem mass spectrometry. Among the investigated textile products, 11 clothes were for babies, toddlers, and children. Eight of the 11 compounds included in the investigation were detected in the textiles. Benzothiazole was present in 23 of 26 investigated garments in concentrations ranging from 0.45 to 51 μg/g textile. The garment with the highest concentration of benzothiazole contained a total amount of 8.3 mg of the chemical. The third highest concentration of benzothiazole (22 μg/g) was detected in a baby body made from “organic cotton” equipped with the “Nordic Ecolabel” (“Svanenmärkt”). It was also found that concentrations of benzothiazoles in general were much higher than those for benzotriazoles. This study implicates that clothing textiles can be a possible route for human exposure to harmful chemicals by skin contact, as well as being a potential source of environmental pollutants via laundering and release to household wastewater.

  • 5.
    Avagyan, Rozanna
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Sadiktsis, Ioannis
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Östman, Conny
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Determination of benzothiazole and benzotriazole derivates in tire and clothing textile samples by high performance liquid chromatography-electrospray ionization tandem mass spectrometry2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1307, p. 119-125Article in journal (Refereed)
    Abstract [en]

    A high performance liquid chromatography–tandem mass spectrometry method utilizing electrospray ionization in positive and negative mode has been developed for the separation and detection of benzothiazole and benzotriazole derivates. Ultra-sonication assisted solvent extraction of these compounds has also been developed and the overall method demonstrated on a selected clothing textile and an automobile tire sample. Matrix effects and extraction recoveries, as well as linearity and limits of detection have been evaluated. The calibration curves spanned over more than two orders of magnitude with coefficients of correlation R2 > 0.99 and the limits of detection and the limits of quantification were in the range 1.7–58 pg injected and 18–140 pg/g, respectively. The extraction recoveries ranged between 69% and 102% and the matrix effects between 75% and 101%. Benzothiazole and benzotriazole derivates were determined in the textile sample and benzothiazole derivatives determined in the tire sample with good analytical performance.

  • 6.
    Ericson, Hanna
    et al.
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Kumblad, Linda
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Physiological effects of diclofenac, ibuprofen and propranolol on Baltic Sea blue mussels2010In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 99, no 2, p. 223-231Article in journal (Refereed)
    Abstract [en]

    Pharmaceuticals are constantly dispersed into the environment and little is known of the effects on non-target organisms. This is an issue of growing concern. In this study, Baltic Sea blue mussels, Mytilus edulis trossulus, were exposed to diclofenac, ibuprofen and propranolol, three pharmaceuticals that are produced and sold in large quantities and have a widespread occurrence in aquatic environments. The mussels were exposed to pharmaceuticals in concentrations ranging from 1 to 10,000 mu g l(-1). The pharmaceuticals were added both separately and in combination. Mussels exposed to high concentrations of pharmaceuticals showed a clear response compared to controls. Firstly, they had a significantly lower scope for growth, which indicates that the organisms had a smaller part of their energy available for normal metabolism, and secondly, they had lower byssus strength and lower abundance of byssus threads, resulting in reduced ability to attach to the underlying substrate. Mussels exposed to lower concentrations showed tendencies of the same results. The concentration of diclofenac and propranolol was quantified in the mussels using both liquid chromatography coupled to mass spectrometry (LC-MS). The measurements showed a significantly higher concentration in the organisms as compared to the water the mussels were exposed to; the uptake reached concentrations two orders of magnitudes higher than found in sewage treatment plant effluents. This study showed that common pharmaceuticals are taken up and negatively affect the physiology of a non-target species at levels of two to three orders of magnitudes higher than found in sewage treatment plant effluents.

  • 7.
    Eriksson Wiklund, Ann-Kristin
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Oskarsson, Hanna
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Kumblad, Linda
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Behavioural and physiological responses to pharmaceutical exposure in macroalgae and grazers from a Baltic Sea littoral community2011In: Aquatic Biology, ISSN 1864-7782, E-ISSN 1864-7790, Vol. 14, no 1, p. 29-39Article in journal (Refereed)
    Abstract [en]

    Gammarus spp. and Fucus vesiculosus from the Baltic Sea littoral community were exposed to 3 concentrations of the pharmaceuticals ibuprofen and propranolol. Both physiological and behavioural parameters were measured to examine potential effects in the organisms. For Gammarus spp., respiration, feeding rate and activity with and without predator cues were measured, and gross production to respiration ratio (GP/R) and chlorophyll fluorescence were measured for F. vesiculosus. The results showed that propranolol decreased the activity related to movement, and Gammarus spp. could not compensate for the reduced movement when subjected to predator cues. The feeding rates of Gammarus spp. exposed to propranolol were more than 2 times higher at all concentrations compared to the control. Ibuprofen did not significantly affect any of the measured parameters of Gammarus spp. The GP/R was lower in algae exposed to propranolol. The effects of propranolol on both behaviour and physiology of Gammarus spp., in combination with the stress responses in the algae, might cause unexpected indirect and cascade effects which eventually could have implications at both community and ecosystem scales.

  • 8.
    Jamshidi, Sara
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Kharazmi University, Iran.
    Rofouei, Mohammad Kazem
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. IVL Swedish Environmental Research Institute, Sweden.
    Using magnetic core-shell nanoparticles coated with an ionic liquid dispersion assisted by effervescence powder for the micro-solid-phase extraction of four beta blockers from human plasma by ultra high performance liquid chromatography with mass spectrometry detection2019In: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 42, no 3, p. 698-705Article in journal (Refereed)
    Abstract [en]

    In this work, a novel, efficient, and green sorbent, SiO2@Fe3O4 has been created and functionalized with 1-butyl-3-methylimidazolium hexafluorophosphate as an ionic liquid. This sorbent was applied for microextraction of four beta blockers, propranolol, metoprolol, atenolol, and alprenolol with bupivacaine as internal standard from human plasma followed by liquid chromatography with mass spectrometric detection. A mixture of sodium bicarbonate and sodium dihydrogen phosphate was used as an extractant dispersive agent (effervescent power) to enhance the interaction between the magnetic sorbent and analytes. Main affecting parameters on microextraction and elution were optimized. Figures of merit for dispersive solid phase extraction with ionic liquid coated magnetic nanoparticles assisted by effervescent powder were calculated under the optimized conditions. The detection limits for propranolol, metoprolol, atenolol, and alprenolol were found at 0.33, 0.62, 0.03, and 0.44 ng/mL, respectively. For all analytes, good linearity was obtained. Intra-(n = 5) and interday (n = 10) precision were both under 6.3% while the preconcentration factors were obtained in the range between 15-18. The extraction efficiencies for each analyte ranged from 75 to 91%. The method was successfully applied for determination of trace amounts of the beta blockers in human plasma samples.

  • 9.
    Karlsson, Isabella
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Ndreu, Lorena
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Quaranta, Alessandro
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Glycosylation patterns of selected proteins in individual serum and cerebrospinal fluid samples2017In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 145, p. 431-439Article in journal (Refereed)
    Abstract [en]

    A method we previously developed has been applied to the determination of the glycosylation pattern of specific proteins in biological samples. Six proteins (alpha-1-anthrypsin, transferrin, haptoglobin, Cl inhibitor, alpha-1 acid glycoprotein, and immunoglobulin G) were studied in serum samples from five individuals and cerebrospinal fluid (CSF) samples from three individuals, to investigate the expected normal distribution of glycosylation patterns and to assess whether this methodology can be used to discriminate between samples from different individuals. For serum samples, the differences were shown to be small, while much larger differences were found for the CSF samples, with a greater number of glycoforms present. This can be linked to the occurrence of differential glycosylation in proteins expressed in the brain compared with proteins expressed elsewhere in the body. The developed method could distinguish differences in the glycosylation pattern of specific proteins in the individual samples, which was not reflected in the glycan content of total CSF. This is the first time that the glycoforms of several of these proteins have been investigated in CSF.

  • 10.
    Luongo, Giovanna
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Östman, Conny
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Quinolines in clothing textiles-a source of human exposure and wastewater pollution?2014In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, no 12, p. 2747-2756Article in journal (Refereed)
    Abstract [en]

    A production process in which the use of various types of chemicals seems to be ubiquitous makes the textile industry a growing problem regarding both public health as well as the environment. Among several substances used at each stage, the present study focuses on the quinolines, a class of compounds involved in the manufacture of dyes, some of which are skin irritants and/or classified as probable human carcinogens. A method was developed for the determination of quinoline derivatives in textile materials comprising ultrasound-assisted solvent extraction, solid phase extraction cleanup, and final analysis by gas chromatography/mass spectrometry. Quinoline and ten quinoline derivatives were determined in 31 textile samples. The clothing samples, diverse in color, material, brand, country of manufacture, and price, and intended for a broad market, were purchased from different shops in Stockholm, Sweden. Quinoline, a possible human carcinogen, was found to be the most abundant compound present in almost all of the samples investigated, reaching a level of 1.9 mg in a single garment, and it was found that quinoline and its derivatives were mainly correlated to polyester material. This study points out the importance of screening textiles with nontarget analysis to investigate the presence of chemicals in an unbiased manner. Focus should be primarily on clothing worn close to the body.

  • 11.
    Oskarsson, Hanna
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Wiklund, Ann-Kristin Eriksson
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Danielsson, Gabriela
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kumblad, Linda
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Community Interactions Modify the Effects of Pharmaceutical Exposure: A Microcosm Study on Responses to Propranolol in Baltic Sea Coastal Organisms2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, article id e93774Article in journal (Refereed)
    Abstract [en]

    This study investigated the uptake and effects of a common human pharmaceutical, propranolol, on the structure and function of a coastal Baltic Sea model community consisting of macroalga (Ceramium tenuicorne), mussels (Mytilus edulis trossulus), amphipods (Gammarus spp.), water and sediment. The most sensitive species, the mussel, was affected to the same extent as in previous single species studies, while the effects on the amphipod and alga were smaller or even positive compared to experiments performed in less complex test systems. The observed cascade of beneficial effects was a result of inter-specific species interactions that buffered for more severe effects. The poor condition of the mussel led to a feeding shift from alga to mussel by the amphipods. The better food quality, due to the dietary shift, counteracted the effects of the exposure. Less amphipod grazing, together with increased levels of nutrients in the water was favourable for the alga, despite the negative effects of propranolol. This microcosm study showed effects on organisms on different organizational levels as well as interactions among the different components resulting in indirect exposure effects of both functional and structural nature. The combination of both direct and indirect effects would not have been detected using simpler single- or even two-species study designs. The observed structural changes would in the natural environment have a long-term influence on ecosystem function, especially in a low-biodiversity ecosystem like the Baltic Sea.

  • 12.
    Quaranta, Alessandro
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Karlsson, Isabella
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Ndreu, Lorena
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Marini, Federico
    Ingelsson, Martin
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Glycosylation profiling of selected proteins in cerebrospinal fluid from Alzheimer's disease and healthy subjects2019In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 11, no 26, p. 3331-3340Article in journal (Refereed)
    Abstract [en]

    Alteration of glycosylation has been observed in several diseases, such as cancer and neurodegenerative disorders. The study of changes in glycosylation could lead to a better understanding of mechanisms underlying these diseases and to the identification of new biomarkers. In this work the N-linked glycosylation of five target proteins in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and healthy controls have been analyzed for the first time. The investigated proteins, transferrin (TFN), alpha-1-antitrypsin (AAT), C1-inhibitor, immunoglobulin G (IgG), and alpha-1-acid glycoprotein (AGP), were selected based on the availability of VHH antibody fragments and their potential involvement in neurodegenerative and inflammation diseases. AD patients showed alterations in the glycosylation of low abundance proteins, such as C1-inhibitor and alpha-1-acid glycoprotein. These alterations would not have been detected if the glycosylation profile of the total CSF had been analyzed, due to the masking effect of the dominant profiles of high abundance glycoproteins, such as IgG. Information obtained from single proteins was not sufficient to correctly classify the two sample groups; however, by using an advanced multivariate technique a total non-error rate of 72 +/- 3% was obtained. In fact, the corresponding model was able to correctly classify 71 +/- 4% of the healthy subjects and 74 +/- 7% of the AD patients. Even if the results were not conclusive for AD, this approach could be extremely useful for diseases in which glycosylation changes are reported to be more extensive, such as several types of cancer and autoimmune diseases.

  • 13.
    Quaranta, Alessandro
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Sroka-Bartnicka, Anna
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Marie Curie Sklodowska University, Poland.
    Tengstrand, Erik
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    N-Glycan profile analysis of transferrin using a microfluidic compact disc and MALDI-MS2016In: Analusis, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 408, no 17, p. 4765-4776Article in journal (Refereed)
    Abstract [en]

    It has been known for a long time that diseases can be associated with changes to the glycosylation of specific proteins. This has been shown for cancer, immunological disorders, and neurodegenerative diseases. The possibility of using the glycosylation patterns of proteins as biomarkers for disease would be a great asset for clinical research or diagnosis. There is at present a lack of rapid, automated, and cost-efficient analytical techniques for the determination of the glycosylation of specific serum proteins. We have developed a method for determining the glycosylation pattern of proteins based on the affinity capture of a specific serum protein, the enzymatic release of the N-linked glycans, and the analysis of the glycan pattern using MALDI-MS. All sample preparation is performed in a disposable centrifugal microfluidic disc. The sample preparation is miniaturized, requiring only 1 mu L of sample per determination, and automated with the possibility of processing 54 samples in parallel in 3.5 h. We have developed a method for the glycosylation pattern analysis of transferrin. The method has been tested on serum samples from chronic alcohol abusers and a control group. Also, a SIMCA model was created and evaluated to discriminate between the two groups.

  • 14.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Amini, Nahid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Crescenzi, Carlo
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    µ-trap for the SALDI-MS screening of organic compounds prior to LC/MS analysis2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 14, p. 5515-5523Article in journal (Refereed)
    Abstract [en]

    A procedure for rapidly screening and quantitatively analyzing organic molecules is presented, in which a miniaturized solid-phase extraction (SPE) cartridge containing 0.6 mg of graphitized carbon black (the GCB-mu-trap) is used for sample pretreatment. Then surface-assisted laser desorption ionization dine-of-flight mass spectrometry (SALDI-TOF-MS) screening is followed by liquid chromatography/mass spectrometry (LC/MS) for robust quantitative analysis of samples containing analytes of interest. Liquid samples with volumes up to 100 mL were extracted using the GCB-mu-trap, and SALDI screening was performed by transferring a few particles of the GCB 4 sorbent from the mu-trap onto a stainless steel plate. Analytes were then simply ionized and desorbed by irradiating the GCB 4 particles without any further pretreatment. GCB 4 was found to be an excellent surface for the SALDI analysis of small molecules, providing spectra with very clean backgrounds. The small size of the cartridge (micropipet filter tip) results in enrichment of the analytes on a small surface area, affording low SALDI-TOF-MS detection limits. Furthermore, the removal of just a few particles from the p-trap does not significantly affect the subsequent quantitative determination. This approach offers considerable reductions in analytical costs by eliminating unnecessary SPE-LC/MS analyses.

  • 15.
    Sroka-Bartnicka, Anna
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Karlsson, Isabella
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Ndreu, Lorena
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Quaranta, Alessandro
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Pijnappel, Matthijs
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Particle-based N-linked glycan analysis of selected proteins from biological samples using nonglycosylated binders2017In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 132, p. 125-132Article in journal (Refereed)
    Abstract [en]

    Glycosylation is one of the most common and important post-translational modifications, influencing both the chemical and the biological properties of proteins. Studying the glycosylation of the entire protein population of a sample can be challenging because variations in the concentrations of certain proteins can enhance or obscure changes in glycosylation. Furthermore, alterations in the glycosylation pattern of individual proteins, exhibiting larger variability in disease states, have been suggested as biomarkers for different types of cancer, as well as inflammatory and neurodegenerative diseases. In this paper, we present a rapid and efficient method for glycosylation analysis of individual proteins focusing on changes in the degree of fucosylation or other alterations to the core structure of the glycans, such as the presence of bisecting N-acetylglucosamines and a modified degree of branching. Streptavidin-coated magnetic beads are used in combination with genetically engineered immunoaffinity binders, called VHH antibody fragments. A major advantage of the VHHs is that they are nonglycosylated; thus, enzymatic release of glycans from the targeted protein can be performed directly on the beads. After deglycosylation, the glycans are analyzed by MALDI-TOF-MS. The developed method was evaluated concerning its specificity, and thereafter implemented for studying the glycosylation pattern of two different proteins, alpha-1-antitrypsin and transferrin, in human serum and cerebrospinal fluid. To our knowledge, this is the first example of a protein array-type experiment that employs bead-based immunoaffinity purification in combination with mass spectrometry analysis for fast and efficient glycan analysis of individual proteins in biological fluid.

  • 16.
    Thorsén, Gunnar
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Ericson, Hanna
    Kumblad, Linda
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Quantification of human pharmaceuticals in Baltic Sea blue mussels2009In: Abstracts / 12th EuCheMS International conference on chemistry and the environment: 14-17 June 2009, Stockholm university, Stockholm, Sweden, 2009, p. Ana P62-Conference paper (Other academic)
  • 17.
    Thuy, Tran Thi
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Inganas, Mats
    Ekstrand, Gunnar
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Parallel sample preparation of proteins, from crude samples to crystals ready for MALDI-MS, in an integrated microfluidic system2010In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 878, no 28, p. 2803-2810Article in journal (Refereed)
    Abstract [en]

    A microfluidic structure is presented where selective capture of proteins in complex samples, followed by clean-up, enzymatic processing, and MALDI-MS sample preparation of peptides generated, can be performed. The structure uses an affinity column to capture the protein while all other components in the sample are disposed of. The protein of interest is then eluted from the affinity column and captured on a second column on which the enzymatic processing is performed. Salts and hydrophilic contaminants are then removed before the products from the enzymatic reaction are eluted together with a suitable MALDI matrix and the solvent evaporated in a designated MALDI target structure. All steps can be performed automatically in 54 parallel microstructures on a microfluidic compact disc. The process is demonstrated by the selective capture and tryptic digest of recombinant IgG molecules from samples containing other proteins: an excess of bovine serum albumin or spent cell culture media.

  • 18.
    Thuy, Tran Thi
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Tengstrand, Erik
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Åberg, Magnus
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Discrimination between glycosylation patterns of therapeutic antibodies using a microfluidic platform, MALDI-MS and multivariate statistics2012In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 70, p. 47-52Article in journal (Refereed)
    Abstract [en]

    Optimal glycosylation with respect to the efficacy, serum half-life time, and immunogenic properties is essential in the generation of therapeutic antibodies. The glycosylation pattern can be affected by several different parameters during the manufacture of antibodies and may change significantly over cultivation time. Fast and robust methods for determination of the glycosylation patterns of therapeutic antibodies are therefore needed. We have recently presented an efficient method for the determination of glycans on therapeutic antibodies using a microfluidic CD platform for sample preparation prior to matrix-assisted laser-desorption mass spectrometry analysis. In the present work, this method is applied to analyse the glycosylation patterns of three commercially available therapeutic antibodies and one intended for therapeutic use. Two of the antibodies produced in mouse myeloma cell line (SP2/0) and one produced in Chinese hamster ovary (CHO) cells exhibited similar glycosylation patterns but could still be readily differentiated from each other using multivariate statistical methods. The two antibodies with most similar glycosylation patterns were also studied in an assessment of the method's applicability for quality control of therapeutic antibodies. The method presented in this paper is highly automated and rapid. It can therefore efficiently generate data that helps to keep a production process within the desired design space or assess that an identical product is being produced after changes to the process.

  • 19. Thuy, Tran Thi
    et al.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Glycosylation Profiling of Therapeutic Antibodies in Serum Samples Using a Microfluidic CD Platform and MALDI-MS2013In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 24, no 7, p. 1053-1063Article in journal (Refereed)
    Abstract [en]

    The serum clearance rate of therapeutic antibodies is important as it affects the clinical efficacy, required dose, and dose frequency. The glycosylation of antibodies has in some studies been shown to have an impact on the elimination rates in vivo. Monitoring changes to the glycan profiles in pharmacokinetics studies can reveal whether the clearance rates of the therapeutic antibodies depend on the different glycoforms, thereby providing useful information for improvement of the drugs. In this paper, a novel method for glycosylation analysis of therapeutic antibodies in serum samples is presented. A microfluidic compact-disc (CD) platform in combination with MALDI-MS was used to monitor changes to the glycosylation profiles of samples incubated in vitro. Antibodies were selectively purified from serum using immunoaffinity capture on immobilized target antigens. The glycans were enzymatically released, purified, and finally analyzed by MALDI-TOF-MS. To simulate changes to glycan profiles after administration in vivo, a therapeutic antibody was incubated in serum with the enzyme alpha 1-2,3 mannosidase to artificially reduce the amount of the high mannose glycoforms. Glycan profiles were monitored at specific intervals during the incubation. The relative abundance of the high mannose 5 glycoform was clearly found to decrease and, simultaneously, that of high mannose 4 increased over the incubation period. The method can be performed in a rapid, parallel, and automated fashion for glycosylation profiling consuming low amounts of samples and reagents. This can contribute to less labor work and reduced cost of the studies of therapeutic antibodies glycosylation in vitro and in vivo.

  • 20.
    Tran, Thi Thuy
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Inganas, Mats
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    High-throughput profiling of N-linked oligosaccharides in therapeutic antibodies using a microfluidic CD platform and MALDI-MS2011In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 399, no 4, p. 1601-1611Article in journal (Refereed)
    Abstract [en]

    Recombinant therapeutic antibodies have shown a great potential in the treatment of several severe medical conditions such as cancer and autoimmune diseases. Glycosylation plays a critical role in biological activity and immunogenic properties of these compounds. The analysis of glycan profiles is therefore necessary in many steps of the development and manufacturing process from early development to quality control of the final product. In this paper, a fast, parallel, and robust sample preparation platform for glycosylation profiling using a microfluidic compact disc (CD) is presented. A sequential process including selective capture of antibody from a crude cell supernatant using protein A beads, enzymatic release of glycans, purification with a graphitized carbon black column, and crystallisation for MALDI-TOF analysis were performed on the CD. Glycosylation profiles of an antibody intended for therapeutic use produced in two different cell lines were compared.

  • 21.
    Tran, Thuy
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsén, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Glycosylation profiling of therapeutic antibodies in serum samples using a microfluidic CD platform and MALDI-MSManuscript (preprint) (Other academic)
    Abstract [en]

    The serum clearance rate of therapeutic antibodies is important as it affects the clinical efficacy, required dose and dose frequency. The glycosylation of antibodies has in some studies been shown to have an impact on the elimination rates in vivo. Monitoring changes to the glycan profiles in pharmacokinetics studies can reveal whether the clearance rates of the therapeutic antibodies depend on the different glycoforms, thereby providing useful information for improvement of the drugs. In this paper a novel method for glycosylation analysis of therapeutic antibodies in serum samples is presented. A microfluidic CD platform in combination with MALDI-MS was used to monitor changes to the glycosylation profiles of samples incubated in vitro. Antibodies were selectively purified from serum using immunoaffinity capture on immobilized target antigens. The glycans were enzymatically released, purified and finally analyzed by MALDI-TOF-MS. To simulate changes to glycan profiles after administration in vivo, a therapeutic antibody was incubated in serum with the enzyme α1-2,3 mannosidase to artificially reduce the amount of the high mannose glycoforms. Glycan profiles were monitored at specific intervals during the incubation. The relative abundance of the high mannose 5 glycoform was clearly found to decrease and simultaneously, that of high mannose 4 increased over the incubation period. The method can be performed in a rapid, parallel and automated fashion for glycosylation profiling consuming low amounts of samples and reagents. This can contribute to less labor work and reduced cost of the studies of therapeutic antibodies glycosylation in vitro and in vivo.Keywords:

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