TY - JOUR A1 - Weidner, Steffen A1 - Knappe, Patrick A1 - Panne, Ulrich T1 - MALDI-TOF imaging mass spectrometry of artifacts in 'dried droplet' polymer samples N2 - Matrix-assisted laser desorption/ionization-timeof-flight (MALDI-TOF) imaging of polystyrenes with various molecular masses was applied to study spatial molecular mass distribution of polymers in sample spots prepared by the 'dried droplet' method. When different solvents and target surfaces were examined, a segregation of single homologous polymers was observed depending upon the evaporation rate of the solvent. For the observed Patterns left by the evaporating droplet, a hypothesis is offered taking into account different hydrodynamic interactions and diffusion. The results illustrate that spot preparation using the conventionally 'dried droplet' method is prone to artifacts and should be avoided for reliable and reproducible MALDI mass spectrometry experiments with regards to the Determination of molecular masses and mass distributions. KW - MALDI KW - Mass spectrometry imaging KW - Polymer KW - Droplet PY - 2011 U6 - https://doi.org/10.1007/s00216-011-4773-1 SN - 1618-2642 SN - 1618-2650 VL - 401 IS - 1 SP - 127 EP - 134 PB - Springer CY - Berlin AN - OPUS4-24538 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Thünemann, Andreas A1 - Rolf, Simone A1 - Knappe, Patrick A1 - Weidner, Steffen T1 - In Situ Analysis of a Bimodal Size Distribution of Superparamagnetic Nanoparticles N2 - The dispersed iron oxide nanoparticles of ferrofluids in aqueous solution are difficult to characterize due to their protective polymer coatings. We report on the bimodal size distribution of superparamagnetic iron oxide nanoparticles found in the MRI contrast agent Resovist, which is a representative example of commercial nanoparticle-based pharmaceutical formulations. The radii of the majority of the nanoparticles (>99%) range from 4 to 13 nm (less than 1% of the particles display radii up to 21 nm). The maxima of the size distributions are at 5.0 and 9.9 nm. The analysis was performed with in situ characterization of Resovist via online coupling of asymmetrical flow field-flow fractionation (A4F) with small-angle X-ray scattering (SAXS) using a standard copper X-ray tube as a radiation source. The outlet of the A4F was directly coupled to a flow capillary on the SAXS instrument. SAXS curves of nanoparticle fractions were recorded at 1-min time intervals. We recommend using the A4F-SAXS coupling as a routine method for analysis of dispersed nanoparticles with sizes in the range of 1-100 nm. It allows a fast and quantitative comparison of different batches without the need for sample preparation. PY - 2009 U6 - https://doi.org/10.1021/ac802009q SN - 0003-2700 SN - 1520-6882 VL - 81 IS - 1 SP - 296 EP - 301 PB - American Chemical Society CY - Washington, DC AN - OPUS4-18658 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Knappe, Patrick A1 - Bienert, Ralf A1 - Weidner, Steffen A1 - Thünemann, Andreas T1 - Characterization of poly/N-vinyl-2-pyrrolidone)s with broad size distributions N2 - We report on the characterization of the solution structure of poly(N-vinyl-2-pyrrolidone)s (PVP) by small-angle X-ray scattering (SAXS) and by online coupling of asymmetrical flow field-flow fractionation (A4F), SAXS and dynamic light scattering (DLS). The commercial products PVP K30 and PVP K90 with nominal molar masses of 40 × 103 and 360 × 103 g mol-1, respectively, were investigated separately and as binary mixture. Detailed information for all polymer fractions is available on the polymer contour lengths and the diffusion coefficients. Key areas of applications for the A4F-SAXS-DLS coupling are seen in comparison to static light scattering for polymers with radii of gyration smaller than 10 nm, for which only SAXS produces precise analytical results on the size of the polymers in solution. KW - Small-angle X-ray scattering KW - SAXS KW - Field-flow fractionation PY - 2010 U6 - https://doi.org/10.1016/j.polymer.2010.02.039 SN - 0032-3861 SN - 1873-2291 VL - 51 IS - 8 SP - 1723 EP - 1727 PB - Springer CY - Berlin AN - OPUS4-21222 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Böhmert, L. A1 - Girod, Matthias A1 - Hansen, Ulf A1 - Maul, Ronald A1 - Knappe, Patrick A1 - Niemann, B. A1 - Weidner, Steffen A1 - Thünemann, Andreas A1 - Lampen, A. T1 - Analytically monitored digestion of silver nanoparticles and their toxicity on human intestinal cells N2 - Orally ingested nanoparticles may overcome the gastrointestinal barrier, reach the circulatory system, be distributed in the organism and cause adverse health effects. However, ingested nanoparticles have to pass through different physicochemical environments, which may alter their properties before they reach the intestinal cells. In this study, silver nanoparticles are characterised physicochemically during the course of artificial digestion to simulate the biochemical processes occurring during digestion. Their cytotoxicity on intestinal cells was investigated using the Caco-2 cell model. Using field-flow fractionation combined with dynamic light scattering and small-angle X-ray scattering, the authors found that particles only partially aggregate as a result of the digestive process. Cell viabilities were determined by means of CellTiter-Blue® assay, 4',6-diamidino-2-phenylindole-staining and real-time impedance. These measurements reveal small differences between digested and undigested particles (1–100 µg/ml or 1–69 particles/cell). The findings suggest that silver nanoparticles may indeed overcome the gastrointestinal juices in their particulate form without forming large quantities of aggregates. Consequently, the authors presume that the particles can reach the intestinal epithelial cells after ingestion with only a slight reduction in their cytotoxic potential. The study indicates that it is important to determine the impact of body fluids on the nanoparticles of interest to provide a reliable interpretation of their nano-specific cytotoxicity testing in vivo and in vitro. KW - Silver nanoparticles KW - In vitro digestion KW - Field-flow fractionation KW - Small-angle X-ray scattering KW - Dynamic light scattering KW - Caco-2 cells PY - 2014 U6 - https://doi.org/10.3109/17435390.2013.815284 SN - 1743-5390 SN - 1743-5404 VL - 8 IS - 6 SP - 631 EP - 642 PB - Informa Healthcare CY - London AN - OPUS4-29926 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Knappe, Patrick A1 - Bienert, Ralf A1 - Weidner, Steffen A1 - Thünemann, Andreas T1 - Poly(acrylic acid): A combined analysis with field-flow fractionation and SAXS N2 - Polyelectrolytes such as PAA and its salts are widely used, but are notoriously difficult to characterize due to their polyelectrolyte properties and broad molecular mass distributions. In this paper, we report on a new PAA analysis by combining asymmetrical flow field-flow fractionation and an advanced SAXS technique using an acoustic levitator to minimize background scattering. The proof-of-principle is demonstrated with a mixture of three standard PAAs with different molecular masses. Detailed information on the PAA fractions is available on radii of gyration, polymer contour lengths, and coil conformation. Our method is expected to be applicable for a wide range of water-soluble synthetic and natural polymers and ideal for molecular masses of 5 × 103–2 × 105 g · mol-1. KW - Fractionation of polymers KW - Molar mass distribution KW - Polyelectrolytes KW - Small-angle X-ray scattering KW - Water-soluble polymers PY - 2010 U6 - https://doi.org/10.1002/macp.201000163 SN - 1022-1352 SN - 1521-3935 VL - 211 IS - 19 SP - 2148 EP - 2153 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-22005 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Knappe, Patrick A1 - Boehmert, L. A1 - Bienert, Ralf A1 - Karmutzki, S. A1 - Niemann, B. A1 - Lampen, A. A1 - Thünemann, Andreas T1 - Processing nanoparticles with A4F-SAXS for toxicological studies: Iron oxide in cell-based assays N2 - Nanoparticles are not typically ready-to-use for in vitro cell culture assays. Prior to their use in assays, powder samples containing nanoparticles must be dispersed, de-agglomerated, fractionated by size, and characterized with respect to size and size distribution. For this purpose we report exemplarily on polyphosphate-stabilized iron oxide nanoparticles in aqueous suspension. Fractionation and online particle size analysis was performed in a time-saving procedure lasting 50 min by combining asymmetrical flow field-flow fractionation (A4F) and small-angle X-ray scattering (SAXS). Narrowly distributed nanoparticle fractions with radii of gyration (Rg) from 7 to 21 nm were obtained from polydisperse samples. The A4F-SAXS combination is introduced for the preparation of well-characterized sample fractions originating from a highly polydisperse system as typically found in engineered nanoparticles. A4F-SAXS processed particles are ready-to-use for toxicological studies. The results of preliminary tests of the effects of fractionated iron oxide nanoparticles with a Rg of 15 nm on a human colon model cell line are reported. KW - Field-flow-fractionation KW - Small-angle X-ray scattering KW - Nanoparticle PY - 2011 U6 - https://doi.org/10.1016/j.chroma.2010.11.012 SN - 0021-9673 VL - 1218 IS - 27 SP - 4160 EP - 4166 PB - Elsevier CY - Amsterdam AN - OPUS4-23951 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Thünemann, Andreas A1 - Knappe, Patrick A1 - Bienert, Ralf A1 - Weidner, Steffen T1 - Online coupling of field-flow fractionation with SAXS and DLS for polymer analysis N2 - We report on a hyphenated polymer analysis method consisting of asymmetrical flow field-flow fractionation (A4F) coupled online with small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). A mixture of six poly(styrene sulfonate)s with molar masses in the range of 6.5 × 103 to 1.0 × 106 g mol-1 was used as a model system for polyelectrolytes in aqueous solutions with a broad molar mass distribution. A complete polymer separation and analysis was performed in 60 min. Detailed information for all polymer fractions are available on i) the radii of gyration, which were determined from the SAXS data interpretation in terms of the Debye model (Gaussian chains), and ii) the diffusion coefficients (from DLS). We recommend using the A4F-SAXS-DLS coupling as a possible new reference method for the detailed analysis of complex polymer mixtures. Advantages of the use of SAXS are seen in comparison to static light scattering for polymers with radii of gyration smaller then 15 nm, for which only SAXS produces precise analytical results on the size of the polymers in solution. PY - 2009 U6 - https://doi.org/10.1039/b9ay00107g SN - 1759-9660 SN - 1759-9679 VL - 1 SP - 177 EP - 182 PB - RSC Publ. CY - Cambridge AN - OPUS4-20567 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lichtenstein, D. A1 - Ebmeyer, J. A1 - Knappe, Patrick A1 - Juling, S. A1 - Böhmert, L. A1 - Selve, S. A1 - Niemann, B. A1 - Braeuning, A. A1 - Thünemann, Andreas A1 - Lampen, A. T1 - Impact of food components during in vitro digestion of silver nanoparticles on cellular uptake and cytotoxicity in intestinal cells N2 - Because of the rising application of nanoparticles in food and food-related products, we investigated the influence of the digestion process on the toxicity and cellular uptake of silver nanoparticles for intestinal cells. The main food components – carbohydrates, proteins and fatty acids – were implemented in an in vitro digestion process to simulate realistic conditions. Digested and undigested silver nanoparticle suspensions were used for uptake studies in the well-established Caco-2 model. Small-angle X-ray scattering was used to estimate particle core size, size distribution and stability in cell culture medium. Particles proved to be stable and showed radii from 3.6 to 16.0 nm. Undigested particles and particles digested in the presence of food components were comparably taken up by Caco-2 cells, whereas the uptake of particles digested without food components was decreased by 60%. Overall, these findings suggest that in vivo ingested poly (acrylic acid)-coated silver nanoparticles may reach the intestine in a nanoscaled form even if enclosed in a food matrix. While appropriate for studies on the uptake into intestinal cells, the Caco-2 model might be less suited for translocation studies. Moreover, we show that nanoparticle digestion protocols lacking food components may lead to misinterpretation of uptake studies and inconclusive results. KW - Nanoparticle KW - Nanosilver KW - Silver PY - 2015 U6 - https://doi.org/10.1515/hsz-2015-0145 SN - 1431-6730 SN - 1432-0355 SN - 1437-4315 VL - 396 IS - 11 SP - 1255 EP - 1264 PB - De Gruyter CY - Berlin [u.a.] AN - OPUS4-34887 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Löwa, N. A1 - Knappe, Patrick A1 - Wiekhorst, F. A1 - Eberbeck, D. A1 - Thünemann, Andreas A1 - Trahms, L. T1 - Hydrodynamic and magnetic fractionation of superparamagnetic nanoparticles for magnetic particle imaging N2 - Resovist® originally developed as a clinical liver contrast agent for Magnetic Resonance Imaging exhibits also an outstanding performance as a tracer in Magnetic Particle Imaging (MPI). In order to study the physical mechanism of the high MPI performance of Resovist®, we applied asymmetric flow field–flow fractionation (A4F) and static magnetic fractionation (SMF) to separate Resovist® into a set of fractions with defined size classes. As A4F based on an elution method separates MNP according to their hydrodynamic size, SMF fractionates a particle distribution by its magnetic moment. The obtained fractions of both separation techniques were then magnetically characterized by magnetorelaxometry measurements to extract the corresponding effective magnetic anisotropy and hydrodynamic size distribution parameters. Additionally, the MPI performance of each fraction was assessed using magnetic particle spectroscopy. With both separation techniques fractions (normalized to their iron amount) an MPI signal gain of a factor of two could be obtained, even though the distribution of effective anisotropy and hydrodynamic size were significantly different. Relating these findings to the results from magnetic characterization allows for a better understanding of the underlying mechanisms of MPI performance of Resovist®. This knowledge may help to improve the design of novel MPI tracers and development of separation methods. KW - Superparamagnetic nanoparticles KW - Asymmetric flow field–flow fractionation KW - Magnetic particle spectroscopy KW - Magnetorelaxometry KW - Magnetic separation KW - Magnetic particle imaging KW - Resovist® KW - Nanotechnology KW - SAXS KW - Nanoparticles PY - 2015 U6 - https://doi.org/10.1016/j.jmmm.2014.08.057 SN - 0304-8853 VL - 380 SP - 266 EP - 270 PB - Elsevier B.V. CY - Amsterdam AN - OPUS4-32562 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Löwa, N. A1 - Knappe, Patrick A1 - Wiekhorst, F. A1 - Eberbeck, D. A1 - Thünemann, Andreas A1 - Trahms, L. T1 - How hydrodynamic fractionation influences MPI performance of resovist N2 - We studied the magnetic resonance imaging liver contrast agent Resovist by a variety of magnetic measurement techniques, in order to understand the physical mechanism of their high magnetic particle imaging (MPI) performance, wirh a focus on the size-dependent contributions of the MPI signal. To this end, we used asymmetric flow field-flow fractionation to separate Resovist into a set of fractions with defined hydrodynamic diameters. The individual fractions were magnetically characterized by static magnetization and magnetorelaxometry measurements to obtain the corresponding effective magnetic anisotropy and effective size distribution parameters. In addition, the MPI performance of each fraction was assessed by magnetic particle spectroscopy. We observed an MPI signal gain of about 100% with respect to their iron amount for the best fraction. Relating these finding to the results from magnetic characterization provides more insight into mechanisms of MPI performance of Resovist. This knowledge may help to improve the design of novel MPI tracers. KW - Nanotechnology KW - Nanoparticles KW - Asymmetric flow field-flow fractionation KW - Magnetic nanoparticles (MNP) KW - Magnetic particle imaging (MPI) KW - Magnetic particle spectroscopy KW - Magnetic separation KW - Magnetorelaxometry (MRX) KW - Resovist PY - 2015 U6 - https://doi.org/10.1109/TMAG.2014.2326833 SN - 0018-9464 SN - 1941-0069 VL - 51 IS - 2 SP - 5300104-1 EP - 5300104-4 PB - Institute of Electrical and Electronics Engineers CY - New York, NY AN - OPUS4-33337 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -