Development and Characterization of a Microfluidic Magnetic Oscillation Reactor for Enzymes

Process development poses one of the main bottlenecks during development of biocatalytic processes for fine and bulk chemicals. Therefore novel tools to decrease the cost of process development have come into the focus of interest. While modelling and small scale liquid handling in multi well based platforms are already employed, there is still a lack of continuous microfluidic reaction systems for enzyme process development. In this thesis the magnetic oscillation reactor for enzymes(μMORE), a novel continuous microfluidic reactor concept for process optimization has been developed. The system is mixed by magnetic beads, on which the enzyme is immobilized, by utilization of an oscillating magnetic field. The concept has been designed to allow for simple parallelization of multiple reactors. A six-fold enzyme microreactor system was constructed. The novel reactor system was developed, characterized and finally tested with benzoylformate decarboxylase from $\textit{Pseudomonas putida}$. This enzyme catalyzes the carboligation of benzaldehyde and acetaldehyde to (S)-2-hydroxypropiophenone. The results indicate that the systemprovides a useful tool for enzyme process optimization, generating process parameters that are useful for scale up of the process from micro- to bench scale

Towards process intensification : remediation of fouling in continuous microscale synthesis of phosphated TiO2

The use of continuous flow microreactors offers an interesting approach among the process intensification tools available. Fouling in a microreactor during synthesis of industrially relevant nanoparticles was investigated. In order to achieve this, microscale synthesis of phosphated TiO2 nanoparticles from titanium(IV) isopropoxide (TTIP) and titanium(IV) butoxide (TBUT) was employed. A continuous three step process, consisting of hydrolysis of the respective alkoxide, phosphate modification and precipitation was developed. The resulting catalyst was characterized by means of nitrogen adsorption, dynamic light scattering and SEM/EDX. It was observed that TTIP resulted in massive fouling, while a stable process was possible with TBUT. This was related to the nucleation time of the particles. The particle size directly after the critical hydrolysis step was investigated. The particles formed with TTIP as a precursor (3.4 nm) were larger than those obtained from TBUT (2.4 nm). Diffusion based reactant concentration gradients within the multilamellar micromixer were calculated, and the corresponding Damköhler numbers for mixing were estimated to be 2.6∙10^-3 for TBUT and 3.5∙10^-2 for TTIP respectively. These numbers highlight the influence of incomplete mixing on fouling for TTIP as a precursor. Thus, our work demonstrates the necessity to consider the reaction kinetics during process intensification by miniaturization

Preparation and tensile properties of guar gum hydrogel films

Guar gum hydrogels may be dried to form polymer films which have the potential for use as biodegradable alternatives to polymers such as low-density polyethylene. In this study, the tensile strength and tensile modulus of guar gel films having moisture contents ranging between 15% and 18% (wet basis) were measured at a strain rate of 1 mm min⁻¹. Mean tensile strengths of the films ranged between 25 MPa and 40 MPa (dependent on composition) which is of similar magnitude to the tensile strength data for polyethylene and cellophane that are reported in the literature. The mean tensile modulus of the films (1.5–2.5 GPa) was higher than the tensile modulus values reported for low-density polyethylene but comparable to those for cellophane (3 GPa)

In-vivo time course of organ uptake and blood-brain-barrier permeation of poly(L-lactide) and poly(perfluorodecyl acrylate) nanoparticles with different surface properties in unharmed and brain-traumatized rats

Background: Traumatic brain injury (TBI) has a dramatic impact on mortality and quality of life and the development of effective treatment strategies is of great socio-economic relevance. A growing interest exists in using polymeric nanoparticles (NPs) as carriers across the blood-brain barrier (BBB) for potentially effective drugs in TBI. However, the effect of NP material and type of surfactant on their distribution within organs, the amount of the administrated dose that reaches the brain parenchyma in areas with intact and opened BBB after trauma, and a possible elicited inflammatory response are still to be clarified. Methods: The organ distribution, BBB permeation and eventual inflammatory activation of polysorbate-80 (Tw80) and sodiumdodecylsulfate (SDS) stabilized poly(L-lactide) (PLLA) and poly(perfluorodecyl acrylate) (PFDL) nanoparticles were evaluated in rats after intravenous administration. The NP uptake into the brain was assessed under intact conditions and after controlled cortical impact (CCI). Results: A significantly higher NP uptake at 4 and 24 h after injection was observed in the liver and spleen, followed by the brain and kidney, with minimal concentrations in the lungs and heart for all NPs. A significant increase of NP uptake at 4 and 24 h after CCI was observed within the traumatized hemisphere, especially in the perilesional area, but NPs were still found in areas away from the injury site and the contralateral hemisphere. NPs were internalized in brain capillary endothelial cells, neurons, astrocytes, and microglia. Immunohistochemical staining against GFAP, Iba1, TNFα, and IL1β demonstrated no glial activation or neuroinflammatory changes. Conclusions: Tw80 and SDS coated biodegradable PLLA and non-biodegradable PFDL NPs reach the brain parenchyma with and without compromised BBB by TBI, even though a high amount of NPs are retained in the liver and spleen. No inflammatory reaction is elicited by these NPs within 24 h after injection. Thus, these NPs could be considered as potentially effective carriers or markers of newly developed drugs with low or even no BBB permeation

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Measurement of the underlying event activity in pp collisions at √s = 0.9 and 7 TeV with the novel jet-area/median approach

Open Access: This article is distributed under the terms of the Creative Commons Attribution License.-- Chatrchyan, S. et al.The first measurement of the charged component of the underlying event using the novel >jet-area/median> approach is presented for proton-proton collisions at centre-of-mass energies of 0.9 and 7 TeV. The data were recorded in 2010 with the CMS experiment at the LHC. A new observable, sensitive to soft particle production, is introduced and investigated inclusively and as a function of the event scale defined by the transverse momentum of the leading jet. Various phenomenological models are compared to data, with and without corrections for detector effects. None of the examined models describe the data satisfactorily. © 2012 SISSA.Acknowledge support from BMWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); MoER, SF0690030s09 and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France);BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); ThEP, IPST and NECTEC (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie program and the European Research Council (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Austrian Science Fund (FWF); the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWTBelgium); the Ministry of Education, Youth and Sports (MEYS) of Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo (Torino); and the HOMING PLUS program of Foundation for Polish Science, cofinanced from European Union, Regional Development Fund.Peer Reviewe

Search for Pair Production of Third-Generation Leptoquarks and Top Squarks in pp Collisions at √s=7 TeV

Results are presented from a search for the pair production of third-generation scalar and vector leptoquarks, as well as for top squarks in R-parity-violating supersymmetric models. In either scenario, the new, heavy particle decays into a τ lepton and a b quark. The search is based on a data sample of pp collisions at √s=7  TeV, which is collected by the CMS detector at the LHC and corresponds to an integrated luminosity of 4.8  fb[superscript -1]. The number of observed events is found to be in agreement with the standard model prediction, and exclusion limits on mass parameters are obtained at the 95% confidence level. Vector leptoquarks with masses below 760 GeV are excluded and, if the branching fraction of the scalar leptoquark decay to a τ lepton and a b quark is assumed to be unity, third-generation scalar leptoquarks with masses below 525 GeV are ruled out. Top squarks with masses below 453 GeV are excluded for a typical benchmark scenario, and limits on the coupling between the top squark, τ lepton, and b quark, λ333′ are obtained. These results are the most stringent for these scenarios to date

Search for physics beyond the standard model in events with a Z boson, jets, and missing transverse energy in pp collisions at √s̅ = 7 TeV

Peer reviewe

Measurement of the sum ofWW and WZ production with W+dijet events in pp collisions at √ s = 7 TeV

A measurement of the inclusive WW+WZ diboson production cross section in proton–proton collisions is reported, based on events containing a leptonically decaying √W boson and exactly two jets. The data sample, collected at s = 7 TeV with the CMS detector at the LHC, corresponds to an integrated luminosity of 5.0 fb−1. The measured value of the sum of the inclusive WW and WZ cross sections is σ(pp → WW + WZ) = 68.9 ± 8.7 (stat.) ± 9.7 (syst.) ± 1.5 (lum.) pb, consistent with the standard model prediction of 65.6±2.2 pb. This is the first measurement of WW+WZ production in pp collisions using this signature. No evidence for anomalous triple gauge couplings is found and upper limits are set on their magnitudes