Novel concepts for efficient and predictable membrane separation in continuous cell retention and downstream processing

Membranes are applied in biotechnological operations for sterile filtration, cell retention during continuous oper-ation, and cell separation as the first step after fermentation. Membranes are also in use in various steps during purification and isolation of certain target components. In all applications the retained substances, mainly bio-genic material such as cells, protein or polysaccharides, form a deposited layer at the membrane surface. This layer acts as an often dominating secondary membrane, which affects the permeability of the whole system more than the membrane as such. Thus, predictability, efficiency and consistency of all affected processing steps are impaired, which might create issues especially in GMP processes. Therefore, a deeper understanding and a better control of deposit formation would be beneficial for biotechnological operations in general and membrane filtrations in continuous processes in particular. This presentation reports on recent work on a better understanding of deposit formation on membrane surfaces. It was the aim to intensify processes by minimizing the effect of deposit formation and, in turn, increasing flux and permeation of target substances. Success factor in all related projects was a better control of deposit for-mation on membrane surfaces, which in particular was enabled by assessing deposit formation along the mem-brane flow path using special membrane module constructions. These modules allow for the measurement of flux, solutes permeation, structure and amount of deposited material as a function of position in an industrially sized membrane system. Ceramic and polymeric membrane materials as well as tubular and spiralwound mod-ule (SWM) configurations are compared. Please click Additional Files below to see the full abstrac

Novel concepts for efficient and predictable membrane separation in continuous cell retention and downstream processing

Membranes are applied in biotechnological operations for sterile filtration, cell retention during continuous oper-ation, and cell separation as the first step after fermentation. Membranes are also in use in various steps during purification and isolation of certain target components. In all applications the retained substances, mainly bio-genic material such as cells, protein or polysaccharides, form a deposited layer at the membrane surface. This layer acts as an often dominating secondary membrane, which affects the permeability of the whole system more than the membrane as such. Thus, predictability, efficiency and consistency of all affected processing steps are impaired, which might create issues especially in GMP processes. Therefore, a deeper understanding and a better control of deposit formation would be beneficial for biotechnological operations in general and membrane filtrations in continuous processes in particular. This presentation reports on recent work on a better understanding of deposit formation on membrane surfaces. It was the aim to intensify processes by minimizing the effect of deposit formation and, in turn, increasing flux and permeation of target substances. Success factor in all related projects was a better control of deposit for-mation on membrane surfaces, which in particular was enabled by assessing deposit formation along the mem-brane flow path using special membrane module constructions. These modules allow for the measurement of flux, solutes permeation, structure and amount of deposited material as a function of position in an industrially sized membrane system. Ceramic and polymeric membrane materials as well as tubular and spiralwound mod-ule (SWM) configurations are compared. Please click Additional Files below to see the full abstrac

Phonon-Metamorphosis in Ferromagnetic Manganite Films: Probing the Evolution of an Inhomogeneous State

The analysis of phonon anomalies provides valuable information about the cooperative dynamics of lattice, spin and charge degrees of freedom. Significant is the anomalous temperature dependence of the external modes observed in La$_{2/3}$Sr$_{1/3}$MnO$_{3}$ (LSMO) films. The two external modes merge close to the ferromagnetic to paramagnetic transition at $T_C$ and, moreover, two new modes evolve in this temperature range with strong resonances at slightly higher frequencies. We propose that this observed phonon metamorphosis probes the inhomogeneous Jahn-Teller distortion, manifest on the temperature scale $T_C$. The analysis is based on the first observation of all eight phonon modes in the metallic phase of LSMO and on susceptibility measurements which identify a Griffiths-like phase.Comment: 4 pages, 4 figure

Properties of magnetohydrodynamic normal modes in the Earth’s magnetosphere

Funding: MDH was supported by NASA 80NSSC19K0127, 80NSSC19K0907, 80NSSC21K1683, 80NSSC21K1677, 80NSSC23K0903, and NSF AGS-2307204. KT was supported by NASA 80NSSC19K0259 and 80NSSC21K0453. MOA was supported by a UKRI (STFC / EPSRC) Stephen Hawking Fellowship EP/T01735X/1. The research of A.W. was funded in part by Science and Technology Facilities Council (STFC) grant ST/W001195/1 (UK). T.E. was funded in part by a Leverhulme Early Career Fellowship ECF-2019-155 (UK). AA and XZ were supported by NASA 80NSSC21K0729 and 80NSSC23K0108. We acknowledge support from ISSI Bern through ISSI International Team projects 483 “The Identification And Classification Of 3D Alfven Resonances” and 546 “Magnetohydrodynamic Surface Waves at Earth’s Magnetosphere (and Beyond).” We acknowledge NASA contract NAS5-02099.The Earth's magnetosphere supports a variety of Magnetohydrodynamic (MHD) normal modes with Ultra Low Frequencies (ULF) including standing Alfvén waves and cavity/waveguide modes. Their amplitudes and frequencies depend in part on the properties of the magnetosphere (size of cavity, wave speed distribution). In this work, we use ∼13 years of Time History of Events and Macroscale Interactions during Substorms satellite magnetic field observations, combined with linearized MHD numerical simulations, to examine the properties of MHD normal modes in the region L > 5 and for frequencies 5 depend on both the magnetopause location and the location of peaks in the radial Alfvén speed profile. Finally, we discuss how these results might be used to better model radiation belt electron dynamics related to ULF waves.PostprintPeer reviewe

The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes

A wide variety of steric and electronic features can be incorporated into transition metal coordination complexes, offering the prospect of rationally-designed therapeutic agents with novel mechanisms of action. Here we compare the chemical reactivity and anticancer activity of organometallic OsII complexes [Os(η6-arene)(XY)Z]PF6 where arene = p-cymene or biphenyl, XY = N,N′-chelated phenyliminopyridine or phenylazopyridine derivatives, and Z = Cl or I. The X-ray crystal structure of [Os(η6-p-cym)(Impy-OH)I]PF6·0.5CH2Cl2·H2O (Impy-OH = 4-[(2-pyridinylmethylene)amino]-phenol) is reported. Like the azopyridine complexes we reported recently (Dalton Trans., 2011, 40, 10553–10562), some iminopyridine complexes are also potently active towards cancer cells (nanomolar IC50 values). However we show that, unlike the azopyridine complexes, the iminopyridine complexes can undergo aquation, bind to the nucleobase guanine, and oxidize coenzyme nicotine adenine dinucleotide (NADH). We report the first detection of an Os-hydride adduct in aqueous solution by 1H NMR (−4.2 ppm). Active iminopyridine complexes induced a dramatic increase in the levels of reactive oxygen species (ROS) in A549 lung cancer cells. The anticancer activity may therefore involve interference in the redox signalling pathways in cancer cells by a novel mechanism

Vinyl sulfone-based ferrocenylation reagents: applications in conjugation and bioconjugation

The easy vinyl sulfone derivatization of ferrocene allows the preparation of some effective, versatile and valuable ferrocenylation reagents. The applicability of such compounds in conjugation and bioconjugation of amine and/or thiol containing molecules and biomolecules through Michael-type addition under mild conditions that preserve the biological function of the latter is described. The feasibility of the methodology is demonstrated by the preparation of a variety of conjugates and bioconjugates (ferrocenyl terminated dendrimers and ferrocene–sugar, ferrocene–cyclodextrin, ferrocene–peptide and ferrocene–protein conjugates).Financial support was provided by Ministerio de Ciencia e Innovación (CTQ2011-29299-CO2-01)