Simultaneous detection and quantification of DNA and protein biomarkers in spectrum of cardiovascular diseases in a microfluidic microbead chip

The rapid and simultaneous detection of DNA and protein biomarkers is necessary to detect the outbreak of a disease or to monitor a disease. For example, cardiovascular diseases are a major cause of adult mortality worldwide. We have developed a rapidly adaptable platform to assess biomarkers using a microfluidic technology. Our model mimics autoantibodies against three proteins, C-reactive protein (CRP), brain natriuretic peptide (BNP), and low-density lipoprotein (LDL). Cell-free mitochondrial DNA (cfmDNA) and DNA controls are detected via fluorescence probes. The biomarkers are covalently bound on the surface of size- (11–15 μm) and dual-color encoded microbeads and immobilized as planar layer in a microfluidic chip flow cell. Binding events of target molecules were analyzed by fluorescence measurements with a fully automatized fluorescence microscope (end-point and real-time) developed in house. The model system was optimized for buffers and immobilization strategies of the microbeads to enable the simultaneous detection of protein and DNA biomarkers. All prime target molecules (anti-CRP, anti-BNP, anti-LDL, cfmDNA) and the controls were successfully detected both in independent reactions and simultaneously. In addition, the biomarkers could also be detected in spiked human serum in a similar way as in the optimized buffer system. The detection limit specified by the manufacturer is reduced by at least a factor of five for each biomarker as a result of the antibody detection and kinetic experiments indicate that nearly 50 % of the fluorescence intensity is achieved within 7 min. For rapid data inspection, we have developed the open source software digilogger, which can be applied for data evaluation and visualization.

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Late-Stage Functionalisation of Peptides on the Solid Phase by an Iodination-Substitution Approach

The functionalisation of peptides at a late synthesis stage holds great potential, for example, for the synthesis of peptide pharmaceuticals, fluorescent biosensors or peptidomimetics. Here we describe an on-resin iodination-substitution reaction sequence on homoserine that is also suitable for peptide modification in a combinatorial format. The reaction sequence is accessible to a wide range of sulfur nucleophiles with various functional groups including boronic acids, hydroxy groups or aromatic amines. In this way, methionine-like thioethers or thioesters and thiosulfonates are accessible. Next to sulfur nucleophiles, selenols, pyridines and carboxylic acids were successfully used as nucleophiles, whereas phenols did not react. The late-stage iodination-substitution approach is not only applicable to short peptides but also to the more complex 34-amino-acid WW domains. We applied this strategy to introduce 7-mercapto-4-methylcoumarin into a switchable Zn^II responsive WW domain to design an iFRET-based Zn^II sensor.     

A Next-Generation Air-Stable Palladium(I) Dimer Enables Olefin Migration and Selective C−C Coupling in Air

We report a new air-stable Pd^I dimer, [Pd(μ-I)(PCy₂^tBu)]₂, which triggers E-selective olefin migration to enamides and styrene derivatives in the presence of multiple functional groups and with complete tolerance of air. The same dimer also triggers extremely rapid C−C coupling (alkylation and arylation) at room temperature in a modular and triply selective fashion of aromatic C−Br, C−OTf/OFs, and C−Cl bonds in poly(pseudo)halogenated arenes, displaying superior activity over previous Pd^I dimer generations for substrates that bear substituents ortho to C−OTf.     

An Isoreticular Family of Microporous Metal–Organic Frameworks Based on Zinc and 2‐Substituted Imidazolate‐4‐amide‐5‐imidate: Syntheses,Structures and Properties

We report on a new series of isoreticular frameworks based on zinc and 2‐substituted imidazolate‐4‐amide‐5‐imidate (IFP‐1–4, IFP=imidazolate framework Potsdam) that form one‐dimensional, microporous hexagonal channels. Varying R in the 2‐substitued linker (R=Me (IFP‐1), Cl (IFP‐2), Br (IFP‐3), Et (IFP‐4)) allowed the channel diameter (4.0–1.7 Å), the polarisability and functionality of the channel walls to be tuned. Frameworks IFP‐2, IFP‐3 and IFP‐4 are isostructural to previously reported IFP‐1. The structures of IFP‐2 and IFP‐3 were solved by X‐ray crystallographic analyses. The structure of IFP‐4 was determined by a combination of PXRD and structure modelling and was confirmed by IR spectroscopy and ¹H MAS and ¹³C CP‐MAS NMR spectroscopy. All IFPs showed high thermal stability (345–400 °C); IFP‐1 and IFP‐4 were stable in boiling water for 7 d. A detailed porosity analysis was performed on the basis of adsorption measurements by using various gases. The potential of the materials to undergo specific interactions with CO₂ was investigated by measuring the isosteric heats of adsorption. The capacity to adsorb CH₄ (at 298 K), CO₂ (at 298 K) and H₂ (at 77 K) at high pressure were also investigated. In situ IR spectroscopy showed that CO₂ is physisorbed on IFP‐1–4 under dry conditions and that both CO₂ and H₂O are physisorbed on IFP‐1 under moist conditions.     

A Long‐Life Lithium Ion Battery with Enhanced Electrode/Electrolyte Interface by Using an Ionic Liquid Solution

In this paper, we report an advanced long‐life lithium ion battery, employing a Pyr₁₄TFSI‐LiTFSI non‐flammable ionic liquid (IL) electrolyte, a nanostructured tin carbon (Sn‐C) nanocomposite anode, and a layered LiNi_1/3Co_1/3Mn_1/3O₂ (NMC) cathode. The IL‐based electrolyte is characterized in terms of conductivity and viscosity at various temperatures, revealing a Vogel–Tammann–Fulcher (VTF) trend. Lithium half‐cells employing the Sn‐C anode and NMC cathode in the Pyr₁₄TFSI‐LiTFSI electrolyte are investigated by galvanostatic cycling at various temperatures, demonstrating the full compatibility of the electrolyte with the selected electrode materials. The NMC and Sn‐C electrodes are combined into a cathode‐limited full cell, which is subjected to prolonged cycling at 40 °C, revealing a very stable capacity of about 140 mAh g^?1 and retention above 99 % over 400 cycles. The electrode/electrolyte interface is further characterized through a combination of electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) investigations upon cell cycling. The remarkable performances reported here definitively indicate that IL‐based lithium ion cells are suitable batteries for application in electric vehicles.     

Entropic Contributions to Sodium Solvation and Solvent Stabilization upon Electrochemical Sodium Deposition from Diglyme and Propylene Carbonate Electrolytes

The formation of an appropriate solid electrolyte interphase (SEI) at the anode of a sodium battery is crucially dependent on the electrochemical stability of solvent and electrolyte at the redox potential of Na/Na⁺ in the respective system. In order to determine entropic contributions to the relative stability of the electrolyte solution, we measure the reaction entropy of Na metal deposition for diglyme (DG) and propylene carbonate (PC) based electrolyte solutions by electrochemical microcalorimetry at single electrodes. We found a large positive reaction entropy for Na⁺ deposition in DG of Δ_R 234 J mol⁻¹ K⁻¹ (c.f.: Δ_R 83 J mol⁻¹ K⁻¹), which signals substantial entropic destabilization of Na⁺ in DG by about 0.73 eV, thus increasing the stability of solvent and electrolyte relative to Na⁺ reduction. We attribute this strong entropic destabilization to a highly negative solvation entropy of Na⁺, due to the low dielectric constant and high freezing entropy of DG.     

Zinc Oxide Based Coatings for the UV-Protection of Wood for Outdoor Applications

Summary: Nano-sized zinc oxide (ZnO) was chosen as a suitable candidate for the UV-protection of coatings. ZnO-based acrylate coatings were applied to polycarbonate plates, glass plates and impregnated wood. Coated samples were artificially weathered (Xenon test) for at least 1500 hours and studied with regards to their optical and mechanical properties, such as color shifts (yellowing), as well as to changes in brightness, transparency or hydrophobicity. The prepared wood coatings showed reduced yellowing and improved optical properties.     

Application of a Viscoelastic Material Model in Electro-Mechanics

In this contribution, the numerical modeling of electro-viscoelastic material is considered. The electro-mechanical problem formulated in terms of a symmetrized stress tensor is extended to a viscoelastic material model. For the incorporation of the viscosity model, the logarithmic strain space setting is utilized which mimics the small strain setting. Therefore a rheological model for viscosity from the geometrically linear theory can be used. Numerical examples for a typical uniaxial tensile test show the capability of the method to demonstrate typical relaxation and creep behavior. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)