A novel sensor measuring local voidage profile inside a fluidised bed reactor

Liquid-solid fluidisation is frequently encountered in drinking water treatment processes, often to obtain a large liquid-solid interfacial surface area. A large surface area is crucial for optimal seeded crystallisation in full-scale softening reactors. Due to crystallisation, particles grow and migrate to a lower zone in the reactor which leads to a stratified bed. Larger particles adversely affect the surface area. To maintain optimal process conditions in the fluidised beds, information is needed about the distribution of particle size, local voidage and available surface area, over the reactor height. In this work, a sensor is developed to obtain the hydraulic state gradient, based on Archimedes’ principle. A cylindrical heavy object is submerged in the fluidised bed and lowered gradually while its weight is measured at various heights using a sensitive force measuring device. Based on accurate fluidisation experiments with calcite grains, the voidage is determined and a straightforward empirical model is developed to estimate the particle size as a function of superficial fluid velocity, kinematic viscosity, suspension density, voidage and particle density. The surface area and specific space velocity can be estimated accordingly, which represent key performance indicators regarding the hydraulic state of the fluidised bed reactor. The prediction error for voidage is 5 ± 2 % and for particle size 9 ± 4 %. The newly developed soft sensor is a more time-effective method for obtaining the hydraulic state in full-scale liquid-solid fluidised bed reactors

New Affinity Probe Targeting VEGF Receptors for Kinase Inhibitor Selectivity Profiling by Chemical Proteomics

Solid tumors are dependent for growth on nutrients and the supply of oxygen, which they often acquire via neoangiogenesis. Vascular endothelial growth factors and the corresponding receptors (VEGFRs) play central roles in this process, and consequently, the blockade of this pathway is one therapeutic strategy for cancer treatment. A number of small molecules inhibiting VEGFR inhibitors have been developed for clinical use, and a comprehensive view of target selectivity is important to assess the therapeutic as well as risk potential of a drug molecule. Recent advances in mass spectrometry-based chemical proteomics allow analyses of drug–target interactions under close-to-physiological conditions, and in this study, we report on the design, synthesis, and application of a small molecule affinity probe as a tool for the selectivity profiling of VEGFR and other kinase inhibitors. The probe is capable of binding >132 protein kinases, including angiokinases such as VEGFRs, PDGFRs, and c-KIT from lysates of cancer cell lines or human placenta tissue. Combining the new probe with Kinobeads in competitive binding assays, we were able to identify nanomolar off-targets of the VEGFR/PDGFR inhibitors pazopanib and axitinib. Because of its broad binding spectrum, the developed chemical tool can be generically used for the discovery of kinase inhibitor targets, which may contribute to a more comprehensive understanding of the mechanisms of action of such drugs

Optimized Chemical Proteomics Assay for Kinase Inhibitor Profiling

Solid supported probes have proven to be an efficient tool for chemical proteomics. The kinobeads technology features kinase inhibitors covalently attached to Sepharose for affinity enrichment of kinomes from cell or tissue lysates. This technology, combined with quantitative mass spectrometry, is of particular interest for the profiling of kinase inhibitors. It often leads to the identification of new targets for medicinal chemistry campaigns where it allows a two-in-one binding and selectivity assay. The assay can also uncover resistance mechanisms and molecular sources of toxicity. Here we report on the optimization of the kinobead assay resulting in the combination of five chemical probes and four cell lines to cover half the human kinome in a single assay (∼260 kinases). We show the utility and large-scale applicability of the new version of kinobeads by reprofiling the small molecule kinase inhibitors Alvocidib, Crizotinib, Dasatinib, Fasudil, Hydroxyfasudil, Nilotinib, Ibrutinib, Imatinib, and Sunitinib