Simultaneous immunoassay for the detection of two lung cancer markers using functionalized SERS nanoprobes

A quick and reproducible SERS-based immunoassay, using functionalized hollow gold nanospheres and magnetic beads, has been developed. Here, a simultaneous detection of dual cancer markers in blood serum has been achieved under a single excitation wavelength. The accuracy and sensitivity for clinical sera from five patients confirms their diagnostic feasibility.     

Preparation of silica-encapsulated hollow gold nanosphere tags using layer-by-layer method for multiplex surface-enhanced raman scattering detection

The use of silica shells offers many advantages in surface-enhanced Raman scattering (SERS)-based biological sensing applications due to their optical transparency, remarkable stability in environmental media, and improved biocompatibility. Here, we report a novel layer-by-layer method for the preparation of silica-hollow gold nanosphere (HGN) SERS tags. Poly(acrylic acid) was used to stabilize Raman reporter-tagged HGNs prior to the adsorption of a coupling agent, after which a silica shell was deposited onto the particle surface using Sto?ber's method. Importantly, competitive adsorption of the Raman reporter molecules and coupling agents, which results in unbalanced loading of reporter molecules on individual nanoparticles, was avoided using this method. As a result, the loading density of reporter molecules could be maximized. In addition, HGNs exhibited strong enhancement effects from the individual particles because of their ability to localize the surface electromagnetic fields through pinholes in the hollow particle structures. The proposed layer-by-layer silica-encapsulated HGN tags showed strong SERS signals as well as excellent multiplexing capabilities.     

Synthesis of sterically congested bicyclic tetrahydrofurans via Pd-catalyzed cyclization

Prins-type cyclization followed by palladium-catalyzed cyclization provided sterically congested bi- or tricyclic tetrahydrofurans, which are very stereoselective as well. cis-2,5-Disubstituted tetrahydrofurans obtained from Prins-type cyclization have an allenyl group and a functional group such as alcohol, carboxylic acid, and aryl halide. The tetrahydrofurans bearing an allene group underwent palladium-catalyzed cyclization to give sterically congested bi- or tricyclic tetrahydrofurans.     

An improved method for the preparations of nanostructured lipid carriers containing heat-sensitive bioactives

Heat-sensitive bioactive compounds such as β-carotene and tocols, are widely used in the pharmaceutical and cosmetic fields. Their chemical stability in delivery systems is one of the major concerns in the production of nanostructured lipid carriers (NLCs). A previously established high-temperature high-pressure homogenisation technique involved in the preparation of NLCs can cause degradation of heat-sensitive compounds. Therefore, a novel preparation process needs to be developed to minimise the degradation of heat-sensitive active compounds during the preparation of NLCs. In this work, modified methods A and B were designed to minimise the degradation of β-carotene and tocols during the production of NLCs. These methods improved the chemical stability of heat-sensitive bioactive compounds (β-carotene and tocols) significantly compared to the previously established method. The physical stability of the formulation was maintained throughout study duration.     

Functional human 5-HT6 receptor assay for high throughput screening of chemical ligands and binding proteins

Continuous identification and validation of novel drug targets require the development of rapid, reliable, and sensitive cell-based high-throughput screening (HTS) methods for proposed targets. Recently, the 5-HT(6) receptor (5-HT(6)R), a member of the class of recently discovered 5-HT receptors, has received considerable attention for its possible implications in depression, cognition, and anxiety. However, the cellular signaling mechanisms of 5-HT(6)R are poorly understood due to the lack of selective 5-HT(6)R ligands. In the present study, we examined functional coupling of the human 5-HT(6)R, 5-HT(7A)R, or 5-HT(7B)R with various Galpha-proteins (Galpha(15), Galpha(qs5), or Galpha(qG66Ds5)) to develop a reliable cell-based HTS method for 5-HT receptors. Among variable couplings between 5-HT receptors and G-proteins, we found that functional coupling of human 5-HT(6)R with Galpha(qG66Ds5) produced the highest levels of Ca(2+) signaling in HEK293 cells as measured by the fluorescence-based HTS plate reader, FDSS6000. After validation of this new 5-HT(6)R HTS system (Z'-factor = 0.56) in 96-well plates and characterization of the pharmacological profile of the 5-HT(6)R, we screened approximately 500 synthetic chemical compounds including butanamide and benzenesulfonamide derivatives. Based on this preliminary screening, we found that the butanamide derivative LSG11104 produced an IC(50) value of 6.3 microM. This compound will serve as a lead structure for further chemical modification to develop novel 5-HT(6)R ligands. Furthermore, we demonstrated that this HTS method can be utilized to identify proteins that modulate 5-HT(6)R function and present Fyn tyrosine kinase as an example, which is already known as a 5-HT(6)R interacting protein. Taken together, these results suggest that the 5-HT(6)R/Galpha(qG66Ds5) FDSS6000 system can be utilized to screen for selective 5-HT(6)R ligands and to examine any functional relationships between 5-HT(6)R and its binding proteins.     

Oscillation and decay of particle current due to a quench and dephasing in an interacting fermionic system

We study the response of a particle current to dissipative dephasing in an interacting, few body fermionic lattice system. The particles are prepared in the many-body interacting ground state in presence of an artificial magnetic gauge field, which is subsequently quenched to zero. The initial current decays non-trivially in the dissipative environment and we explore the emerging dynamics, time scales and their dependence on the various system parameters.