Massively parallel concentration device for multiplexed immunoassays

A massively parallel nanofluidic concentration device array for multiplexed and high-throughput biomolecule detection is demonstrated. By optimizing the microchannel/nanojunction design and channel conductivity, an array of up to 128 nanofluidic concentration devices were fabricated. Operation of the entire array requires only one inlet and one outlet reservoir, with the application of a single operational voltage bias across them. Concentration efficiencies of the devices were found to be uniform within the array, within 5% error. Alternatively, concentration speed in each channel can be individually tuned by controlling the length of the inlet microchannel and thus controlling the flow rate based on change of the tangential electric field. This allows immuno-binding reactions at different concentration ranges to be performed in parallel. Using multiplexed, successive-concentration enhanced detection in the device, we have shown that the dynamic range and reliability of the immunoassay can be significantly increased.     

Determination of melamine in milk powder using gas chromatography-high-resolution isotope dilution mass spectrometry

A GC-high-resolution isotope dilution MS (IDMS) method for the quantification of melamine in milk powder is described. The developed technique is compared to the LC-IDMS/MS technique, typically used for the determination of melamine in various matrices. The accuracy of the GC-high-resolution IDMS method was demonstrated when a small degree of equivalence was obtained in a regional comparative study involving the determination of melamine in milk powder.     

The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters

Background

Tone languages such as Thai and Mandarin Chinese use differences in fundamental frequency (F₀, pitch) to distinguish lexical meaning. Previous behavioral studies have shown that native speakers of a non-tone language have difficulty discriminating among tone contrasts and are sensitive to different F₀ dimensions than speakers of a tone language. The aim of the present ERP study was to investigate the effect of language background and training on the non-attentive processing of lexical tones. EEG was recorded from 12 adult native speakers of Mandarin Chinese, 12 native speakers of American English, and 11 Thai speakers while they were watching a movie and were presented with multiple tokens of low-falling, mid-level and high-rising Thai lexical tones. High-rising or low-falling tokens were presented as deviants among mid-level standard tokens, and vice versa. EEG data and data from a behavioral discrimination task were collected before and after a two-day perceptual categorization training task.

Results

Behavioral discrimination improved after training in both the Chinese and the English groups. Low-falling tone deviants versus standards elicited a mismatch negativity (MMN) in all language groups. Before, but not after training, the English speakers showed a larger MMN compared to the Chinese, even though English speakers performed worst in the behavioral tasks. The MMN was followed by a late negativity, which became smaller with improved discrimination. The High-rising deviants versus standards elicited a late negativity, which was left-lateralized only in the English and Chinese groups.

Conclusion

Results showed that native speakers of English, Chinese and Thai recruited largely similar mechanisms when non-attentively processing Thai lexical tones. However, native Thai speakers differed from the Chinese and English speakers with respect to the processing of late F₀ contour differences (high-rising versus mid-level tones). In addition, native speakers of a non-tone language (English) were initially more sensitive to F₀ onset differences (low-falling versus mid-level contrast), which was suppressed as a result of training. This result converges with results from previous behavioral studies and supports the view that attentive as well as non-attentive processing of F₀ contrasts is affected by language background, but is malleable even in adult learners.     

Secondary ion yields produced by keV atomic and polyatomic ion impacts on a self-assembled monolayer surface

A suite of keV polyatomic or 'cluster' projectiles was used to bombard unoxidized and oxidized self-assembled monolayer surfaces. Negative secondary ion yields, collected at the limit of single ion impacts, were measured and compared for both molecular and fragment ions. In contrast to targets that are orders of magnitude thicker than the penetration range of the primary ions, secondary ion yields from polyatomic projectile impacts on self-assembled monolayers show little to no enhancement when compared with monatomic projectiles at the same velocity. This unusual trend is most likely due to the structural arrangement and bonding characteristics of the monolayer molecules with the Au(111). Copyright 1999 John Wiley & Sons, Ltd.     

Palladium complexes of bidentate pyridine N‐heterocyclic carbenes: Optical resolution,antimicrobial and cytotoxicity studies

A series of bidentate pyridine‐functionalized palladium N‐heterocyclic carbene (Pd NHC) complexes with various wingtip substituents (R = methyl, phenyl and tert‐butyl) have been synthesized and evaluated for their potential biomedical applications as antimicrobials and antiproliferative drug candidates. The obtained Pd NHC complexes were applied in a standard broth microdilution assay for determination of their antimicrobial activities against thirteen strains of pathogenic microorganisms. In addition to that, cytotoxic activities of the Pd NHC complexes were also evaluated against three human cancer cell lines, namely breast (MCF‐7), colon (HCT116) and oral (H103) cancer cells, using a standard MTT assay. Upon coordination to palladium, the Pd NHC complexes show significant antimicrobial activities with minimum inhibitory concentrations in the micromolar range, and they are cytotoxic to the tested carcinomas with IC₅₀ ranging from 13 to 38 μM. Evidences for influence of both wingtip substituents and optical isomerism on the biological activities of the complexes have been found.     

Grafting of nanoporous alumina membranes and films with organic acids

In this study, direct surface grafting of nanoporous alumina membranes and glass‐supported alumina films was carried out with three different fluorinated organic acids: trifluoroacetic acid, perfluoropentanoic acid and 2,3,4,5,6‐pentafluorobenzoic acid. Elemental surface composition and chemical environment of alumina were investigated using X‐ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Alumina surfaces grafted with fluoro‐organic acids exhibited increased hydrophobic properties compared to ungrafted surfaces when measured using goniometry and atomic force microscopy (AFM). This work describes the evidence for surface chemical modification of alumina using direct reaction with organic acids. An AFM study of the adsorption of the immunoglobulin G (IgG) molecules on the fluoro‐organic‐acid‐grafted surfaces is reported. The results show that an ordered arrangement of immunoglobulin G structures with in‐filling of pores could be achieved only on the more hydrophobic fluoro‐organic‐acid‐grafted alumina membranes. Copyright © 2007 John Wiley & Sons, Ltd.     

Providing a traceable assigned value in a proficiency testing programme on the determination of benzoic acid in orange juice

A proficiency testing (PT) programme on the determination of benzoic acid in orange juice was organised by the Chemical Metrology Laboratory, Health Sciences Authority, Singapore, for the local food testing laboratories. The PT programme used a metrologically traceable assigned value determined by isotope dilution mass spectrometry to assess the performance of the participating laboratories. This paper discusses the reasons and approach to applying metrological principles to determine the assigned value of a PT programme. The procedure undertaken by the Laboratory to prepare a batch of PT sample, conduct homogeneity and stability testings, as well as value assignment, is presented. The discussions also include the estimation of the measurement uncertainties arising from the characterisation, testing for homogeneity and testing for stability of the PT sample. The Coordinator of the PT programme used the assigned value and its associated measurement uncertainty, together with those of the participating laboratories to assess their performances. Statistical tools applied in the performance evaluations are also presented.     

Self-assembled amorphous drug-polyelectrolyte nanoparticle complex with enhanced dissolution rate and saturation solubility

The dissolution rate and solubility of poorly soluble drugs can be enhanced by formulating them into stable amorphous nanoparticle complex (nanoplex). For this purpose, a highly sustainable self-assembly drug-polyelectrolyte complexation process is developed, with ciprofloxacin and dextran sulfate as the drug and polyelectrolyte models, respectively. The nanoplex are prepared by mixing two aqueous salt solutions - one containing the drug and the other containing the oppositely charged polyelectrolyte. The nanoplex suspension is transformed into stable dry-powder form by freeze-drying. The effects of drug concentration, drug-to-polyelectrolyte charge ratio, and salt concentration on the complexation efficiency, yield, drug loading, and nanoplex morphology are examined. The dissolution rates and solubility of the nanoplex are characterized and compared to raw drug crystals. Nearly spherical amorphous nanoplex having fairly uniform sizes in the range of 200-400 nm and 80% drug loading are successfully produced at ≥80% complexation efficiency and yield. The complexation efficiency is governed by the drug concentration and its ratio to the salt concentration. The nanoplex powders exhibit approximately twice higher dissolution rate and solubility than raw drug crystals and remain stable after one-month storage. Overall, amorphous nanoplex represent a promising bioavailability-enhanced formulation of poorly soluble drugs owed to their superior characteristics and ease of preparation.     

Asymmetric hydroarsination reactions toward synthesis of alcohol functionalised C-chiral As–P ligands promoted by chiral cyclometallated complexes

The asymmetric hydroarsination reactions between diphenylarsine and 3-diphenylphosphanyl-but-3-en-1-ol and 2-diphenylphosphanyl-prop-2-en-1-ol have been achieved using the organopalladium complex containing ortho-metallated (R)-[1-(dimethylamino)ethylnaphthalene as the chiral reaction template in high stereoselectivities under mild conditions. Hydroarsination of 3-diphenylphosphanyl-but-3-en-1-ol with diphenylarsine generated only one stereoisomer as five-membered As–P bidentate chelate on chiral naphthylamine palladium template. Using the same chiral metal template, similar hydroarsination reaction was carried out on 2-diphenylphosphanyl-prop-2-en-1-ol which gave two different products in the ratio of 2.6 to 1. The major isomer was identified as the expected five-membered As–P bidentate ligand and the minor isomer was identified as the elimination product. The naphthylamine auxiliary could be removed chemoselectively by treatment with concentrated hydrochloric acid. Optically pure As–P ligands containing the hydroxy groups at the chiral carbon centres were prepared by ligand displacement. The absolute configuration and coordination properties of the complexes have been established by single crystal X-ray analysis.     

A bilateral study for the establishment of comparability in the measurement of ethanol in bioethanol fuel using isotope dilution mass spectrometry

A bilateral comparative study between two metrology institutes was conducted for the determination of ethanol in bioethanol fuel by isotope dilution mass spectrometry. Measurement procedures were independently developed by the Health Sciences Authority (Singapore) and the National Institute of Metrology (People??s Republic of China). The methods used included headspace gas chromatography?Chigh-resolution mass spectrometry, headspace gas chromatography?Cmass spectrometry (GC-MS) and direct injection to GC-MS. An investigation of all potential sources of uncertainty, including a component of uncertainty due to the effect of using different instruments such as gas chromatography?Cflame ionization detector method, commonly adopted for the analysis of organic volatiles, was carried out. The results of the analyses are consistent within the associated measurement uncertainty of each laboratory, reported at approximately 95% confidence level.