Pixel-based biosensor for enhanced control: silicon nanowires monolithically integrated with field-effect transistors in fully depleted silicon on insulator technology.

Silicon nanowires (SiNWs) are a widely used technology for sensing applications. Complementary metal-oxide-semiconductor (CMOS) integration of SiNWs advances lab-on-chip (LOC) technology and offers opportunities for read-out circuit integration, selective and multiplexed detection. In this work, we propose novel scalable pixel-based biosensors exploiting the integration of SiNWs with CMOS in fully-depleted silicon-on-insulator technology. A detailed description of the wafer-scale fabrication of SiNW pixels using the CMOS compatible sidewall-transfer-lithography as an alternative to widely investigated time inefficient e-beam lithography is presented. Each 60 nm wide SiNWs sensor is monolithically connected to a control transistor and novel on-chip fluid-gate forming an individual pixel that can be operated in two modes: biasing transistor frontgate (V G) or substrate backgate (V BG). We also present the first electrical results of single N and P-type SiNW pixels. In frontgate mode, N and P-type SiNW pixels exhibit subthreshold slope (SS) ≈ 70-80 mV/dec and I on/I off ≈ 105. The N-type and P-type pixels have an average threshold voltage, Vth of -1.7 V and 0.85 V respectively. In the backgate mode, N and P-type SiNW pixels exhibit SS ≈ 100-150 mV/dec and I on/I off ≈ 106. The N and P-type pixels have an average V th of 5 V and -2.5 V respectively. Further, the influence of the backgate and frontgate voltage on the switching characteristics of the SiNW pixels is also studied. In the frontgate mode, the V th of the SiNW pixels can be tuned at 0.2 V for 1 V change in V BG for N-type or at -0.2 V for -1 V change in V BG for P-type pixels. In the backgate mode, it is found that for stable operation of the pixels, the V G of the N and P-type transistors must be in the range 0.5-2.5 V and 0 V to -2.5 V respectively.

A comparison of 24 chemicals in the six-well bacterial reverse mutation assay to the standard 100-mm Petri plate bacterial reverse mutation assay in two laboratories.

The bacterial reverse mutation assay (Ames) is a fundamental genetic toxicology test, and efforts to miniaturize the regulatory GLP version are essential in assessing genotoxic liabilities earlier in the drug development pipeline. Two versions of the Ames were compared: the six-well (miniaturized) plate and the standard 100-mm plate test at two different laboratories. Of twenty-four chemicals tested, a subset of six chemicals was tested in the six-well test only and the remaining eighteen were evaluated in both versions of the test. The plate incorporation procedure was used with one Escherichia coli and four different Salmonella strains. The six-well test uses the same plating procedure and evaluation methods as the standard Ames assay in 100-mm plates, but the smaller format requires 20% of the test chemical. Additionally, the six-well test uses a limit concentration of 1000 µg/well versus the standard Petri plate test limit concentration of 5000 µg/plate. Testing across the two formats resulted in 100% concordance in overall mutagenicity judgement and 94% concordance across all tester strains and conditions. Known mutagenic positive control chemicals were correctly detected as positive in both formats. The overall conclusion is that the six-well assay results are concordant with the standard assay format in this evaluation and could be a reliable alternative.

A microscopic evaluation of collagen-bilirubin interactions: in vitro surface phenomenon.

This study is carried out to understand the morphology variations of collagen I matrices influenced by bilirubin. The characteristics of bilirubin interaction with collagen ascertained using various techniques like XRD, CLSM, fluorescence, SEM and AFM. These techniques are used to understand the distribution, expression and colocalization patterns of collagen-bilirubin complexes. The present investigation mimic the in vivo mechanisms created during the disorder condition like jaundice. Fluorescence technique elucidates the crucial role played by bilirubin deposition and interaction during collagen organization. Influence of bilirubin during collagen fibrillogenesis and banding patterns are clearly visualize using SEM. As a result, collagen-bilirubin complex provides different reconstructed patterns because of the influence of bilirubin concentration. Selectivity, specificity and spatial organization of collagen-bilirubin are determined through AFM imaging. Consequently, it is observed that the morphology and quantity of the bilirubin binding to collagen varied by the concentrations and the adsorption rate in protein solutions. Microscopic studies of collagen-bilirubin interaction confirms that bilirubin influence the fibrillogenesis and alter the rate of collagen organization depending on the bilirubin concentration. This knowledge helps to develop a novel drug to inhibit the interface point of interaction between collagen and bilirubin.

Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by an energy deficiency state of the colonic epithelium. This study evaluated mitochondrial electron transport chain (ETC) complex activity in normal and disease mucosa in patients with UC. Alterations in ETC complexes were also investigated in experimental colitis in mice. METHODS: Biopsies were obtained from macroscopically normal and diseased colonic mucosa of 43 patients with UC and 35 controls undergoing screening colonoscopy and ETC complex activity was assayed biochemically. ETC complex activities were also assayed in colonic epithelial cells isolated from Swiss albino mice with dextran sodium sulfate (DSS)-induced colitis at various stages of induction of colitis. Mucosal nitrite levels and protein carbonyl content were determined. RESULTS: The activity of Complex II was significantly decreased in colonic biopsies from UC patients compared with controls, while activities of other mitochondrial complex were normal. Complex II activity was equally decreased in diseased and normal mucosa in UC; the degree of reduction did not correlate with clinical, endoscopic, or histological grading of disease activity. In DSS-fed mice, a reduction in activity of Complex IV and Complex II was observed. Activity of other complex was not affected. Administration of aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, attenuated all parameters of colitis as well as the reductions in Complex IV and Complex II activity. CONCLUSIONS: Reduction in Complex II activity appears to be a specific change in UC, present in quiescent and active disease. Mitochondrial complex dysfunction occurs in DSS colitis in mice and appears to be mediated by nitric oxide.

Vibrational spectroscopic studies and ab initio calculations of Goniothalamin, a natural product.

5,6-Dihydro-6-styryl-2-pyrone (Goniothalamin), is isolated from the leaves of Goniothalamus wightii and identified by spectral analysis and X-ray diffraction studies. FT-IR spectroscopy has also been used to characterize the vibrational bands. The vibrational wavenumbers and corresponding vibrational assignments are examined theoretically using the Gaussian03 set of quantum chemistry codes. Predicted IR and Raman intensities are reported.

Larvicidal and growth inhibition of the malaria vector Anopheles stephensi by triterpenes from Dysoxylum malabaricum and Dysoxylum beddomei.

Secondary metabolites from Dysoxylum malabaricum and Dysoxylum beddomei were tested against mature and immature stage of the mosquito vector Anopheles stephensi under laboratory conditions. The triterpenes 3beta,24,25-trihydroxycycloartane and beddomeilactone from D. malabaricum and D. beddomei showed strong larvicidal, pupicidal and adulticidal activity. They also affected the reproductive potential of adults by acting as oviposition deterrents. The highest concentration tested (10 ppm) of both compounds evoked more than 90% mortality and oviposition deterrence.

Beddomeilactone: a new triterpene from Dysoxylum beddomei.

An investigation of the leaves of Dysoxylum beddomei has yielded a novel triterpene, named beddomeilactone, together with six known triterpenoids: 3-oxotirucalla-7,24-dien-23-ol, dipterocarpol, niloticin, melianone, melianodiol and 24-epi-melianodiol. The structure and stereochemistry of the new compound were determined on the basis of mass, 1D and 2D NMR spectroscopies including NOE difference and spin-spin decoupling studies.

Triterpenoids from Dysoxylum malabaricum.

Two triterpenes 21R,23R-epoxy-21alpha-ethoxy-24S,25-dihydroxyapotirucall-7-en-3-one and 24R-acetoxy-3beta,25-dihydroxycycloartane were isolated from the leaves of Dysoxylum malabaricum together with eight known compounds lupeone, lupeol. sitosterol, dipterocarpol, cycloart-25-ene-3beta,24-diol, 24R,25-dihydroxycycloartan-3-one, 3beta,24R,25-trihydroxycycloartane and ergosta-5,24(24(1))-diene-3beta,4beta,20S-triol. The complete 1H and 13C NMR spectral assignment of the new apotirucallene triterpenoid has been achieved by 1H-1H COSY, HMQC and HMBC experiments.