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Sample records for highly sensitive uplc-ms

  1. An UPLC-MS/MS method for highly sensitive high-throughput analysis of phytohormones in plant tissues

    PubMed Central

    2012-01-01

    Background Phytohormones are the key metabolites participating in the regulation of multiple functions of plant organism. Among them, jasmonates, as well as abscisic and salicylic acids are responsible for triggering and modulating plant reactions targeted against pathogens and herbivores, as well as resistance to abiotic stress (drought, UV-irradiation and mechanical wounding). These factors induce dramatic changes in phytohormone biosynthesis and transport leading to rapid local and systemic stress responses. Understanding of underlying mechanisms is of principle interest for scientists working in various areas of plant biology. However, highly sensitive, precise and high-throughput methods for quantification of these phytohormones in small samples of plant tissues are still missing. Results Here we present an LC-MS/MS method for fast and highly sensitive determination of jasmonates, abscisic and salicylic acids. A single-step sample preparation procedure based on mixed-mode solid phase extraction was efficiently combined with essential improvements in mobile phase composition yielding higher efficiency of chromatographic separation and MS-sensitivity. This strategy resulted in dramatic increase in overall sensitivity, allowing successful determination of phytohormones in small (less than 50 mg of fresh weight) tissue samples. The method was completely validated in terms of analyte recovery, sensitivity, linearity and precision. Additionally, it was cross-validated with a well-established GC-MS-based procedure and its applicability to a variety of plant species and organs was verified. Conclusion The method can be applied for the analyses of target phytohormones in small tissue samples obtained from any plant species and/or plant part relying on any commercially available (even less sensitive) tandem mass spectrometry instrumentation. PMID:23173950

  2. A sensitive method for the determination of hordenine in human serum by ESI(+) UPLC-MS/MS for forensic toxicological applications.

    PubMed

    Steiner, Irina; Brauers, Gernot; Temme, Oliver; Daldrup, Thomas

    2016-03-01

    We present the determination of the alkaloid hordenine and its forensic relevance as a qualitative and quantitative marker for beer consumption. A simple, rapid and sensitive ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method for the determination of hordenine in human serum samples was developed and validated. The application was tested with serum samples after enzymatic cleavage. After addition of the synthesized internal standard hordenine-D 4, a liquid-liquid extraction with dichloromethane and diethyl ether was performed. Chromatographic separation was conducted with a Waters Acquity® UPLC system with gradient elution on an Agilent Eclipse XDB-C18 column (4.6 mm × 150 mm, 5-μm particle size). For quantification, a Waters Acquity® TQ detector (version SNC 627) with a positive electrospray ionization probe and multiple reaction monitoring mode was used. A flow rate of 0.4 ml/min was applied. The retention time for both the analyte and the internal standard was 3.67 min. Linearity was demonstrated from 0.2 to 16 ng/ml (R (2) > 0.999). The lower limit of quantification was 0.3 ng/ml in serum. Matrix effects and extraction recoveries for low and high concentrations were within acceptable limits of 75-125 % and 50 %, respectively. To the best of our knowledge there is no corresponding method for the determination of hordenine by UPLC-MS/MS in serum. By our drinking studies we demonstrate that beer consumption leads to detectable hordenine concentrations in serum and observed a linear elimination of total hordenine correlating to blood alcohol concentration, which shows that hordenine can be used as a reliable qualitative and quantitative marker for beer consumption. The validated method was successfully applied to serum from actual forensic cases. Graphical Abstract Determination of hordenine in human serum samples by ESI(+) UPLC-MS/MS. PMID:26869341

  3. A Simple and High-Throughput Analysis of Amatoxins and Phallotoxins in Human Plasma, Serum and Urine Using UPLC-MS/MS Combined with PRiME HLB μElution Platform.

    PubMed

    Zhang, Shuo; Zhao, Yunfeng; Li, Haijiao; Zhou, Shuang; Chen, Dawei; Zhang, Yizhe; Yao, Qunmei; Sun, Chengye

    2016-01-01

    Amatoxins and phallotoxins are toxic cyclopeptides found in the genus Amanita and are among the predominant causes of fatal food poisoning in China. In the treatment of Amanita mushroom poisoning, an early and definite diagnosis is necessary for a successful outcome, which has prompted the development of protocols for the fast and confirmatory determination of amatoxins and phallotoxins in human biological fluids. For this purpose, a simple, rapid and sensitive multiresidue UPLC-MS/MS method for the simultaneous determination of α-amanitin, β-amanitin, γ-amanitin, phalloidin (PHD) and phallacidin (PCD) in human plasma, serum and urine was developed and validated. The diluted plasma, serum and urine samples were directly purified with a novel PRiME technique on a 96-well μElution plate platform, which allowed high-throughput sample processing and low reagent consumption. After purification, a UPLC-MS/MS analysis was performed using positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. This method fulfilled the requirements of a validation test, with good results for the limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, intra- and inter-assay precision, recovery and matrix effects. All of the analytes were confirmed and quantified in authentic plasma, serum and urine samples obtained from cases of poisoning using this method. Using the PRiME μElution technique for quantification reduces labor and time costs and represents a suitable method for routine toxicological and clinical emergency analysis. PMID:27153089

  4. A Simple and High-Throughput Analysis of Amatoxins and Phallotoxins in Human Plasma, Serum and Urine Using UPLC-MS/MS Combined with PRiME HLB μElution Platform

    PubMed Central

    Zhang, Shuo; Zhao, Yunfeng; Li, Haijiao; Zhou, Shuang; Chen, Dawei; Zhang, Yizhe; Yao, Qunmei; Sun, Chengye

    2016-01-01

    Amatoxins and phallotoxins are toxic cyclopeptides found in the genus Amanita and are among the predominant causes of fatal food poisoning in China. In the treatment of Amanita mushroom poisoning, an early and definite diagnosis is necessary for a successful outcome, which has prompted the development of protocols for the fast and confirmatory determination of amatoxins and phallotoxins in human biological fluids. For this purpose, a simple, rapid and sensitive multiresidue UPLC-MS/MS method for the simultaneous determination of α-amanitin, β-amanitin, γ-amanitin, phalloidin (PHD) and phallacidin (PCD) in human plasma, serum and urine was developed and validated. The diluted plasma, serum and urine samples were directly purified with a novel PRiME technique on a 96-well μElution plate platform, which allowed high-throughput sample processing and low reagent consumption. After purification, a UPLC-MS/MS analysis was performed using positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. This method fulfilled the requirements of a validation test, with good results for the limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, intra- and inter-assay precision, recovery and matrix effects. All of the analytes were confirmed and quantified in authentic plasma, serum and urine samples obtained from cases of poisoning using this method. Using the PRiME μElution technique for quantification reduces labor and time costs and represents a suitable method for routine toxicological and clinical emergency analysis. PMID:27153089

  5. A validated UPLC-MS/MS assay using negative ionization mode for high-throughput determination of pomalidomide in rat plasma.

    PubMed

    Iqbal, Muzaffar; Ezzeldin, Essam; Al-Rashood, Khalid A; Shakeel, Faiyaz

    2015-03-01

    In this study, a sensitive UPLC-MS/MS assay was developed and validated for high-throughput determination of pomalidomide in rat plasma using celecoxib as an internal standard (IS). Liquid liquid extraction using dichloromethane was employed to extract pomalidomide and IS from 200?L of plasma. Chromatographic separation was carried on Acquity BEH C18 column (50mm2.1mm, 1.7?m) using an isocratic mobile phase of acetonitrile: 10mM ammonium acetate (80:20, v/v), at a flow rate of 0.250mL/min. Both pomalidomide and IS were eluted at 0.660.03 and 0.800.03min, respectively, with a total run time of 1.5min only. A triple quadruple tandem mass spectrometer using electrospray ionization in negative mode was employed for analyte detection. The precursor to product ion transitions of m/z 272.01?160.89 for pomalidomide and m/z 380.08?316.01 for IS were used to quantify them respectively, multiple reaction monitoring mode. The developed method was validated according to regulatory guideline for bioanalytical method validation. The linearity in plasma sample was achieved in the concentration range of 0.47-400ng/mL (r(2)?0.997). The intra and inter-day precision values were ?11.1% (RSD, %) whereas accuracy values ranged from -6.8 to 8.5% (RE, %). In addition, other validation results were within the acceptance criteria and the method was successfully applied in a pharmacokinetic study of pomalidomide in rats. PMID:25621435

  6. Ultrasensitive determination of bisphenol A and its chlorinated derivatives in urine using a high-throughput UPLC-MS/MS method.

    PubMed

    Grignon, Claire; Venisse, Nicolas; Rouillon, Steeve; Brunet, Bertrand; Bacle, Astrid; Thevenot, Sarah; Migeot, Virginie; Dupuis, Antoine

    2016-03-01

    Bisphenol A (BPA) is a well-known endocrine disruptor. Chlorinated derivatives of BPA (ClxBPA) may be formed by reaction of chlorine with BPA present in drinking water. ClxBPA exhibit a higher level of estrogenic activity than BPA. While many studies have reported detectable BPA concentrations in urine, only very few studies were conducted in regards to ClxBPA. Since ClxBPA are potentially more toxic, it is important to assess large-scale exposure of the general population. Indeed, in the field of environment health, large studies are required to assess exposure to pollutants at ultratrace concentrations; therefore, analytical methods have to be rapid and sensitive. This work intends to validate a highly sensitive and rapid analytical method suitable to evaluate BPA and ClxBPA exposures during large-scale biomonitoring studies. For that purpose, a method based on online solid-phase extraction coupled with isotope dilution ultrahigh - performance liquid chromatography-tandem mass spectrometry was developed and validated according to accepted guidelines. The matrix-matched calibration curve ranged from 0.25 to 16.0 ng mL(-1) and from 0.025 to 1.60 ng mL(-1) for BPA and ClxBPA, respectively. This method was precise (the intra- and inter-day coefficients of variation of quality control were <16.4 %) and accurate (bias ranged from -4.0 to 16.8 %). The limit of quantification was validated at 0.25 and 0.025 ng mL(-1), for BPA and ClxBPA, respectively. The limit of detection was estimated for each experiment performed. Finally, this method is rapid and sensitive enough to be carried out during biomonitoring studies of BPA and ClxBPA in human urine. Graphical abstract Rapid and sensitive determination of bisphenol A (BPA) and its chlorinated derivatives (ClxBPA) in human urine using online solid-phase extraction (SPE) coupled with ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), suitable for large-scale biomonitoring study. PMID:26753970

  7. A simple and sensitive assay for eflornithine quantification in rat brain using pre-column derivatization and UPLC-MS/MS detection.

    PubMed

    Yang, Sihyung; Peng, Kuan-Wei; Wang, Michael Zhuo

    2015-06-01

    Eflornithine (α-difluoromethylornithine) has been used to treat second-stage (or meningoencephalitic-stage) human African trypanosomiasis and currently is under clinical development for cancer prevention. In this study, a new ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based assay was developed and validated for the quantification of eflornithine in rat brain. To improve chromatographic retention and MS detection, eflornithine was derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate for 5 min at room temperature prior to injection. Derivatized eflornithine was separated on a reverse-phase C18 UPLC column with a 6-min gradient; elution occurred at approximately 1.5 min. Prior to derivatization, eflornithine was reproducibly extracted from rat brain homogenate by methanol protein precipitation (~70% recovery). Derivatized eflornithine was stable in the autosampler (6 °C) for at least 24 h. This new assay had acceptable intra- and interday accuracy and precision over a wide dynamic range (5000-fold) and excellent sensitivity with a lower limit of quantification of 0.1 µm (18 ng/mL) using only 10 μL of rat brain homogenate. The validated eflornithine assay was applied successfully to determine eflornithine distribution in different regions of rat brain in an in situ rat brain perfusion study. PMID:25365958

  8. Development and validation of a sensitive UPLC-MS/MS method for the simultaneous determination of dapoxetine and its two metabolites in human plasma.

    PubMed

    Zhang, Wei-min; Qiang, Wu; Ying-Fei, Wang; Ming, Sun; Wang, Rong

    2016-02-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) method was developed to determine dapoxetine and its two major metabolites (dapoxetine-N-oxide and desmethyldapoxetine) in human plasma simultaneously. After a simple protein precipitation, the analytes and the combined internal standard (carbamazepine) were separated on an Acquity UPLC BEH C18 column using a mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution. Mass spectrometric analysis was performed using a XEVO TQD triple quadruple mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions are of m/z 306.3→261.2, m/z 322.2→261.2, m/z 292.2→261.2 and m/z 237.1→194.2 for dapoxetine, dapoxetine-N-oxide, desmethyldapoxetine and IS, respectively. The linearity of this method was found to be within the concentration range of 1.0-200ng/mL for dapoxetine; 0.5-100ng/mL for dapoxetine-N-oxide; and 0.1-5.0ng/mL for desmethyldapoxetine in human plasma, respectively. Only 4.0min was needed for an analytical run. Intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all of the concentrations. This assay was successfully used to support a clinical pharmacokinetic study following oral administration of dapoxetine tablets in healthy Chinese subjects. PMID:26641706

  9. A selective and sensitive method based on UPLC-MS/MS for quantification of momordin Ic in rat plasma: application to a pharmacokinetic study.

    PubMed

    Yan, Huiyu; Song, Yanqing; Zhou, Wei; Zhang, Sixi

    2015-11-10

    A selective and sensitive method was developed and validated based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). This method was applied to quantify momordin Ic in rat plasma. Chromatographic separation was performed on a Hypersil GOLD HPLC C18 column (150mm×4.6mm, 5μm) using an isocratic mobile phase of acetonitrile/water (80:20, v/v) at a flow rate of 0.6mL/min. An electrospray ionization source was applied and operated in negative ion mode; selected reaction monitoring (SRM) mode was used for quantification by monitoring the precursor-to-product ion transitions of m/z 763.4→m/z 455.3 for momordin Ic, and m/z 649.4→m/z 487.3 for IS. Calibration curves showed good linearity over the range of 22.0-2200ng/mL for momordin Ic in rat plasma. The developed method was applied to a pharmacokinetic study of momordin Ic in rats after single intravenous doses at 0.52, 1.56, and 4.67mg/kg. The elimination half-life (t1/2) values were 1.22±0.39, 1.14±0.10, and 1.83±0.39h, respectively. The plasma concentration at 2min (C2min) and area under the curve (AUC) for the intravenous doses of momordin Ic were approximately dose proportional. PMID:26218506

  10. High-throughput screening of inhibitory effects of Bo-yang-hwan-o-tang on human cytochrome P450 isoforms in vitro using UPLC/MS/MS.

    PubMed

    Lee, Miran; Park, Jeonghyeon; Lim, Mi-sun; Seong, Sook Jin; Lee, Joomi; Seo, Jeong Ju; Park, Yong-Ki; Lee, Hae Won; Yoon, Young-Ran

    2012-01-01

    Bo-yang-hwan-o-tang (BHT) is an oriental herbal medicine for treating brain disorders such as cerebral ischemia. The objective of this study was to develop an economically feasible and time-saving high-throughput screening method to monitor the potential inhibitory effects of BHT on human cytochrome P450 (CYP) enzymes in vitro. Two cocktail sets were used for incubation of human liver microsomes: Cocktail A: 6 probe substrates for CYP1A2, CYP2A6, CYP2C8, CYP2C19, CYP2D6, CYP3A4; Cocktail B: 3 for CYP2B6, CYP2C9, CYP2E1. The concentrations of the substrate metabolites were simultaneously analyzed using UPLC/MS/MS. The BHT extract had almost negligible inhibitory effects on the nine human CYP isoforms tested, with the half-maximal inhibitory concentration value ranged from 3624.99 to 45412.44 μg/ml. The results suggest that BHT extract has no inhibitory effects on CYP isoforms within the clinically recommended dosage range. We conclude that BHT might be free of drug-herb interactions when co-administered with other medicines. However, more in vivo human studies are needed to confirm these results. The high-throughput screening method can be a useful tool for drug discovery and for understanding drug interactions. PMID:23232241

  11. Determination of caramel colorants' by-products in liquid foods by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

    PubMed

    Goscinny, Séverine; Hanot, Vincent; Trabelsi, Hasna; Van Loco, Joris

    2014-01-01

    2-Methylimidazole, 4-methylimidazole (2-MI and 4-MI), 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl) imidazole (THI) and 5-hydroxymethylfurfural (5-HMF) are neo-formed compounds generated during the manufacture of caramel colours and are transferred to the processed food. These contaminants are known to have a toxicological profile that may pose health risks. Hence, to characterise THI, 2- and 4-MI and 5-HMF levels in liquid foods, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and sample preparation was divided into two analytical strategies depending on the concentration range expected in the type of foods targeted. For the determination of the imidazole substitutes (THI, 2- and 4-MI), a sample enrichment and clean-up step by strong cation solid-phase extraction was developed. This method is capable of quantifying over a range of 5 ng ml⁻¹ (LOQ) to 500 ng ml⁻¹ with recoveries of 75.4-112.4% and RSDs of 1.5-15%. For determination of 5-HMF, a standard addition method was applied covering the linear range of 0.25-30 µg ml⁻¹ with RSDs from 2.8% (for intraday precision) to 9.2% (for intermediate precision). The validated analytical methods were applied to 28 liquid food samples purchased from local markets. THI was found only in the beer samples at levels up to 141.2 ng ml⁻¹. For 2-MI, non-quantifiable traces were observed for all samples, while 4-MI was observed in all samples with large concentration variations (from < LOQ to 563.9 ng ml⁻¹). 5-HMF was found at expected concentrations, except for a sherry vinegar sample (113 µg ml⁻¹), which required a high level of dilution before following the standard addition protocol. PMID:25060737

  12. Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC-MS/MS method: application to an oral bioavailability study of genistein in mice

    PubMed Central

    Yang, Zhen; Zhu, Wei; Gao, Song; Xu, Haiyan; Wu, Baojian; Kulkarni, Kaustubh; Singh, Rashim; Tang, Lan; Hu, Ming

    2012-01-01

    The purpose of this research was to develop a sensitive and reproducible UPLC-MS/MS method to simultaneously quantify genistein, genistein-7-O-glucuronide (G-7-G), genistein-4’-O-glucuronide (G-4’-G), genistein-4’-O-sulfate (G-4’-S) and genistein-7-Osulfate (G-7-S) in mouse blood samples. After the method was fully validated over a wide linear range, it was applied to quantify the levels of genistein and its metabolites in a mouse bioavailability study. The linear response range were 19.5–10,000 nM for genistein, 12.5–3,200 nM for G-7-G, 20–1280 nM for G-4’-G, 1.95–2,000 nM for G-4’-S, and 1.56–3,200 nM for G-7-S, respectively. The lower limit of quantification (LLOQ) was 4.88, 6.25, 5, 0.98 and 0.78 nM for genistein, G-7-G, G-4’-G, G-4’-S and G-7-S, respectively. Only 20 µl mouse blood sample from i.v. and p.o. administration were needed for analysis because of the high sensitivity of the method. The intra- and inter-day variance is less than 15% and accuracy is within 85–115%. The analysis was finished within 4.5 min. The applicability of this assay was demonstrated and successfully applied for bioavailability study in FVB mouse after i.v. and p.o. administration of 20 mg/kg of genistein, and its oral bioavailability was ~24%. PMID:20378296

  13. Development and validation of a sensitive UPLC-MS/MS method for the analysis of narcotic analgesics in urine and whole blood in forensic context.

    PubMed

    Verplaetse, Ruth; Tytgat, Jan

    2012-02-10

    Narcotic analgesics are widely (ab) used and sometimes only occur in low concentrations in biological samples. Therefore, a highly sensitive liquid chromatography tandem mass spectrometry method was developed for simultaneous analysis of 9 narcotic analgesics and metabolites (buprenorphine, O-desmethyltramadol, fentanyl, norbuprenorphine, norfentanyl, pethidine, piritramide, tilidine and tramadol) in urine and whole blood. Sample preparation was performed on a mixed-mode cation exchange solid phase extraction cartridge with an additional alkaline wash step to decrease matrix effects and thus increase sensitivity. Ionization with electrospray ionization was found to be more efficient than atmospheric pressure chemical ionization. The use of a mobile phase of high pH resulted in higher electrospray ionization signals than the conventional low pH mobile phases. In the final method, gradient elution with 10mM ammonium bicarbonate (pH 9) and methanol was performed on a small particle column (Acquity C18, 1.7 ?m, 2.1 mm 50 mm). Selectivity, matrix effects, recovery, linearity, sensitivity, precision, accuracy and stability were validated in urine and whole blood. All parameters were successfully evaluated and the method showed very high sensitivity, which was the major aim of this study. The applicability of the method was demonstrated by analysis of several forensic cases involving narcotic analgesics. PMID:21356580

  14. A novel UPLC-MS/MS method for sensitive quantitation of boldine in plasma, a potential anti-inflammatory agent: application to a pharmacokinetic study in rats.

    PubMed

    Zeng, Rong-Jie; Li, Yu; Chen, Jian-Zhong; Chou, Gui-Xin; Gao, Yu; Shao, Jing-Wei; Jia, Lee; Wu, Sheng-Dong; Wu, Shui-Sheng

    2015-03-01

    Boldine is a potential anti-inflammatory agent found in several different plants. Published bioanalytical methods using HPLC with ultraviolet and fluorescent detection lacked enough sensitivity and required tedious sample preparation procedures. Herein, we describe the development of a novel ultra-high performance LC with MS/MS for determination of boldine in plasma. Boldine in plasma was recovered by liquid-liquid extraction using 1 mL of methyl tert-butyl ether. Chromatographic separation was performed on a C18 column at 45°C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple-quadrupole MS/MS by positive ion multiple reaction monitoring mode. Good linearity (r(2) > 0.9926) was achieved in a concentration range of 2.555-2555 ng/mL with a lower limit of quantification of 2.555 ng/mL for boldine. The intra- and inter-day precisions of the assay were 1.2-6.0 and 1.8-7.4% relative standard deviation with an accuracy of -6.0-8.0% relative error. This newly developed method was successfully applied to a single low-dose pharmacokinetic study in rats and was demonstrated to be simpler and more sensitive than the published methods, allowing boldine quantification in reduced plasma volume. PMID:25065486

  15. A sensitive and selective UPLC-MS/MS method for simultaneous determination of 10 alkaloids from Rhizoma Menispermi in rat plasma and its application to a pharmacokinetic study.

    PubMed

    Wei, Jinxia; Fang, Linlin; Liang, Xinlei; Su, Dan; Guo, Xingjie

    2015-11-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry method has been developed and validated for simultaneous quantitation of 10 alkaloids (dauricine, daurisoline, N-desmethyldauricine, dauricicoline, dauriporphinoline, bianfugecine, dauricoside, stepholidine, acutumine and acutumidine) from Rhizoma Menispermi in rat plasma. After addition of internal standard (verapamil), plasma samples were pretreated by a single-step protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters BEH C18 column with gradient elution using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The analytes were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The validated method exhibited good linearity over a wide concentration range (r≥0.9914), and the lower limits of quantification were 0.01-5.0 ng/mL for all the analytes. The intra-day and inter-day precisions (RSD) at three different levels were both less than 13.4% and the accuracies (RE) ranged from -12.8% to 13.5%. The mean extraction recoveries of analytes and IS from rat plasma were all more than 77%. The validated method was successfully applied to a comparative pharmacokinetic study of 10 alkaloids in rat plasma after oral administration of Rhizoma Menispermi extract. PMID:26452875

  16. Determination of Pinaverium Bromide in Human Plasma by a Sensitive and Robust UPLC-MS-MS Method and Application to a Pharmacokinetic Study in Mexican Subjects.

    PubMed

    Patiño-Rodríguez, Omar; Zapata-Morales, Juan Ramón; Escobedo-Moratilla, Abraham; Díaz de León-Cabrero, Manuel; Torres-Roque, Irma; Pérez-Urizar, José

    2015-09-01

    A high-throughput ultra-performance liquid chromatography coupled to tandem mass spectrometry (LC-ESI-MS-MS) method was developed for the determination of pinaverium bromide in human plasma. Protein precipitation with acetonitrile was used to extract pinaverium and itraconazole (as internal standard) from 500 µL plasma samples. The chromatographic separation was achieved with an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) using a mixture of acetonitrile-5 mM ammonium formate (80:20, v/v) as mobile phase. Isocratic elution at 0.3 mL/min was used. Detection was performed by positive ion electrospray tandem mass spectrometry on a XEVO TQ-S by multiple reaction monitoring mode. The mass transitions monitorized were as follows: m/z 511.2 → 230 for pinaverium bromide, and m/z 705.29 → 392.18 for the itraconazole. The method was validated over a concentration range of 12-12,000 pg/mL. The chromatographic method runtime is 2.5 min and was applied to characterize the pharmacokinetics of pinaverium bromide after the oral administration of 100 mg to healthy Mexican subjects. PMID:25862744

  17. Depletion of urinary zilpaterol residues in horses as measured by ELISA and UPLC-MS/MS.

    PubMed

    Shelver, Weilin L; Thorson, Jennifer F; Hammer, Carolyn J; Smith, David J

    2010-04-14

    Three horses were dosed with dietary zilpaterol and the urine concentrations measured from withdrawal day 0 to withdrawal day 21. The analyses were carried out using both enzyme-linked immunosorbent assay (ELISA) and an ultraperformance liquid chromatography with triple-quadrupole-tandem mass spectrometric detection (UPLC-MS/MS). The UPLC-MS/MS method was developed to provide rapid analysis with positive analyte identification by following three product ions and computing the two independent ion ratios. When urinary zilpaterol concentrations were between 0.2 and 2 ng/mL, the ELISA had interday recoveries of 114-120% with coefficients of variation (CV) of <22%; intraday recoveries were 79-111% with CVs of <13%. For urinary zilpaterol concentrations of 0.4-40 ng/mL the UPLC-MS/MS method had interday recoveries of 94-104% with CVs of <8%; intraday recoveries were 97-102% with CVs of < or = 7.5%. Correlation analysis demonstrated that the ELISA and UPLC-MS/MS methods returned essentially the same results, especially at urinary zilpaterol concentrations below 2000 ng/mL. Urinary excretion peaked rapidly after dosing between 5300 and 10800 ng/mL (UPLC-MS/MS) or between 5900 and 17900 ng/mL (ELISA) for the different horses, much higher than observed in other species. Urinary zilpaterol concentrations declined rapidly to below 3000 ng/mL within 24 h of study day 1. After about 5 days, zilpaterol elimination slowed markedly, taking nearly 10 days for an order of magnitude decrease. The analytical methods were able to detect zilpaterol in the urine even at withdrawal day 21, demonstrating the sensitivity of each analytical method and the slow rate of zilpaterol depuration from horses. PMID:20218607

  18. UPLC-MS/MS assay of 21-aminosteroid (lazaroid U74389G) for application in pharmacokinetic study.

    PubMed

    Gadgil, P; Ibrahim, F; Chow, D S-L

    2016-04-15

    Lazaroids are potent inhibitors of lipid peroxidation, both in vitro and in vivo. Additionally, a member of the lazaroid family, U-74389G (LAZ) has been shown to have specific radio-protective and anti-proliferative effects. However, there is no quantitative analytical method developed for measuring the therapeutic levels of LAZ for the aforementioned effects. This article highlights the development and validation of a sensitive UPLC-MS/MS method for the quantification of LAZ, and its subsequent application in pharmacokinetic studies in rats with the lower limit of quantification (LLOQ) of 1.95ng/mL. LAZ and internal standard diadzein (IS) were separated using ACQUITY UPLC(®) BEH C18 column. Gradient elution was used at a flow rate of 0.45mL/min with mobile phases consisting of 0.1% formic acid in water and 0.1% formic in acetonitrile. LAZ (m/z 612→260) and IS (m/z 255→199) were detected by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in a positive mode on QTRAP(®) 5500 System. The UPLC-MS/MS method was validated as per the US FDA Guidelines for Bio-analytical Validation. LAZ was extracted from rat plasma (100μL) using protein precipitation by acetonitrile with mean recovery and matrix factor in range of 47.7-56.1%, and 85.6-89.4%, respectively. The calibration curve for LAZ was linear in the range of 1.95-250ng/mL. The inter-day and intra-day accuracy and precision values for LLOQ, low, medium, high and very high concentration QC samples were within ±15%. LAZ was tested under different storage conditions, for short-term bench-top stability (1h and 3h at 25°C), long-term stability (1 month at -80°C), freeze-thaw cycle stability (1 cycle and 3 cycles) and stability of processed samples in auto-sampler (24h at 10°C) with stability values within ±15% range of nominal concentrations. The validated UPLC-MS/MS method was further applied to a pharmacokinetic study in rats after a single intravenous dose of LAZ at 5mg/kg. PMID:26848737

  19. Determination of sotolon content in South African white wines by two novel HPLC-UV and UPLC-MS methods.

    PubMed

    Gabrielli, Mario; Buica, Astrid; Fracassetti, Daniela; Stander, Marietjie; Tirelli, Antonio; du Toit, Wessel J

    2015-02-15

    Sotolon has been reported to play an important role in the atypical ageing and aroma character of many wines. A number of analytical techniques for sotolon analysis in wine have been reported, but these often require extensive sample preparation. In this work we report a HPLC-UV method and a novel UPLC-MS method to determine sotolon concentrations in white wines with little sample preparation applied for the first time for the evaluation of sotolon levels in South African wines. The validation showed that the instrumental methods had good accuracy, repeatability and linearity, but the UPLC-MS method proved more sensitive. For both methods, quantification limits were lower than the sotolon odour threshold in wine (10μg/L), 0.86μg/L and 0.013μg/L, for HPLC-UV and UPLC-MS methods, respectively. Sotolon levels in 65 South African white wines were often found to be lower than the reported odour threshold, with the highest concentration being 9.11μg/L. However, for low levels (<1μg/L), unknown interferences in certain wines led to sotolon not being quantified with the HPLC-UV method, which made the UPLC-MS method more suitable. PMID:25236214

  20. Pharmacokinetic and bioavailability study of angeloylgomisin H in rat plasma by UPLC-MS/MS

    PubMed Central

    Chen, Shanjiang; Jia, Zhuyin; Dong, Ledan; Geng, Peiwu; Liu, Zezheng; Yang, Suping; Wen, Congcong; Liu, Fuli

    2015-01-01

    Angeloylgomisin H, as a major lignin in the fruits, was reported to have the potential to improve insulin-stimulated glucose uptake by activating PPAR-?. In this work, a sensitive and selective UPLC-MS/MS method for determination of angeloylgomisin H in rat plasma is developed. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm 100 mm, 1.7 ?m) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 523.2-315.1 for angeloylgomisin H, and m/z 611.1-303.1 for IS. Calibration plots were linear throughout the range 5-2000 ng/mL for angeloylgomisin H in rat plasma. Mean recoveries of angeloylgomisin H in rat plasma ranged from 86.2% to 92.5%. RSD of intra-day and inter-day precision were both < 11%. The accuracy of the method was between 93.0% and 104.1%. The method was successfully applied to pharmacokinetic study of angeloylgomisin H after either oral or intravenous administration. The absolute bioavailability of angeloylgomisin H was reported as high as 4.9%. PMID:26770391

  1. Validated UPLC/MS/MS assay for quantitative bioanalysis of elbasvir in rat plasma and application to pharmacokinetic study.

    PubMed

    Liu, Haiyan; Xu, Hongjiang; Song, Wei; Zhang, Yinsheng; Yu, Sen; Huang, Xin

    2016-03-15

    Rapid, sensitive, selective and accurate ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of elbasvir (ELB) in rat plasma with deuterated elbasvir (ELB-D6) as internal standard (IS).Sample preparation was done by protein precipitation using acetonitrile containing 50ng/mL IS. Chromatographic separation was achieved by an UPLC BEH C18 column (2.1mm×50mm, 1.7μm) column with a gradient mobile phase consisting of acetonitrile-water (containing 5.0mM ammonium acetate with 0.01% acetic acid, pH 4.5) as mobile phase at a flow rate of 0.3mL/min for 3min. ELB was monitored using positive electrospray triple quadrupole mass spectrometer (Waters Xevo TQ-S) via multiple reaction monitoring (MRM) mode. The monitored transitions were set at m/z 882.51→656.42 and m/z 888.49→662.43 for ELB and ELB-D6, respectively. The achieved lower limit of quantification was 1.0ng/mL. The validated method had an excellent linearity in the range of 1.0-2000ng/mL (r(2)>0.996). Recovery efficiency at three levels QC concentrations of 2.0 (low), 160 (medium) and 1600 (high) ng/mLwas in the range of 98.29-106.40% for ELB. Matrix effect was found to be minimal. The intra- and inter-day precisions were less than 7.01%. The intra- and inter-day accuracies were determined to be within ±6.23% for all accuracy measurements. The validated simple and rapid UPLC-MS/MS method was successfully used to the pharmacokinetics study of ELB in rats, providing its applicability in relevant preclinical studies. PMID:26927874

  2. Assessment of Oxidative Damage to Proteins and DNA in Urine of Newborn Infants by a Validated UPLC-MS/MS Approach

    PubMed Central

    Kuligowski, Julia; Torres-Cuevas, Isabel; Quintás, Guillermo; Rook, Denise; van Goudoever, Johannes B.; Cubells, Elena; Asensi, Miguel; Lliso, Isabel; Nuñez, Antonio; Vento, Máximo; Escobar, Javier

    2014-01-01

    The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography–tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO2-Tyr), 3-Cl-tyrosine (3Cl-Tyr), 2′-deoxyguanosine (2dG) and 8-hydroxy-2′-deoxyguanosine (8OHdG). Following the FDA-based guidelines, appropriate levels of accuracy and precision, as well as adequate levels of sensitivity with limits of detection (LODs) in the low nanomolar (nmol/L) range were confirmed after method validation. The validity of the proposed UPLC-MS/MS method was assessed by analysing urine samples from a clinical trial in extremely low birth weight (ELBW) infants randomized to be resuscitated with two different initial inspiratory fractions of oxygen. PMID:24695409

  3. Chemical derivatization of neurosteroids for their trace determination in sea lamprey by UPLC-MS/MS.

    PubMed

    Bussy, Ugo; Huertas, Mar; Chung-Davidson, Yu-Wen; Li, Ke; Li, Weiming

    2016-03-01

    This article describes the development and validation of a sensitive and robust method for the determination of neurosteroids in sea lamprey, an ancestral animal in vertebrate evolution. Chemical derivatization was used to enhance the detection of neurosteroids containing ketone function by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Iminooxy derivatives of 12 oxosteroids and three internal standards were monitored by positive electrospray tandem mass spectrometry using the neutral loss of sulfate. Limit of quantification, extraction recovery and matrix effect were first evaluated and SPE using C18 sorbent was selected after comparison with liquid/liquid extraction and protein precipitation. Matrix effect ranged from 89.6% to 113.1% in plasma and from 79.8% to 100.0% in the brain. Recovery values ranged from 80.0% to 103.8% in plasma and from 86.3% to 107.9% in the brain. Chromatographic separation was achieved by reverse phase chromatography (2.1mm×100mm, 1.7µm particle size, C18) with a binary gradient between methanol and 0.1% formic acid in water. Limit of quantification ranged from 5 to 10pg/mL and was up to 80 times lower than those for non-derivatized steroids. Accuracy and precision parameters were determined and inter- and intra-day at three concentrations: 50, 500 and 5000pg/mL. This method was applied to analyze real samples. progesterone (P), pregnenolone (P5), 7-hydroxy-pregnenolpne (7P5), 17-hydroxy-pregnenolpne (17P5)dehydroepiandrosterone (DHEA), androstenedienone (A4), testosterone (T), dihydrotestosterone (DHT), allopregnanolone (THP), 11-hydroxy-androstenedienone (11A4) and 11-Deoxycortisol (S) were measured in sea lamprey brain and plasma matrixes. PMID:26717848

  4. Integration of Electrochemistry with Ultra Performance Liquid Chromatography/Mass Spectrometry (UPLC/MS)

    PubMed Central

    Cai, Yi; Zheng, Qiuling; Liu, Yong; Helmy, Roy; Loo, Joseph A.; Chen, Hao

    2015-01-01

    This study presents the development of ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) combined with electrochemistry (EC) for the first time and its application for the structural analysis of disulfide bond-containing proteins/peptides. In our approach, a protein/peptide mixture sample undergoes fast UPLC separation and subsequent electrochemical reduction in an electrochemical flow cell followed by online MS and MS/MS analyses. The electrochemical cell is coupled to MS using our recently developed desorption electrospray ionization (DESI) interface. Using this UPLC/EC/DESI-MS method, disulfide bond-containing peptides can be differentiated from those without disulfide bonds as the former are electroactive and reducible. Tandem MS analysis of the disulfide-reduced peptide ions provides increased sequence and disulfide linkage pattern information. In a reactive DESI-MS detection experiment in which a supercharging reagent was used to dope the DESI spray solvent, increased charging was obtained for the UPLC-separated proteins. Strikingly, upon online electrolytic reduction, supercharged proteins (e.g., α-lactalbumin) showed even higher charging, which would be useful in top-down protein structure analysis as increased charges are known to promote protein ion dissociation. Also, the separation speed and sensitivity are enhanced by approximately 1~2 orders of magnitude by using UPLC for the LC/EC/MS platform, in comparison to the previously used high performance liquid chromatography (HPLC). This UPLC/EC/DESI-MS method combines the power of fast UPLC separation, fast electrochemical conversion and online MS structural analysis for a potentially valuable tool for proteomics research and bioanalysis. PMID:26307715

  5. Screening and quantitative determination of drugs of abuse in diluted urine by UPLC-MS/MS.

    PubMed

    Hegstad, Solfrid; Hermansson, Sigurd; Betnér, Ingvar; Spigset, Olav; Falch, Berit Margrethe Hasle

    2014-02-01

    The purpose of this work was to develop and evaluate a fast, robust and specific UPLC-MS/MS screening platform for the determination and quantification of a variety of commonly used drugs of abuse in urine, i.e. a high-throughput quantitative analysis. Substances in the drug classes opioids, central nervous system stimulants and benzodiazepines and related agents were included in addition to cannabis and pregabalin, a total of 35 different analytes. Based on the concentrations and the physico-chemical properties of the substances, three UPLC-MS/MS methods were developed in parallel. Prior to analysis, sample preparation consisted of two different simple dilutions with 60 and 100 μL urine, respectively, using a Tecan Freedom Evo pipetting robot platform. A Waters Xevo TQ-S tandem quadrupole mass spectrometer coupled to a Waters I-class UPLC was used for quantitative analysis of one quantitative and one qualifying MRM transition for each analyte, except for tramadol for which the metabolite O-desmethyl-tramadol was included in the MRM method to confirm tramadol identity. Deuterated analogs were included as internal standards. The between-assay relative standard deviations varied from 2% to 11% and the limits of quantification were in the range 1-200 ng/mL for the various analytes. After development and initial testing, the method has been successfully implemented and routinely used at our hospital for quantitative screening of drugs of abuse in more than 35,000 urinary samples. PMID:24413020

  6. Simultaneous determination of 38 veterinary antibiotic residues in raw milk by UPLC-MS/MS.

    PubMed

    Han, R W; Zheng, N; Yu, Z N; Wang, J; Xu, X M; Qu, X Y; Li, S L; Zhang, Y D; Wang, J Q

    2015-08-15

    A selective and rapid method has been developed to determine, simultaneously, 38 veterinary antibiotic residues in raw milk by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). One milliliter of raw milk was diluted with 0.5 mL water and 3 mL acetonitrile, then purified using an Oasis HLB cartridge. The eluates were evaporated by nitrogen drying and then reconstituted to 4 mL with water/acetonitrile (8:1) before being injected into the UPLC-MS/MS system. The results indicated recoveries of 68-118% for 14 β-lactams, 79-118% for eight quinolones, 71-106% for eight sulfonamides, 76-116% for four tetracyclines, 78-106% for three macrolides, and 88-103% for one lincosamides, with coefficients of variation less than 15% for intraday and interday precisions. The limit of quantification for all antibiotics was 0.03-10 μg kg(-1). This methodology was then applied to field-collected real raw milk samples and trace levels of four antibiotics were detected. PMID:25794729

  7. Development and validation of an UPLC-MS/MS method for the quantification of tamoxifen and its main metabolites in human scalp hair.

    PubMed

    Drooger, Jan C; Jager, Agnes; Lam, Mei-Ho; den Boer, Mathilda D; Sleijfer, Stefan; Mathijssen, Ron H J; de Bruijn, Peter

    2015-10-10

    The aim of this study was to validate an earlier developed high-performance highly sensitive ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for quantification of tamoxifen and its three main metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen) in scalp hair. This non-invasive method might, by segmental analysis of hair, be useful in the determination of the concentration of drugs and its metabolites over time, which can be used to study a wide variety of clinical relevant questions. Hair samples (150-300 hair strands, cut as close to the scalp as possible from the posterior vertex region of the head) were collected from female patients taking tamoxifen 20mg daily (n=19). The analytes were extracted using a liquid-liquid extraction procedure with carbonate buffer at pH 8.8 and a mixture of n-hexane/isopropranol method, followed by UPLC-MS/MS chromatography, based on an earlier validated method. The calibration curves were linear in the range of 1.00-200 pmol for tamoxifen and N-desmethyl-tamoxifen, with lower limit of quantitation of 1.00 pmol and 0.100-20.0 pmol with lower limit of quantitation of 0.100 pmol for endoxifen and 4-hydroxy-tamoxifen. Assay performance was fair with a within-run and between-run variability less than 9.24 at the three quality control samples and less than 15.7 for the lower limit of quantitation. Importantly, a steep linear decline was observed from distal to proximal hair segments. Probably, this is due to UV exposure as we showed degradation of tamoxifen and its metabolites after exposure to UV-light. Furthermore, higher concentrations of tamoxifen were found in black hair samples compared to blond and brown hair samples. We conclude that measurement of the concentration of tamoxifen and its main metabolites in hair is possible, with the selective, sensitive, accurate and precise UPLC-MS/MS method. However, for tamoxifen, it seems not possible to determine exposure over time with segmental analysis of hair, probably largely due to the effect of UV irradiation. Further research should therefore focus on quantification of other anticancer drugs, in segmented scalp hair, that are less sensitive to UV irradiation. PMID:26119504

  8. Validation of a Rapid and Sensitive UPLC-MS-MS Method Coupled with Protein Precipitation for the Simultaneous Determination of Seven Pyrethroids in 100 µL of Rat Plasma by Using Ammonium Adduct as Precursor Ion.

    PubMed

    Singh, Sheelendra Pratap; Dwivedi, Nistha; Raju, Kanumuri Siva Rama; Taneja, Isha; Wahajuddin, Mohammad

    2016-04-01

    United States Environmental Protection Agency has recommended estimating pyrethroids' risk using cumulative exposure. For cumulative risk assessment, it would be useful to have a bioanalytical method for quantification of one or several pyrethroids simultaneously in a small sample volume to support toxicokinetic studies. Therefore, in the present study, a simple, sensitive and high-throughput ultraperformance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous analysis of seven pyrethroids (fenvalerate, fenpropathrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, cypermethrin and deltamethrin) in 100 µL of rat plasma. A simple single-step protein precipitation method was used for the extraction of target compounds. The total chromatographic run time of the method was 5 min. The chromatographic system used a Supelco C18 column and isocratic elution with a mobile phase consisting of methanol and 5 mM ammonium formate in the ratio of 90 : 10 (v/v). Mass spectrometer (API 4000) was operated in multiple reaction monitoring positive-ion mode using the electrospray ionization technique. The calibration curves were linear in the range of 7.8-2,000 ng/mL with correlation coefficients of ≥0.99. All validation parameters such as precision, accuracy, recovery, matrix effect and stability met the acceptance criteria according to the regulatory guidelines. The method was successfully applied to the toxicokinetic study of cypermethrin in rats. To the best of our knowledge, this is the first LC-MS-MS method for the simultaneous analysis of pyrethroids in rat plasma. This validated method with minimal modification can also be utilized for forensic and clinical toxicological applications due to its simplicity, sensitivity and rapidity. PMID:26801239

  9. From cells to muropeptide structures in 24 h: Peptidoglycan mapping by UPLC-MS

    PubMed Central

    Kühner, Daniel; Stahl, Mark; Demircioglu, Dogan D.; Bertsche, Ute

    2014-01-01

    Peptidoglycan (PGN) is ubiquitous in nearly all bacterial species. The PGN sacculus protects the cells against their own internal turgor making PGN one of the most important targets for antibacterial treatment. Within the last sixty years PGN composition has been intensively studied by various methods. The breakthrough was the application of HPLC technology on the analysis of muropeptides. However, preparation of pure PGN relied on a very time consuming method of about one week. We established a purification protocol for both Gram-positive and Gram-negative bacteria which can be completely performed in plastic reaction tubes yielding pure muropeptides within 24 hours. The muropeptides can be analyzed by UPLC-MS, allowing their immediate determination. This new rapid method provides the feasibility to screen PGN composition even in high throughput, making it a highly useful tool for basic research as well as for the pharmaceutical industry. PMID:25510564

  10. Graphene based pipette tip solid phase extraction of marine toxins in shellfish muscle followed by UPLC-MS/MS analysis.

    PubMed

    Shen, Qing; Gong, Like; Baibado, Joewel T; Dong, Wei; Wang, Yixuan; Dai, Zhiyuan; Cheung, Hon-Yeung

    2013-11-15

    Graphene is a novel carbonic material with great potentials for the use as sorbent due to its ultrahigh surface area. Herein, we report the use of graphene as sorbent in solid-phase extraction (SPE) using pipette tip as cartridge namely GPT-SPE, together with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), for the analysis of lipophilic marine toxins (LMTs), including yessotoxins (YTX), okadaic acid (OA), dinophysistoxin-1 (DTX1), gymnodimine (GYM), spirolides-1 (SPX1), pectenotoxin-2 (PTX2) and azaspiracid-1 (AZA1) in shellfish. The GPT-SPE procedure was optimized and the performance of graphene was fully validated. Results with high-sensitivity and good reproducibility was obtained and compared with that of other sorbents like C18 silica, multi-walled carbon nanotubes (MWCNTs), commercial Oasis HLB, and Strata-X for the extraction of LMTs, which showed superiority and advantages of graphene, such as good recoveries, stability and compatibility with various solvents. In order to exhibit the potentials of graphene as an excellent sorbent material, 67 mussel samples from six coastal cities of China were analyzed. OA was found to be the dominant contaminant, while YTX was also detected with low level. PMID:24148472

  11. Untargeted UPLC-MS Profiling Pipeline to Expand Tissue Metabolome Coverage: Application to Cardiovascular Disease

    PubMed Central

    2015-01-01

    Metabolic profiling studies aim to achieve broad metabolome coverage in specific biological samples. However, wide metabolome coverage has proven difficult to achieve, mostly because of the diverse physicochemical properties of small molecules, obligating analysts to seek multiplatform and multimethod approaches. Challenges are even greater when it comes to applications to tissue samples, where tissue lysis and metabolite extraction can induce significant systematic variation in composition. We have developed a pipeline for obtaining the aqueous and organic compounds from diseased arterial tissue using two consecutive extractions, followed by a different untargeted UPLC-MS analysis method for each extract. Methods were rationally chosen and optimized to address the different physicochemical properties of each extract: hydrophilic interaction liquid chromatography (HILIC) for the aqueous extract and reversed-phase chromatography for the organic. This pipeline can be generic for tissue analysis as demonstrated by applications to different tissue types. The experimental setup and fast turnaround time of the two methods contributed toward obtaining highly reproducible features with exceptional chromatographic performance (CV % < 0.5%), making this pipeline suitable for metabolic profiling applications. We structurally assigned 226 metabolites from a range of chemical classes (e.g., carnitines, α-amino acids, purines, pyrimidines, phospholipids, sphingolipids, free fatty acids, and glycerolipids) which were mapped to their corresponding pathways, biological functions and known disease mechanisms. The combination of the two untargeted UPLC-MS methods showed high metabolite complementarity. We demonstrate the application of this pipeline to cardiovascular disease, where we show that the analyzed diseased groups (n = 120) of arterial tissue could be distinguished based on their metabolic profiles. PMID:25664760

  12. Untargeted UPLC-MS profiling pipeline to expand tissue metabolome coverage: application to cardiovascular disease.

    PubMed

    Vorkas, Panagiotis A; Isaac, Giorgis; Anwar, Muzaffar A; Davies, Alun H; Want, Elizabeth J; Nicholson, Jeremy K; Holmes, Elaine

    2015-04-21

    Metabolic profiling studies aim to achieve broad metabolome coverage in specific biological samples. However, wide metabolome coverage has proven difficult to achieve, mostly because of the diverse physicochemical properties of small molecules, obligating analysts to seek multiplatform and multimethod approaches. Challenges are even greater when it comes to applications to tissue samples, where tissue lysis and metabolite extraction can induce significant systematic variation in composition. We have developed a pipeline for obtaining the aqueous and organic compounds from diseased arterial tissue using two consecutive extractions, followed by a different untargeted UPLC-MS analysis method for each extract. Methods were rationally chosen and optimized to address the different physicochemical properties of each extract: hydrophilic interaction liquid chromatography (HILIC) for the aqueous extract and reversed-phase chromatography for the organic. This pipeline can be generic for tissue analysis as demonstrated by applications to different tissue types. The experimental setup and fast turnaround time of the two methods contributed toward obtaining highly reproducible features with exceptional chromatographic performance (CV % < 0.5%), making this pipeline suitable for metabolic profiling applications. We structurally assigned 226 metabolites from a range of chemical classes (e.g., carnitines, α-amino acids, purines, pyrimidines, phospholipids, sphingolipids, free fatty acids, and glycerolipids) which were mapped to their corresponding pathways, biological functions and known disease mechanisms. The combination of the two untargeted UPLC-MS methods showed high metabolite complementarity. We demonstrate the application of this pipeline to cardiovascular disease, where we show that the analyzed diseased groups (n = 120) of arterial tissue could be distinguished based on their metabolic profiles. PMID:25664760

  13. Quantitation of leukotriene B(4) in human sputum as a biomarker using UPLC-MS/MS.

    PubMed

    Jian, Wenying; Edom, Richard W; Xue, Xiaohua; Huang, Mike-Qingtao; Fourie, Anne; Weng, Naidong

    2013-08-01

    Leukotriene B4 (LTB4) is a potent mediator of inflammation and has been recognized as an important target for therapeutic intervention for treatment of diseases such as asthma. In the current work, a highly selective and sensitive UPLC-MS/MS assay was developed for quantitation of LTB4 in human sputum as a biomarker for LTB4 biosynthesis inhibition. A fit-for-purpose strategy for method development, assay qualification, and study support was adopted for this biomarker project. A surrogate matrix (protein buffer) was used for preparation of calibration samples and certain levels of quality control (QC) samples to avoid interference from endogenous analyte, while the low QC was prepared in authentic matrix, human sputum. The analytical methodology utilized a liquid-liquid extraction procedure in 96-well plate format. Chromatographic separation was achieved with a reversed-phase ultra high pressure liquid chromatography (UPLC) column using gradient elution, and the run time was 4.5min per sample. The lower limit of quantitation (LLOQ) was 0.2ng/mL, and the calibration curve range was 0.2-20ng/mL. Acceptable accuracy, precision, linearity, specificity, recovery, and matrix effect was obtained. Bench-top stability (6h), freeze-thaw stability (3 cycles at -20°C), and autosampler stability (97h at ambient temperature) all met acceptance criteria. Frozen long-term stability for 166 days at -20°C in sputum did not meet acceptance criteria by showing only ≥75% of nominal concentration and the information was taken into consideration for study support. Two important observations in the current work were: (1) LTB4 was unstable in sputum in the presence of liquification reagent dithiothreitol (DTT). Therefore, a non-DTT treatment method for sputum processing was developed and applied to the bioanalytical assay and clinical study support; and (2) chromatographic separation of LTB4 from its three non-enzymatically derived isomers, i.e. 6-trans-LTB4, 12-epi-LTB4, and 6-trans-12-epi-LTB4, was achieved. This assay was successfully applied to a Phase II clinical study for proof-of-concept of a LTA4 hydrolase inhibitor for treatment of asthma. PMID:23831697

  14. A rapid and sensitive UPLC-MS/MS method for the simultaneous quantification of serum androsterone glucuronide, etiocholanolone glucuronide, and androstan-3α, 17β diol 17-glucuronide in postmenopausal women.

    PubMed

    Ke, Yuyong; Gonthier, Renaud; Isabelle, Maxim; Bertin, Jonathan; Simard, Jean-Nicolas; Dury, Alain Y; Labrie, Fernand

    2015-05-01

    Quantification of steroidal glucuronide conjugates by the indirect methods of immunoassay and GC-MS/MS may underestimate some conjugates since hydrolysis is needed in sample processing. In the present work, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous direct quantification of androsterone glucuronide, etiocholanolone glucuronide, and androstan-3α, 17β diol 17-glucuronide in postmenopausal women's serum. The quantification limits are 0.1ng/mL for 3α-diol-17G and 4ng/mL for both ADT-G and Etio-G, respectively, with an extraction from 200μL serum while the total run time is less than 6min for all three glucuronides. In this method, solid phase extraction is used for sample preparation. The assay has been validated in compliance with EndoCeutics SOPs and FDA guidelines for bioanalytical method development and validation. The recovery of glucuronides in stripped serum is consistent with that in unstripped serum, where the average difference in stripped and unstripped is less than 10%. A linear regression model fits well the standard curves of all three compounds with R≥0.99 where the weighting factor is 1/X. Interday accuracy and CV for all levels of QCs are within the range of 15% in both stripped and unstripped serum while all calibration curves are within the range of 6% except for LLOQs, which are within the range of 9%. Other parameters have also been assessed such as selectivity, matrix, lipemic and hemolysis effects as well as stabilities in solution and matrix. Incurred sample reanalysis has been performed with a result of over 93% within 20% of the original values. This reliable, sensitive and fast method is ready for large-scale clinical sample assays. PMID:25701608

  15. Development and validation of a sensitive UPLC-MS/MS method for the quantitation of [(13)C]sucrose in rat plasma, blood, and brain: Its application to the measurement of blood-brain barrier permeability.

    PubMed

    Miah, Mohammad K; Bickel, Ulrich; Mehvar, Reza

    2016-03-15

    Accurate and reproducible measurement of blood-brain barrier (BBB) integrity is critical in the assessment of the pathophysiology of the central nervous system disorders and in monitoring therapeutic effects. The widely-used low molecular weight marker [(14)C]sucrose is non-specific in the absence of chromatographic separation. The purpose of this study was to develop and validate a sensitive and reproducible LC-MS/MS method for the analysis of stable isotope-modified [(13)C12]sucrose in brain, plasma, and blood to determine BBB permeability to sucrose. After addition of internal standard (IS, [(13)C6]sucrose), the marker and IS were recovered from diluted rat blood, plasma, and brain homogenate by protein precipitation using acetonitrile. The recovery of the marker and IS was almost quantitative (90-106%) for all three matrices. The recovered samples were directly injected into an isocratic UPLC system with a run time of 6min. Mass spectrometry was conducted using multiple reaction monitoring in negative mode. The method was linear (r(2)≥0.99) in the concentration ranges tested for the diluted blood and plasma (10-1000ng/mL) and brain homogenate (1-200ng/mL). The lower limit of quantitation of the assay was 0.5pg injected on column. The assay was validated (n=5) based on acceptable intra- and inter-run accuracy and precision values. The method was successfully used for the measurement of serial blood and plasma and terminal brain concentrations of [(13)C12]sucrose after a single intravenous dose (10mg/kg) of the marker to rats. As expected, the apparent brain uptake clearance values of [(13)C12]sucrose were low in healthy rats. The method may be useful for determination of the BBB integrity in animal models. PMID:26919445

  16. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS

    PubMed Central

    Fitian, Asem I.; Nelson, David R.; Liu, Chen; Xu, Yiling; Ararat, Miguel; Cabrera, Roniel

    2014-01-01

    Background & Aims The metabolic pathway disturbances associated with hepatocellular carcinoma (HCC) remain unsatisfactorily characterized. Determination of the metabolic alterations associated with the presence of HCC can improve our understanding of the pathophysiology of this cancer and may provide opportunities for improved disease monitoring of patients at risk for HCC development. To characterize the global metabolic alterations associated with HCC arising from hepatitis C (HCV)-associated cirrhosis using an integrated non-targeted metabolomics methodology employing both gas chromatography/mass spectrometry (GC/MS) and ultrahigh-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC/MS-MS). Methods The global serum metabolomes of 30 HCC patients, 27 hepatitis C cirrhosis disease controls and 30 healthy volunteers were characterized using a metabolomics approach that combined two metabolomics platforms, GC/MS and UPLC/MS-MS. Random forest, multivariate statistics and receiver operator characteristic analysis were performed to identify the most significantly altered metabolites in HCC patients vs. HCV-cirrhosis controls and which therefore exhibited a close association with the presence of HCC. Results Elevated 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, sphingosine, γ-glutamyl oxidative stress-associated metabolites, xanthine, amino acids serine, glycine and aspartate, and a-cylcarnitines were strongly associated with the presence of HCC. Elevations in bile acids and dicarboxylic acids were highly correlated with cirrhosis. Conclusions Integrated metabolomic profiling through GC/MS and UPLC/MS-MS identified global metabolic disturbances in HCC and HCV-cirrhosis. Aberrant amino acid biosynthesis, cell turnover regulation, reactive oxygen species neutralization and eicosanoid pathways may be hallmarks of HCC. Aberrant dicarboxylic acid metabolism, enhanced bile acid metabolism and elevations in fibrinogen cleavage peptides may be signatures of cirrhosis. PMID:24661807

  17. A method for the direct injection and analysis of small volume human blood spots and plasma extracts containing high concentrations of organic solvents using revered-phase 2D UPLC/MS.

    PubMed

    Rainville, Paul D; Simeone, Jennifer L; Root, Dan S; Mallet, Claude R; Wilson, Ian D; Plumb, Robert S

    2015-03-21

    The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data quality, reduce animal usage, and save costs in safety assessment studies. The analysis of these samples presents new challenges for bioanalytical scientists, both in terms of sample processing and analytical sensitivity. The use of two dimensional LC/MS with, at-column-dilution for the direct analysis of highly organic extracts prepared from biological fluids such as dried blood spots and plasma is demonstrated. This technique negated the need to dry down and reconstitute, or dilute samples with water/aqueous buffer solutions, prior to injection onto a reversed-phase LC system. A mixture of model drugs, including bromhexine, triprolidine, enrofloxacin, and procaine were used to test the feasibility of the method. Finally an LC/MS assay for the probe pharmaceutical rosuvastatin was developed from dried blood spots and protein-precipitated plasma. The assays showed acceptable recovery, accuracy and precision according to US FDA guidelines. The resulting analytical method showed an increase in assay sensitivity of up to forty fold as compared to conventional methods by maximizing the amount loaded onto the system and the MS response for the probe pharmaceutical rosuvastatin from small volume samples. PMID:25655051

  18. Tissue distribution study of salvianolic acid B long-circulating liposomes in mice by UPLC-MS/MS determination.

    PubMed

    Pi, Jiaxin; Liu, Zhidong; Shu, Lexin; Li, Lin; Wang, Ying; Li, Nan; Li, Jiawei

    2015-01-01

    In targeting delivery system research on salvianolic acid B, it's vital but hard to evaluate the tissue distribution for its low concentrations in tissues. So the simple, rapid, selective and sensitive UPLC-MS/MS method was provided hereby to determine the concentration of salvianolic acid B in mice tissues after intravenous administration of salvianolic acid B injections, conventional liposomes and long-circulating liposomes. The UPLC was conducted by a C(18) column with a gradient mobile phase consisting of acetonitrile and water containing 0.1% formic acid. The tandem mass spectrometry was operated in negative-electrospray ionization selected-reaction-monitoring mode, and the optimized characteristic precursor to product ion transition m/z 717.3→519.1 was selected. The biosamples were homogenized and treated with a protein precipitation, which led to an acceptable matrix effect and extraction recovery. The linear calibration curves were plotted in the given concentration ranges. The intra-day and inter-day precisions were less than 13.9% and the accuracies were in the range of 86.3-109.2%. The tissue distribution results determined by UPLC-MS/MS we developed showed that the conventional and long-circulating liposomes we made had succeeded in prolonging the retention time and increasing the level of salvianolic acid B in certain distribution tissues such as liver, kidney and brain. PMID:25553697

  19. Tissue distribution model and pharmacokinetics of nuciferine based on UPLC-MS/MS and BP-ANN

    PubMed Central

    Xu, Yanyan; Bao, Shihui; Tian, Weiqiang; Wen, Congcong; Hu, Lufeng; Lin, Chongliang

    2015-01-01

    Nuciferine has shown remarkable biological activities and been considered as a promising drug. In this study, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of nuciferine in tissue and plasma. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 296.0→265.1 for nuciferine, and m/z 322.0→307.0 for berberrubine internal standard (IS). Based on the UPLC-MS/MS method, the tissue distribution profile of nuciferine in mice and plasma pharmacokinetics in rat were studied. The results showed nuciferine was absorbed through intestinal tract and distributed into tissues rapidly. The bioavailability of nuciferine was identified at 17.9%. It can across through blood brain barrier, the concentrations in liver and kidney are highest, then followed by spleen, lung heart and brain. Nuciferine is eliminated quickly in the tissues and plasma, the t1/2 within 5 hour. The concentrations in these tissues are correlated to each other, and can be predicted by a back-propagation artificial neural network model. PMID:26770351

  20. UPLC-MS/MS quantification of nanoformulated ritonavir, indinavir, atazanavir, and efavirenz in mouse serum and tissues

    PubMed Central

    Huang, Jiangeng; Gautam, Nagsen; Bathena, Sai Praneeth R; Roy, Upal; McMillan, JoEllyn; Gendelman, Howard E.; Alnouti, Yazen

    2011-01-01

    Animal pharmacokinetic and tissue distribution assays of antiretroviral therapeutic drugs require accurate drug quantification in biological fluids and tissues. Here we report a simple, rapid, and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of commonly used antiretroviral drugs ritonavir (RTV), indinavir (IDV), atazanavir (ATV), and efavirenz (EFV) in mouse serum and tissues (liver, kidney, lung, and spleen). These antiretroviral drugs are currently the cornerstones of common therapeutic regimens for human immunodeficiency virus (HIV) infection. Chromatographic separation was achieved using a gradient mobile phase (5% acetonitrile in methanol and 7.5 mM ammonium acetate (pH 4.0)) on an ACQUITY UPLC® BEH Shield RP 18 column. All compounds eluted within a seven min run time. Lopinavir was used as an internal standard. Detection was achieved by dual positive and negative ionization modes on a quadrupole linear ion trap hybrid mass spectrometer with an electrospray ionization (ESI) source. The dynamic range was 0.2–1000 ng/mL for RTV, IDV, and ATV, and 0.5–1000 for EFV. The method was validated and showed high and consistent intra-day and inter-day accuracy and precision for all analytes. This method is used to support the preclinical development studies of targeted- and sustained-release combination ART (nanoART). The current data demonstrate a 1.5–4 fold increase in serum and tissue AUC of nanoformulated ATV, RTV, and EFV administered to mice when compared to native drug. In addition, the tested formulation enhanced exposure of the same anti-HIV drugs in mouse tissues. PMID:21752731

  1. A Validated UPLC-MS-MS Assay for the Rapid Determination of Lorcaserin in Plasma and Brain Tissue Samples.

    PubMed

    Bajrai, Amal A; Ezzeldin, Essam; Al-Rashood, Khalid A; Raish, Mohammad; Iqbal, Muzaffar

    2016-03-01

    Lorcaserin is a novel, potent and highly efficacious 5-HT2C receptor agonist, recently approved by US Food and Drug Administration for the treatment of obesity. It has some abuse potential also and is listed as a Schedule IV drug in the Controlled Substances Act. Herein, a sensitive, selective and reliable UPLC-MS-MS assay was developed and validated for the quantitative analysis of lorcaserin in rat plasma and brain tissue using carbamazepine as an internal standard (IS). After the extraction of samples by protein precipitation, both lorcaserin and IS were separated on an Acquity BEH™ C18 (50 × 2.1 mm, 1.7 µm) column using a mobile phase consisting of acetonitrile-10 mM ammonium acetate-formic acid (85:15:0.1, v/v/v) at a flow rate of 0.25 mL/min. Detection and quantification were performed on a positive electrospray ionization interface in the multiple-reaction monitoring (MRM) mode. The MS-MS ion transitions were monitored at m/z 195.99 > 143.91 for lorcaserin and m/z 237.00 > 178.97 for IS, respectively. The calibration curves were linear over a concentration range of 1.08-500 ng/mL in plasma and 3.07-500 ng/mL in brain tissue homogenates, respectively. All the validation parameters results were within the acceptable range described in guidelines for bioanalytical method validation. The assay was successfully applied in a pharmacokinetic study of lorcaserin after oral administration in rats. PMID:26567546

  2. Detection of β-methylphenethylamine, a novel doping substance, by means of UPLC/MS/MS.

    PubMed

    Chołbiński, Piotr; Wicka, Mariola; Kowalczyk, Katarzyna; Jarek, Anna; Kaliszewski, Paweł; Pokrywka, Andrzej; Bulska, Ewa; Kwiatkowska, Dorota

    2014-06-01

    Novel substances of expected doping activity are constantly introduced to the market. β-Methylphenethylamine (BMPEA) is classified as a doping agent by the World Anti-Doping Agency as it is a positional isomer of amphetamine. In this work, the development and application of a simple and rapid analytical procedure that enables discrimination between both isomers is described. The analytes of interest were extracted from urine by a two-step liquid-liquid extraction and then analyzed by UPLC/MS/MS under isocratic conditions. The entire analytical procedure was validated by evaluating its selectivity, discrimination capabilities, carry-over, sensitivity, and influence of matrix effects on its performance. Application of the method resulted in detection of BMPEA in eight anti-doping samples, including the first report of adverse analytical finding regarding its use. Further analysis showed that BMPEA may be eliminated unchanged along with its phase II conjugates, the hydrolysis of which may considerably improve detection capabilities of the method. Omission of the hydrolysis step may therefore, produce false-negative results. Testing laboratories should also carefully examine their LC/MS/MS-based amphetamine and BMPEA findings as both isomers fragment yielding comparable collision-induced dissociation spectra and their insufficient chromatographic separation may result in misidentification. This is of great importance in case of forensic analyses as BMPEA is not controlled by the public law, and its manufacturing, distribution, and use are legal. PMID:24633566

  3. Pharmacokinetic study of indocyanine Green after intravenous administration by UPLC-MS/MS

    PubMed Central

    Chen, Yu; Chen, Dongxin; Hu, Wenhao; Lin, Guanyang; Huang, Shiyong

    2015-01-01

    Indocyanine Green is widely used in medical diagnosis and to evaluate liver function and other regional blood flows in clinical application or animal experiments. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of Indocyanine Green in rat plasma was developed and validated. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm 100 mm, 1.7 ?m) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 753.4?330.2 for Indocyanine Green, and m/z 611.1?303.1 for IS. Calibration plots were linear throughout the range 20-5000 ng/mL for Indocyanine Green in rat plasma. Mean recoveries of Indocyanine Green in rat plasma ranged from 79.5% to 85.4%. RSD of intra-day and inter-day precision were both < 12%. The accuracy of the method was between 95.9% and 113.9%. The method was successfully applied to pharmacokinetic study of Indocyanine Green after intravenous administration. PMID:26629038

  4. Ultra-performance liquid chromatography tandem mass-spectrometry (uplc-ms/ms) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel, rapid and sensitive Ultra Performance Liquid-Chromatography tandem Mass-Spectrometry (UPLC-MS/MS) method for the simultaneous determination of several B-vitamins in human milk was developed. Resolution by retention time or multiple reaction monitoring (MRM) for thiamin, riboflavin, flavin a...

  5. Determination of anthelmintic drug residues in milk using UPLC-MS/MS with rapid polarity switching

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new UPLC-MS/MS (ultra-performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added...

  6. Brain distribution pharmacokinetics and integrated pharmacokinetics of Panax Notoginsenoside R1, Ginsenosides Rg1, Rb1, Re and Rd in rats after intranasal administration of Panax Notoginseng Saponins assessed by UPLC/MS/MS.

    PubMed

    Guo, Qingli; Li, Pengyue; Wang, Zhen; Cheng, Yanke; Wu, Huichao; Yang, Bing; Du, Shouying; Lu, Yang

    2014-10-15

    Panax notoginseng saponins (PNS) constitute the main active components of a traditional Chinese medicine, Panax notoginseng (Burk.) F.H. Chen (Sanqi). To investigate brain distribution of Panax Notoginsenoside R1, Ginsenosides Rg1, Rb1, Re, and Rd, and the integrated PNS in rats, their contents in cortex, striatum, hypothalamus, medulla oblongata, hippocampus and olfactory bulb were simultaneously measured by UPLC-MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal Digoxin standard. The method described here was highly efficient, with short run time, excellent specificity and sensitivity, and successfully applied for pharmacokinetics studies. NGR1, GRg1, GRb1, GRe and GRd from PNS have been detected in all six brain regions studied and quantified accurately. These findings provide more insight for further understanding of the main ways from the nasal cavity to brain as well as the migration of nasally applied drugs into the CNS parenchyma. PMID:25203723

  7. An UPLC-MS/MS method for the analysis of glimepiride and fluoxetine in human plasma.

    PubMed

    Qiu, Xiangjun; Wang, Hong-wei; Yuan, Ye; Wang, Ying-fei; Sun, Ming; Huang, Xue-sun

    2015-02-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine glimepiride (GPD) and fluoxetine (FLU) in human plasma using diazepam as the internal standard (IS) simultaneously. The presented method used an Acquity UPLC BEH C18 column for chromatographic separation with tandem mass spectrometric detection on a QTrap5500 mass spectrometer operated in positive ESI mode. The mobile phase is a mixture of acetonitrile and 1% formic acid in water with gradient elution at a flow rate of 0.40mL/min. The GPD, FLU and IS were eluted at 1.46, 1.27 and 1.39min, respectively. The MRM transitions of m/z 491.3→126.3 and m/z 310.5→148.1 were used to quantify for GPD and FLU, respectively. The linearity of this method was found to be within the concentration range of 2.5-300ng/mL and 0.1-20ng/mL for GPD and FLU in human plasma, respectively. The intra- and inter-day precision (RSD%) were less than 10.3% and accuracy (RE%) was within ±7.3%. The matrix effect were 95.3-100.7% for GPD and FLU. GPD and FLU were sufficiently stable under all relevant analytical conditions. The method was also successfully applied to the clinical samples after a single oral dose of 2mg GLP and 40mg FLU in patients. PMID:25589252

  8. Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepatotoxicity.

    PubMed

    Gonzalez, Esperanza; van Liempd, Sebastiaan; Conde-Vancells, Javier; Gutierrez-de Juan, Virginia; Perez-Cormenzana, Miriam; Mayo, Rebeca; Berisa, Agustin; Alonso, Cristina; Marquez, Cesar A; Barr, Jonathan; Lu, Shelly C; Mato, Jose M; Falcon-Perez, Juan M

    2012-01-01

    A key interest in clinical diagnosis and pharmaceutical industry is to have a repertoire of noninvasive biomarkers to-individually or in combination-be able to infer or predict the degree of liver injury caused by pathological conditions or drugs. Metabolomics-a comprehensive study of global metabolites-has become a highly sensitive and powerful tool for biomarker discovery thanks to recent technological advances. An ultra-performance liquid chromatography/time-of-flight tandem mass spectrometry (UPLC/TOF MS/MS)-based metabolomics approach was employed to investigate sera from galactosamine-treated rats to find potential biomarkers for acute liver injury. Hepatic damage was quantified by determining serum transaminase activity and in situ liver histological lesions. Principal component analysis in combination with coefficient of correlation analysis was used for biomarker selection and identification. According to the data, serum levels of several metabolites including glucose, amino acids, and membrane lipids were significantly modified, some of them showing a high correlation with the degree of liver damage determined by histological examination of the livers. In conclusion, this study supports that UPLC-MS/MS based serum metabolomics in experimental animal models could be a powerful approach to search for biomarkers for drug- or disease-induced liver injury. PMID:23139648

  9. Removal of malathion from aqueous solution using De-Acidite FF-IP resin and determination by UPLC-MS/MS: equilibrium, kinetics and thermodynamics studies.

    PubMed

    Naushad, Mu; Alothman, Z A; Khan, M R

    2013-10-15

    In the present study, De-Acidite FF-IP resin was used to remove a highly toxic and persistent organophosphorus pesticide (malathion) from the aqueous solution. Batch experiments were performed as a function of various experimental parameters such as effect of pH (2-10), contact time (10-120 min), resin dose (0.05-0.5 g), initial malathion concentration (0.5-2.5 g mL(-1)) and temperature (25-65C). The concentration of malathion was determined using a sensitive, selective and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The uptake rate of malathion on De-Acidite FF-IP resin was rapid and equilibrium established within 40 min. Kinetics studies showed better applicability for pseudo-second-order model. The equilibrium data was fitted to Langmuir and Freundlich isotherm models and the isotherm constants were calculated for malathion. The values of thermodynamic parameters (?G(0), ?H(0) and ?S(0)) were computed from the Van't Hoff plot of lnKC vs. 1/T which showed that the adsorption of malathion was feasible, endothermic and spontaneous. The regeneration studies were carried out which demonstrated a decrease in the recovery of malathion from 95% to 68% after five consecutive cycles. Breakthrough and exhaustive capacities of malathion were found to be 1.25 mg g(-1) and 3.5 mg g(-1), respectively. PMID:24054556

  10. Simultaneous determination of 30 hormones illegally added to anti-ageing functional foods using UPLC-MS/MS coupled with SPE clean-up.

    PubMed

    He, Xiaoqin; Xi, Cunxian; Tang, Bobin; Wang, Guomin; Chen, Dongdong; Peng, Tao; Mu, Zhaode

    2014-01-01

    A novel analytical method employing solid-phase extraction (SPE) coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 30 hormones in anti-ageing functional foods (capsules, powders and tablets). The analytes were extracted with acetic acid-acetonitrile (1-99 v/v), methanol and acetone, respectively. The extract was purified using a combined column, followed by analyte detection with electrospray ionisation in positive- or negative-ion modes. The results indicated that the 30 compounds had good linear correlations in the range of 1-1000 μg kg⁻¹, and the correlation coefficients were above 0.99. The limits of detection (LOD) and limits of quantification (LOQ) were 0.03-2 and 0.1-5 μg kg⁻¹, respectively. The average recovery of 30 compounds at the three spiked levels varied from 74.7% to 124.1%, and the relative standard deviation (RSD) was 2.4-15.0%. This method was applied to the analysis of hormones in 14 real samples of which seven hormones (such as estrone, dienestrol) were detected in four samples, but the remainder of the hormones were not detected. The developed method is sensitive, efficient, reliable and applicable to real samples. PMID:25188907

  11. Rapid UPLC-MS/MS method for the determination of sufentanil in human plasma and its application in target-controlled infusion system.

    PubMed

    Liang, Lili; Wan, Shanhe; Xiao, Jinfang; Zhang, Jiajie; Gu, Miaoning

    2011-03-25

    A rapid, selective and highly sensitive ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of sufentanil in human plasma. Sufentanil was separated on an ACQUITY™ UPLC BEH C(18) column (50 mm × 2.1 mm, ID 1.7 μm) and analyzed in positive-ion (PI) electrospray-ionization (ESI) mode. The mobile phase (MP) consisted of acetonitrile:water (45:55, v/v) under isocratic conditions at a flow rate of 0.2 ml/min. Sufentanil and internal-standard (IS) fentanyl were eluted at 1.47 and 1.16 min, respectively, and their responses were optimized at the transitions m/z 387.2>238.0 and m/z 337.2>188.0, respectively. The calibration curve was linear over the range 0.071-4.56 ng/ml, with coefficients of determination >0.999. The accuracy and precision of the method were between 96.49% and 100.37% (RSD<9%), and the mean recovery of sufentanil was 84.08 ± 7.29%. The method was successfully applied to evaluate the predictive accuracy of Gepts pharmacokinetic sets in a target-controlled infusion (TCI) model, and the Gepts parameters were capable of predicting sufentanil plasma concentrations when multi-level target concentrations were acquired during surgery. PMID:21144689

  12. Simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by UPLC-MS/MS after QuEChERS preparation.

    PubMed

    Mu, Pengqian; Xu, Nana; Chai, Tingting; Jia, Qi; Yin, Zhiqiang; Yang, Shuming; Qian, Yongzhong; Qiu, Jing

    2016-06-15

    A fast method for the simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by ultra-high liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The analytes included anti-influenza drugs (amantadine, rimantadine, oseltamivir, oseltamivir carboxylate, memantine, arbidol, and moroxydine), anti-herpes drugs (acyclovir, ganciclovir, famciclovir, penciclovir, ribavirin and its main metabolite TCONH2), and an immunomodulator (imiquimod). The samples were pretreated using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. The determination of the target compounds was conducted in less than 11.0min, and specificity was ensured by the use of multiple reaction monitoring (MRM) acquisition mode. Good linearities (R(2)>0.9928) were obtained in the range of 0.1-100μg/L, and the recovery rates were 56.2-113.4% with RSDs of 1.7-10.3% for intra-day precision and 2.4-8.8% for inter-day precision. The LODs and LOQs of all analytes were in the ranges of 0.02-1.0 and 0.05-2.5μg/kg, respectively. An analysis of real samples suggested that this method is simple, sensitive, reliable and practical for the detection of antiviral drugs in animal tissue. PMID:27174693

  13. Development and Validation of a UPLC-MS/MS Method to Monitor Cephapirin Excretion in Dairy Cows following Intramammary Infusion

    PubMed Central

    Ray, Partha; Knowlton, Katharine F.; Shang, Chao; Xia, Kang

    2014-01-01

    Cephapirin, a cephalosporin antibiotic, is used by the majority of dairy farms in the US. Fecal and urinary excretion of cephapirin could introduce this compound into the environment when manure is land applied as fertilizer, and may cause development of bacterial resistance to antibiotics critical for human health. The environmental loading of cephapirin by the livestock industry remains un-assessed, largely due to a lack of appropriate analytical methods. Therefore, this study aimed to develop and validate a cephapirin quantification method to capture the temporal pattern of cephapirin excretion in dairy cows following intramammary infusion. The method includes an extraction with phosphate buffer and methanol, solid-phase extraction (SPE) clean-up, and quantification using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The LOQ values of the developed method were 4.02 µg kg−1 and 0.96 µg L−1 for feces and urine, respectively. This robust method recovered >60% and >80% cephapirin from spiked blank fecal and urine samples, respectively, with acceptable intra- and inter-day variation (<10%). Using this method, we detected trace amounts (µg kg−1) of cephapirin in dairy cow feces, and cephapirin in urine was detected at very high concentrations (133 to 480 µg L−1). Cephapirin was primarily excreted via urine and its urinary excretion was influenced by day (P = 0.03). Peak excretion (2.69 mg) was on day 1 following intramammary infusion and decreased sharply thereafter (0.19, 0.19, 0.08, and 0.17 mg on day 2, 3, 4, and 5, respectively) reflecting a quadratic pattern of excretion (Quadratic: P = 0.03). The described method for quantification of cephapirin in bovine feces and urine is sensitive, accurate, and robust and allowed to monitor the pattern of cephapirin excretion in dairy cows. This data will help develop manure segregation and treatment methods to minimize the risk of antibiotic loading to the environment from dairy farms. PMID:25375097

  14. UPLC-MS/MS assay for the simultaneous determination of ethinyl estradiol, norgestimate and 17-Desacetyl norgestimate at low pg/mL in human plasma.

    PubMed

    Huang, Mike-Qingtao; Kang, Lijuan; Wang, Weimin; Skee, Donna; Chen, Mu; Lin, Zhongping John; Verhaeghe, Tom; Weng, Naidong

    2016-04-01

    Previously, because of the difficulty of measuring very low levels (pg/mL) of norgestimate (NGM) due to rapid metabolism to its active and major metabolite, 17-Desacetyl norgestimate (DNGM), only DNGM and the co-administered ethinyl estradiol (EE2) were required to be analyzed in bioequivalence (BE) studies for oral contraceptive NGM/EE2 tablets. Recently, with more sensitive assays available, health authorities have requested that bioequivalence of NGM be also demonstrated in addition to DNGM and EE2. Therefore, it was important to establish a 3-in-1 method for the quantitation of EE2, NGM and DNGM in human plasma. Here a UPLC-MS/MS method for the simultaneous quantitation of EE2, NGM and DNGM in human plasma at low pg/mL range is described. EE2, NGM, DNGM and their isotopic labeled internal standards (IS) EE2-d4, NGM-d6 and DNGM-d6 in 0.4mL of human plasma were extracted with hexane/ethyl acetate. The extracts were evaporated to dryness and derivatized with dansyl chloride, to enhance the mass spec response. The derivatives were reconstituted with methanol and analyzed by UPLC-MS/MS. In order to minimize the ex-vivo conversion of NGM to DNGM, sodium fluoride/potassium oxalate was used as anti-coagulant. To achieve desirable throughput for sample analysis, UPLC-MS/MS with a run time of 4.4min was utilized. The calibration curve ranges were 5-500pg/mL for EE2 and NGM, and 25-2500pg/mL for DNGM, respectively. The chromatographic separation was achieved on a Waters Acquity UPLC HSS T3 (100×2.1mm, 1.8μm) column with a gradient elution. Assay accuracy, precision, linearity, selectivity, sensitivity and analyte stability covering sample storage and analysis were established. This validated UPLC-MS/MS method has been applied to a BE study for the determination of EE2, NGM and DNGM concentrations in human plasma. PMID:26930373

  15. Validated UPLC-MS/MS assay for the determination of synthetic phosphodiesterase type-5 inhibitors in postmortem blood samples.

    PubMed

    Proença, Paula; Mustra, Carla; Marcos, Mariana; Franco, João Miguel; Corte-Real, Francisco; Vieira, Duarte Nuno

    2013-08-01

    The use of synthetic phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of erectile dysfunction: sildenafil citrate (Viagra(®)), tadalafil (Cialis(®)) and vardenafil hydrochloride (Levitra(®)) has increased dramatically over the past 2 years. These substances are prescription drugs and must be used under medical supervision. However, they can easily be obtained over the internet from illegal sites, being a potential for a threat to public health. The development of an electrospray ionisation (ESI) ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) procedure for the simultaneous identification and quantification of three PDE5 inhibitors in blood samples was desired. Samples were prepared using Oasis(®) HLB solid-phase cartridges (3 cc, 60 mg) and chromatographic separation was achieved on an Acquity UPLC(®) HSS T3 (100 × 2.1 mm i.d., 1.8 μm particles) column with a gradient mobile phase of 0.1% formic acid and acetonitrile at a 0.5 mL/min flow rate. Quantification was achieved by multiple reaction monitoring (MRM) of two transitions per compound: m/z 475.1 > 58 e m/z 475.1 > 311.1 for sildenafil; m/z 389.9 > 267.9 e m/z 389.9 > 134.8 for tadalafil and m/z 489 > 71.9 e m/z 489 > 150.9 for vardenafil. Zolpidem-d6 (m/z 314.5 > 235.3) was used as the internal standard. Calibration curves were linear over the concentration range of 5-1000 ng/mL, with a coefficient of determination better than 0.997. The lower limits of detection and quantification for these substances were ≤ 3 ng/mL and ≤ 8 ng/mL, respectively. The method showed a satisfactory sensitivity, precision, accuracy, recovery and selectivity. A rapid, selective and sensitive UPLC-MS/MS method using solid-phase extraction was developed for the simultaneous determination and quantification of sildenafil, vardenafil and tadalafil in blood samples. PMID:23910856

  16. Simultaneous determination of four furostanol glycosides in rat plasma by UPLC-MS/MS and its application to PK study after oral administration of Dioscorea nipponica extracts.

    PubMed

    Liao, Min; Dai, Cong; Liu, Mengping; Chen, Jiefeng; Chen, Zuanguang; Xie, Zhiyong; Yao, Meicun

    2016-01-01

    A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for simultaneous quantification of four furostanol glycosides in rat plasma was established and validated. Ginsenoside Rb1 was used as an internal standard. Plasma samples were pretreated by liquid-liquid extraction with n-butanol and chromatographed on a C18 column (2.1×50 mm i.d., 2.6 μm) using a gradient elution program consisting of acetonitrile and water (containing 0.03% formic acid and 0.1 mM lithium acetate) at a flow rate of 0.4 mL/min. Lithium adduct ions were employed to enhance the response of the analytes in electrospray positive ionization mode and multiple reaction monitoring transitions were performed for detection. All calibration curves exhibited good linearity (r>0.999) over the range of 10-20,000 ng/mL for protodioscin and 2-4000 ng/mL for protogracillin, pseudoprotodioscin and pseudoprotogracillin. The recoveries of the whole analytes were more than 80.3% and exhibited no severe matrix effect. Meanwhile, the intra- and inter-day precisions were all less than 10.7% and accuracies were within the range of -8.1-12.9%. The four saponins showed rapid excretion and relative high plasma concentrations when the validated method was applied to the PK study of Dioscorea nipponica extracts by intragastric administration at low, medium and high dose to rats. Moreover, the T(1/2) and AUC(0-t) of each compound turned out to behave in a dose-dependent pattern by comparing them at different dose levels. PMID:26433169

  17. Pharmacokinetics of Dibutyl Phthalate (DBP) in the Rat Determined by UPLC-MS/MS

    PubMed Central

    Chang, Li-Wen; Hou, Mei-Ling; Tsai, Tung-Hu

    2013-01-01

    Dibutyl phthalate (DBP) is commonly used to increase the flexibility of plastics in industrial products. However, several plasticizers have been illegally used as clouding agents to increase dispersion of aqueous matrix in beverages. This study thus develops a rapid and validated analytical method by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) for the evaluation of pharmacokinetics of DBP in free moving rats. The UPLC-MS/MS system equipped with positive electrospray ionization (ESI) source in multiple reaction monitoring (MRM) mode was used to monitor m/z 279.25→148.93 transitions for DBP. The limit of quantification for DBP in rat plasma and feces was 0.05 μg/mL and 0.125 μg/g, respectively. The pharmacokinetic results demonstrate that DBP appeared to have a two-compartment model in the rats; the area under concentration versus time (AUC) was 57.8 ± 5.93 min μg/mL and the distribution and elimination half-life (t1/2,α and t1/2,β) were 5.77 ± 1.14 and 217 ± 131 min, respectively, after DBP administration (30 mg/kg, i.v.). About 0.18% of the administered dose was recovered from the feces within 48 h. The pharmacokinetic behavior demonstrated that DBP was quickly degraded within 2 h, suggesting a rapid metabolism low fecal cumulative excretion in the rat. PMID:23344044

  18. Rapid qualitative and quantitative analyses of proanthocyanidin oligomers and polymers by UPLC-MS/MS.

    PubMed

    Engström, Marica T; Pälijärvi, Maija; Fryganas, Christos; Grabber, John H; Mueller-Harvey, Irene; Salminen, Juha-Pekka

    2014-04-16

    This paper presents the development of a rapid method with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the qualitative and quantitative analyses of plant proanthocyanidins directly from crude plant extracts. The method utilizes a range of cone voltages to achieve the depolymerization step in the ion source of both smaller oligomers and larger polymers. The formed depolymerization products are further fragmented in the collision cell to enable their selective detection. This UPLC-MS/MS method is able to separately quantitate the terminal and extension units of the most common proanthocyanidin subclasses, that is, procyanidins and prodelphinidins. The resulting data enable (1) quantitation of the total proanthocyanidin content, (2) quantitation of total procyanidins and prodelphinidins including the procyanidin/prodelphinidin ratio, (3) estimation of the mean degree of polymerization for the oligomers and polymers, and (4) estimation of how the different procyanidin and prodelphinidin types are distributed along the chromatographic hump typically produced by large proanthocyanidins. All of this is achieved within the 10 min period of analysis, which makes the presented method a significant addition to the chemistry tools currently available for the qualitative and quantitative analyses of complex proanthocyanidin mixtures from plant extracts. PMID:24665824

  19. Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC-MS/MS.

    PubMed

    Wang, Xianqin; Wang, Shuanghu; Lin, Feiyan; Zhang, Qingwei; Chen, HuiLing; Wang, Xianchuan; Wen, Congcong; Ma, Jianshe; Hu, Lufeng

    2015-03-01

    Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal-epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5-5000ng/mL (r(2)>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC-MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration-time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues. PMID:25638029

  20. Ultrafast quantification of ?-lactam antibiotics in human plasma using UPLC-MS/MS.

    PubMed

    Carlier, Mieke; Stove, Veronique; De Waele, Jan J; Verstraete, Alain G

    2015-01-26

    There is an increasing interest in monitoring plasma concentrations of ?-lactam antibiotics. The objective of this work was to develop and validate a fast ultra-performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS) for simultaneous quantification of amoxicillin, cefuroxime, ceftazidime, meropenem and piperacillin with minimal turn around time. Sample clean-up included protein precipitation with acetonitrile containing 5 deuterated internal standards, and subsequent dilution of the supernatant with water after centrifugation. Runtime was only 2.5 min. Chromatographic separation was performed on a Waters Acquity UPLC system using a BEH C18 column (1.7 ?m, 100 mm 2.1 mm) applying a binary gradient elution of water and methanol both containing 0.1% formic acid and 2 mmol/L ammonium acetate on a Water TQD instrument in MRM mode. All compounds were detected in electrospray positive ion mode and could be quantified between 1 and 100 mg/L for amoxicillin and cefuroxime, between 0.5 and 80 mg/L for meropenem and ceftazidime, and between 1 and 150 mg/L for piperacillin. The method was validated in terms of precision, accuracy, linearity, matrix effect and recovery and has been compared to a previously published UPLC-MS/MS method. PMID:25531875

  1. Simultaneous determination of mangiferin and neomangiferin in rat plasma by UPLC-MS/MS and its application for pharmacokinetic study.

    PubMed

    Qiu, Xiangjun; Zhao, Jian-Long; Hao, Cong; Yuan, Canli; Tian, Nuan; Xu, Zhi-Sheng; Zou, Ruan-Min

    2016-05-30

    In this study, a sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine mangiferin and neomangiferin in rat plasma simultaneously. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a Xevo TQD triple quadruple mass spectrometer coupled with an electrospray ionization (ESI) source. The MRM transitions of m/z 423.2→303.1 and m/z 585.0→273.1 were used to quantify for mangiferin and neomangiferin, respectively. The linearity of this method was found to be within the concentration range of 5-2000ng/mL for mangiferin, and 2-1000ng/mL for neomangiferin in rat plasma, respectively. Only 3.0min was needed for an analytical run. This assay was used to support a preclinical study to investigate the pharmacokinetics of mangiferin and neomangiferin in rats. PMID:26945635

  2. Monitoring sea lamprey pheromones and their degradation using rapid stream-side extraction coupled with UPLC-MS/MS

    USGS Publications Warehouse

    Wang, Huiyong; Johnson, Nicholas; Bernardy, Jeffrey; Hubert, Terry; Li, Weiming

    2013-01-01

    Pheromones guide adult sea lamprey (Petromyzon marinus) to suitable spawning streams and mates, and therefore, when quantified, can be used to assess population size and guide management. Here, we present an efficient sample preparation method where 100 mL of river water was spiked with deuterated pheromone as an internal standard and underwent rapid field-based SPE and elution in the field. The combination of field extraction with laboratory UPLC-MS/MS reduced the sample consumption from 1 to 0.1 L, decreased the sample process time from more than 1 h to 10 min, and increased the precision and accuracy. The sensitivity was improved more than one order of magnitude compared with the previous method. The influences of experimental conditions were assessed to optimize the separation and peak shapes. The analytical method has been validated by studies of stability, selectivity, precision, and linearity and by the determination of the limits of detection and quantification. The method was used to quantify pheromone concentration from five streams tributary to Lake Ontario and to estimate that the environmental half-life of 3kPZS is about 26 h.

  3. UPLC-MS-MS Determination of Dihydrocodeine in Human Plasma and Its Application to a Pharmacokinetic Study.

    PubMed

    Zhang, Wei-Min; Duan, Yan-Pei; Li, Wei; Qiu, Jian-Fei; Zhang, Zhi-Yin

    2016-04-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method was developed to determine dihydrocodeine (DHC) in human plasma using diazepam as the internal standard (IS). Sample preparation was accomplished through a liquid-liquid extraction procedure with ethyl acetate. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) with the mobile phase of acetonitrile and 1% formic acid in water with gradient elution at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with positive-ion electrospray ionization by multiple reaction monitoring (MRM) of the transitions at m/z 302.3 → 199.2 for DHC and m/z 285.1 → 193.1 for IS. The linearity of this method was found to be within the concentration range of 0.5-100 ng/mL with a lower limit of quantification of 0.5 ng/mL. The overall run time was 4.0 min. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of DHC in healthy Chinese volunteers after oral administration. PMID:26689716

  4. Preclinical pharmacokinetics and tissue distribution of a novel multikinase inhibitor BZG by validated UPLC-MS/MS assay.

    PubMed

    Lou, Yan; Wang, Li; Qian, Qinbin; You, Jian; Qiu, Wenqi; Wang, Qian; Zhu, Kundan; Qiu, Yunqing

    2016-03-20

    A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of BZG in rat plasma and tissues. All biological samples were prepared by protein precipitation method using Imatinib as an internal standard (IS). The analyte and IS were separated on a C18 reverse phase analytical column with 4.5min of analytical run, at flow rate of 0.3mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 451.0→254.0 for BZG and m/z 494.3→394.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 0.5-2500ng/mL with a lower limit of quantification of 0.5ng/mL. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The method was successfully applied to a pharmacokinetic and tissue distribution study of BZG in rats. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of BZG. PMID:26799978

  5. Determination of Sertraline in Human Plasma by UPLC-MS/MS and its Application to a Pharmacokinetic Study.

    PubMed

    Yue, Xiao-Hong; Wang, Zhen; Tian, Dong-Dong; Zhang, Jian-Wei; Zhu, Kang; Ye, Qiang

    2016-02-01

    A sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method was developed to determine sertraline in human plasma. Sample preparation was accomplished through a simple liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using a gradient mobile phase system composed of acetonitrile and 1% formic acid in water at a flow rate of 0.40 mL/min. Mass spectrometric analysis was performed using a XEVO TQD mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 306.3 → 275.2 and 326.2 → 291.1 were used to quantify for sertraline and midazolam (internal standard), respectively. The linearity of this method was found to be within the concentration range of 1.0-100.0 ng/mL with a lower limit of quantification of 1.0 ng/mL. Only 2.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after an oral administration of 100 mg sertraline to 20 Chinese healthy male volunteers. PMID:26324195

  6. UPLC-MS/MS determination of ractopamine residues in retinal tissue of treated food-producing pigs.

    PubMed

    Vulić, Ana; Pleadin, Jelka; Perši, Nina; Milić, Dinka; Radeck, Wolfgang

    2012-05-01

    Ractopamine is a β(2)-adrenergic agonist, which reduces fat deposition and promotes muscle growth in animals for meat production. In the European Union countries, systematic monitoring and control of this contaminant residue is regularly performed by use of validated analytical methods of detection in different biological materials. The aim of the present study was to assess persistence of ractopamine in retina as a pigmented tissue by determination of its residues using UPLC-MS/MS as a quantitative confirmatory method after pig exposure to a ractopamine dose of 0.51 mg/kg b.w. Experimental group (n=9) of pigs were orally administered ractopamine for 28 days and then randomly sacrificed (n=3) on days 1, 3 and 8 of treatment discontinuation, whereas control animals (n=3) were left untreated. Study results showed mean ractopamine residue concentrations of 110.36 μg/kg, 67.11 μg/kg and 89.93 μg/kg on days 1, 3 and 8 after withdrawal, respectively, indicating high accumulation of ractopamine in retina despite a low dose applied. These data pointed to high affinity of ractopamine for binding to the pigmented segment of the eye, thus supporting the use of pigmented tissues as matrices in the regulatory monitoring of this β(2)-adrenergic agonist. PMID:22483331

  7. Rapid quantification of quinine and its major metabolite (3S)-3-hydroxyquinine in diluted urine by UPLC-MS/MS.

    PubMed

    Heaton, James; Rahmioglu, Nilufer; Ahmadi, Kourosh R; Legido-Quigley, Cristina; Smith, Norman W

    2011-06-01

    A rapid UPLC-MS/MS quantitative assay for the quantification of quinine and (3S)-3-hydroxyquinine requiring minimal sample pre-treatment - dilute-and-shoot type approach - has been developed. The assay was run at 0.6mL/min using gradient elution with (pH 10; 10mM) ammonium bicarbonate and methanol with a total cycle time of 2.5min on a 50mm×2.1mm ID, 1.7μm Acquity BEH column. Peak shapes were highly symmetrical allowing for accurate peak integration. Calibration curves for both analytes were constructed from 1.00 to 20.00ng/mL, yielding R(2) values >0.995. Intra- and inter-batch assay precision and accuracy were evaluated using 6 injections of QC solutions on 3 separate days (n=18) and were found to be within ±10% and 90-110% respectively. The method was shown to be suitable for quantitatively determining the ratio of quinine to (3S)-3-hydroxyquinine for a cohort of samples from an epidemiological study. PMID:21377309

  8. Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats.

    PubMed

    Basu, Sumit; Zeng, Min; Yin, Taijun; Gao, Song; Hu, Ming

    2016-03-15

    The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN-38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats. Irinotecan, SN-38 and SN-38 glucuronide has been resolved and separated by C18 column using acetonitrile and 0.1% formic acid in water used as the mobile phases. Triple quadruple mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode were employed to perform mass analysis. The results showed that the linear response range of irinotecan and SN-38 in plasma, feces, liver and kidney is 4.88-10000nM, 39-5000nM, 48.8-6250nM and 48.8-6250nM, respectively (R(2)>0.99). In case of SN-38 glucuronide, the standard curves were linear in the concentration range of 6.25-2000nM, 4.88-1250nM, 9.8-1250nM and 9.8-1250nM in plasma, feces, liver and kidney homogenates, respectively. The lower limit of detection (LLOD) of irinotecan, SN-38 and SN-38 glucuronide was determined to be less than 25nM in all bio-matrices as well as tissue homogenates. Recoveries of irinotecan, SN-38 and SN-38 glucuronide at three different concentrations (low, medium and high) were not less than 85% at three different concentrations in plasma and feces. The percentage matrix factors in different bio-matrices and tissues were within 20%. The UPLC-MS/MS method was validated with intra-day and inter-day precision of less than 15% in plasma, feces, liver and kidney. Owing to the high sensitivity of this method, only 20μl of plasma, urine and homogenates of liver, kidney and feces is needed. The validated method has been successfully employed for pharmacokinetic evaluation of irinotecan in male wistar rats to quantify irinotecan, SN-38 and SN-38 glucuronide in plasma, feces, and urine samples. PMID:26894853

  9. Free amino acid profiling in the giant puffball mushroom (Calvatia gigantea) using UPLC-MS/MS.

    PubMed

    Kıvrak, İbrahim; Kıvrak, Şeyda; Harmandar, Mansur

    2014-09-01

    Wild edible and medicinal mushroom, Calvatia gigantea, was quantitatively analyzed for the determination of its free amino acids using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The concentrations of total free amino acids, essential and non-essential amino acids were 199.65 mg/100 g, 113.69 mg/100 g, and 85.96 mg/100 g in C. gigantea, respectively. This study showed that C. gigantea, so called a giant puffball mushroom, has free amino acids content. The essential amino acids: tryptophan, isoleucine, valine, phenylalanine, leucine, threonine, lysine, histidine, methionine, and the non-essential amino acids: tyrosine, 4-hyrdroxy proline, arginine, proline, glycine, serine, alanine, glutamine, glutamic acid, aspargine, aspartic acid were detected. PMID:24731318

  10. DETERMINATION OF ECOLOGICALLY RELEVANT PHARMACEUTICALS AND THEIR SELECTED METABOLITES IN EFFLUENT AND SURFACE WATER USING UPLC/MS/MS

    EPA Science Inventory

    Objective is to develop analytical methods including SPE and UPLC/MS/MS needed to analyze over 60 human prescription pharamceuticals and metabolites belonging to a multitude of different classes in surface waters and wastewater effluent. The methods will be used in future studies...

  11. Determination of a potential antitumor quassinoid in rat plasma by UPLC-MS/MS and its application in a pharmacokinetic study.

    PubMed

    Zhang, Qiang; Yuan, Yonghui; Cui, Jianchun; Xiao, Tingting; Deng, Zhipeng; Jiang, Daqing

    2016-05-30

    A sensitive UPLC-MS/MS method was developed and validated for the determination of brusatol in rat plasma. Chromatographic separation was carried out on a C18 column using methanol and 10mM ammonium acetate containing 0.1% (v/v) formic acid (55:45, v/v). The lower limit of quantification (LLOQ) was 1.0ng/mL for brusatol in plasma. The intra- and inter-day precision for the analyte ranged from 3.2% to 9.2% and 1.3% to 7.8%, and the accuracy was between 97.3% and 108.5%. The method was successfully applied in a pharmacokinetic study of brusatol following intravenous injection (0.5, 1.0, and 2.0mg/kg) of brusatol. PMID:26945636

  12. A method of analysis for T-2 toxin and neosolaniol by UPLC-MS/MS in apple fruit inoculated with Trichothecium roseum.

    PubMed

    Tang, Yamei; Xue, Huali; Bi, Yang; Li, Yongcai; Wang, Yi; Zhao, Ying; Shen, Keping

    2015-01-01

    Trichothecenes are one of the most important groups of mycotoxins produced by Trichothecium roseum, which causes core rot of apple. A reliable and sensitive method was developed and successfully applied for the rapid detection of trichothecenes including T-2 toxin and neosolaniol in harvested apple using UPLC-MS/MS. After the extraction of the two mycotoxins from the apple matrix with methanol/water (80/20, v/v), the concentrated extracts were cleaned-up by PriboFast M270 columns and then analysed by UPLC-MS/MS. T-2 toxin and neosolaniol were effectively separated as unique peaks. The validity of this method was established by its linearity (R(2) ≥ 0.9995), precision (relative standard deviation ≤ 3.6%), accuracy, selectivity, limit of detection of 2-5 μg kg(-1), limit of quantification of 5-10 μg kg(-1) and average recovery of 73-96%. Levels of T-2 toxin were found in the range 7.1-128.4 µg kg(-1) in the core rot lesion of three cultivars apple (cvs. Red Delicious, Fuji and Ralls). T-2 was detected not only in the lesion, but also in the tissue without any disease symptoms. However, neosolaniol was only detected in the lesion on 'Red Delicious' apples. In addition, the concentration of T-2 toxin in the susceptible cultivar (cv. Fuji) was significantly higher than that in the resistant one (cv. Ralls). This method proved to be suitable at detecting T-2 and neosolaniol simultaneously in apples infected with T. roseum. PMID:25254921

  13. Quantitative UPLC-MS/MS analysis of the gut microbial co-metabolites phenylacetylglutamine, 4-cresyl sulphate and hippurate in human urine: INTERMAP Study

    PubMed Central

    Wijeyesekera, Anisha; Clarke, Philip A.; Bictash, Magda; Brown, Ian J.; Fidock, Mark; Ryckmans, Thomas; Yap, Ivan K. S.; Chan, Queenie; Stamler, Jeremiah; Elliott, Paul; Holmes, Elaine; Nicholson, Jeremy K.

    2013-01-01

    The role of the gut microbiome in human health, and non-invasive measurement of gut dysbiosis are of increasing clinical interest. New high-throughput methods are required for the rapid measurement of gut microbial metabolites and to establish reference ranges in human populations. We used ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) -- positive and negative electrospray ionization modes, multiple reaction monitoring transitions -- to simultaneously measure three urinary metabolites (phenylacetylglutamine, 4-cresyl sulphate and hippurate) that are potential biomarkers of gut function, among multi-ethnic US men and women aged 40–59 from the INTERMAP epidemiologic study (n = 2000, two timed 24-hr urine collections/person). Metabolite concentrations were quantified via stable isotope labeled internal standards. The assay was linear in the ranges 1ng/mL (lower limit of quantification) to 1000ng/mL (phenylacetylglutamine and 4-cresyl sulfate) and 3ng/mL to 3000ng/mL (hippurate). These quantitative data provide new urinary reference ranges for population-based human samples: mean (standard deviation) 24-hr urinary excretion for phenylacetylglutamine was: 1283.0 (751.7) μmol/24-hr (men), 1145.9 (635.5) μmol/24-hr (women); for 4-cresyl sulphate, 1002.5 (737.1) μmol/24-hr (men), 1031.8 (687.9) μmol/24-hr (women); for hippurate, 6284.6 (4008.1) μmol/24-hr (men), 4793.0 (3293.3) μmol/24-hr (women). Metabolic profiling by UPLC-MS/MS in a large sample of free-living individuals has provided new data on urinary reference ranges for three urinary microbial co-metabolites, and demonstrates the applicability of this approach to epidemiological investigations. PMID:23946767

  14. Validation data for the quantification of the Annonaceous acetogenin annonacin in Rat brain by UPLC-MS/MS.

    PubMed

    Bonneau, Natacha; Schmitz-Afonso, Isabelle; Brunelle, Alain; Touboul, David; Champy, Pierre

    2016-06-01

    Annonaceous acetogenins (AAGs) are environmental neurotoxins from the fruit pulp of several Annonaceae species, whose consumption was linked to the occurrence of sporadic atypical Parkinsonism with dementia. The quantification of the prototypical AAG annonacin in Rat brain homogenates was performed by UPLC-MS/MS in selected reaction monitoring (SRM) mode, using a triple quadrupole mass analyzer. A natural analog of annonacin was used as an internal standard. Analyzed data set of the analytical validation of this method is presented, including stability of the samples, extraction recovery and matrix effect, supporting the results described in the article "Quantification of the environmental neurotoxin annonacin in Rat brain by UPLC-MS/MS" N. Bonneau, I. Schmitz-Afonso, D. Touboul, A. Brunelle, P. Champy (2016) [1]. PMID:27222866

  15. Validation data for the quantification of the Annonaceous acetogenin annonacin in Rat brain by UPLC-MS/MS

    PubMed Central

    Bonneau, Natacha; Schmitz-Afonso, Isabelle; Brunelle, Alain; Touboul, David; Champy, Pierre

    2016-01-01

    Annonaceous acetogenins (AAGs) are environmental neurotoxins from the fruit pulp of several Annonaceae species, whose consumption was linked to the occurrence of sporadic atypical Parkinsonism with dementia. The quantification of the prototypical AAG annonacin in Rat brain homogenates was performed by UPLC-MS/MS in selected reaction monitoring (SRM) mode, using a triple quadrupole mass analyzer. A natural analog of annonacin was used as an internal standard. Analyzed data set of the analytical validation of this method is presented, including stability of the samples, extraction recovery and matrix effect, supporting the results described in the article “Quantification of the environmental neurotoxin annonacin in Rat brain by UPLC-MS/MS” N. Bonneau, I. Schmitz-Afonso, D. Touboul, A. Brunelle, P. Champy (2016) [1].

  16. Determination of Glucocorticoids in UPLC-MS in Environmental Samples from an Occupational Setting

    PubMed Central

    Oddone, Enrico; Negri, Sara; Bellinzona, Massimo; Martino, Silvia; Di Tuccio, Marcello; Grignani, Elena; Cottica, Danilo; Imbriani, Marcello

    2015-01-01

    Occupational exposures to glucocorticoids are still a neglected issue in some work environments, including pharmaceutical plants. We developed an analytical method to quantify simultaneously 21 glucocorticoids using UPLC coupled with mass spectrometry to provide a basis to carry out environmental monitoring. Samples were taken from air, hand-washing tests, pad-tests and wipe-tests. This paper reports the contents of the analytical methodology, along with the results of this extensive environmental and personal monitoring of glucocorticoids. The method in UPLC-MS turned out to be suitable and effective for the aim of the study. Wipe-test and pad-test desorption was carried out using 50 mL syringes, a simple technique that saves time without adversely affecting analyte recovery. Results showed a widespread environmental pollution due to glucocorticoids. This is of particular concern. Evaluation of the dose absorbed by each worker and identification of a biomarker for occupational exposure will contribute to assessment and prevention of occupational exposure. PMID:25821468

  17. Simultaneous Analysis of Cannabinoid and Synthetic Cannabinoids in Dietary Supplements Using UPLC with UV and UPLC-MS-MS.

    PubMed

    Heo, Seok; Yoo, Geum Joo; Choi, Ji Yeon; Park, Hyoung Joon; Do, Jung-Ah; Cho, Sooyeul; Baek, Sun Young; Park, Sung-Kwan

    2016-06-01

    The primary purpose of this study was to develop and validate a method based on UPLC with UV and UPLC-MS-MS for the simultaneous analysis of different cannabinoids and synthetic cannabinoids in food as well as in herbal and dietary supplements. The limits of detection and quantitation of the method ranged from 0.1 to 0.3 and 0.3 to 0.9 μg/mL by UPLC with UV, respectively. The coefficient of determination was >0.999; the intra- and interday precision of the method were 0.1-3.7 and 0.9-4.1%, respectively. The intra- and interday accuracy were 94.8-103.1 and 98.3-100.9%, respectively. The mean recoveries of nine cannabinoids obtained from tablet samples ranged from 81.1 to 105.4%. The mean extraction recoveries of nine target cannabinoids obtained from various types of samples (tablets, capsules, powders, liquids, cookies and candies) ranged from 82.26 to 112.40%. The relative standard deviation (RSD) of the stability of the prepared sample solutions was <1.80%. Identification and quantification of the nine cannabinoids were accomplished by ion spray UPLC-MS-MS using multiple reaction monitoring. The UPLC-MS-MS method was validated for linearity (R(2) > 0.99); the precision was 0.1-4.0% (intraday) and 0.1-2.8% (interday), and the accuracy was 98.0-103.5% (intraday) and 97.1-103.2% (interday). The mean extraction recoveries of six types of samples were 82.2-114.5% and the RSD of stability was <6.54%, complying with the established international guidelines. The results indicated that the method can be used for rapid and accurate screening of cannabinoids present in food. PMID:27185817

  18. Determination of a novel anticancer c-Met inhibitor LS-177 in rat plasma and tissues with a validated UPLC-MS/MS method: application to pharmacokinetics and tissue distribution study.

    PubMed

    Ju, Ping; Liu, Zhenzhen; Jiang, Yu; Zhao, Simin; Zhang, Lunhui; Zhang, Yuanyuan; Gu, Liqiang; Tang, Xing; Bi, Kaishun; Chen, Xiaohui

    2015-07-01

    LS-177 is a novel small-molecule kinase inhibitor employed to interrupt the c-Met signaling pathway. A rapid and sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of LS-177 in rat plasma and tissues. The biosamples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a C18 column (50 × 4.6 mm, 2.6 µm) using a gradient elution mobile phase consisting of acetonitrile-0.1% formic acid water. Under the optimal conditions, the selectivity of the method was satisfactory with no endogenous interference. The intraday and interday precisions (relative standard deviation) were <10.5% and the accuracy (relative error) was from -12.5 to 12.5% at all quality control levels. Excellent recovery and negligible matrix effects were observed. Stability studies showed that LS-177 was stable during the preparation and analytical processes. The UPLC-MS/MS method was successfully applied to pharmacokinetic and tissue distribution studies. The results indicated that there was no significant drug accumulation after multiple-dose oral administration of LS-177. The tissue distribution study exhibited significant higher uptakes of LS-177 in stomach, intestine, lung and liver among all of the tissues. The results in pharmacokinetics and tissue distribution may provide a meaningful basis for clinical application. PMID:25472760

  19. A reversed-phase capillary ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for comprehensive top-down/bottom-up lipid profiling

    PubMed Central

    Gao, Xiaoli; Zhang, Qibin; Meng, Da; Issac, Giorgis; Zhao, Rui; Fillmore, Thomas L.; Chu, Rosey K.; Zhou, Jianying; Tang, Keqi; Hu, Zeping; Moore, Ronald J.; Smith, Richard D.; Katze, Michael G.; Metz, Thomas O.

    2012-01-01

    Lipidomics is a critical part of metabolomics and aims to study all the lipids within a living system. We present here the development and evaluation of a sensitive capillary UPLC-MS method for comprehensive top-down/bottom-up lipid profiling. Three different stationary phases were evaluated in terms of peak capacity, linearity, reproducibility, and limit of quantification (LOQ) using a mixture of lipid standards representative of the lipidome. The relative standard deviations of the retention times and peak abundances of the lipid standards were 0.29% and 7.7%, respectively, when using the optimized method. The linearity was acceptable at >0.99 over 3 orders of magnitude, and the LOQs were sub-fmol. To demonstrate the performance of the method in the analysis of complex samples, we analyzed lipids extracted from a human cell line, rat plasma, and a model human skin tissue, identifying 446, 444, and 370 unique lipids, respectively. Overall, the method provided either higher coverage of the lipidome, greater measurement sensitivity, or both, when compared to other approaches of global, untargeted lipid profiling based on chromatography coupled with MS. PMID:22354571

  20. UPLC-MS/MS-Based Profiling of Eicosanoids in RAW264.7 Cells Treated with Lipopolysaccharide.

    PubMed

    Lee, Jae Won; Mok, Hyuck Jun; Lee, Dae-Young; Park, Seung Cheol; Ban, Myeong Soon; Choi, Jehun; Park, Chun Geon; Ahn, Young-Sup; Kim, Kwang Pyo; Kim, Hyung Don

    2016-01-01

    While both the pro- and anti-inflammatory effects of several eicosanoids have been widely studied, the degree of inflammation in cells that results from various eicosanoids has yet to be comprehensively studied. The objective of this study was to assess the effect of lipopolysaccharide (LPS) treatment on eicosanoid content in RAW264.7 cells. An Ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)-based profiling method was used to analyze the eicosanoid contents of RAW264.7 cells treated with different LPS concentrations. The profiling data were subjected to statistical analyses, such as principal component analysis (PCA) and hierarchical clustering analysis. LPS treatment increased nitric oxide production and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in a concentration-dependent manner. In total, 79 eicosanoids were identified in the cells. RAW264.7 cells treated with different LPS concentrations were well differentiated in the PCA score plot. A heatmap was used to identify the eicosanoids that were up- or down-regulated according to the degree of inflammation and LPS concentration. Thirty-nine eicosanoids were upregulated and seven were down-regulated by LPS treatment in a concentration-dependent manner. Our novel UPLC-MS/MS technique can profile eicosanoids, and can evaluate the correlations between inflammation and eicosanoid metabolism. PMID:27058537

  1. Determination of Asymmetric and Symmetric Dimethylarginine in Serum from Patients with Chronic Kidney Disease: UPLC-MS/MS versus ELISA.

    PubMed

    Boelaert, Jente; Schepers, Eva; Glorieux, Griet; Eloot, Sunny; Vanholder, Raymond; Lynen, Frédéric

    2016-01-01

    Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, and its structural isomer symmetric dimethylarginine (SDMA) are uremic toxins accumulating in chronic kidney disease (CKD) patients. The objective of this study was to develop and validate a robust UPLC-MS/MS method for the simultaneous determination of ADMA and SDMA in human serum. Chromatographic separation after butyl ester derivatization was achieved on an Acquity UPLC BEH C18 column, followed by tandem mass spectrometric detection. After validation, the applicability of the method was evaluated by the analysis of serum samples from 10 healthy controls and 77 CKD patients on hemodialysis (CKD5HD). Both ADMA (0.84 ± 0.19 µM vs. 0.52 ± 0.07 µM) and SDMA concentrations (2.06 ± 0.82 µM vs. 0.59 ± 0.13 µM) were significantly (p < 0.001) elevated in CKD5HD patients compared to healthy controls. In general, low degrees of protein binding were found for both ADMA and SDMA. In addition, an established commercially available ELISA kit was utilized on the same samples (n = 87) to compare values obtained both with ELISA and UPLC-MS/MS. Regression analysis between these two methods was significant (p < 0.0001) but moderate for both ADMA (R = 0.78) and SDMA (R = 0.72). PMID:27187471

  2. UPLC-MS/MS-Based Profiling of Eicosanoids in RAW264.7 Cells Treated with Lipopolysaccharide

    PubMed Central

    Lee, Jae Won; Mok, Hyuck Jun; Lee, Dae-Young; Park, Seung Cheol; Ban, Myeong Soon; Choi, Jehun; Park, Chun Geon; Ahn, Young-Sup; Kim, Kwang Pyo; Kim, Hyung Don

    2016-01-01

    While both the pro- and anti-inflammatory effects of several eicosanoids have been widely studied, the degree of inflammation in cells that results from various eicosanoids has yet to be comprehensively studied. The objective of this study was to assess the effect of lipopolysaccharide (LPS) treatment on eicosanoid content in RAW264.7 cells. An Ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)-based profiling method was used to analyze the eicosanoid contents of RAW264.7 cells treated with different LPS concentrations. The profiling data were subjected to statistical analyses, such as principal component analysis (PCA) and hierarchical clustering analysis. LPS treatment increased nitric oxide production and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in a concentration-dependent manner. In total, 79 eicosanoids were identified in the cells. RAW264.7 cells treated with different LPS concentrations were well differentiated in the PCA score plot. A heatmap was used to identify the eicosanoids that were up- or down-regulated according to the degree of inflammation and LPS concentration. Thirty-nine eicosanoids were upregulated and seven were down-regulated by LPS treatment in a concentration-dependent manner. Our novel UPLC-MS/MS technique can profile eicosanoids, and can evaluate the correlations between inflammation and eicosanoid metabolism. PMID:27058537

  3. A combined experimental/computational study on metal-organic framework MIL-101(Cr) as a SPE sorbent for the determination of sulphonamides in environmental water samples coupling with UPLC-MS/MS.

    PubMed

    Dai, Xinpeng; Jia, Xiuna; Zhao, Pan; Wang, Ting; Wang, Jian; Huang, Peiting; He, Lu; Hou, Xiaohong

    2016-07-01

    As a novel kind of materials, metal-organic frameworks (MOFs) have great potential for the preconcentration of trace analytes. In our work, MIL-101(Cr) was prepared and applied as a solid phase extraction (SPE) sorbent for the pretreatment of sulfadiazine (SDA), sulfamethazine (SMZ), sulfachloropyridazine (SCP) and sulfamethoxazole (SMX) in different environmental water samples coupling with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection. Experimental parameters, such as SPE materials, pH of water sample, volume of sample, flow rate, and type and volume of elution solvent, were properly optimized. Under the optimum conditions, good sensitivity levels were achieved with the detection limits of 0.03-0.08μg/L and the quantitation limits of 0.11-0.27μg/L. The linear ranges were from 0.2-40 or 0.5-100μg/L (r(2)>0.996) for the analytes, and the relative recoveries were in the range from 83.5% to 107.3% with the relative standard deviations (RSD) between 0.2% and 8.0% (n=6). In addition, computational simulation was primarily used to predict the adsorption of MIL-101(Cr) toward sulphonamides (SAs), and also demonstrated the molecular interactions and free binding energies with the molecular modeling method. The results revealed that the combination of experimental and computational study not only accurately recognized the adsorption of MIL-101(Cr) on SAs, but also provided a new strategy on the trace contaminant analysis. PMID:27154718

  4. Quantitative determination of fluconazole by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) in human plasma and its application to a pharmacokinetic study.

    PubMed

    Song, J-J; Li, W; Wang, Z; Tian, D-D; Yin, W-Y

    2015-01-01

    In this study, a simple, rapid and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method is described for determination of fluconazole (FLA) in human plasma samples using phenacetin as the internal standard (IS). Sample preparation was accomplished through one-step protein precipitation by methanol, and chromatographic separation was performed on an Acquity BEH C18 column (2.1 mm×50 mm, 1.7 μm) with mobile phase consisted of acetonitrile and water containing 0.1% formic acid (40:60, v/v) at a flow of 0.45 mL/min. Mass spectrometric analysis was performed using a QTrap 5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transition of m/z 307.2→238.2 was used to quantify for FLA. The linearity of this method was found to be within the concentration range of 10-6 000 ng/mL for FLA in human plasma. Only 1.0 min was needed for an analytical run. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of FLA in healthy Chinese volunteers after oral administration. PMID:25093302

  5. Determination of a novel Aurora-A (AurA) kinase AKI603 by UPLC-MS/MS and its application to a bioavailability study in rat.

    PubMed

    Zhao, Zhenzhen; Huang, Lingjie; Gou, Xiaoli; Li, Zhangwei; Chen, Jiangying; Wen, Dingsheng; Jiang, Fulin; Lu, Gui; Bi, Huichang; Huang, Min; Zhong, Guoping

    2016-06-01

    A simple, sensitive and accurate ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of AKI603 in rat plasma has been firstly developed and validated. After a simple liquid-liquid extraction (LLE) with ethyl acetate, the analytes were separated on C18 column (2.1×100mm, 1.9μm, Thermo) by gradient elution with mobile phase of water (A) (containing 5mM ammonium acetate and 0.1% formic acid) and methanol (B) with a flow rate of 0.3mLmin(-1) and then analyzed by mass spectrometry in the positive multiple reactions monitoring (MRM) mode. The mass transitions monitored were m/z 410.0→352.9, m/z 457.1→367.9 for AKI603 and internal standard (Ly-7z), respectively. The developed method was validated for specificity, linearity and lower limit of quantification, intra- and inter-day precision and accuracy, extraction recovery, matrix effect and stability whose values satisfied the acceptable limits. The calibration curves for AKI603 was linear in concentration ranges of 0.025-5000ngmL(-1). The method has been successfully used to the bioavailability study of AKI603 administered to rats intravenously (2.5mg/kg) or orally (25mg/kg). The oral bioavailability of AKI603 in rats was calculated as 28.7±9.7%. PMID:27070132

  6. Development and validation of a UPLC-MS/MS method for the determination of cucurbitacin B in rat plasma and application to a pharmacokinetic study.

    PubMed

    Zhao, Waiou; Xu, Dahai; Yan, Weiwei; Wang, Yushi; Zhang, Nan

    2016-04-01

    Cucurbitacin B (CuB), one of the most abundant forms of cucurbitacins, is a promising natural anticancer drug candidate. Although the anticancer activity of CuB has been well demonstrated, information regarding the pharmacokinetics is limited. A rapid, selective and sensitive UPLC-MS/MS for CuB was developed and validated using hemslecin A (HeA) as internal standard (IS). Plasma samples were pre-treated by liquid-liquid extraction with dichloromethane. Separation was achieved on a reversed-phase C18 column (50 × 4.6 mm, 5 µm) at 35°C using isocratic elution with water-methanol (25:75, v/v) at a flow rate of 0.3 mL/min. The analytes were monitored by a triple quadrupole tandem mass spectrometer with positive electrospray ionization mode. The calibration curve was linear (r > 0.995) in a concentration range of 0.3-100 ng/mL with a limit of quantification of 0.3 ng/mL. Intra- and inter-day accuracy and precision were validated by percentage relative error and relative standard deviation, respectively, which were both lower than the limit of 15%. This assay was successfully applied to a pharmacokinetic study of CuB in Wistar rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26207321

  7. Differentiating organically and conventionally grown oregano using ultraperformance liquid chromatography mass spectrometry (UPLC-MS), headspace gas chromatography with flame ionization detection (headspace-GC-FID), and flow injection mass spectrum (FIMS) fingerprints combined with multivariate data analysis.

    PubMed

    Gao, Boyan; Qin, Fang; Ding, Tingting; Chen, Yineng; Lu, Weiying; Yu, Liangli Lucy

    2014-08-13

    Ultraperformance liquid chromatography mass spectrometry (UPLC-MS), flow injection mass spectrometry (FIMS), and headspace gas chromatography (headspace-GC) combined with multivariate data analysis techniques were examined and compared in differentiating organically grown oregano from that grown conventionally. It is the first time that headspace-GC fingerprinting technology is reported in differentiating organically and conventionally grown spice samples. The results also indicated that UPLC-MS, FIMS, and headspace-GC-FID fingerprints with OPLS-DA were able to effectively distinguish oreganos under different growing conditions, whereas with PCA, only FIMS fingerprint could differentiate the organically and conventionally grown oregano samples. UPLC fingerprinting provided detailed information about the chemical composition of oregano with a longer analysis time, whereas FIMS finished a sample analysis within 1 min. On the other hand, headspace GC-FID fingerprinting required no sample pretreatment, suggesting its potential as a high-throughput method in distinguishing organically and conventionally grown oregano samples. In addition, chemical components in oregano were identified by their molecular weight using QTOF-MS and headspace-GC-MS. PMID:25050447

  8. A rapid UPLC-MS/MS method for the determination of oleanolic acid in rat plasma and liver tissue: application to plasma and liver pharmacokinetics.

    PubMed

    Li, Tian-Xue; Chu, Chao-Sen; Zhu, Jia-Yu; Yang, Tian-Yi; Zhang, Jie; Hu, Yu-Tao; Yang, Xing-Hao

    2016-04-01

    A reliable high-throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for oleanolic acid (OA) determination in rat plasma and liver tissue using glycyrrhetic acid as the internal standard (IS). Plasma and liver homogenate samples were prepared using solid-phase extraction. Chromatographic separation was achieved on a C18 column using an isocratic mobile phase system. The detection was performed by multiple reaction monitoring mode via positive electrospray ionization interface. The calibration curves showed good linearity (R(2) > 0.9997) within the tested concentration ranges. The lower limit of quantification for plasma and liver tissue was ≤0.75 ng/mL. The intra- and inter-day precision and accuracy deviations were within ±15% in plasma and liver tissue. The mean extraction recoveries ranged from 80.8 to 87.0%. In addition, the carryover, matrix effect, stability and robustness involved in the method were also validated. The method was successfully applied to the plasma and hepatic pharmacokinetics of OA after oral administration to rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26234772

  9. [Authentication and ultra performance liquid chromatography (UPLC)/MS analysis of magic mint, Salvia divinorum and its related plants].

    PubMed

    Maruyama, Takuro; Kamakura, Hiroyuki; Kikura-Hanajiri, Ruri; Goda, Yukihiro

    2008-01-01

    Ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) analysis was performed to investigate whether commercial Salvia cultivars available in the Japanese market contain salvinorin A (1), which is an hallucinogen present in magic mint (Salvia divinorum) prior to the regulation of S. divinorum by the Japanese Pharmaceutical Affairs Law. In addition, a previously reported method to authenticate S. divinorum, utilizing an amplification refractory mutation system (ARMS) was applied to the same samples to estimate the method's accuracy. As a result of the UPLC/MS analysis, it was clear that none of the tested cultivars possessed 1 while S. divinorum leaves and its processed products "concentrated salvia" contained 1 in the range from 0.19% to 0.58%. Furthermore, the ARMS method could clearly distinguish S. divinorum from the tested cultivars. In conclusion, the authentication method is considered to be useful for the practical regulation of S. divinorum due to its simplicity and accuracy. PMID:18176071

  10. A new method to identify hydrolytic degradants in drug substances with UPLC-MS using (18)O-labelled water.

    PubMed

    Ludvigsson, Jufang Wu; Andersson, Thomas; Kjellberg, Viktor

    2016-04-15

    Drug substances are susceptible to many different degradation pathways due to diverse nature of the molecule structures. Hydrolysis is one of the most common reactions seen for drug substances and drug products since water is ubiquitously present either as moisture or included in some formulations such as parenteral products. The hydrolytic degradation of fluticasone propionate, duloxetine and amlodipine was studied in this work using (18)O-labelled water with UPLC-MS. The structural proposals of the degradants are based solely on the molecular mass of the degradants with enhanced certainty by corresponding results from (18)O labeling experiments. The advantage of using (18)O labeling experiments is the extra information from knowing whether a water molecule is incorporated into a degradant or not, therefore enabling either confirmation or rejection of a proposed molecular structure. PMID:26829516

  11. Rapid qualitative and quantitative analysis of proanthocyanidin oligomers and polymers by ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We developed a rapid method with ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS) for the qualitative and quantitative analysis of plant proanthocyanidins (PAs) directly from crude plant extracts. The method utilizes a range of cone voltages to achieve the depolymeriza...

  12. Determination of 25-OCH3-PPD and the related substances by UPLC-MS/MS and their cytotoxic activity.

    PubMed

    Ding, Meng; Lu, Jingjing; Zhao, Chen; Zhang, Sainan; Zhao, Yuqing

    2016-06-01

    20(R)-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH3-PPD) is a promising antitumor compound belonging to triterpenoid saponins isolated from radix notoginseng. A systematic research on the related impurities in raw material of 25-OCH3-PPD has not been conducted. In this study, three impurities obtained by HPLC-ELSD and characterized by (13)C NMR and MS were observed in the raw material of 25-OCH3-PPD. Cytotoxic activities of the related substances were also evaluated, of which impurity B with 25-OCH3-PPD showed synergistic inhibitory activity against BGC-823 with IC50 values of 8.33μM. Furthermore, a rapid and selective UPLC-MS/MS method was developed for simultaneous determination of the principal component and three related substances in the raw material of 25-OCH3-PPD. Multiple reaction monitoring scan mode was used for the quantification of 20(R)-25-OCH3-PPD and its three related substances. The four constituents were separated within 11min on a BEH C18 column (100 mm×2.1mm, 1.7μm) using a mobile phase comprising methanol and 0.03% formic acid water (82:18, v/v) at a flow rate of 0.2mL/min. The proposed UPLC-MS/MS method displayed acceptable levels of linearity, precision, repeatability, and accuracy. In addition, the proposed method was successfully applied for the establishment of a rational quality control standard for the raw material of 25-OCH3-PPD. PMID:27128861

  13. Quantitative Determination of Levonorgestrel in Fish Plasma using UPLC-MS/MS

    EPA Science Inventory

    In this study, a sensitive high-performance liquid chromatography electrospray tandem mass spectrometric method was developed for the determination of levonorgestrel in fish plasma using levonorgestrel-d6 as an internal standard (IS). In the laboratory, the fish cunner, (Tautogol...

  14. Simultaneous determination of icariin, naringin and osthole in rat plasma by UPLC-MS/MS and its application for pharmacokinetic study after oral administration of Gushudan capsules.

    PubMed

    Lu, Yuejuan; Li, Ning; Deng, Ying; Zhao, Longshan; Guo, Xingjie; Li, Famei; Xiong, Zhili

    2015-07-01

    A rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of icariin, naringin and osthole in rat plasma. Plasma samples pretreatment involved a one-step liquid-liquid extraction with a mixture of ethyl acetate-methyl tert-butyl ether (3:1, ν/ν). The separation was performed on an ACQUITY UPLC™ BEH C18 column with a gradient mobile phase system of methanol and water. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM), with the transitions at m/z 513.3→366.8 (icariin), m/z 579.3→150.9 (naringin), m/z 245.1→189.0 (osthole) and m/z 237.1→194.1 (IS), respectively. A good linear response was observed over the concentration ranges of 1.06-424ng/ml, 2.10-525ng/ml and 1.05-1.05×10(3)ng/ml with lower limit of quantification (LLOQ) of 1.06, 2.10 and 1.05ng/ml for icariin, naringin and osthole, respectively. The intra- and inter-day precisions (R.S.D.) were within 14.3%, and the accuracy (R.E.) ranged from -4.1% to 4.6% at three quality control levels. The sensitive and selective method was applied to a pharmacokinetic study of icarrin, naringin and osthole in rats after oral administration of Gushudan capsule. PMID:26000860

  15. Simultaneous determination of phenolic acids by UPLC-MS/MS in rat plasma and its application in pharmacokinetic study after oral administration of Flos Lonicerae preparations.

    PubMed

    Zhou, Wei; Liu, Shijia; Ju, Wenzheng; Shan, Jinjun; Meng, Minxin; Cai, Baochang; Di, Liuqing

    2013-12-01

    The current study aims to investigate the pharmacokinetic study of five phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 3,5-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid) following oral administration of Flos Lonicerae preparations in rats. A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously determine the five phenolic acids in rat plasma. After mixing with the internal standard (IS) tinidazole, plasma samples were pretreated by liquid-liquid extraction with ethyl acetate/n-hexane (9:1, v/v). The separation was performed on an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mlmin(-1), and acetonitrile/methanol (4:1, v/v)-0.4% formic acid was used as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive ionization mode. All calibration curves had good linearity (r>0.991) over the concentration ranges of 0.74-378ngml(-1) for neochlorogenic acid, 0.50-1030ngml(-1) for chlorogenic acid, 1.9-250ngml(-1) for cryptochlorogenic acid, 0.74-380ngml(-1) for 3,5-dicaffeoylquinic acid, and 5.1-328ngml(-1) for 3,4-dicaffeoylquinic acid. The intra-and inter-day precision were within 15% and the accuracy ranged from 86.2% to 114.1%. PMID:24004636

  16. Simultaneous determination of nintedanib and its metabolite BIBF 1202 in different tissues of mice by UPLC-MS/MS and its application in drug tissue distribution study.

    PubMed

    Xu, Xiao-wei; Su, Xin-juan; Zhang, Yu-niao; Zheng, Xiao-kang; Lv, Peng-fei; Hu, Jie

    2015-10-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneous determine nintedanib and BIBF 1202 in mice plasma and tissue using carbamazepine as the internal standard (IS). Sample preparation was accomplished through a protein precipitation procedure with acetonitrile. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1mm50mm, 1.7?m) with the mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution at a flow rate of 0.40mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 540.3?113.1 for nintedanib, m/z 526.3?113.1 for BIBF 1202 and m/z 237.1?194.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 1-1000ng/mL with a lower limit of quantification of 1.0ng/mL for each drug. Only 3.0min was needed for an analytical run. The inter-day and intra-day precision and accuracy of quality control (QC) samples, evaluated both in plasma and tissue homogenates, were all within 15%. The method was successfully applied to the pharmacokinetic and tissue distribution study of nintedanib and BIBF 1202 in mice after oral administration of nintedanib. PMID:26342166

  17. A UPLC-MS/MS method for simultaneous quantitation of three monoterpene glycosides and four alkaloids in rat plasma: application to a comparative pharmacokinetic study of Huo Luo Xiao Ling Dan and single herb extract.

    PubMed

    Ai, Yu; Wu, Yun; Wang, Fenrong; Ma, Wen; Bian, Qiaoxia; Lee, David Y-W; Dai, Ronghua

    2015-03-01

    The objective of this study was to develop a sensitive and reliable ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantitation of three monoterpene glycosides (paeoniflorin, alibiflorin and oxypaeoniflorin) and four alkaloids (tetrahydropalmatine, corydaline, dehydrocorydaline and berberine), the main active ingredients of Radix Paeoniae Rubra extract (RPE) and Corydalis yanhusuo extract (CYE) in Huo Luo Xiao Ling Dan (HLXLD), and to compare the pharmacokinetics of these active ingredients in normal and arthritic rats orally administrated with HLXLD or RPE/CYE alone. The analytes and internal standard (IS) (geniposide) were separated on a XBridge C18 column (150 × 4.6 mm, 3.5 µm) using gradient elution with the mobile phase consisting of methanol and 0.01% formic acid in water at a flow rate of 0.6 ml/min. The detection of the analytes was performed on Acquity UPLC-MS/MS system with an electrospray ionization and multiple reaction monitoring mode via polarity switching between negative (for monoterpene glycosides) and positive (for alkaloids) ionization mode. The lower limits of quantification were 2.5, 1, 0.5, 0.2, 0.2, 0.02 and 0.01 ng/ml for paeoniflorin, alibiflorin, oxypaeoniflorin, tetrahydropalmatine, corydaline, dehydrocorydaline and berberine, respectively. Intra-day and inter-day precision and accuracy of analytes were well within acceptance criteria (15%). The mean extraction recoveries of analytes and IS from rat plasma were all more than 83.1%. The validated method has been successfully applied to determination of the analytes. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes between herbal formula and single herb group, normal and arthritic group. PMID:25800193

  18. A validated, rapid UPLC-MS/MS method for simultaneous ivabradine, reboxetine, and metoprolol analysis in human plasma and its application to clinical trial samples.

    PubMed

    Zoerner, Alexander A; Schroeder, Christoph; Kayacelebi, Arslan Arinc; Suchy, Maria T; Gutzki, Frank-Mathias; Stichtenoth, Dirk O; Tank, Jens; Jordan, Jens; Tsikas, Dimitrios

    2013-05-15

    A recent clinical trial assessing human autonomic cardiovascular regulation applied pacemaker channel inhibition with ivabradine, norepinephrine transporter blockade with reboxetine, and beta-adrenoreceptor blockade with metoprolol. To verify patient adherence, we developed and validated a fast UPLC-MS/MS assay measuring all three compounds simultaneously. Deuterium-labeled drugs, d3-ivabradine, d5-reboxetine and d7-metoprolol, served as internal standards. Sample preparation of 200μL human plasma consisted of a single liquid-liquid extraction step by means of ethyl acetate. Chromatographic separation was performed on a 50-mm long BEH C18 column with gradient elution using a mixture of water and methanol each containing 2mM ammonium acetate over 4.5min. The mass spectrometer was operated in the positive electrospray ionization (ESI+) mode. Characteristic product ions resulting from collision-induced dissociation of unlabeled and deuterium-labeled drugs with argon were used for quantification in the selected-reaction monitoring mode. We validated the method according to the European Medicines Agency (EMA) guideline on bioanalytical method validation over the range from 1ng/mL to 500ng/mL for all three analytes. Linear responses with correlation coefficients>0.99 over that range were acquired. The LOQ value was 1ng/mL for each drug. Regulatory criteria for accuracy (80-120%) and precision (RSD<15%) were met for all drugs. The internal standard-normalized matrix factor was close to 1 for low and high analyte concentrations. We successfully measured ivabradine, reboxetine, and metoprolol concentrations in 107 human plasma samples from a clinical trial. Quality control samples processed in parallel confirmed the method's reliability in a clinical setting. PMID:23434314

  19. Comparison of sample preparation methods, validation of an UPLC-MS/MS procedure for the quantification of tetrodotoxin present in marine gastropods and analysis of pufferfish.

    PubMed

    Nzoughet, Judith Kouassi; Campbell, Katrina; Barnes, Paul; Cooper, Kevin M; Chevallier, Olivier P; Elliott, Christopher T

    2013-02-15

    Tetrodotoxin (TTX) is one of the most potent marine neurotoxins reported. The global distribution of this toxin is spreading with the European Atlantic coastline now being affected. Climate change and increasing pollution have been suggested as underlying causes for this. In the present study, two different sample preparation techniques were used to extract TTX from Trumpet shells and pufferfish samples. Both extraction procedures (accelerated solvent extraction (ASE) and a simple solvent extraction) were shown to provide good recoveries (80-92%). A UPLC-MS/MS method was developed for the analysis of TTX and validated following the guidelines contained in the Commission Decision 2002/657/EC for chemical contaminant analysis. The performance of this procedure was demonstrated to be fit for purpose. This study is the first report on the use of ASE as a mean for TTX extraction, the use of UPLC-MS/MS for TTX analysis, and the validation of this method for TTX in gastropods. PMID:23194566

  20. Simultaneous determination of acetaminophen and dihydrocodeine in human plasma by UPLC-MS/MS: Its pharmacokinetic application.

    PubMed

    Qiu, Xiangjun; Lou, Dan; Su, Ding; Liu, Zebin; Gao, Pengtao; Zhang, Nan-sheng

    2015-06-15

    An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine acetaminophen (AAP) and dihydrocodeine (DHC) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard midazolam were separated on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 151.2→110.0 and m/z 302.3→199.2 were used to quantify for AAP and DHC, respectively. The linearity of this method was found to be within the concentration range of 50-10000ng/mL for AAP, and 1-100ng/mL for DHC in human plasma, respectively. The lower limit of quantification (LLOQ) was 50ng/mL and 1ng/mL for AAP and DHC in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 10% for both AAP and DHC. The analysis time of per sample was 1.0min. The developed and validated method was successfully applied to a pharmacokinetic study of AAP (500mg) with DHC (20mg) capsule in Chinese healthy volunteers (N=20). PMID:25965875

  1. Validation of JWH-018 and its metabolites in blood and urine by UPLC-MS/MS: Monitoring in forensic cases.

    PubMed

    Erol Öztürk, Yeter; Yeter, Oya; Alpertunga, Buket

    2015-03-01

    The herbal products referred to as 'Spice' have been used as 'legal alternatives' to cannabis worldwide since 2004. The first synthetic cannabinoid JWH-018 was detected in 'Spice' products in 2008, and has been banned by many legal authorities since the beginning of 2009. In order to prove use of JWH cannabinoids (JWHs), specific and robust methods were needed. We have developed a specific and reliable method for the detection and quantification of JWH-018, JWH-018 N-pentanoic acid, and JWH-018 N-(5-hydroxypentyl) in blood and urine using solid-phase extraction followed by UPLC-MS/MS analysis. The method has been validated in terms of linearity (0.1-50ng/mL), selectivity, intra-assay and inter-assay accuracy and precision (CV<15%), recovery (85-98%), limits of detection (LOD) (0.08-0.14ng/mL), and quantification (LOQ) (0.10-0.21ng/mL). Matrix effects, stability, and process efficiency were also assessed. The method has been applied to 868 authentic samples received by the Department of Chemistry (Istanbul) in the Council of Forensic Medicine of the Ministry of Justice. PMID:25616218

  2. Assessment of biological activity and UPLC-MS based chromatographic profiling of ethanolic extract of Ochradenus arabicus.

    PubMed

    Ali, M Ajmal; Farah, M Abul; Al-Hemaid, Fahad M; Abou-Tarboush, Faisal M; Al-Anazi, Khaled M; Wabaidur, S M; Alothman, Z A; Lee, Joongku

    2016-03-01

    Natural products from wild and medicinal plants, either in the form of crude extracts or pure compounds provide unlimited opportunities for new drug leads owing to the unmatched availability of chemical diversity. In the present study, the cytotoxic potential of crude ethanolic extract of Ochradenus arabicus was analyzed by MTT cell viability assay in MCF-7 adenocarcinoma breast cancer cells. We further investigated its effect against oxidative stress induced by anticancer drug doxorubicin. In addition, Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) based chromatographic profiling of crude extract of O. arabicus was performed. The MTT assay data showed that the extract is moderately toxic to the MCF-7 cells. However, its treatment alone does not induce oxidative stress while doxorubicin increases the level of oxidative stress in MCF-7 cells. Whereas, simultaneous treatment of plant extract and doxorubicin significantly (p < 0.05) decreased the level of intracellular reactive oxygen species (ROS) and lipid peroxidation while an increase in the reduced glutathione and superoxide dismutase activity was observed in time and dose dependent manner. Hence, our finding confirmed cytotoxic and antioxidant potential of crude extract of O. arabicus in MCF-7 cells. However, further investigations on O. arabicus as a potential chemotherapeutic agent are needed. The analysis of bioactive compounds present in the plant extracts involving the applications of common phytochemical screening assays such as chromatographic techniques is discussed. PMID:26981004

  3. Quality Evaluation of Traditional Chinese Medicine Compounds in Xiaoyan Lidan Tablets: Fingerprint and Quantitative Analysis Using UPLC-MS.

    PubMed

    Yang, Na; Xiong, Aizhen; Wang, Rui; Yang, Li; Wang, Zhengtao

    2016-01-01

    XiaoyanLidan tablets (XYLDTs) are traditional Chinese medicines frequently used for syndromes of the liver and gallbladder, cholecystitis and cholangitis. To evaluate the consistency of the quality of commercial XYLDT preparations, we established a simple and reliable ultra-performance liquid chromatography (UPLC) method with a photodiode array (PDA) detector and mass spectrometry (MS), including a fingerprint analysis and quantification of the main pharmacologically-active markers. In the UPLC-PDA detection-based fingerprint analysis of XYLDTs, approximately 39 peaks were found in the XYLDT chromatogram, 26 of which were attributed to Picrasmaquassioides, nine to Andrographis and four to Isodonserra. Subsequently, the structures of these bioactive markers were identified through ESI-MS analyses. Using the chemometricmethods of similarity analysis and principal component analysis, the five significant herbal componentswere determined as 4-methoxy-5-hydroxycanthin-6-one, andrographolide, dehydroandrographolide, neoandrographolide and rosmarinic acid, and these components were qualitatively assessed. Our experimental results demonstrated that combining the fingerprint analysis with UPLC-MS and multi-ingredient determination is useful for rapid pharmaceutical quality evaluation. Moreover, the combined approach can potentially differentiate the origin, determine the authenticity and assess the overall quality of the formulae. PMID:26805803

  4. Simultaneous detection of multiple DNA adducts in human lung samples by isotope-dilution UPLC-MS/MS.

    PubMed

    Monien, Bernhard H; Schumacher, Fabian; Herrmann, Kristin; Glatt, Hansruedi; Turesky, Robert J; Chesné, Christophe

    2015-01-01

    Recent studies have demonstrated that various DNA adducts can be detected in human tissues and fluids using liquid chromatography connected to tandem mass spectrometry (LC-MS/MS). However, the utility of a single DNA adduct as a biomarker in risk assessment is debatable because humans are exposed to many genotoxicants. We established a method to measure DNA adducts derived from 16 ubiquitous genotoxicants and developed an analytical technique for their simultaneous quantification by ultra performance liquid chromatography (UPLC)-MS/MS. Methods for the enrichment of the analytes from DNA hydrolysates and chromatographic separation preceding mass spectrometric analysis were optimized, and the resultant technique was used for the simultaneous analysis of the 16 DNA adducts in human lung biopsy specimens. Eleven adducts (formed by benzo[a]pyrene, 1-methylpyrene, 4-aminobiphenyl, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 1-methoxy-3-indolylmethylglucosinolate, 5-hydroxymethylfurfural, and malondialdehyde) were not detected in any tissue sample (limits of detection: 0.02-7.1 adducts/10(8) nucleosides). 3,N(4)-etheno-2'-deoxycytidine and 1,N(6)-etheno-2'-deoxyadenosine, formed from 2,3-epoxyaldehydes of endogenous lipid peroxidation products, were present in all subjects (16.9-115.3 and 27.2-179/10(8) nucleosides, respectively). The same was true for N(2)-(trans-methylisoeugenol-3'-yl)-2'-deoxyguanosine, the major adduct of methyleugenol (1.7-23.7/10(8) nucleosides). A minor adduct of methyleugenol and two adducts of furfuryl alcohol were detected in several pulmonary specimens. Taken together, we developed a targeted approach for the simultaneous mass spectrometric analyses of 16 DNA adducts, which can be easily extended by adducts formed from other mutagens. The method allowed one to detect adducts of furfuryl alcohol and methyleugenol in samples of human lung. PMID:25423194

  5. Simultaneous Detection of Multiple DNA Adducts in Human Lung Samples by Isotope-Dilution UPLC-MS/MS

    PubMed Central

    2015-01-01

    Recent studies have demonstrated that various DNA adducts can be detected in human tissues and fluids using liquid chromatography connected to tandem mass spectrometry (LC-MS/MS). However, the utility of a single DNA adduct as a biomarker in risk assessment is debatable because humans are exposed to many genotoxicants. We established a method to measure DNA adducts derived from 16 ubiquitous genotoxicants and developed an analytical technique for their simultaneous quantification by ultra performance liquid chromatography (UPLC)-MS/MS. Methods for the enrichment of the analytes from DNA hydrolysates and chromatographic separation preceding mass spectrometric analysis were optimized, and the resultant technique was used for the simultaneous analysis of the 16 DNA adducts in human lung biopsy specimens. Eleven adducts (formed by benzo[a]pyrene, 1-methylpyrene, 4-aminobiphenyl, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 1-methoxy-3-indolylmethylglucosinolate, 5-hydroxymethylfurfural, and malondialdehyde) were not detected in any tissue sample (limits of detection: 0.02–7.1 adducts/108 nucleosides). 3,N4-etheno-2′-deoxycytidine and 1,N6-etheno-2′-deoxyadenosine, formed from 2,3-epoxyaldehydes of endogenous lipid peroxidation products, were present in all subjects (16.9–115.3 and 27.2–179/108 nucleosides, respectively). The same was true for N2-(trans-methylisoeugenol-3′-yl)-2′-deoxyguanosine, the major adduct of methyleugenol (1.7–23.7/108 nucleosides). A minor adduct of methyleugenol and two adducts of furfuryl alcohol were detected in several pulmonary specimens. Taken together, we developed a targeted approach for the simultaneous mass spectrometric analyses of 16 DNA adducts, which can be easily extended by adducts formed from other mutagens. The method allowed one to detect adducts of furfuryl alcohol and methyleugenol in samples of human lung. PMID:25423194

  6. Simultaneous determination of ten compounds in rat plasma by UPLC-MS/MS: Application in the pharmacokinetic study of Ma-Zi-Ren-Wan.

    PubMed

    Hu, Dong-Dong; Han, Quan-Bin; Zhong, Linda Li-Dan; Li, Yan-Hong; Lin, Cheng-Yuan; Ho, Hing-Man; Zhang, Man; Lin, Shu-Hai; Zhao, Ling; Huang, Tao; Mi, Hong; Tan, Hong-Sheng; Xu, Hong-Xi; Bian, Zhao-Xiang

    2015-09-01

    Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C18 column (100mm×2.1mm, 1.7μm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r(2)>0.995) over the concentration range from 3.9 to 125.0ng/mL for emodin, 3.9-500.0ng/mL for amygdalin, 2.0-4000.0ng/mL for naringin and hesperidin, 3.9-2000.0ng/mL for magnolol, 7.8-2000.0ng/mL for rhein and 3.9-4000.0ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from -13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0ng/mL and 7.8ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future. PMID:26231677

  7. Simultaneous determination of cyromazine and dicyclanil in animal edible tissues using UPLC-MS/MS.

    PubMed

    Hou, Xiaolin; Zhou, Degang; Huai, Wenhui; Beier, Ross C; Sun, Yingjian; Lu, Yan; Wu, Guojuan; Sun, Zhiwen; Wu, Yongning

    2013-01-01

    Cyromazine and dicyclanil are both used as insect growth regulators. This paper describes an easy and innovative simultaneous extraction method for residues of cyromazine and dicyclanil in food of animal origin, and a confirmation procedure using UHPLC-MS/MS. The sample was extracted, deproteinised by 1% trichloracetic acid in water-acetonitrile, followed by selective defatting using hexane based on the degree of matrix complexity; cleaned-up on an mixed-mode cation exchange (MCX) cartridge; and quantified by using matrix-matched calibration. The mean recoveries were all between 62.0% and 99.2%, and the RSDs were all below 9.94%. The present method was rapid, sensitive and reliable, which was applied to the quantitative analysis of these residues in animal tissues. PMID:23469982

  8. Analysis of different fates of DNA adducts in adipocytes post-sulfur mustard exposure in vitro and in vivo using a simultaneous UPLC-MS/MS quantification method.

    PubMed

    Wang, Peng; Zhang, Yajiao; Chen, Jia; Guo, Lei; Xu, Bin; Wang, Lili; Xu, Hua; Xie, Jianwei

    2015-06-15

    Sulfur mustard (SM) is a powerful alkylating vesicant that can rapidly penetrate skin, ocular, and lung bronchus mucous membranes and react with numerous nucleophiles in vivo. Although the lesion mechanisms of SM remain unclear, DNA damage is believed to be the most crucial factor in initiating SM-induced toxicity. Four major DNA adducts were identified for retrospective detection and DNA lesion evaluation, namely, N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (N(7)-HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA), and O(6)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (O(6)-HETEG). Because of previous observations that the levels of SM-DNA adducts were relatively higher in adipose-rich organs, such as the brain, we focused on the in vitro and in vivo fates of the DNA adducts in exposed adipocytes. A UPLC-MS/MS method developed in our laboratory was used to profile the N(7)-HETEG, Bis-G, and N(3)-HETEA levels in human mature adipocytes (HA-s) that had differentiated from human subcutaneous preadipocytes (HPA-s). This method was also used to profile three other cell lines related to the targeting of major tissues, including human keratinocytes (HaCaT), human hepatocytes (L-02), and human lung fibroblasts (HLF). Long-lasting adduct persistence and a high proportion of Bis-G were found in exposed adipocytes in vitro. The survival properties of exposed adipocytes were also tested. At the same time, the fate of SM-DNA adducts in vivo was characterized using a rat model exposed to 1 and 10 mg/kg doses of SM. The level of DNA adducts in the exposed adipose tissue (AT) was much lower than those in other organs studied in our previous work. The adduct persistence behavior was observed in AT with an extremely high proportion of Bis-G, which was higher than N(7)-HETEG. In light of these results, we suggest that an adipose-rich environment may promote the formation of Bis-G and that adipocyte-specific DNA repair mechanisms may result in adduct persistence and the survival of adipocytes after SM exposure. These conclusions should be further investigated. PMID:25955432

  9. Two rapid ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) methods with common sample pretreatment for therapeutic drug monitoring of immunosuppressants compared to immunoassay.

    PubMed

    Tszyrsznic, Wlodzimierz; Borowiec, Agnieszka; Pawlowska, Emilia; Jazwiec, Radoslaw; Zochowska, Dorota; Bartlomiejczyk, Irena; Zegarska, Jolanta; Paczek, Leszek; Dadlez, Michal

    2013-06-01

    Therapeutic drug monitoring of immunosuppressive agents is a critical and essential part of patient therapy after organ transplantation. We have developed high-throughput, robust, and rapid liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) methods with common pretreatment procedures for simultaneous quantification of four immunosuppressive agents (everolimus, sirolimus, tacrolimus, and cyclosporin A) in whole blood and one immunosuppressant (mycophenolic acid) in plasma. The new approach used in this work is based on improved sample preparation procedures allowing the analysis of five immunosuppressive drugs. Whole blood was prepared by transferring 100μL of blood into a 1.5-mL silanized conical test tube. Zinc sulfate solution (150μL), containing deuterated internal standards, was added to perform hemolysis. The samples were vortexing for 10s, followed by the addition of 250μL acetonitrile, containing internal standard for cyclosporin A, to precipitate proteins. The mixture was vortexed for 1min and centrifuged for 2min at 14,000rpm. The whole supernatant was transferred to a vial. To prepare blood plasma, the hemolysis step involving the addition of zinc sulfate was omitted and, instead of acetonitrile, methanol was used as the solvent for the internal standard (mycophenolic acid-d3). The volumes of chemicals used in this procedure were the same as those used in the procedure for immunosuppressants in whole blood. The basic validation parameters for the analytical methods were limits of detection (0.5ng/mL for everolimus, sirolimus and tacrolimus, 25ng/mL for cyclosporin A and 100ng/mL for mycophenolic acid), precision (<15%), recovery (>84%), repeatability and reproducibility. Possible mutual ion suppression was eliminated in the presence of internal standards. The method developed for the quantitation of immunosuppressants in whole blood was used to analyze 276 patient samples containing tacrolimus and 55 samples containing cyclosporin A. The results from LC/MS/MS were compared to those obtained from immunoassays of the same samples. Immunoassays significantly overestimated the concentrations of immunosuppressants. PMID:23584041

  10. Quantitation of the Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Warfarin in Plasma Using Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS).

    PubMed

    Noguez, Jaime H; Ritchie, James C

    2016-01-01

    This chapter describes a method to measure the oral anticoagulants dabigatran, rivaroxaban, apixaban, and warfarin in plasma samples using ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS). The instrument is operated in multiple reaction monitoring (MRM) mode with an electrospray ionization (ESI) source in positive ionization mode. Samples are extracted with a 90:10 methanol/0.1 N hydrochloric acid solution containing stable isotope-labeled internal standards for each analyte. After centrifugation the supernatant is transferred to a mass spectrometry vial, injected onto the UPLC-ESI-MS/MS, and quantified using an eight-point calibration curve. PMID:26660170

  11. UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

    PubMed

    Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

    2015-10-10

    A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 2.1 mm, 1.8 ?m) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 14.2 ?g/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. PMID:26070162

  12. Simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after administration of Reduning injection.

    PubMed

    Wang, Yanjuan; Wen, Jing; Zheng, Weihua; Zhao, Longshan; Fu, Xiaohuan; Wang, Zhenzhong; Xiong, Zhili; Li, Famei; Xiao, Wei

    2015-01-01

    A simple, specific and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma using puerarin as an internal standard (IS). Plasma samples were pretreated by a one-step direct protein precipitation procedure with acetonitrile after acidified using as little as 50 μL plasma. Chromatographic separation was performed on an Acquity BEH C18 column (100 × 2.1 mm, 1.7 µm) at a flow rate of 0.2 mL/min by a gradient elution, using 0.2% acetic acid-methanol as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via electrospray ionization source with negative ion mode. Calibration curves showed good linearity (r > 0.995) over wide concentration ranges. The intra- and inter-day precisions were <15%, and the accuracy was within ±8.0%. The validated method was successfully applied to a pharmacokinetic study of the four bioactive components in rats after intravenous administration of Reduning injection. PMID:24842397

  13. Quantitative Assessment of the Influence of Rhizoma Zingiberis on the Level of Aconitine in Rat Gut Sacs and Qualitative Analysis of the Major Influencing Components of Rhizoma Zingiberis on Aconitine Using UPLC/MS

    PubMed Central

    Xin, Yang; Liu, Shuying

    2015-01-01

    This study attempted to clarify the material basis for the detoxification of Rhizoma Zingiberis (RZ) on aconitine, an analgesic drug, by quantitatively assessing the influence of RZ on the in vitro intestinal concentration of aconitine using an everted gut sac model and by qualitatively identifying the components in the RZ extract. To quantify aconitine in rat everted gut sacs, both an accurate processing method and a sensitive detection method were required. We developed a three-step sample processing method to protect the components from decomposition and applied ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC/TQMS) to quantify aconitine, glucose and digoxin. In addition, ultra-performance liquid chromatography coupled with linear ion trap mass spectrometry (UPLC/ITMS) was applied to detect the potential antidotal components in the RZ extract. Finally, the RZ extract reduced the level of aconitine in everted gut sacs, and eleven gingerols were successfully identified, which could be considered potential antidotal components for aconitine. This study demonstrated the application of two UPLC/MS methods for analyzing the material basis for the reciprocity between Chinese medicine components in everted gut sacs. PMID:25978042

  14. UPLC-MS/MS determination of ephedrine, methylephedrine, amygdalin and glycyrrhizic acid in Beagle plasma and its application to a pharmacokinetic study after oral administration of Ma Huang Tang.

    PubMed

    Yan, Tianhua; Fu, Qiang; Wang, Jing; Ma, Shiping

    2015-02-01

    An ultra performance liquid chromatography-mass spectrometric (UPLC-MS) method was developed to investigate the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of Ma Huang Tang (MHT) in Beagles. Beagle plasma samples were pretreated using liquid-liquid extraction, and chromatographic separation was performed on a C18 column using a linear gradient of water-formic acid mixture (0.1%). The pharmacokinetic parameters of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid from MHT in Beagles were quantitatively determined by UPLC with tandem mass detector. The qualitative detection of the four compounds was accomplished by selected ion monitoring in negative/positive ion modes electrospray ionization-mass spectrometry (ESI-MS). Detection was based on multiple reaction monitoring with the precursor-to-product ion transitions m/z 166.096-116.983 (ephedrine), m/z 179.034-146.087 (methylephedrine), m/z 456.351-323.074 (amygdalin), and m/z 821.606-351.062 (glycyrrhizic acid). The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression, and stability were within the acceptable ranges. The method described was successfully applied to reveal the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of MHT in Beagles. PMID:24824649

  15. Statistical search space reduction and two-dimensional data display approaches for UPLC-MS in biomarker discovery and pathway analysis.

    PubMed

    Crockford, Derek J; Lindon, John C; Cloarec, Olivier; Plumb, Robert S; Bruce, Stephen J; Zirah, Severine; Rainville, Paul; Stumpf, Chris L; Johnson, Kelly; Holmes, Elaine; Nicholson, Jeremy K

    2006-07-01

    A new analytical strategy for biomarker recovery from directly coupled ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC Tof MS) data on biofluids is presented and exemplified using a study on hydrazine-induced liver toxicity. A key step in the strategy involves a novel procedure for reducing the spectroscopic search space by differential analysis of cohorts of normal and pathological samples using an orthogonal projection to latent structures discriminant analysis (O-PLS-DA). This efficiently sorts principal discriminators of toxicity from the background of thousands of metabolic features commonly observed in data sets generated by UPLC-MS analysis of biological fluids and is thus a powerful tool for biomarker discovery. PMID:16808447

  16. Quantitative analysis of unconjugated and total bisphenol A in human urine using solid-phase extraction and UPLC-MS/MS: method implementation, method qualification and troubleshooting.

    PubMed

    Buscher, Brigitte; van de Lagemaat, Dick; Gries, Wolfgang; Beyer, Dieter; Markham, Dan A; Budinsky, Robert A; Dimond, Stephen S; Nath, Rajesh V; Snyder, Stephanie A; Hentges, Steven G

    2015-11-15

    The aim of the presented investigation was to document challenges encountered during implementation and qualification of a method for bisphenol A (BPA) analysis and to develop and discuss precautions taken to avoid and to monitor contamination with BPA during sample handling and analysis. Previously developed and published HPLC-MS/MS methods for the determination of unconjugated BPA (Markham et al. Journal of Analytical Toxicology, 34 (2010) 293-303) [17] and total BPA (Markham et al. Journal of Analytical Toxicology, 38 (2014) 194-203) [20] in human urine were combined and transferred into another laboratory. The initial method for unconjugated BPA was developed and evaluated in two independent laboratories simultaneously. The second method for total BPA was developed and evaluated in one of these laboratories to conserve resources. Accurate analysis of BPA at sub-ppb levels is a challenging task as BPA is a widely used material and is ubiquitous in the environment at trace concentrations. Propensity for contamination of biological samples with BPA is reported in the literature during sample collection, storage, and/or analysis. Contamination by trace levels of BPA is so pervasive that even with extraordinary care, it is difficult to completely exclude the introduction of BPA into biological samples and, consequently, contamination might have an impact on BPA biomonitoring data. The applied UPLC-MS/MS method was calibrated from 0.05 to 25ng/ml. The limit of quantification was 0.1ng/ml for unconjugated BPA and 0.2ng/ml for total BPA, respectively, in human urine. Finally, the method was applied to urine samples derived from 20 volunteers. Overall, BPA can be analyzed in human urine with acceptable recovery and repeatability if sufficient measures are taken to avoid contamination throughout the procedure from sample collection until UPLC-MS/MS analysis. PMID:26465088

  17. First Detection of Tetrodotoxin in Greek Shellfish by UPLC-MS/MS Potentially Linked to the Presence of the Dinoflagellate Prorocentrum minimum

    PubMed Central

    Vlamis, Aristidis; Katikou, Panagiota; Rodriguez, Ines; Rey, Verónica; Alfonso, Amparo; Papazachariou, Angelos; Zacharaki, Thetis; Botana, Ana M.; Botana, Luis M.

    2015-01-01

    During official shellfish control for the presence of marine biotoxins in Greece in year 2012, a series of unexplained positive mouse bioassays (MBA) for lipophilic toxins with nervous symptomatology prior to mice death was observed in mussels from Vistonikos Bay–Lagos, Rodopi. This atypical toxicity coincided with (a) absence or low levels of regulated and some non-regulated toxins in mussels and (b) the simultaneous presence of the potentially toxic microalgal species Prorocentrum minimum at levels up to 1.89 × 103 cells/L in the area’s seawater. Further analyses by different MBA protocols indicated that the unknown toxin was hydrophilic, whereas UPLC-MS/MS analyses revealed the presence of tetrodotoxins (TTXs) at levels up to 222.9 μg/kg. Reviewing of official control data from previous years (2006–2012) identified a number of sample cases with atypical positive to asymptomatic negative MBAs for lipophilic toxins in different Greek production areas, coinciding with periods of P. minimum blooms. UPLC-MS/MS analysis of retained sub-samples from these cases revealed that TTXs were already present in Greek shellfish since 2006, in concentrations ranging between 61.0 and 194.7 μg/kg. To our knowledge, this is the earliest reported detection of TTXs in European bivalve shellfish, while it is also the first work to indicate a possible link between presence of the toxic dinoflagellate P. minimum in seawater and that of TTXs in bivalves. Confirmed presence of TTX, a very heat-stable toxin, in filter-feeding mollusks of the Mediterranean Sea, even at lower levels to those inducing symptomatology to humans, indicates that this emerging risk should be seriously taken into account by the EU to protect the health of shellfish consumers. PMID:26008234

  18. Development and validation of an UPLC-MS/MS method for the determination of 7-hydroxymitragynine, a μ-opioid agonist, in rat plasma and its application to a pharmacokinetic study

    PubMed Central

    Vuppala, Pradeep K.; Jamalapuram, Seshulatha; Furr, Edward B.; McCurdy, Christopher R.; Avery, Bonnie A.

    2014-01-01

    A simple, sensitive and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated to determine the concentrations of 7-hydroxymitragynine in rat plasma. Following a single step liquid-liquid extraction of plasma samples using chloroform, 7-hydroxymitragynine and the internal standard (tryptoline) were separated on an Acquity UPLC™ BEH C18 (1.7 μm, 2.1 mm×50 mm) column using an isocratic elution at a flow rate of 0.2 mL/min. The mobile phase consisted of 0.1% acetic acid in water and 0.1% acetic acid in acetonitrile (10:90, v/v). The run was 2.5 min. The analysis was carried out under the multiple reaction-monitoring mode using positive electrospray ionization. Protonated ions [M+H]+ and their respective product ions were monitored at the following transitions: 415>190 for 7-hydroxymitragynine and 173>144 for the internal standard. The calibration curve was linear over the range of 10 to 4000 ng/mL (r2=0.999) with a lower limit of quantification (LLOQ) of 10 ng/mL. The extraction recoveries ranged from 62.0% to 67.3% at concentrations (20, 600, 3200 ng/mL). Intra- and inter-day assay precisions (relative standard deviation) were less than 15% and the accuracy was within 96.5% to 104.0%. This validated method was successfully applied to quantify 7-hydroxymitragynine in rat plasma following intravenous administration. PMID:23893615

  19. A UPLC-MS/MS method for simultaneous determination of danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine in rat plasma, and its application to pharmacokinetic studies of Shenxiong glucose injection in rats.

    PubMed

    Zheng, Lin; Gong, Zipeng; Lu, Yuan; Xie, Yumin; Huang, Yong; Liu, Yue; Lan, Yanyu; Wang, Aimin; Wang, Yonglin

    2015-08-01

    A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of the four major active ingredients, danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine, in the traditional Chinese medicine Shenxiong glucose injection in rat plasma. Acidified and alkalized plasma samples were extracted using ethyl acetate, and separated on a Waters C18 column (2.1mm×50mm, 1.7μm) by using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid and luteoloside as an internal standard. Electrospray ionization in the positive-ion mode and multiple reaction monitoring were used to identify and quantitate the active components. All calibration curves showed good linearity (r>0.994) over the concentration range, with a lower limit of quantification (LLOQ) between 0.02 and 0.21μg/mL. The precision of the in vivo study was evaluated by intra- and inter-day assays, and the percentage of relative standard deviation was within 15%. Moreover, satisfactory extraction efficiency was obtained (between 83.94 and 117.81%) by liquid-liquid extraction. The validated method was successfully applied in a pharmacokinetic study in rats after intravenous administration of Shenxiong glucose injection. The results showed that the four bioactive ingredients in Shenxiong glucose injection have linear pharmacokinetic properties in rats after intravenous injection within the administered dose range and partially different ones compared to single ingredient. PMID:26118621

  20. Preclinical pharmacokinetics, tissue distribution and excretion studies of a novel anti-candidal agent-thiosemicarbazide derivative of isoniazid (TSC-INH) by validated UPLC-MS/MS assay.

    PubMed

    Iqbal, Muzaffar; Ezzeldin, Essam; Bhat, Mashooq A; Raish, Mohammad; Al-Rashood, Khalid A

    2016-01-01

    A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of thiosemicarbazide derivative of isoniazid (TSC-INH), a potent anti-candidal agent in rat plasma, tissues, urine and feces. All biological samples were prepared by protein precipitation method using celecoxib as an internal standard (IS). Chromatographic separation was achieved on Acquity BEH™ C18 (50×2.1 mm, 1.7 μm) column using gradient mobile phase of acetonitrile and water (containing 0.1% formic acid) at flow rate of 0.3 mL/min. The MRM transitions were monitored at m/z 305.00→135.89 for TSC-INH and m/z 380.08→316.03 for IS in ESI negative mode. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The pharmacokinetic study showed that the compound TSC-INH was orally active with 66% absolute bioavailability in rats. It was rapidly absorbed with peak plasma concentration of 1985.92 ng/mL achieved within 1 h after single oral dose (10 mg/kg) administration. TSC-INH exhibited rapid distribution across the body with highest levels in liver and lungs. Penetration in brain tissues suggests that TSC-INH crossed the blood brain barrier. Only 5.23% of the orally administered drug was excreted as unconverted form in urine and feces implying that TSC-INH was metabolized extensively before excretion. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of compound TSC-INH in future studies. PMID:26355768

  1. Simultaneous determination of parecoxib sodium and its active metabolite valdecoxib in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after intravenous and intramuscular administration.

    PubMed

    Liu, Meina; Yu, Qiuyang; Li, Ping; Zhu, Meng; Fang, Mingming; Sun, Bingjun; Sun, Mengchi; Sun, Yinghua; Zhang, Peng; He, Zhonggui; Sun, Jin; Wang, Yongjun; Liu, Xiaohong

    2016-06-01

    In this study, we developed and validated a new, rapid, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to simultaneously determine parecoxib sodium (PX) and its active metabolite, valdecoxib (VX), in rat plasma. Plasma samples were prepared by plasma protein precipitation combined with a liquid-liquid extraction method. The separation was carried out on a Kinetex C18 column (2.1mm×50mm, 2.6μm) with a gradient elution using methanol (A) and a 2mM ammonium acetate aqueous solution (B). The analysis was performed in less than 3min with a flow rate of 0.2mL/min. Ketoprofen was used as an internal standard (IS). Mass spectrometric detection was conducted with a triple quadrupole detector equipped with electrospray ionization in the negative ion mode (ESI(-)) using multiple reaction monitoring (MRM). The calibration curves were linear over the concentration ranges of 5-4000ng/mL for PX and 5-2000ng/mL for VX with all correlation coefficients greater than 0.998. The intra- and inter-day relative standard deviations (RSD) for both analytes were within 15% and the accuracy was within 85-115% at all quality control levels. The mean extraction recoveries for all analytes obtained from three concentrations of QC plasma samples were more than 89.0% efficient. Selectivity, matrix effect, dilution integrity and stability were also validated. The method was successfully used to investigate the pharmacokinetics of PX and VX in rat plasma after intravenous and intramuscular administration of PX. PMID:27107851

  2. Evaluation of the migration of 15 photo-initiators from cardboard packaging into Tenax(®) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

    PubMed

    Van Den Houwe, K; van de Velde, S; Evrard, C; Van Hoeck, E; Van Loco, J; Bolle, F

    2014-04-01

    Photo-initiators are widely used to cure ink on packaging materials used in food applications such as plastic films or cartonboards. In migration studies, food simulants are very often used to simulate food, like Tenax(®), which is the simulant for dry foodstuffs. In this paper a fast and reliable confirmation method for the determination of the following photo-initiators in Tenax(®) is described: benzophenone (BP), 4,4'-bis(diethylamino)benzophenone (DEAB), 2-chloro-9H-thioxanthen-9-one (CTX), 1-chloro-4-propoxy-9H-thioxanthen-9-one (CPTX), 2,4-diethyl-9H-thioxanthen-9-one (DETX), 2,2-dimethoxy-2-phenyl acetophenone (DMPA), 4-(dimethylamino)benzophenone (DMBP), 2-ethylanthraquinone (EA), ethyl-4-dimethylaminobenzoate (EDMAB), 1-hydroxylcyclohexyl phenyl ketone (HCPK), 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (HMMP), 2-isopropyl-9H-thioxanthen-9-one (ITX), 4-methylbenzophenone (MBP), Michler's ketone (MK), and 4-phenylbenzophenone (PBZ). After the migration study was completed, the simulant Tenax(®) was extracted using acetonitrile, followed by analysis on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Quantification was carried out using benzophenone-d10 (BP-d10) as internal standard. The presented method is validated in terms of matrix effect, specificity, linearity, recovery, precision and sensitivity, showing the method can detect all photo-initiators at very low concentrations (LOD < 0.125 µg g(-1) for all substances). Finally, the procedure was applied to real samples, proving the capabilities of the presented method. PMID:24447245

  3. Simultaneous determination of seven coumarins by UPLC-MS/MS: Application to a comparative pharmacokinetic study in normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan or single-herb extract.

    PubMed

    Wu, Yun; Wang, Fenrong; Ai, Yu; Ma, Wen; Bian, Qiaoxia; Lee, David Y-W; Dai, Ronghua

    2015-06-01

    A simple, sensitive and reliable ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for simultaneous quantitation of seven coumarins, the bio-active ingredients of Huo Luo Xiao Ling Dan (HLXLD), in rat plasma. The liquid-liquid extraction method with ether-dichloromethane (2:1, v/v) was used to prepare the plasma samples. Analytes and internal standard (IS) of bifendate were separated on a Shim-pack XR-ODS column (75mm×3.0mm, 2.2μm particles) using gradient elution with the mobile phase consisting of methanol and 0.05% formic acid in water at a flow rate of 0.4mL/min. Detection was performed on a triple quadrupole (TQ) tandem mass spectrometry equipped with an electrospray ionization source in the positive ionization and multiple reaction monitoring (MRM) mode. The lower limits of quantitation (LLOQ) were 0.03-0.25ng/mL for all the analytes. Intra- and inter-day precision and accuracy of the seven analytes were well within acceptance criteria (15%). The matrix effect and the mean extraction recoveries of the analytes and IS from rat plasma were all within satisfaction. The validated method has been successfully applied to compare pharmacokinetic profiles of the seven active ingredients in rat plasma between normal and arthritic rats after oral administration of HLXLD, Angelica pubescens extract and Notopterygium incisum extract, respectively. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes among the different groups. PMID:25932790

  4. Determination of six Alternaria toxins with UPLC-MS/MS and their occurrence in tomatoes and tomato products from the Swiss market.

    PubMed

    Noser, Jürg; Schneider, Patrick; Rother, Martin; Schmutz, Hansruedi

    2011-11-01

    An ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method was developed for the determination of the Alternaria toxins tenuazonic acid, alternariol, alternariol monomethyl ether, altenuene, altertoxin I and tentoxin. Owing to its instability, altenusin could not be determined. The sample preparation includes an acidic acetonitrile/water/methanol extraction, followed by SPE clean-up step, before injection into the UPLC-MS/MS system. The separation was made on an Acquity UPLC column using a water/acetonitrile gradient with ammonium hydrogen carbonate as a modifier. Matrix compounds of real samples led to enhancement as well as suppression of the target compounds, depending on analyte and matrix. The recoveries were between 58 and 109% at a level of 10 μg/kg. Eighty-five tomato products, consisting of peeled and minced tomatoes, soup and sauces, tomato purées and concentrates, ketchup as well as dried and fresh tomatoes, were taken from the Swiss market in 2010. Tenuazonic acid was found most frequently (81 out of 85 samples) and in the highest levels of up to 790 μg/kg. Alternariol and alternariol monomethyl ether were found in lower concentrations, ranging from <1 to 33 μg/kg for alternariol and <5 to 9 μg/kg for alternariol monomethyl ether. Only a few samples were positive for altenuene and tentoxin. Altertoxin I was never detected. PMID:23605928

  5. Simultaneous Determination of Typhaneoside and Isorhamnetin-3-O-Neohesperidoside in Rats After Oral Administration of Pollen Typhae Extract by UPLC-MS/MS.

    PubMed

    Cao, Sali; Ni, Boran; Feng, Lijun; Yin, Xingbin; Dou, Haoran; Fu, Jing; Lin, Longfei; Ni, Jian

    2015-07-01

    For the first time, a selective and rapid ultra-performance liquid chromatography method with tandem mass spectrometric (UPLC-MS/MS) detection for simultaneous determination of typhaneoside and isorhamnetin-3-O-neohesperidoside in rat plasma was developed and validated, which was applied to the pharmacokinetic study of Pollen Typhae extract. The separation was carried out on an ACQUITY UPLC(TM) BEH C18 column with gradient elution using mobile phase including acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.4 mL/min. The detection was conducted by means of electrospray ionization mass spectrometry in negative ion mode with multiple reaction monitoring. The assays were linear over the concentration range of 0.5-100 ng/mL, and the lower limit of quantification was 0.5 ng/mL for typhaneoside and isorhamnetin-3-O-neohesperidoside. The method was validated in terms of intra- and interday precision (<9.37%), accuracy (within ±10.91%), linearity, specificity and stability, and has been successfully applied to a pharmacokinetic study of Pollen Typhae extract in rats after oral administration. PMID:25349196

  6. Evaluation of the Effects of Ketoconazole and Voriconazole on the Pharmacokinetics of Oxcarbazepine and Its Main Metabolite MHD in Rats by UPLC-MS-MS.

    PubMed

    Chen, Xinxin; Gu, Ermin; Wang, Shuanghu; Zheng, Xiang; Chen, Mengchun; Wang, Li; Hu, Guoxin; Cai, Jian-Ping; Zhou, Hongyu

    2016-03-01

    Oxcarbazepine (OXC), a second-generation antiepileptic drug, undergoes rapid reduction with formation of the active metabolite 10,11-dihydro-10-hydroxy-carbazepine (MHD) in vivo. In this study, a method for simultaneous determination of OXC and MHD in rat plasma using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS) was developed and validated. Under given chromatographic conditions, OXC, MHD and internal standard diazepam were separated well and quantified by electrospray positive ionization mass spectrometry in the multiple reaction monitoring transitions mode. The method validation demonstrated good linearity over the range of 10-2,000 ng/mL for OXC and 5-1,000 ng/mL for MHD. The lower limit of quantification was 5 ng/mL for OXC and 2.5 ng/mL for MHD, respectively. The method was successfully applied to the evaluation of the pharmacokinetics of OXC and MHD in rats, with or without pretreatment by ketoconazole (KET) and voriconazole (VOR). Statistics indicated that KET and VOR significantly affected the disposition of OXC and MHD in vivo, whereas VOR predominantly interfered with the disposition of MHD. This method is suitable for pharmacokinetic study in small animals. PMID:26499119

  7. Quantitative determination of nine urinary metabolites of organophosphate flame retardants using solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

    PubMed

    Kosarac, Ivana; Kubwabo, Cariton; Foster, Warren G

    2016-03-01

    Over the last few years, the use of organophosphate flame retardants (OPFRs) has been on the rise; however, there are knowledge gaps in both the human health effects of OPFRs and levels of human exposure. Currently, human biomonitoring data on the levels of OPFR metabolites in the Canadian population are still non-existent. Herein we describe a novel method to measure nine urinary OPFR metabolites using solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). The method detection limits were between 0.08 and 0.25ng/mL for target metabolites. The newly developed and validated method was applied to the analysis of 24 urine samples collected in 2010-12 from pregnant Canadian women. The most frequently detected OPFR metabolite in urine of study participants (detection frequency: 97%) was diphenyl phosphate (DPHP), with concentrations ranging between <0.13-25.2ng/mL, followed (75%) by the sum of two metabolites (DoCP: Di-o-cresyl phosphate and DpCP: Di-p- cresyl phosphate) of tricresyl phosphate, with concentrations between <0.13-4.38ng/mL. With the exception of desbutyl-tris-(2-butoxy-ethyl) phosphate which was not detected in any of the samples, all other OPFR metabolites measured were found among study participants with variable detection frequency, suggesting pregnant Canadian women may be exposed to OPFRs. PMID:26869296

  8. Optimization and validation method to evaluate the residues of β-lactams and tetracyclines in kidney tissue by UPLC-MS/MS.

    PubMed

    de Almeida, Marcos Pego; Rezende, Cristiana Perdigão; Ferreira, Flavia Domingues; de Souza, Leonardo Francisco; de Assis, Débora Cristina Sampaio; de Figueiredo, Tadeu Chaves; de Oliveira Leite, Mônica; de Vasconcelos Cançado, Silvana

    2015-11-01

    Methods are validated by a process that defines the analytical requirements and confirms that the investigated method is capable of performing consistently. A quantitative and confirmatory method for determining the presence of β-lactam and tetracycline multiresidues in avian, bovine, equine, and swine kidney tissues using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed, optimized, and validated. Analytes were extracted from the kidneys by a mixture of water and acetonitrile, and the extract was then purified with hexane and C18 (dispersive phase). The method was evaluated by the following parameters: linearity, matrix effect, specificity, decision limits (CCα), detection capability (CCβ), accuracy, precision, trueness, limits of detection (LOD), limits of quantification (LOQ), and robustness. The validated method presented a broad linear study range and significant matrix effect. The limit of detection (LOD) was defined from 2.5 to 25.0 µg kg(-1), and the limit of quantification (LOQ) was defined from 5.0 to 50.0 µg kg(-1) for individual analytes. The resultant recovery values ranged from 98.1% to 107.3% in repeatability conditions and from 95.2% to 106% under intralaboratory reproducibility conditions for the studied analytes. It was concluded that the performance parameters demonstrated total method adequacy for detecting and quantifying β-lactam and tetracycline residues in swine, equine, bovine, and avian kidneys. PMID:26452909

  9. Monitoring the Response of the Human Urinary Metabolome to Brief Maximal Exercise by a Combination of RP-UPLC-MS and (1)H NMR Spectroscopy.

    PubMed

    Pechlivanis, Alexandros; Papaioannou, Konstantinos G; Tsalis, George; Saraslanidis, Ploutarchos; Mougios, Vassilis; Theodoridis, Georgios A

    2015-11-01

    The delineation of exercise biochemistry by utilizing metabolic fingerprinting has become an established strategy. We present a combined RP-UPLC-MS and (1)H NMR strategy, supplemented by photometric assays, to monitor the response of the human urinary metabolome to short maximal exercise. Seventeen male volunteers performed two identical sprint sessions on separate days, consisting of three 80 m maximal runs. Using univariate and multivariate analyses, we followed the fluctuation of 37 metabolites at 1, 1.5, and 2 h postexercise. 2-Hydroxyisovalerate, 2-hydroxybutyrate, 2-oxoisocaproate, 3-methyl-2-oxovalerate, 3-hydroxyisobutyrate, 2-oxoisovalerate, 3-hydroxybutyrate, 2-hydroxyisobutyrate, alanine, pyruvate, and fumarate increased 1 h postexercise and then returned toward baseline. Lactate and acetate were higher than baseline at 1 and 1.5 h. Hypoxanthine and inosine remained above baseline throughout the postexercise period. Urate decreased at 1 h and increased at 1.5 h before returning to baseline. Valine, isoleucine, succinate, citrate, trimethylamine, trimethylamine N-oxide, tyrosine, and formate decreased at 1 h and/or 1.5 h postexercise and then returned to baseline. Creatinine gradually decreased over the sampling period. Glycine, 4-aminohippurate, and hippurate remained below baseline throughout the postexercise period. Our findings show that even one-half minute of maximal exercise elicited major perturbations in human metabolism, several of which persisted for at least 2 h. PMID:26419189

  10. Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study.

    PubMed

    Fornasaro, Stefano; Ziberna, Lovro; Gasperotti, Mattia; Tramer, Federica; Vrhovšek, Urška; Mattivi, Fulvio; Passamonti, Sabina

    2016-01-01

    Anthocyanins exert neuroprotection in various in vitro and in vivo experimental models. However, no details regarding their brain-related pharmacokinetics are so far available to support claims about their direct neuronal bioactivity as well as to design proper formulations of anthocyanin-based products. To gather this missing piece of knowledge, we intravenously administered a bolus of 668 nmol cyanidin 3-glucoside (C3G) in anaesthetized Wistar rats and shortly after (15 s to 20 min) we collected blood, brain, liver, kidneys and urine samples. Extracts thereof were analysed for C3G and its expected metabolites using UPLC/MS-MS. The data enabled to calculate a set of pharmacokinetics parameters. The main finding was the distinctive, rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range (19-355 nM). This is the first report that accurately determines the distribution pattern of C3G in the brain, paving the way to the rational design of future tests of neuroprotection by C3G in animal models and humans. PMID:26965389

  11. A novel UPLC-MS-MS method for simultaneous determination of seven uremic retention toxins with cardiovascular relevance in chronic kidney disease patients.

    PubMed

    Boelaert, Jente; Lynen, Frédéric; Glorieux, Griet; Eloot, Sunny; Van Landschoot, Maria; Waterloos, Marie-Anne; Sandra, Pat; Vanholder, Raymond

    2013-02-01

    Chronic kidney disease (CKD) is a devastating illness characterized by accumulation of uremic retention solutes in the body. The objective of this study was to develop and validate a simple, rapid, and robust UPLC-MS-MS method for simultaneous determination, in serum, of seven organic acid uremic retention toxins, namely uric acid (UA), hippuric acid (HA), indoxylsulfate (IS), p-cresylglucuronide (pCG), p-cresylsulfate (pCS), indole-3-acetic acid (IAA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). Isotopically labeled internal standards (d(5)-HA; 1,3-(15)N(2)-UA, and d(5)-IAA) were used to correct for variations in sample preparation and system performance. Separation on a C18 column was followed by negative electrospray ionization and tandem mass spectrometric detection. Accuracy was below the 15 % threshold. Within-day precision varied from 0.60 to 4.54 % and between-day precision was below 13.33 % for all compounds. The applicability of the method was evaluated by analyzing 78 serum samples originating both from healthy controls and from patients at different stages of CKD. These results were compared with those obtained by use of conventional HPLC-PDA-FLD methods. A good correlation was obtained between both methods for all compounds. PMID:23307120

  12. Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study

    PubMed Central

    Fornasaro, Stefano; Ziberna, Lovro; Gasperotti, Mattia; Tramer, Federica; Vrhovšek, Urška; Mattivi, Fulvio; Passamonti, Sabina

    2016-01-01

    Anthocyanins exert neuroprotection in various in vitro and in vivo experimental models. However, no details regarding their brain-related pharmacokinetics are so far available to support claims about their direct neuronal bioactivity as well as to design proper formulations of anthocyanin-based products. To gather this missing piece of knowledge, we intravenously administered a bolus of 668 nmol cyanidin 3-glucoside (C3G) in anaesthetized Wistar rats and shortly after (15 s to 20 min) we collected blood, brain, liver, kidneys and urine samples. Extracts thereof were analysed for C3G and its expected metabolites using UPLC/MS-MS. The data enabled to calculate a set of pharmacokinetics parameters. The main finding was the distinctive, rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range (19–355 nM). This is the first report that accurately determines the distribution pattern of C3G in the brain, paving the way to the rational design of future tests of neuroprotection by C3G in animal models and humans. PMID:26965389

  13. Determination of tapentadol and tapentadol-O-glucuronide in human serum samples by UPLC-MS/MS.

    PubMed

    Hillewaert, Vera; Pusecker, Klaus; Sips, Luc; Verhaeghe, Tom; de Vries, Ronald; Langhans, Manfred; Terlinden, Rolf; Timmerman, Philip

    2015-02-15

    Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action, MOR agonism and noradrenaline (NA) reuptake inhibition in a single molecule. It is the first member of a new therapeutic class, MOR-NRI. A high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantitative analysis of tapentadol and its O-glucuronide metabolite in human serum. Simultaneous quantification was deemed to be challenging because of the large difference in concentrations between tapentadol and its O-glucuronide metabolite in clinical samples. Therefore, a method was established using a common processed sample, but with different injection volumes and chromatographic conditions for each analyte. Tapentadol and tapentadol-O-glucuronide were determined by protein precipitation of 0.100ml of the samples with acetonitrile. The internal standards used are D₆-tapentadol and D₆-tapentadol-O-glucuronide. The validated concentration range was 0.200-200 ng/ml (tapentadol) and 10.0-10,000 ng/ml (tapentadol-O-glucuronide). Chromatographic separation was achieved by gradient elution on a Waters Acquity UPLC BEH C18 (1.7 μm, 2.1 × 50 mm) column, with mobile phase consisting of 0.01 M ammonium formate (adjusted to pH 4 using formic acid) (A) and methanol (B). A separate injection was done for measurement of each analyte, with a different gradient and run time. The analytes were detected by using an electrospray ion source on a triple quadrupole mass spectrometer operating in positive ionization mode. The run time was 1.6 min for tapentadol and 1.5 min for tapentadol-O-glucuronide. The high sensitivity and acceptable performance of the assay allowed its application to the analysis of serum samples in clinical trials. The validated method was used for analysis of tapentadol in over 17,000 samples. PMID:25600054

  14. Analysis of ecologically relevant pharmaceuticals in wastewater and surface water using selective solid phase extraction and UPLC/MS/MS

    EPA Science Inventory

    A rapid and sensitive method has been developed for the analysis of 48 human prescription active pharmaceutical ingredients (APIs) and 6 metabolites of interest, utilizing selective solid-phase extraction (SPE) and ultra performance liquid chromatography in combination with tripl...

  15. Simultaneous determination of mequindox, quinocetone, and their major metabolites in chicken and pork by UPLC-MS/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research presents a sensitive and confirmatory multi-residue method for mequindox (MEQ), quinocetone (QCT), and their 11 metabolites in chicken and pork samples. After extracted with acetonitrile-ethyl acetate, acidulated, and extracted again with ethyl acetate sequentially, each sample was pu...

  16. A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease

    PubMed Central

    Li, Naijing; Liu, Ying; Li, Wei; Zhou, Ling; Li, Qing; Wang, Xueqing; He, Ping

    2015-01-01

    Background Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results The impaired cognitive function and increased hippocampal Aβ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD. PMID:26843817

  17. Method development for quantification of the environmental neurotoxin annonacin in Rat plasma by UPLC-MS/MS and application to a pharmacokinetic study.

    PubMed

    Bonneau, Natacha; Schmitz-Afonso, Isabelle; Brunelle, Alain; Touboul, David; Champy, Pierre

    2015-11-01

    Annonacin is an environmental neurotoxin identified in the pulp of several fruits of the Annonaceae family (for example in Annona muricata, Asimina triloba), whose consumption was linked with the occurrence of sporadic atypical Parkinsonism with dementia. Pharmacokinetic parameters of this molecule are unknown. A method for its quantification in Rat plasma was developed, using its analogue annonacinone as an internal standard. Extraction from plasma was performed using ethylacetate with a good recovery. Quantification was performed by UPLC-MS/MS in SRM mode, based on the loss of the γ-methyl-γ-lactone (-112amu) from the sodium-cationized species [M+Na](+) of both annonacin and internal standard. The limit of quantification was 0.25ng/mL. Despite strong matrix effects, a good linearity was obtained over two distinct ranges 0.25-10ng/mL and 10-100ng/mL. The intra- and inter-day precisions (RSD) were lower than 10%, while accuracy was within ±10%. This method was applied to a pharmacokinetic study in the Rat. After oral administration of 10mg/kg annonacin, a Cmax of 7.9±1.5ng/mL was reached at Tmax 0.25h; T1/2 was 4.8±0.7h and apparent distribution volume was 387.9±64.6L. The bioavailability of annonacin was estimated to be 3.2±0.3% of the ingested dose. PMID:26444335

  18. Antioxidant properties and quantitative UPLC-MS analysis of phenolic compounds from extracts of fenugreek (Trigonella foenum-graecum) seeds and bitter melon (Momordica charantia) fruit.

    PubMed

    Kenny, O; Smyth, T J; Hewage, C M; Brunton, N P

    2013-12-15

    Freeze-dried fenugreek (Trigonella foenum-graecum) seeds and bitter melon (Momordica charantia) fruit were extracted sequentially using non-polar to polar solvents, with further separation carried out on polar extracts by molecular weight cut off dialysis. The fenugreek ethyl acetate crude extract (FGE3) demonstrated the highest antioxidant activity, in terms of Trolox Equivalents (TE), for both the DPPH (35.3380.908 mg TE/g) and FRAP (77.3520.627 mg TE/g) assays. This extract also contained the highest phenolic content, in terms of Gallic Acid Equivalents (GAE) (106.3160.377 mg GAE/g). Despite having considerably lower antioxidant activity than fenugreek, the highest antioxidant activities for bitter fruit were observed in the hexane (BME1) and methanol hydrophilic<3.5 kDa dialysed (BME4<3.5 kDa) extracts, while the highest phenolic content was found in the methanol hydrophilic>3.5 kDa (BME4>3.5 kDa) dialysed extract. UPLC-MS was used to quantify 18 phenolic compounds from fenugreek and 13 from bitter melon in active crude extracts. The flavonoids apigenin-7-O-glycoside (1955.55 ng/mg) and luteolin-7-O-glycoside (725.50 ng/mg) were the most abundant compounds in FGE3, while bitter melon extracts contained only small amounts of mainly phenolic acids. A further 5 fenugreek and 1 bitter melon compounds were identified in trace amounts from the same extracts, respectively. PMID:23993618

  19. Simultaneous determination of 12 illicit drugs in whole blood and urine by solid phase extraction and UPLC-MS/MS.

    PubMed

    Zhang, Lin; Wang, Zhao-Hong; Li, Hong; Liu, Yong; Zhao, Meng; Jiang, Ye; Zhao, Wen-Song

    2014-04-01

    A rapid and sensitive method based on solid phase extraction and ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) for the simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylene-dioxymethamphetamine, N-methyl-1-(3,4-methyl-enedioxyphenyl)-2-butanamine, 3,4-methylenedioxyethylamphetamine, p-methoxymethamphetamine, ephedrine, N-methylephedrine, cathinone, methcathinone, and ketamine in whole blood and urine was developed and validated. Following solid phase extraction, the analytes were separated on ACQUITY UPLC BEH Phenyl column (100mm×2.1mm, 1.7μm) under gradient elution using a mobile phase containing of acetonitrile and 0.3% formic acid in water at a flow rate of 0.4mLmin(-1) and analyzed by a triplequadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode. The proposed method was linear for each analyte with correlation coefficients over 0.99. Recovery validation studies showed accuracy bias below 4.4%. Acceptable precision was also obtained with a relative standard deviation below 8.9%. The sensitivity of the assay was found to be adequate for the quantitation of the illicit drugs in whole blood and urine sample and was higher than reported methods. The present method was proved to be reliable and robust for drug screening in forensic toxicological analysis. PMID:24631805

  20. Simultaneous determination of lovastatin and its metabolite lovastatin acid in rat plasma using UPLC-MS/MS with positive/negative ion-switching electrospray ionization: Application to a pharmacokinetic study of lovastatin nanosuspension.

    PubMed

    Guo, Mengran; Zhao, Longshan; Li, Mo; Fu, Qiang; Pu, Xiaohui; Liu, Bingyang; He, Zhonggui; Yang, Li

    2016-06-15

    Lovastatin (LOV) is an antihyperlipidemic agent which exhibits low bioavailability due to its poor solubility. Therefore, a nanosuspension (NS) was developed as an efficient strategy to improve its oral bioavailability. To evaluate the pharmacokinetics of LOV-NS, a novel, sensitive, and rapid UPLC-MS/MS method was developed and validated for the simultaneous determination of LOV and its metabolite lovastatin acid (LOVA) in rat plasma. Simvastatin (IS) was chosen as the internal standard, and a liquid-liquid extraction method was used to isolate LOV and LOVA from biological matrices. The analytes were analyzed on an Acquity UPLC BEH C18 column, and a gradient program was applied at a flow rate of 0.2mL/min. Then, a tandem quadrupole mass spectrometer coupled with a positive/negative ion-switching electrospray ionization interface was employed to detect the analytes. Quantitation of the analytes was performed in the multiple reaction monitoring mode to monitor the transitions of m/z 427.1→325.0 for LOV and m/z 441.1→325.0 for IS in the positive ion mode and m/z 421.0→101.0 for LOVA in the negative ion mode, respectively. The method was validated over the concentration range 0.25-500ng/mL (r(2)≥0.99) for both LOV and LOVA. The intra-day and inter-day precision (RSD%) of LOV and LOVA were less than 12.87% and the accuracy (RE%) was less than 5.22%. The average extraction recoveries were 90.1% and 91.9% for LOV and LOVA, and the matrix effects were found to be between 85% and 115%. The stability study showed that both analytes were stable during the experiment. Finally, this method has been successfully applied to a pharmacokinetic study in rats following a single oral dose of 10mg/kg LOV-NS. PMID:27200472

  1. UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small molecule natural product libraries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Generation of natural product libraries containing column fractions, each with only a few small molecules, by a high throughput, automated fractionation system has made it possible to implement an improved dereplication strategy for selection and prioritization of hits in a natural product discovery...

  2. Assessment of nicotine for second hand smoke exposure in some public places in Romania by UPLC-MS

    PubMed Central

    2014-01-01

    Background Air nicotine monitoring is a well-known procedure for estimation of exposure to second hand smoke. Few research studies were realized in Romania to evaluate environmental tobacco smoke (ETS) exposure of humans in different public places. The levels of airborne nicotine from environmental tobacco smoke and urinary cotinine and nicotine levels of some subjects were analyzed. In order to better implement/enforce the European legislation regarding the interdiction of smoking in the public places the national authorities need a rapid and reliable analytical method to quickly asses the state of the pollution with cigarette smoke of these populated areas. Results The nicotine concentration in the air from different types of public buildings was determined. The median concentration of nicotine in the air from 32 pubs where the smoking was allowed was 590 ng · L-1, comparing with the pubs where the smoking was not permitted (22 locations) where the median concentration of nicotine was only 32 ng · L-1. Similarly, the median concentration of nicotine in restaurants where the smoking was allowed (23 locations) was 510 ng · L-1, in comparison with the restaurants where the smoking was prohibited (11 places) where the median value was 19 ng · L-1. The lowest concentrations of nicotine were found in high schools (8 locations, median concentration 7.4 ng · L-1), universities (5 locations, 23 ng · L-1) and hospitals (6 locations, 16 ng · L-1). Conclusions The method was validated and gave good linearity, precision, accuracy and limit of detection. The buildings included hospitals, high schools, universities, pubs and restaurants. The presence of air nicotine was recorded in all buildings studied. The highest median levels of air nicotine were found in pubs and restaurants. The presence of air nicotine in indoor public buildings indicates weak implementation of the smoke free law in Romania. PMID:24839459

  3. Distinguishing heroin abuse from codeine administration in the urine of Chinese people by UPLC-MS-MS.

    PubMed

    Bu, Jun; Zhan, Changshu; Huang, Yi; Shen, Baohua; Zhuo, Xianyi

    2013-04-01

    Heroin is a highly addictive drug, and heroin abuse is considered to be a serious criminal act. The major metabolite of heroin, morphine, can usually be detected as evidence of heroin abuse. However, it is difficult to determine heroin use when morphine and codeine are both detected, because codeine use will also result in the presence of morphine in urine. Therefore, it is important to distinguish heroin abuse from codeine administration. In this study, urine samples from 21 volunteers with various ingestion patterns of a compound codeine phosphate oral solution were used as negative controls, and urine samples from 89 alleged heroin users were used as positive controls. Urine from single and multiple doses of codeine administration were collected at different time points for a systematic comparison. After protein precipitation, the urine samples were analyzed for the presence of free morphine, free codeine and their metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The method of percentiles, with median and standard interquartile ranges, was used to describe and analyze the data based on the normality of the distribution. The ratios of concentration of morphine and morphine to codeine were found to be the possible criteria to distinguish heroin users from codeine users in Chinese people. PMID:23316032

  4. Quantitation of aldosterone in human plasma by ultra high performance liquid chromatography tandem mass spectrometry.

    PubMed

    Hinchliffe, Edward; Carter, Stephanie; Owen, Laura J; Keevil, Brian G

    2013-01-15

    Aldosterone is a mineralocorticoid steroid hormone whose measurement in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Traditionally measurement of aldosterone has been performed by radioimmunoassay, however these assays lack specificity as they are prone to interference from structurally related steroid hormones. Herein, we have developed a novel, sensitive and specific method utilising solid phase extraction and quantitation of aldosterone from human plasma by UPLC-MS/MS. Standards, quality controls and samples (250μL) were extracted using Oasis(®) HLB 96-well plates. Extract (30μL) was injected onto a Krudcatcher UPLC In-Line Filter, 0.5μm guard column, coupled to a Kinetex PFP, 100mm×2.1mm, 2.6μm column with methanolic mobile phase gradient elution. Eluant was connected to a Waters(®) Xevo TQS tandem mass spectrometer operating in electrospray negative mode. We detected multiple reaction monitoring (MRM) transitions of m/z 359.0>189.1 for aldosterone and 366.0>194.1 for d7-aldosterone respectively, which co-eluted at 2.65min. Ion suppression was negligible. Mean recovery was 89.6%, limit of detection and lower limit of quantitation were 26pmol/L and 30pmol/L respectively. The assay was linear up to 3200pmol/L (r(2)=0.9999). Mean intra- and inter-assay imprecision and bias were all <10%. Comparison of the UPLC-MS/MS method with an immunoassay in routine clinical use in the UK yielded the equation UPLC-MS/MS=0.789(RIA)-41.7, linear regression r(2)=0.88, n=54. We have developed a sensitive and specific method for the extraction and measurement of aldosterone from human plasma. The method features a simple 96-well plate solid phase extraction procedure, highly selective column chemistry and short chromatographic run times. PMID:23266360

  5. A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

    PubMed

    Torres, Luz-María; Rivera-Espinosa, Liliana; Chávez-Pacheco, Juan L; Navas, Carlos F; Demetrio, Joel A; Alemón-Medina, Radamés; Trujillo, Francisca; Pérez, Martín; Zapata, Martha M; Cárdenas, Rocío; Salinas, Citlaltepetl; Aquino, Arnoldo; Velázquez-Cruz, Rafael; Castillejos, Manuel-de-Jesús

    2015-01-01

    Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4-Q75 29.0) and 3.8 μmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients. PMID:26600181

  6. Validation and application of an UPLC-MS/MS method for the quantification of synthetic cannabinoids in urine samples and analysis of seized materials from the Portuguese market.

    PubMed

    Simões, Susana Sadler; Silva, Inês; Ajenjo, Antonio Castañera; Dias, Mário João

    2014-10-01

    An UPLC-MS/MS method using ESI+ionization and MRM was developed and fully validated according to international guidelines for the qualitative and quantitative analysis of nine synthetic cannabinoids and/or their metabolites in urine samples (1mL). Prior to extraction the samples were subjected to an enzymatic hydrolysis using β-glucuronidase followed by a SPE procedure using Oasis(®) HLB 3cc (60mg) columns. The chromatographic separation was performed with an Acquity UPLC(®) HSS T3 (50mm×2.1mm i.d., 1.8μm) reversed-phase column using a gradient with methanol-ammonium formate 2mM (0.1% formic acid) and with a run time of 9.5min. The method was validated in terms of selectivity, capacity of identification, limits of detection (0.01-0.5ng/mL) and quantification (0.05-0.5ng/mL), recovery (58-105%), carryover, matrix effect, linearity (0.05-50ng/mL), intra-assay precision, inter-assay accuracy and precision (CV<20%). The method was applied to 80 authentic samples, five of them (6.2%) were confirmed or suspected to be positive for the metabolites JWH-018 N-hydroxypentyl and JWH-018 N-pentanoic acid of JWH-018 and for the metabolite JWH-122 N-(5-hydroxypentyl) of JWH-122, and three of them in association with THC and/or THCCOOH (substances included in the method, together with the 11-OH-THC). Additionally, 17 spice products were analyzed, for which were confirmed the presence of the following substances: AM-2201, JWH-018, JWH-022 JWH-073, JWH-122, JWH-203, JWH-210, JWH-250, HU-210 and RCS-4, according to the comparison with authentic reference material and published data. The analytical method developed allowed the analysis of synthetic cannabinoids and the notification of the first cases in Portugal. PMID:25127518

  7. A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours

    PubMed Central

    Chávez-Pacheco, Juan L.; Navas, Carlos F.; Demetrio, Joel A.; Alemón-Medina, Radamés; Trujillo, Francisca; Pérez, Martín; Zapata, Martha M.; Cárdenas, Rocío; Salinas, Citlaltepetl; Aquino, Arnoldo; Velázquez-Cruz, Rafael; Castillejos, Manuel-de-Jesús

    2015-01-01

    Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4–Q75 29.0) and 3.8 μmol/L (Q25 1.5–Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients. PMID:26600181

  8. Development and validation of an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantitative determination of rhamnolipid congeners.

    PubMed

    Rudden, Michelle; Tsauosi, Konstantina; Marchant, Roger; Banat, Ibrahim M; Smyth, Thomas J

    2015-11-01

    Rhamnolipids (RLs) are synthesised as a complex mixture of congeners comprising either one or two molecules of rhamnose glycosidically linked to a dimer of 3-hydroxy fatty acids varying in chain length and degree of saturation. Currently, HPLC-MS/MS is the most precise and accurate method for RL determination, while accurate quantification is limited. In this study, a rapid ultra pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the rapid and quantification of individual RL congeners. Increased RLs specificity was achieved using tandem mass spectrometry in multiple reaction monitoring (MRM) mode which was used to quantify RL isomer pairs such as Rha-Rha-C8-C10/Rha-Rha-C10-C8 which are difficult to resolve chromatographically. UPLC showed an 18-fold reduction in retention time for Rha-Rha-C10-C10 (1.07 min) and a 17-fold reduction for Rha-C10-C10 (1.36), the major rhamnolipids present, compared to HPLC, with a total run time less than 2.2 min. The results show that the linear range for the main RL congeners (Rha-C10-C10 and Rha-Rha-C10-C10) is 0.1 to 100 μg/mL. The LOD and LOQ for Rha-C10-C10 is 0.05 and 0.1 μg/mL and for Rha-Rha-C10-C10 is 0.1 and 0.5 μg/mL, respectively. The method was validated for linearity, intra- and inter-day precision and accuracy in accordance with FDA guidelines. The method was applied for the quantification of 14 individual RL congeners produced by Pseudomonas aeruginosa ST5 and comparison of RLs composition on four different carbon sources. Quantification of the individual congeners showed a conserved congener distribution irrespective of carbon source with a preferential selection for C10 β-hydroxyacids as the lipid component of RLs. The only statistically significant differences detected were between actual RL yields on the various carbon sources. PMID:26272088

  9. Simultaneous determination of caffeic acid derivatives by UPLC-MS/MS in rat plasma and its application in pharmacokinetic study after oral administration of Flos Lonicerae-Fructus Forsythiae herb combination.

    PubMed

    Zhou, Wei; Shan, Jinjun; Wang, Shouquan; Ju, Wenzheng; Meng, Minxin; Cai, Baochang; Di, Liuqing

    2014-02-15

    The current study aims to investigate the pharmacokinetic study of eight caffeic acid derivatives (forsythoside A, isoforsythoside, forsythoside B, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 3,5-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid) following oral administration of Flos Lonicerae-Fructus Forsythiae herb combination in rats. A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine the eight caffeic acid derivatives simultaneously in rat plasma. After mixing with the internal standard (IS) tinidazole, plasma samples were pretreated by liquid-liquid extraction with n-butyl alcohol/ethyl acetate (7:3, v/v). The separation was performed on an Acquity UPLC HSS T3 C18 column (100mm×2.1mm, 1.8μm) at a flow rate of 0.4mLmin(-1), and acetonitrile/methanol (4:1, v/v)-0.4% formic acid was used as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive and negative ionization modes. All calibration curves had good linearity (r>0.991) over the concentration ranges of 1.097-2246ngmL(-1) for neochlorogenic acid, 6.535-6692ngmL(-1) for chlorogenic acid, 2.103-2153ngmL(-1) for cryptochlorogenic acid, 0.5058-129.5ngmL(-1) for 3,5-dicaffeoylquinic acid, 0.3205-82.05ngmL(-1) for 3,4-dicaffeoylquinic acid, 1.002-512.8ngmL(-1) for isoforsythoside, 0.4795-982.1ngmL(-1) for forsythoside A and 0.7587-776.9ngmL(-1) for forsythoside B, respectively. The intra- and inter-batch precisions were all within 15% and the accuracy (relative error, RE%) all ranged from 85.68% to 114.7%. It was shown from pharmacokinetic parameters that the rank order of AUC0-t, Cmax and T1/2k for phenolic acids was chlorogenic acid>neochlorogenic acid≥cryptochlorogenic acid>3,4-dicaffeoylquinic acid≥3,5-dicaffeoylquinic acid (most of them had significant differences), which corresponded to their administration dosages to rats, but that of MRT0-t and T1/2z were opposite. Besides, the AUC0-t, Cmax, MRT and T1/2z except T1/2k of isoforsythoside and forsythoside B had no significant difference, compared to that of forsythoside A though their administration dosages were significantly lower than that of forsythoside A. All results showed that the method was applied to the pharmacokinetic study of the eight caffeic acid derivatives in rat plasma successfully after oral administration of Flos Lonicerae-Fructus Forsythiae herb combination, and there were significant differences of caffeic acid derivatives even isomers in the pharmacokinetic parameters. PMID:24441018

  10. Development and validation of a sample stabilization strategy and a UPLC-MS/MS method for the simultaneous quantitation of acetylcholine (ACh), histamine (HA), and its metabolites in rat cerebrospinal fluid (CSF).

    PubMed

    Zhang, Yanhua; Tingley, F David; Tseng, Elaine; Tella, Max; Yang, Xin; Groeber, Elizabeth; Liu, Jianhua; Li, Wenlin; Schmidt, Christopher J; Steenwyk, Rick

    2011-07-15

    A UPLC-MS/MS assay was developed and validated for simultaneous quantification of acetylcholine (ACh), histamine (HA), tele-methylhistamine (t-mHA), and tele-methylimidazolacetic acid (t-MIAA) in rat cerebrospinal fluid (CSF). The biological stability of ACh in rat CSF was investigated. Following fit-for-purpose validation, the method was applied to monitor the drug-induced changes in ACh, HA, t-mHA, and t-MIAA in rat CSF following administration of donepezil or prucalopride. The quantitative method utilizes hydrophilic interaction chromatography (HILIC) Core-Shell HPLC column technology and a UPLC system to achieve separation with detection by positive ESI LC-MS/MS. This UPLC-MS/MS method does not require extraction or derivatization, utilizes a stable isotopically labeled internal standard (IS) for each analyte, and allows for rapid throughput with a 4 min run time. Without an acetylcholinesterase (AChE) inhibitor present, ACh was found to have 1.9±0.4 min in vitro half life in rat CSF. Stability studies and processing modification, including the use of AChE inhibitor eserine, extended this half life to more than 60 min. The UPLC-MS/MS method, including stabilization procedure, was validated over a linear concentration range of 0.025-5 ng/mL for ACh and 0.05-10 ng/mL for HA, t-mHA, and t-MIAA. The intra-run precision and accuracy for all analytes were 1.9-12.3% CV and -10.2 to 9.4% RE, respectively, while inter-run precision and accuracy were 4.0-16.0% CV and -5.3 to 13.4% RE, respectively. By using this developed and validated method, donepezil caused increases in ACh levels at 0.5, 1, 2, and 4h post dose as compared to the corresponding vehicle group, while prucalopride produced approximately 1.6- and 3.1-fold increases in the concentrations of ACh and t-mHA at 1h post dose, respectively, compared to the vehicle control. Overall, this methodology enables investigations into the use of CSF ACh and HA as biomarkers in the study of these neurotransmitter systems and related drug discovery efforts. PMID:21684223

  11. Human liver cytosolic sulfotransferase 2A1-dependent dehydroepiandrosterone sulfation assay by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Bansal, Sumit; Lau, Aik Jiang

    2016-02-20

    Sulfotransferase 2A1 (SULT2A1) is a major catalyst of the sulfation of dehydroepiandrosterone (DHEA) to dehydroepiandrosterone sulfate (DHEA-S) in human liver cytosol. However, there is a lack of a sensitive and fast analytical method for the human liver cytosolic SULT2A1-dependent DHEA sulfation assay. Therefore, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify DHEA-S and used it to optimize the human liver cytosolic SULT2A1-dependent DHEA sulfation assay. DHEA-S and cortisol (internal standard) eluted at 2.95 and 2.75min, respectively. Negative multiple reaction monitoring was used to quantify DHEA-S (m/z 367.3→97.0) and cortisol (m/z 407.2→331.3). No interfering peaks were observed in blank samples. The lower limit of quantification was 0.2pmol DHEA-S and the calibration curve was linear from 0.2 to 200pmol. The intra-day and inter-day accuracy and precision was <11.7%. DHEA-S in the quality control samples was stable at room temperature, 4°C, and -20°C. The cytosolic matrix (20-100μg cytosolic protein) did not affect DHEA-S quantification. Our UPLC-MS/MS method was applied to optimize the human liver cytosolic SULT2A1-dependent DHEA sulfation assay. The optimal levels of MgCl2 and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) cofactor were 2.5mM and 20μM, respectively. Reducing agents, including 2-mercaptoethanol and DL-dithiothreitol, did not affect the enzyme activity. A linear relationship existed between DHEA sulfation and amount of human liver cytosol (20-200μg cytosolic protein) or incubation time (5-30min). This UPLC-MS/MS approach is safer, easier, and faster than existing radiometric-based sulfotransferase enzyme assays, and it is the first UPLC-MS/MS method for determining SULT2A1-dependent DHEA sulfation in human liver cytosol. PMID:26760244

  12. Development of a sensitive and selective liquid chromatography-mass spectrometry method for high throughput analysis of paralytic shellfish toxins using graphitised carbon solid phase extraction.

    PubMed

    Boundy, Michael J; Selwood, Andrew I; Harwood, D Tim; McNabb, Paul S; Turner, Andrew D

    2015-03-27

    Routine regulatory monitoring of paralytic shellfish toxins (PST) commonly employs oxidative derivitisation and complex liquid chromatography fluorescence detection methods (LC-FL). The pre-column oxidation LC-FL method is currently implemented in New Zealand and the United Kingdom. When using this method positive samples are fractionated and two different oxidations are required to confirm the identity and quantity of each PST analogue present. There is a need for alternative methods that are simpler, provide faster turnaround times and have improved detection limits. Hydrophilic interaction liquid chromatography (HILIC) HPLC-MS/MS analysis of PST has been used for research purposes, but high detection limits and substantial sample matrix issues have prevented it from becoming a viable alternative for routine monitoring purposes. We have developed a HILIC UPLC-MS/MS method for paralytic shellfish toxins with an optimised desalting clean-up procedure on inexpensive carbon solid phase extraction cartridges for reduction of matrix interferences. This represents a major technical breakthrough and allows sensitive, selective and rapid analysis of paralytic shellfish toxins from a variety of sample types, including many commercially produced bivalve molluscan shellfish species. Additionally, this analytical approach avoids the need for complex calculations to determine sample toxicity, as unlike other methods each PST analogue is able to be quantified as a single resolved peak. This article presents the method development and optimisation information. A thorough single laboratory validation study has subsequently been performed and this data will be presented elsewhere. PMID:25704772

  13. Development of a high-throughput ultra performance liquid chromatography-mass spectrometry assay to profile 18 eicosanoids as exploratory biomarkers for atherosclerotic diseases.

    PubMed

    Rago, Brian; Fu, Cexiong

    2013-10-01

    Abundant evidence suggests a prominent role for eicosanoids and metabolites in the pathogenesis and prognosis of inflammatory diseases. A sensitive and high-throughput SPE UPLC-MS/MS method was developed to quantitatively interrogate the levels of 18 eicosanoids in human and monkey plasma samples. A limit of quantitation of 0.25ng/mL was achieved for all 18 investigated compounds with linear ranges spanning four orders of magnitude. Bioanalytical performance of this assay was fully characterized including SPE extraction efficiency, matrix effect, autosampler stability, benchtop stability and freeze-thaw cycle variability. Endogenous levels of the eicosanoids and analogs within a set of monkey plasma samples challenged with lipopolysaccharide and human plasma samples were quantified by this ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay. Quantitative eicosanoid profiles of the human samples were further analyzed by a non-supervised cluster analysis, which revealed a set of potential positive and negative lipid biomarkers to distinguish the following three groups: healthy individuals, hypertensive patients and severe atherosclerosis patients. The components of the negative biomarker cluster (8-HETE, LTB4, 9-HODE and 13-HODE) are putative ligands of peroxisome proliferator-activated receptors (PPARs), a family of master genes controlling the resolution of inflammatory signaling. PMID:23973531

  14. Simultaneous detection of endocrine disrupting chemicals including conjugates in municipal wastewater and sludge with enhanced sample pretreatment and UPLC-MS/MS.

    PubMed

    Zhu, Bing; Ben, Weiwei; Yuan, Xiangjuan; Zhang, Yu; Yang, Min; Qiang, Zhimin

    2015-08-01

    The co-existence of free and conjugated estrogens and the interference from complex matrices often lead to largely variable detected concentrations and sometimes even negative removal efficiencies of typical endocrine disrupting chemicals (EDCs) in wastewater treatment plants (WWTPs). In this study, a highly selective and sensitive method was developed for simultaneous extraction, elution, and detection of 12 EDCs (i.e., 4 free estrogens, 6 conjugated estrogens, and 2 phenolic compounds) in municipal wastewater and sludge. Sample pretreatment and ultra-performance liquid chromatography-tandem mass spectrometry detection were optimized to improve the detection selectivity and sensitivity. The results indicate that the additional purification process was highly effective in reducing the matrix interference, and the limits of quantification reached as low as 0.04-2.2 ng L(-1) in wastewater and 0.05-4.9 ng g(-1) in sludge for all target EDCs. The developed method was successfully applied to explore the behavior of target EDCs in a local WWTP. The conjugates occupied a considerable portion (4.3-76.9% in molar ratio) of each related estrogen in the influent. Most of the target EDCs could not be completely removed in WWTPs, thus posing a potential threat to aquatic ecosystems. PMID:26161687

  15. High-Sensitivity Spectrophotometry.

    ERIC Educational Resources Information Center

    Harris, T. D.

    1982-01-01

    Selected high-sensitivity spectrophotometric methods are examined, and comparisons are made of their relative strengths and weaknesses and the circumstances for which each can best be applied. Methods include long path cells, noise reduction, laser intracavity absorption, thermocouple calorimetry, photoacoustic methods, and thermo-optical methods.…

  16. High-Sensitivity Spectrophotometry.

    ERIC Educational Resources Information Center

    Harris, T. D.

    1982-01-01

    Selected high-sensitivity spectrophotometric methods are examined, and comparisons are made of their relative strengths and weaknesses and the circumstances for which each can best be applied. Methods include long path cells, noise reduction, laser intracavity absorption, thermocouple calorimetry, photoacoustic methods, and thermo-optical methods.

  17. Quantitative Analysis of Staphylococcal Enterotoxins A and B in Food Matrices Using Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS)

    PubMed Central

    Zuberovic Muratovic, Aida; Hagström, Thomas; Rosén, Johan; Granelli, Kristina; Hellenäs, Karl-Erik

    2015-01-01

    A method that uses mass spectrometry (MS) for identification and quantification of protein toxins, staphylococcal enterotoxins A and B (SEA and SEB), in milk and shrimp is described. The analysis was performed using a tryptic peptide, from each of the toxins, as the target analyte together with the corresponding 13C-labeled synthetic internal standard peptide. The performance of the method was evaluated by analyzing spiked samples in the quantification range 2.5–30 ng/g (R2 = 0.92–0.99). The limit of quantification (LOQ) in milk and the limit of detection (LOD) in shrimp was 2.5 ng/g, for both SEA and SEB toxins. The in-house reproducibility (RSD) was 8%–30% and 5%–41% at different concentrations for milk and shrimp, respectively. The method was compared to the ELISA method, used at the EU-RL (France), for milk samples spiked with SEA at low levels, in the quantification range of 2.5 to 5 ng/g. The comparison showed good coherence for the two methods: 2.9 (MS)/1.8 (ELISA) and 3.6 (MS)/3.8 (ELISA) ng/g. The major advantage of the developed method is that it allows direct confirmation of the molecular identity and quantitative analysis of SEA and SEB at low nanogram levels using a label and antibody free approach. Therefore, this method is an important step in the development of alternatives to the immune-assay tests currently used for staphylococcal enterotoxin analysis. PMID:26378579

  18. Validation of Simultaneous Quantitative Method of HIV Protease Inhibitors Atazanavir, Darunavir and Ritonavir in Human Plasma by UPLC-MS/MS

    PubMed Central

    Mishra, Tulsidas; Shrivastav, Pranav S.

    2014-01-01

    Objectives. HIV protease inhibitors are used in the treatment of patients suffering from AIDS and they act at the final stage of viral replication by interfering with the HIV protease enzyme. The paper describes a selective, sensitive, and robust method for simultaneous determination of three protease inhibitors atazanavir, darunavir and ritonavir in human plasma by ultra performance liquid chromatography-tandem mass spectrometry. Materials and Methods. The sample pretreatment consisted of solid phase extraction of analytes and their deuterated analogs as internal standards from 50 μL human plasma. Chromatographic separation of analytes was performed on Waters Acquity UPLC C18 (50 × 2.1 mm, 1.7 μm) column under gradient conditions using 10 mM ammonium formate, pH 4.0, and acetonitrile as the mobile phase. Results. The method was established over a concentration range of 5.0–6000 ng/mL for atazanavir, 5.0–5000 ng/mL for darunavir and 1.0–500 ng/mL for ritonavir. Accuracy, precision, matrix effect, recovery, and stability of the analytes were evaluated as per US FDA guidelines. Conclusions. The efficiency of sample preparation, short analysis time, and high selectivity permit simultaneous estimation of these inhibitors. The validated method can be useful in determining plasma concentration of these protease inhibitors for therapeutic drug monitoring and in high throughput clinical studies. PMID:24587725

  19. UPLC-MS/MS determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma and its application to a pharmacokinetic study after oral administration of Si-Ni-San decoction.

    PubMed

    Wen, Jing; Qiao, Ying; Yang, Jie; Liu, Xinyu; Song, Yang; Liu, Zhigang; Li, Famei

    2012-07-01

    A UPLC-MS/MS method was developed for the simultaneous determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma. A Waters BEH C(18) column was used with a gradient mobile phase system of methanol-water containing 2 mM ammonium acetate. The analysis was performed on a positive ionization electrospray mass spectrometer via multiple reaction monitoring (MRM). One-step protein precipitation with acetonitrile was used to extract the analytes from plasma. The limits of quantification were 9.800 ng/ml for paeoniflorin, 5.100 ng/ml for naringin, 5.200 ng/ml for naringenin and 10.60 ng/ml for glycyrrhetinic acid, respectively. The intra- and inter-day precision (relative standard deviation, RSD) ranged 4.9-12% and 2.8-13%, respectively. The accuracy (relative error, RE) was from -7.3% to 7.5% at all quality control (QC) levels. The validated method was applied to a pharmacokinetic study in rats after oral administration of Si-Ni-San decoction. PMID:22521636

  20. Rapid screening of mycotoxins in liquid milk and milk powder by automated size-exclusion SPE-UPLC-MS/MS and quantification of matrix effects over the whole chromatographic run.

    PubMed

    Wang, Xiupin; Li, Peiwu

    2015-04-15

    An automated, size-exclusion solid phase extraction (SPE)-UPLC-MS/MS protocol without pre-treatment of samples was developed to screen for four mycotoxins (OTA, ZEN, AFB1, and AFM1) in liquid milk and milk powder. Firstly, a mixed macropore-silica gel cartridge was established as a size-exclusion SPE column. The proposed methodology could be a candidate in green analytical chemistry because it saves on manpower and organic solvent. Permanent post-column infusion of mycotoxin standards was used to quantify matrix effects throughout the chromatographic run. Matrix-matched calibration could effectively compensate for matrix effects, which may be caused by liquid milk or milk powder matrix. Recovery of the four mycotoxins in fortified liquid milk was in the range 89-120% and RSD 2-9%. The LOD for the four mycotoxins in liquid milk and milk powder were 0.05-2 ng L(-1) and 0.25-10 ng kg(-1), respectively. The LOQ for the four mycotoxins in liquid milk and milk powder were 0.1-5 ng L(-1) and 0.5-25 ng kg(-1), respectively. PMID:25466104

  1. Determination of Free and Total Carnitine and Choline in Infant Formulas and Adult Nutritional Products by UPLC/MS/MS: Single-Laboratory Validation, First Action 2014.04.

    PubMed

    Jing, Wei; Thompson, Joseph J; Jacobs, Wesley A; Salvati, Louis M

    2015-01-01

    A single-laboratory validation (SLV) has been performed for a method that simultaneously determines choline and carnitine in nutritional products by ultra performance LC (UPLC)/MS/MS. All 11 matrixes from the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) were tested. Depending on the sample preparation, either the added (free, with a water dilution and filtering) or total (after microwave digestion at 120°C in nitric acid and subsequent neutralization with ammonia) species can be detected. For nonmilk containing products, the total carnitine is almost always equal to the free carnitine. A substantial difference was noted between free and total choline in all products. All Standard Method Performance Requirements for carnitine and choline have been met. This report summarizes the material sent to the AOAC Expert Review Panel for SPIFAN nutrient methods for the review of this method, as well as some additional data from an internal validation. The method was granted AOAC First Action status for carnitine in 2014 (2014.04), but the choline data are also being presented. A comparison of choline results to those from other AOAC methods is given. PMID:26110467

  2. Determination of vitamins D2 and D3 in infant formula and adult nutritionals by ultra-pressure liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS): First Action 2011.12.

    PubMed

    Stevens, Jack; Dowell, Dawn

    2012-01-01

    The method for the "Determination of Vitamins D2 and D3 in Infant Formula and Adult Nutritionals by Ultra-Pressure Liquid Chromatography with Tandem Mass Spectrometry Detection (UPLC-MS/MS)" was adopted as AOAC Official First Action during the "Standards Development and International Harmonization: AOAC INTERNATIONAL Mid-Year Meeting" held June 29, 2011. During the meeting, an Expert Review Panel (ERP) evaluated the available validation information against standard method performance requirements (SMPRs) articulated by stakeholders. The method, approved by the ERP, is applicable for the determination of vitamin D (total vitamins D2 and D3). A range of products had been tested during a single-laboratory validation study. The products included butter, National Institute of Standards and Technology SRM 1849, eggs, cheese, yogurt, ready-to-eat cereal, bread, mushrooms, and tuna. The testing of the method established linearity in the range of 0.005-50 microg/mL. The recovery range was 93.4-100.9% for vitamin D2 and 102.4-106.2% for vitamin D3. The LOD and LOQ for vitamin D2 were reported as 0.20 and 0.61 microgl100 g, respectively; for vitamin D3, the reported values were 0.47 and 1.44 microg/100 g, respectively. The method met the SMPRs set by the Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN). It was, therefore, decided that the method was appropriate for Official First Action Method status. PMID:22816246

  3. Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs)

    PubMed Central

    Wang, Rui; Xiong, Ai-Zhen; Teng, Zhong-Qiu; Yang, Qi-Wei; Shi, Yan-Hong; Yang, Li

    2012-01-01

    Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl4-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl4 injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed. PMID:23203085

  4. SPE-UPLC-MS/MS for the determination of phthalate monoesters in rats urine and its application to study the effects of food emulsifier on the bioavailability of priority controlling PAEs.

    PubMed

    Xu, R; Gao, H T; Zhu, F; Cao, W X; Yan, Y H M; Zhou, X; Xu, Q; Ji, W L

    2016-02-15

    This research was mainly focused on the effects of food emulsifier on the bioavailability of six priority controlling phthalate acid esters (PAEs) for the further accurate assessment of their toxic effects, using the corresponding phthalate acid monoesters (PAMEs) in rats urine as biomarkers. Glycerin monostearate was chosen as typical food emulsifier. A method was established to determine PAMEs in urine from rats either in experimental group (integrated gavaged with glycerin monostearate and PAEs) or in control group (gavaged with PAEs only), by using solid-phase extraction (SPE) coupled with ultra performance liquid chromatography tandem mass spectrometry (SPE-UPLC-MS/MS). Extraction recoveries were more than 75% for all the PAMEs; the calibration curve was linear in the range of 1.0-1000.0ng/mL with R(2)>0.995; the limits of detection (LOD) were 0.30ng/mL-0.50ng/mL. In addition, by analysing quality control (QC) urine samples in 3 days, it showed that the method was precise and accurate, for the intra-day and inter-day RSD within 16%, and the accuracy more than 82%. Internal exposure amount of all PAEs in experimental group was significantly higher than that in control group with p values of less than 0.05 except for butyl benzyl phthalates (BBP) (P=0.07). The bioavailability of all PAEs ranged from 5.03% to 109.35% with the presence of food emulsifiers glycerin monostearate, observably higher than that without glycerin monostearate (1.12% to 54.39%). It indicated that food emulsifiers increased the bioavailability of PAEs and may lead to potential food safety risk, which should bring awareness and be further studied. PMID:26815919

  5. Direct Quantitative Analysis of a 20 kDa PEGylated Human Calcitonin Gene Peptide Antagonist in Cynomolgus Monkey Serum Using In-Source CID and UPLC-MS/MS

    NASA Astrophysics Data System (ADS)

    Li, Hongyan; Rose, Mark J.; Holder, Jerry Ryan; Wright, Marie; Miranda, Les P.; James, Christopher A.

    2011-09-01

    PEGylation is a successful strategy to improve the pharmacokinetic and pharmaceutical properties of therapeutic peptides. However, quantitative analysis of PEGylated peptides in biomatrix by LC-MS/MS poses significant analytical challenge due to the polydispersity of the polyethylene glycol (PEG), and the multiple charge states observed for both the peptide and PEG moieties. In this report, a novel LC-MS/MS method for direct quantitative analysis of 20 kDa PEGylated CGRP[Cit, Cit] in cynomolgus monkey serum is presented. CGRP[Cit, Cit] is an investigational human calcitonin gene peptide receptor antagonist with amino acid sequence Ac -WVTH[Cit]LAGLLS[Cit]SGGVVRKNFVPT DVGPFAF- NH 2 . In-source collision-induced dissociation (in-source CID) of 20 kDa PEGylated peptide was used to generate CGRP[Cit, Cit] fragment ions, among which the most abundant b {8/+} ion was selected and measured as a surrogate for the 20 kDa PEGylated peptide. A solid phase extraction (SPE) method was used to extract the PEGylated peptides from the biomatrix prior to the UPLC-MS/MS analysis. This method achieved a lower limit of quantitation (LLOQ) of 5.00 ng/mL with a serum sample volume of 100 μL, and was linear over the calibration range of 5.00 to 500 ng/mL in cynomolgus monkey serum. Intraday and interday accuracy and precision from QC samples were within ±15%. This method was successfully applied to a pharmacokinetic study of the 20 kDa PEGylated CGRP[Cit, Cit] in cynomolgus monkeys.

  6. Simultaneous determination of puerarin and its active metabolite in human plasma by UPLC-MS/MS: application to a pharmacokinetic study.

    PubMed

    Jung, Hyo-Rin; Kim, Sook-Jin; Ham, Seong-Ho; Cho, Jung-Hee; Lee, Yong-Bok; Cho, Hea-Young

    2014-11-15

    A rapid, selective and sensitive ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry method about the simultaneous determination of puerarin and its major active metabolite, daidzein, in human plasma was developed and validated in order to investigate the pharmacokinetics (PKs) of Gegen after the usual oral dose administration to human. Chromatography was carried out on a Kinetex C18 column (2.1mm×50mm, 1.7μm) using 0.05% acetic acid in water and 0.05% acetic acid in methanol as mobile phase with a gradient elution. Liquid-liquid extraction with ethyl acetate in acidic condition could remove the interference and minimize the matrix effect of human plasma. The lower limit of quantification in human plasma was 0.2ng/mL for both of compounds, puerarin and daidzein. The calibration curves for puerarin and daidzein in human plasma were linear over all the concentration range of 0.2-100ng/mL with correlation coefficients greater than 0.998. This assay procedure was successfully applied to the PKs of puerarin and daidzein, after the usual oral dose of Gegen extract powder (2.56g, containing 9.984mg puerarin) in human subjects. PMID:25264914

  7. Ultrasound-assisted hydrolysis of conjugated parabens in human urine and their determination by UPLC-MS/MS and UPLC-HRMS.

    PubMed

    Schlittenbauer, Linda; Seiwert, Bettina; Reemtsma, Thorsten

    2016-02-01

    Parabens are preservatives widely used in personal care products, pharmaceutical formulations as well as in food, and they are considered endocrine disruptors. For application in biomonitoring studies we developed a method for the determination of eight parabens from human urine. Sample preparation was enhanced and simplified by the combination of ultrasound-assisted enzymatic hydrolysis of conjugates (glucuronide and sulfate) followed by an extraction-free cleanup step. Quantification, using deuterated parabens as internal standards, was performed by ultrahigh-performance liquid chromatography coupled to either triple-quadrupole (UPLC-QqQ) or time-of-flight (UPLC-QqTOF) mass spectrometry. Full chromatographic separation of three butyl paraben isomers was achieved. Limits of quantification for both mass analyzers ranged from 0.1 to 0.5 μg/L for methyl, ethyl, n-/isopropyl, n-/isobutyl, and benzyl paraben in 200 μL of urine sample. The method was tested for applicability and showed high precision (intra- and interday 0.9-14.5 %) as well as high accuracy (relative recovery 95-132 %). A total of 39 urine samples were analyzed by both mass analyzers. The results agreed well, with a trend to higher deviation at low concentrations (less than 10 μg/L). Methyl, ethyl, and n-propyl paraben were detected most frequently (in more than 87 % of the samples) with median concentrations ranging from 0.8 to 16.6 μg/L. Female urine showed higher median concentrations for all parabens, which may indicate higher exposure due to lifestyle. This method permits accurate and high-throughput analysis of parabens for epidemiological studies. Further, the UPLC-QqTOF approach provides additional information on human exposure to other compounds by post-acquisition analysis. Graphical abstract Analytical procedure for paraben analysis from human urine samples including ultrasound-enhanced enzymatic digestion of glucuronide and sulfate conjugates, extraction-free clean-up and quantification by UHPLC-MS/MS. PMID:26753983

  8. Natural occurrence of fumonisins and ochratoxin A in some herbs and spices commercialized in Poland analyzed by UPLC-MS/MS method.

    PubMed

    Waśkiewicz, Agnieszka; Beszterda, Monika; Bocianowski, Jan; Goliński, Piotr

    2013-12-01

    Unsanitary conditions during harvesting, drying, packing and storage stages in production and processing of spices and herbs could introduce mycotoxin contamination. The occurrence of ochratoxin A and fumonisins in popular spices and herbs was studied, using liquid chromatography-electrospray-mass spectrometry. Apart from mycotoxins, ergosterol as a factor indicating fungal development was also analysed. A total of 79 different samples commercialized in Poland were randomly purchased from popular markets were tested for mycotoxins. The frequency of samples with fumonisins was lower (31%) than ochratoxin A (49%). Free from mycotoxins were samples of bay leaf and white mustard. ERG content - in spice samples with high concentration level of mycotoxins - was also significantly higher than in samples with little to no mycotoxins. PMID:24010625

  9. Study of the ESI and APCI interfaces for the UPLC-MS/MS analysis of pesticides in traditional Chinese herbal medicine.

    PubMed

    Chen, Lina; Song, Fengrui; Liu, Zhiqiang; Zheng, Zhong; Xing, Junpeng; Liu, Shuying

    2014-02-01

    In this work, 53 selected pesticides of different chemical groups were extracted from Chinese herbal medicines and determined by ultra-high-performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS/MS) using both electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI). Extracts were obtained using the acetonitrile-based quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation technique. Cleanup was performed by dispersive solid-phase extraction using primary secondary amine, graphitized carbon black, and octadecylsilane. Two atmospheric-pressure interfaces, ESI and APCI, were checked and compared. The validation study, including detection limits, linearity, and matrix effects, was conducted on fritillaria, radix ginseng, folium isatidis, semen persicae, and flos lonicerae in multiple reaction monitoring mode. These matrices represent a variety of plants used in traditional Chinese medicine. Fritillaria and radix ginseng were chosen as representatives for roots, folium isatidis was chosen as a representative for leaves, semen persicae was chosen as a representative for seeds, and flos lonicerae was chosen as a representative for flowers. The limits of detection for pesticides were lower in the UHPLC-ESI-MS/MS method than in the UHPLC-APCI-MS/MS method. Matrix effects on the two ionizations were evaluated for the five matrices. Soft signal enhancement in UHPLC-APCI-MS/MS and signal suppression in UHPLC-ESI-MS/MS were observed. PMID:24346143

  10. Dose-Independent ADME Properties and Tentative Identification of Metabolites of α-Mangostin from Garcinia mangostana in Mice by Automated Microsampling and UPLC-MS/MS Methods.

    PubMed

    Han, Seung Yon; You, Byoung Hoon; Kim, Yu Chul; Chin, Young-Won; Choi, Young Hee

    2015-01-01

    The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME) is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of α-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. α-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5-20 mg/kg and oral doses of 10-100 mg/kg. The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of α-mangostin in mice provide an important basis for preclinical applications of α-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice. PMID:26176540

  11. Dose-Independent ADME Properties and Tentative Identification of Metabolites of α-Mangostin from Garcinia mangostana in Mice by Automated Microsampling and UPLC-MS/MS Methods

    PubMed Central

    Kim, Yu Chul; Chin, Young-Won; Choi, Young Hee

    2015-01-01

    The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME) is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of α-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. α-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5–20 mg/kg and oral doses of 10–100 mg/kg. The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of α-mangostin in mice provide an important basis for preclinical applications of α-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice. PMID:26176540

  12. [Determination of six amide pesticide residues in vegetables and fruits by solid phase extraction-ultra high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Ma, Lin; Chen, Jianbo; Zhao, Li; Zhan, Xiuping

    2015-10-01

    A solid phase extraction coupled with ultra high performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) method was developed for simultaneous determination of six amide pesticides, cyantraniliprole, mandipropamid, boscalid, fluopicolide, thifluzamide and flubendiamide, in vegetables and fruits. After extraction with acetonitrile, purification with Florisil SPE cartridges and dissolution with methanol, the targets in the sample solutions were analyzed by UPLC-MS/MS on an Agilent Proshell 120 EC-C18 column with a mixture of 0.1% formic acid solution and methanol as the mobile phases under gradient elution conditions. The mass spectrometer operated in multiple reaction monitoring (MRM) mode with the negative and positive modes. Good linearity was obtained for the six amide pesticides at the mass concentrations of 0.000 5 - 1.00 mg/L with the correlation coefficients more than 0.999. The fortified recoveries were in the range of 72.4% - 119.4% with the concentration levels at 0.01, 0.1 and 1.0 mg/kg for cyantraniliprole, mandipropamid, boscalid, fluopicolide, thifluzamide, and 0.001, 0.01 and 0.1 mg/kg for flubendiamide. The relative standard deviations (RSDs) were less than 15% and the limits of quantification were 0.01 mg/kg for cyantraniliprole, mandipropamid, boscalid, fluopicolide, thifluzamide, and 0.001 mg/kg for flubendiamide. All the above observations indicate that the established analytical method is simple, efficient and sensitive, and suitable for the determination of the six amide pesticides in vegetables and fruits. PMID:26930957

  13. High-Sensitivity Microwave Optics.

    ERIC Educational Resources Information Center

    Nunn, W. M., Jr.

    1981-01-01

    Describes a 3.33-cm wavelength (9 GHz) microwave system that achieves a high overall signal sensitivity and a well-collimated beam with moderate-size equipment. The system has been used to develop microwave versions of the Michelson interferometer, Bragg reflector, Brewster's law and total internal reflection, and Young's interference experiment.…

  14. High sensitive airborne radioiodine monitor.

    PubMed

    Ogata, Yoshimune; Yamasaki, Tadashi; Hanafusa, Ryuji

    2013-11-01

    Airborne radioiodine monitoring includes a problem in that commercial radioactive gas monitors have inadequate sensitivity. To solve this problem, we designed a highly sensitive monitoring system. The higher counting efficiency and lower background made it possible to perform the low-level monitoring. The characteristics of the system were investigated using gaseous (125)I. The minimum detectable activity concentration was 1 × 10(-4)Bq cm(-3) for 1 min counting, which is one tenth of the legal limit for the radiation controlled areas in Japan. PMID:23602709

  15. High-sensitivity magnetoresistive transducers

    NASA Astrophysics Data System (ADS)

    Pant, Bharat B.; Krahn, Donald R.

    1991-04-01

    Magnetoresistive transducers, combined with appropriate signal conditioning, can be used to detect magnetic-field changes from small currents, geomagnetic anomalies, and perturbations in the earth's field from ferromagnetic objects. Two different designs of transducers are reported on-herringbone type, and barberpole biased type. Sensitivities as high as 3.5 mV/V/Oe have been obtained. The highest reported value seen in published literature is 1.75 mV/V/Oe (Philips Technical Publication 268), whereas values around 1.0 mV/V/Oe are typical. These high-sensitivity transducers are designed and fabricated based on previously published theoretical analysis [B. Pant, J. Appl. Phys. 67, 414 (1990)] of the response of thin magnetoresistive strips to external fields. This analysis indicates that to increase the sensitivity of these transducers one must reduce the ratio of strip thickness to its width and rotate the easy axis away from the long dimension of the strip wherever appropriate. The theoretical and experimental curves of bias field versus sensitivity for the herringbone design, and the transfer function for the barberpole design, are reported.

  16. High-sensitivity nanosensors for biomarker detection†

    PubMed Central

    Swierczewska, Magdalena; Liu, Gang

    2013-01-01

    High sensitivity nanosensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples. In this tutorial review, we introduce the type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers and provide distinctive examples of high-sensitivity sensors. The use of such high-sensitivity nanosensors can offer earlier detection of disease than currently available to patients and create significant improvements in clinical outcomes. PMID:22187721

  17. Fast, high sensitivity dewpoint hygrometer

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E. (Inventor)

    1998-01-01

    A dewpoint/frostpoint hygrometer that uses a surface moisture-sensitive sensor as part of an RF oscillator circuit with feedback control of the sensor temperature to maintain equilibrium at the sensor surface between ambient water vapor and condensed water/ice. The invention is preferably implemented using a surface acoustic wave (SAW) device in an RF oscillator circuit configured to generate a condensation-dependent output signal, a temperature sensor to measure the temperature of the SAW device and to distinguish between condensation-dependent and temperature-dependent signals, a temperature regulating device to control the temperature of the SAW device, and a feedback control system configured to keep the condensation-dependent signal nearly constant over time in the presence of time-varying humidity, corrected for temperature. The effect of this response is to heat or cool the surface moisture-sensitive device, which shifts the equilibrium with respect to evaporation and condensation at the surface of the device. The equilibrium temperature under feedback control is a measure of dewpoint or frostpoint.

  18. Cryogenic High-Sensitivity Magnetometer

    NASA Technical Reports Server (NTRS)

    Day, Peter; Chui, Talso; Goodstein, David

    2005-01-01

    A proposed magnetometer for use in a cryogenic environment would be sensitive enough to measure a magnetic-flux density as small as a picogauss (10(exp -16) Tesla). In contrast, a typical conventional flux-gate magnetometer cannot measure a magnetic-flux density smaller that about 1 microgauss (10(exp -10) Tesla). One version of this device, for operation near the low end of the cryogenic temperature range, would include a piece of a paramagnetic material on a platform, the temperature of which would be controlled with a periodic variation. The variation in temperature would be measured by use of a conventional germanium resistance thermometer. A superconducting coil would be wound around the paramagnetic material and coupled to a superconducting quantum interference device (SQUID) magnetometer.

  19. Nano-textured high sensitivity ion sensitive field effect transistors

    NASA Astrophysics Data System (ADS)

    Hajmirzaheydarali, M.; Sadeghipari, M.; Akbari, M.; Shahsafi, A.; Mohajerzadeh, S.

    2016-02-01

    Nano-textured gate engineered ion sensitive field effect transistors (ISFETs), suitable for high sensitivity pH sensors, have been realized. Utilizing a mask-less deep reactive ion etching results in ultra-fine poly-Si features on the gate of ISFET devices where spacing of the order of 10 nm and less is achieved. Incorporation of these nano-sized features on the gate is responsible for high sensitivities up to 400 mV/pH in contrast to conventional planar structures. The fabrication process for this transistor is inexpensive, and it is fully compatible with standard complementary metal oxide semiconductor fabrication procedure. A theoretical modeling has also been presented to predict the extension of the diffuse layer into the electrolyte solution for highly featured structures and to correlate this extension with the high sensitivity of the device. The observed ultra-fine features by means of scanning electron microscopy and transmission electron microscopy tools corroborate the theoretical prediction.

  20. Simultaneous determination of 11 β-agonists in human urine using high-performance liquid chromatography/tandem mass spectrometry with isotope dilution.

    PubMed

    Wang, Xiaoli; Guo, Tao; Wang, Shanshan; Yuan, Jinpeng; Zhao, Rusong

    2015-04-01

    The misuse of β-agonists constitutes a potential risk to public health and has been forbidden in many countries. In this study, we describe a method for specific, sensitive and rapid detection of β-agonists in human urine. Urine samples were extracted with ethyl acetate, without any additional purification step, and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) with Clenbuterol-D9 and Salbuterol-D3 as internal standards. The intra- and interday precision values of the method were all <5.60% and the accuracy ranged from 94.5 to 109%. Extraction recovery for 11 β-agonists varied from 66.7 to 108%. One UPLC-MS-MS analysis could be completed within 12 min and the limits of detection for 11 β-agonists were 0.1 ng/mL in the experiment. β-Agonists in human urines from 24 volunteers were analyzed by our validated method and 1.70 ng/mL salbutamol was detected in one volunteer. The application of UPLC-MS-MS method in β-agonists detection of human urine will be helpful in veterinary control of β-agonists and for studying the effect of β-agonists on human health. PMID:25542892

  1. A high-temperature heat sensitive element

    NASA Technical Reports Server (NTRS)

    Oguro, M.

    1986-01-01

    This invention concerns the high-temperature heat sensitive element which is stable at high temperatures. A solid solution of the main component MgO-Al2O3-Cr2O3-Fe2O3 which contains spinel crystal structure is mixed with the secondary component ZrO2 at the mol ratio of 100 : 0.1 to 5.0 and sintered to prepare a high-temperature heat sensitive element.

  2. Development and validation of a UPLC-MS/MS method for the novel folate-targeted small molecule drug conjugate EC1456 and its metabolites in tumor homogenates from mice.

    PubMed

    Rao, Satish I; Pugh, Michael; Nelson, Melissa; Reddy, Joseph A; Klein, Patrick J; Leamon, Christopher P

    2016-04-15

    EC1456 is a novel folate-targeted small molecule drug conjugate of tubulysin B hydrazide being developed as an anticancer agent for patients with advanced solid tumors expressing the folate receptor. To try and correlate circulating systemic levels of EC1456 and its metabolites to tumor concentrations and potentially develop a PK/PD model, a sensitive bioanalytical method was developed and validated for the quantitation of the analytes in KB tumor homogenates. The method involved homogenizing tumors with buffer containing N-maleoyl-β-alanine, mannitol and acetic acid, precipitation of the homogenate with acetone followed by heating at 55°C for 1h to convert tubulysin B hydrazide to its corresponding hydrazone. The extracts were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method demonstrated good inter-day (3 runs, n=18) accuracy (-2.3% to 7.3%) and precision (1.7% to 10.3%) for all three analytes. Stability was established for three freeze-thaw cycles, 4h on the bench-top on ice, 20h in the autosampler at 8°C and for at least 46days frozen at -70°C. This method was successfully used to determine concentration of EC1456 and its metabolites tubulysin B hydrazide and tubulysin B in tumor homogenates in preliminary experiments with KB tumor bearing mice dosed intravenously with EC1456. PMID:26855286

  3. Multi-drug and metabolite quantification in postmortem blood by liquid chromatography-high-resolution mass spectrometry: comparison with nominal mass technology.

    PubMed

    Rosano, Thomas G; Na, Seo; Ihenetu, Kenneth; Swift, Thomas A; Wood, Michelle

    2014-10-01

    High-resolution mass spectrometry (HRMS) is being applied in postmortem drug screening as an alternative to nominal mass spectrometry, and additional evaluation in quantitative casework is needed. We report quantitative analysis of benzoylecgonine, citalopram, cocaethylene, cocaine, codeine, dextromethorphan, dihydrocodeine, diphenhydramine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone and oxymorphone in postmortem blood by ultra-performance liquid chromatography (UPLC)-MS(E)/time-of-flight (TOF). The method employs analyte-matched deuterated internal standardization and MS(E) acquisition of precursor and product ions at low (6 eV) and ramped (10-40 eV) collision energies, respectively. Quantification was performed using precursor ion data obtained with a mass extraction window of 5 ppm. Fragment and residual precursor ion acquisitions at ramped collision energies were evaluated as additional analyte identifiers. Extraction recovery of >60% and matrix effect of <20% were determined for all analytes and internal standards. Defined limits of detection (10 ng/mL) and quantification (25 ng/mL) were validated along with a linearity analytical range of 25-3,000 ng/mL (R(2) > 0.99) for all analytes. Parallel UPLC-MS(E)/TOF and UPLC-MS/MS analysis showed comparable precision and bias along with concordance of 253 positive (y = 1.002x + 1.523; R(2) = 0.993) and 2,269 negative analyte findings in 159 postmortem cases. Analytical performance and correlation studies demonstrate accurate quantification by UPLC-MS(E)/TOF and extended application of HRMS in postmortem casework. PMID:25217537

  4. Absolute quantification of UGT1A1 in various tissues and cell lines using isotope-free UPLC-MS/MS method determines its turnover number and correlates with its glucuronidation activities

    PubMed Central

    Xu, Beibei; Gao, Song; Wu, Baojian; Yin, Taijun; Hu, Ming

    2014-01-01

    Uridine5′-diphosphate-glucuronosyltransferase (UGT)1A1 is a major phase II metabolism enzyme responsible for glucuronidation of drugs and endogenous compounds. The purpose of this study was to determine the expression level of UGT1A1 in human liver microsomes and human cell lines by using an isotope-free LC-MS/MS method. A Waters Ultra performance liquid chromatography (UPLC) system coupled with an API 5500Qtrap mass spectrometer was used for the analysis. Two signature peptides (Pep-1, and Pep-2) were employed to quantify UGT1A1 by multiple reaction monitoring (MRM) method. Standard addition method was used to validate the assay to account for the matrix effect. 17β-Estradiol was used as the marker substrate to determine UGT1A1 activities. The validated method has a linear range of 200–0.0195 nM for both signature peptides. The precision, accuracy, and matrix effect were in acceptable ranges. UGT1A1 expression levels were then determined using 8 individual human liver microsomes, a pooled human liver microsomes, three UGT1A1 genotyped human liver microsomes, and four cell lines (Caco-2, MCF-7, Hela, and HepG2). The correlations study showed that the UGT1A1 protein levels were strongly correlated with its glucuronidation activities in human liver microsomes (R2 =0.85) and in microsomes prepared from cell lines (R2 =0.95). The current isotope-labeled peptides were not necessary as the designated standard for LC-MS/MS quantitation of proteins. The isotope label-free absolute quantification method used here had good accuracy, sensitivity, linear range, and reproducibility, and were used successfully for the accurate determination of UGT1A1 from tissues and cell lines. PMID:24055854

  5. Absolute quantification of UGT1A1 in various tissues and cell lines using isotope label-free UPLC-MS/MS method determines its turnover number and correlates with its glucuronidation activities.

    PubMed

    Xu, Beibei; Gao, Song; Wu, Baojian; Yin, Taijun; Hu, Ming

    2014-01-01

    Uridine 5'-diphosphate-glucuronosyltransferase (UGT)1A1 is a major phase II metabolism enzyme responsible for glucuronidation of drugs and endogenous compounds. The purpose of this study was to determine the expression level of UGT1A1 in human liver microsomes and human cell lines by using an isotope label-free LC-MS/MS method. A Waters Ultra performance liquid chromatography (UPLC) system coupled with an API 5500Qtrap mass spectrometer was used for the analysis. Two signature peptides (Pep-1, and Pep-2) were employed to quantify UGT1A1 by multiple reaction monitoring (MRM) approach. Standard addition method was used to validate the assay to account for the matrix effect. 17β-Estradiol was used as the marker substrate to determine UGT1A1 activities. The validated method has a linear range of 200-0.0195nM for both signature peptides. The precision, accuracy, and matrix effect were in acceptable ranges. UGT1A1 expression levels were then determined using 8 individual human liver microsomes, a pooled human liver microsomes, three UGT1A1 genotyped human liver microsomes, and four cell lines (Caco-2, MCF-7, Hela, and HepG2). The correlations study showed that the UGT1A1 protein levels were strongly correlated with its glucuronidation activities in human liver microsomes (R(2)=0.85) and in microsomes prepared from cell lines (R(2)=0.95). Isotope-labeled peptides were not necessary for LC-MS/MS quantitation of proteins. The isotope label-free absolute quantification method used here had good accuracy, sensitivity, linear range, and reproducibility, and were used successfully for the accurate determination of UGT1A1 from tissues and cell lines. PMID:24055854

  6. Development and validation of an UPLC-MS/MS assay for quantitative analysis of the ghrelin receptor inverse agonist PF-5190457 in human or rat plasma and rat brain.

    PubMed

    Ghareeb, Mwlod; Leggio, Lorenzo; El-Kattan, Ayman; Akhlaghi, Fatemeh

    2015-07-01

    PF-5190457 is a ghrelin receptor inverse agonist that is currently undergoing clinical development for the treatment of alcoholism. Our aim was to develop and validate a simple and sensitive assay for quantitative analysis of PF-5190457 in human or rat plasma and rat brain using liquid chromatography-tandem mass spectrometry. The analyte and stable isotope internal standard were extracted from 50 μL plasma or rat brain homogenate by protein precipitation using 0.1% formic acid in acetonitrile. Chromatography was carried out on an Acquity UPLC BEH C18 (2.1 mm × 50 mm) column with 1.7 μm particle size and 130 Å pore size. The flow rate was 0.5 mL/min and total chromatographic run time was 2.2 min. The mobile phase consisted of a gradient mixture of water: acetonitrile 95:5% (v/v) containing 0.1% formic acid (solvent A) and 100% acetonitrile containing 0.1% formic acid (solvent B). Multiple reaction monitoring was carried out in positive electro-spray ionization mode using m/z 513.35 → 209.30 for PF-5190457 and m/z 518.47 → 214.43 for the internal standard. The recovery ranged from 102 to 118% with coefficient of variation (CV) less than 6% for all matrices. The calibration curves for all matrices were linear over the studied concentration range (R(2) ≥ 0.998, n = 3). The lower limit of quantification was 1 ng/mL in rat or human plasma and 0.75 ng/g in rat brain. Intra- and inter-run mean percent accuracies were between 85 and 115% and percent imprecision was ≤15%. The assays were successfully utilized to measure the concentration of PF-5190457 in pre-clinical and clinical pharmacology studies of the compound. PMID:25943263

  7. UPLC-MS-based Urine Metabolomics Reveals Indole-3-lactic acid and Phenyllactic acid as Conserved Biomarkers for Alcohol-induced Liver Disease in the Ppara-null Mouse Model

    PubMed Central

    Manna, Soumen K.; Patterson, Andrew D.; Yang, Qian; Krausz, Kristopher W.; Idle, Jeffrey R.; Fornace, Albert J.; Gonzalez, Frank J.

    2011-01-01

    Since the development and prognosis of alcohol-induced liver disease (ALD) vary significantly with genetic background, identification of a genetic background-independent noninvasive ALD biomarker would significantly improve screening and diagnosis. This study explored the effect of genetic background on the ALD-associated urinary metabolome using the Ppara-null mouse model on two different backgrounds, C57BL/6 (B6) and 129/SvJ (129S), along with their wild-type counterparts. Reversed-phase gradient UPLC-ESI-QTOF-MS analysis revealed that urinary excretion of a number of metabolites, such as, ethylsulfate, 4-hydroxyphenylacetic acid, 4-hydroxyphenylacetic acid sulfate, adipic acid, pimelic acid, xanthurenic acid, and taurine were background-dependent. Elevation of ethyl-β-D-glucuronide and N-acetylglycine was found to be common signature of the metabolomic response to alcohol exposure in wild-type as well as in Ppara-null mice of both strains. However, increased excretion of indole-3-lactic acid and phenyllactic acid was found to be a conserved feature exclusively associated with the alcohol-treated Ppara-null mouse on both backgrounds that develop liver pathologies similar to the early stages of human ALD. These markers reflected the biochemical events associated with early stages of ALD pathogenesis. The results suggest that indole-3-lactic acid and phenyllactic acid are potential candidates for conserved and pathology-specific high-throughput noninvasive biomarkers for early stages of ALD. PMID:21749142

  8. UPLC-MS, HPLC-radiometric, and NMR-spectroscopic studies on the metabolic fate of 3-fluoro-[U-14C]-aniline in the bile-cannulated rat.

    PubMed

    Athersuch, T J; Castro-Perez, J; Rodgers, C; Nicholson, J K; Wilson, Ian D

    2010-07-01

    1. A study of the rates and routes of excretion of 3-fluoro-[U-(14)C]aniline following intraperitoneal administration to male bile-cannulated rats by liquid scintillation counting (LSC) gave a total recovery of approximately 90% in the 48 h following dosing, with the majority of the dose being excreted in the urine during the first 24 h (approximately 49%). 2. The total recovery as determined by (19)F-nuclear magnetic resonance ((19)F-NMR) was approximately 49%, with the majority of the dose excreted in the first 24 h (approximately 41%). The comparatively low recovery in comparison to that obtained from LSC was due to matrix effects in bile and a contribution from metabolic defluorination. 3. High-performance liquid chromatography with radiometric profiling of urine and bile revealed a complex pattern of metabolites with the bulk of the dose excreted as a single peak. 4. Ultra-performance liquid chromatography-orthogonal acceleration time of flight mass spectrometry profiling also showed a complex pattern of metabolites, detecting approximately 21 metabolites of 3-fluoroaniline (3-FA) with six of these detected only in urine and four solely in bile. 5. (19)F-NMR revealed the presence of the parent compound and 15 metabolites in urine collected during the first 24 h after -dosing. The matrix effects of bile on (19)F-NMR spectroscopy made metabolite profiling impractical for this biofluid. The major metabolite of 3-FA was identified as 2-fluoro-4-acetamidophenol-sulfate. PMID:20443683

  9. UPLC-MS/MS method for the simultaneous quantification of anti-HBV nucleos(t)ides analogs: Entecavir, lamivudine, telbivudine and tenofovir in plasma of HBV infected patients.

    PubMed

    De Nicolò, Amedeo; Simiele, Marco; Pensi, Debora; Boglione, Lucio; Allegra, Sarah; Di Perri, Giovanni; D'Avolio, Antonio

    2015-10-10

    Hepatitis B infection affects two billion people worldwide and 350 million of these are chronically infected. Chronic hepatitis B virus is one of the most important cause of mortality and morbidity worldwide. If it is left untreated, about one-third of affected people will develop progressive and possibly fatal liver disease, like hepatic cirrhosis and primary hepatocellular carcinoma. Currently, five nucleos(t)ide analogs are approved for the treatment of chronic HBV infection. They are: lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. In this work, we developed and validated an UPLC-Tandem mass spectrometry assay method capable of monitoring lamivudine, telbivudine, tenofovir and entecavir plasma concentrations. Both standards and quality controls (high, medium and low) were prepared in human plasma. Each sample was added with internal standard (5'amino-5'deoxy-thymidine) and then drugs were extracted through a protein precipitation protocol with acetonitrile+0.1% formic acid and then dried. The extracts were resuspended in water and then injected into the chromatographic system. The chromatographic separation was performed on an Acquity UPLC HSS T3 1.8 μm 2.1 × 150 mm column, with a gradient of water and acetonitrile, both added with formic acid (0.05%). Accuracy, intra-day and inter-day precision at quality controls levels fitted all FDA guidelines for all analytes, while matrix effects and recoveries resulted stable between samples for each analyte. Finally, we tested this method by monitoring plasma concentrations in 30 HBV+ patients with good results. This simple analytical method could represent a useful tool for the management of anti-HBV therapy. PMID:26037161

  10. High Sensitivity deflection detection of nanowires

    SciTech Connect

    Sanii, Babak; Ashby, Paul

    2009-10-28

    A critical limitation of nanoelectromechanical systems (NEMS) is the lack of a high-sensitivity position detection mechanism. We introduce a noninterferometric optical approach to determine the position of nanowires with a high sensitivity and bandwidth. Its physical origins and limitations are determined by Mie scattering analysis. This enables a dramatic miniaturization of detectable cantilevers, with attendant reductions to the fundamental minimum force noise in highly damping environments. We measure the force noise of an 81{+-}9??nm radius Ag{sub 2}Ga nanowire cantilever in water at 6{+-}3??fN/{radical}Hz.

  11. High sensitivity deflection detection of nanowires.

    PubMed

    Sanii, Babak; Ashby, Paul D

    2010-04-01

    A critical limitation of nanoelectromechanical systems (NEMS) is the lack of a high-sensitivity position detection mechanism. We introduce a noninterferometric optical approach to determine the position of nanowires with a high sensitivity and bandwidth. Its physical origins and limitations are determined by Mie scattering analysis. This enables a dramatic miniaturization of detectable cantilevers, with attendant reductions to the fundamental minimum force noise in highly damping environments. We measure the force noise of an 81+/-9 nm radius Ag(2)Ga nanowire cantilever in water at 6+/-3 fN/square root(Hz). PMID:20481957

  12. High Sensitivity Optically Pumped Quantum Magnetometer

    PubMed Central

    Tiporlini, Valentina; Alameh, Kamal

    2013-01-01

    Quantum magnetometers based on optical pumping can achieve sensitivity as high as what SQUID-based devices can attain. In this paper, we discuss the principle of operation and the optimal design of an optically pumped quantum magnetometer. The ultimate intrinsic sensitivity is calculated showing that optimal performance of the magnetometer is attained with an optical pump power of 20 μW and an operation temperature of 48°C. Results show that the ultimate intrinsic sensitivity of the quantum magnetometer that can be achieved is 327 fT/Hz1/2 over a bandwidth of 26 Hz and that this sensitivity drops to 130 pT/Hz1/2 in the presence of environmental noise. The quantum magnetometer is shown to be capable of detecting a sinusoidal magnetic field of amplitude as low as 15 pT oscillating at 25 Hz. PMID:23766716

  13. High-sensitivity bunch charge monitor

    NASA Astrophysics Data System (ADS)

    Lebedev, N. I.; Fateev, A. A.

    2008-12-01

    The conceptual design for a high-sensitivity bunch charge monitor is presented. The device operates with short, spaced bunches. For optimal performance, the bunch duration should be less than 10 ns and bunch spacing should be more than 100 ns. Sensitivity of the monitor is close to 10 V per nanocoulomb. The equivalent scheme and the output signal shape are also presented. Such a monitor seems to be promising for the bunch charge measurements of beams like those in TESLA or ILC projects.

  14. Single photon detector with high polarization sensitivity.

    PubMed

    Guo, Qi; Li, Hao; You, LiXing; Zhang, WeiJun; Zhang, Lu; Wang, Zhen; Xie, XiaoMing; Qi, Ming

    2015-01-01

    Polarization is one of the key parameters of light. Most optical detectors are intensity detectors that are insensitive to the polarization of light. A superconducting nanowire single photon detector (SNSPD) is naturally sensitive to polarization due to its nanowire structure. Previous studies focused on producing a polarization-insensitive SNSPD. In this study, by adjusting the width and pitch of the nanowire, we systematically investigate the preparation of an SNSPD with high polarization sensitivity. Subsequently, an SNSPD with a system detection efficiency of 12% and a polarization extinction ratio of 22 was successfully prepared. PMID:25875225

  15. Fiber specklegram sensors sensitivities at high temperatures

    NASA Astrophysics Data System (ADS)

    Rodriguez-Cobo, L.; Lomer, M.; Lopez-Higuera, J. M.

    2015-09-01

    In this work, the sensitivity of Fiber Specklegram Sensors to high temperatures (up to 800ºC) have been studied. Two multimode silica fibers have been introduced into a tubular furnace while a HeNe laser source was launched into a fiber edge, projecting speckle patterns to a commercial webcam. A computer generated different heating and cooling sweeps while the specklegram evolution was recorded. The achieved results exhibit a remarkably linearity in FSS's sensitivity for temperatures under 800ºC, following the thermal expansion of fused silica.

  16. High efficiency porphyrin sensitized mesoscopic solar cells

    NASA Astrophysics Data System (ADS)

    Giordano, Fabrizio; Yi, Chenyi; Teuscher, Joël.; Zakeeruddin, Shaik M.; Grätzel, Michael

    2014-10-01

    Dye-Sensitized Solar Cells (DSSC) represents a reliable technology, ready for the market and able to compete with silicon solar cells for specific fields of application. Porphyrin dyes allow reaching high power conversion efficiency in conjunction with cobalt redox electrolytes due to larger open circuit potentials. The bigger size of the cobalt complexes compared to standard iodide/triiodide redox couple hampers its percolation through the meso-porous TiO2 network, thus impairing the regeneration process. In case of porphyrin dyes mass transport problems in the electrolyte need to be carefully handled, due to the large size of the sensitizing molecule and the bulky cobalt complexes. Herein we report the study of structural variations on porphyrin sensitizers and their influence on the DSSC performance with cobalt based redox electrolyte.

  17. High blood pressure and visual sensitivity

    NASA Astrophysics Data System (ADS)

    Eisner, Alvin; Samples, John R.

    2003-09-01

    The study had two main purposes: (1) to determine whether the foveal visual sensitivities of people treated for high blood pressure (vascular hypertension) differ from the sensitivities of people who have not been diagnosed with high blood pressure and (2) to understand how visual adaptation is related to standard measures of systemic cardiovascular function. Two groups of middle-aged subjects-hypertensive and normotensive-were examined with a series of test/background stimulus combinations. All subjects met rigorous inclusion criteria for excellent ocular health. Although the visual sensitivities of the two subject groups overlapped extensively, the age-related rate of sensitivity loss was, for some measures, greater for the hypertensive subjects, possibly because of adaptation differences between the two groups. Overall, the degree of steady-state sensitivity loss resulting from an increase of background illuminance (for 580-nm backgrounds) was slightly less for the hypertensive subjects. Among normotensive subjects, the ability of a bright (3.8-log-td), long-wavelength (640-nm) adapting background to selectively suppress the flicker response of long-wavelength-sensitive (LWS) cones was related inversely to the ratio of mean arterial blood pressure to heart rate. The degree of selective suppression was also related to heart rate alone, and there was evidence that short-term changes of cardiovascular response were important. The results suggest that (1) vascular hypertension, or possibly its treatment, subtly affects visual function even in the absence of eye disease and (2) changes in blood flow affect retinal light-adaptation processes involved in the selective suppression of the flicker response from LWS cones caused by bright, long-wavelength backgrounds.

  18. Highly Energetic, Low Sensitivity Aromatic Peroxy Acids.

    PubMed

    Gamage, Nipuni-Dhanesha H; Stiasny, Benedikt; Stierstorfer, Jörg; Martin, Philip D; Klapötke, Thomas M; Winter, Charles H

    2016-02-01

    The synthesis, structure, and energetic materials properties of a series of aromatic peroxy acid compounds are described. Benzene-1,3,5-tris(carboperoxoic) acid is a highly sensitive primary energetic material, with impact and friction sensitivities similar to those of triacetone triperoxide. By contrast, benzene-1,4-bis(carboperoxoic) acid, 4-nitrobenzoperoxoic acid, and 3,5-dinitrobenzoperoxoic acid are much less sensitive, with impact and friction sensitivities close to those of the secondary energetic material 2,4,6-trinitrotoluene. Additionally, the calculated detonation velocities of 3,5-dinitrobenzoperoxoic acid and 2,4,6-trinitrobenzoperoxoic acid exceed that of 2,4,6-trinitrotoluene. The solid-state structure of 3,5-dinitrobenzoperoxoic acid contains intermolecular O-H⋅⋅⋅O hydrogen bonds and numerous N⋅⋅⋅O, C⋅⋅⋅O, and O⋅⋅⋅O close contacts. These attractive lattice interactions may account for the less sensitive nature of 3,5-dinitrobenzoperoxoic acid. PMID:26743434

  19. An ultra-high performance liquid chromatography-tandem mass spectrometric assay for quantifying 3-ketocholanoic acid: Application to the human liver microsomal CYP3A-dependent lithocholic acid 3-oxidation assay.

    PubMed

    Bansal, Sumit; Chai, Swee Fen; Lau, Aik Jiang

    2016-06-15

    Lithocholic acid (LCA), a hepatotoxic and carcinogenic bile acid, is metabolized to 3-ketocholanoic acid (3-KCA) by cytochrome P450 3A (CYP3A). In the present study, the objectives were to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify 3-KCA and apply it to the human liver microsomal CYP3A-dependent LCA 3-oxidation assay. Chromatographic separation was achieved on a Waters ACQUITY™ UPLC C18 column (50×2.1mm, 1.7μm) with a gradient system consisting of 0.1% v/v formic acid in water (solvent A) and 0.1% v/v formic acid in acetonitrile (solvent B). The retention time was 3.73min for 3-KCA and 2.73min for cortisol (internal standard). Positive electrospray ionization with multiple reaction monitoring (MRM) mode was used to quantify 3-KCA (m/z 375.4→135.2) and cortisol (m/z 363.5→121.0). The limit of detection of 3-KCA was 10μM, the lower limit of quantification was 33.3μM, and the calibration curve was linear from 0.05-10μM with r(2)>0.99. Intra-day and inter-day accuracy and precision were <13.7%. The quality control samples were stable when assessed after 4h at room temperature, 24h at 4°C, 14days at -20°C, and three freeze-thaw cycles. The liver microsomal matrix did not affect 3-KCA quantification. The amount of KCA formed in the human liver microsomal LCA 3-oxidation assay was linear with respect to the amount of microsomal protein (up to 40μg) and incubation time (5-30min). Enzyme kinetics experiment indicated that LCA 3-oxidation followed the Michaelis-Menten model with an apparent Km of 26±7μM and Vmax of 303±50pmol/min/mg protein. This novel UPLC-MS/MS method for quantifying 3-KCA offers a specific, sensitive, and fast approach to determine liver microsomal LCA 3-oxidation. PMID:27153105

  20. Highly sensitive beam steering with plasmonic antenna

    NASA Astrophysics Data System (ADS)

    Rui, Guanghao; Zhan, Qiwen

    2014-08-01

    In this work, we design and study a highly sensitive beam steering device that integrates a spiral plasmonic antenna with a subwavelength metallic waveguide. The short effective wavelength of the surface plasmon polaritons (SPPs) mode supported by the metallic waveguide is exploited to dramatically miniaturize the device and improve the sensitivity of the beam steering. Through introducing a tiny displacement of feed point with respect to the geometrical center of the spiral plasmonic antenna, the direction of the radiation can be steered at considerably high angles. Simulation results show that steering angles of 8°, 17° and 34° are obtainable for a displacement of 50 nm, 100 nm and 200 nm, respectively. Benefiting from the reduced device size and the shorter SPP wavelength, the beam steering sensitivity of the beam steering is improved by 10-fold compared with the case reported previously. This miniature plasmonic beam steering device may find many potential applications in quantum optical information processing and integrated photonic circuits.

  1. High-sensitive cardiac troponin T

    PubMed Central

    Xu, Ru-Yi; Zhu, Xiao-Fa; Yang, Ye; Ye, Ping

    2013-01-01

    Cardiac troponin is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI). The recent development of a high-sensitive cardiac troponin T (hs-cTnT) assay permits detection of very low levels of cTnT. Using the hs-cTnT assay improves the overall diagnostic accuracy in patients with suspected AMI, while a negative result also has a high negative predictive value. The gain in sensitivity may be particularly important in patients with a short duration from symptom onset to admission. Measurement of cardiac troponin T with the hs-cTnT assay may provide strong prognostic information in patients with acute coronary syndromes, stable coronary artery disease, heart failure and even in the general population; however, increased sensitivity comes at a cost of decreased specificity. Serial testing, as well as clinical context and co-existing diseases, are likely to become increasingly important for the interpretation of hs-cTnT assay results. PMID:23610580

  2. Highly sensitive nanoscale spin-torque diode

    NASA Astrophysics Data System (ADS)

    Miwa, S.; Ishibashi, S.; Tomita, H.; Nozaki, T.; Tamura, E.; Ando, K.; Mizuochi, N.; Saruya, T.; Kubota, H.; Yakushiji, K.; Taniguchi, T.; Imamura, H.; Fukushima, A.; Yuasa, S.; Suzuki, Y.

    2014-01-01

    Highly sensitive microwave devices that are operational at room temperature are important for high-speed multiplex telecommunications. Quantum devices such as superconducting bolometers possess high performance but work only at low temperature. On the other hand, semiconductor devices, although enabling high-speed operation at room temperature, have poor signal-to-noise ratios. In this regard, the demonstration of a diode based on spin-torque-induced ferromagnetic resonance between nanomagnets represented a promising development, even though the rectification output was too small for applications (1.4 mV mW-1). Here we show that by applying d.c. bias currents to nanomagnets while precisely controlling their magnetization-potential profiles, a much greater radiofrequency detection sensitivity of 12,000 mV mW-1 is achievable at room temperature, exceeding that of semiconductor diode detectors (3,800 mV mW-1). Theoretical analysis reveals essential roles for nonlinear ferromagnetic resonance, which enhances the signal-to-noise ratio even at room temperature as the size of the magnets decreases.

  3. High sensitive materials in medical holographic microscopy

    NASA Astrophysics Data System (ADS)

    Osanlou, A.; Snashall, E.; Osanlou, O.; Osanlou, R.; Mirlis, E.; Shi, Lishen; Bjelkhagen, H.

    2015-02-01

    High sensitivity is defined in relation to the energy required to perform holographic recording. High sensitivity in silver halide materials is their main advantage over other similarly high resolving power holographic recording materials. This work reports progress on the development of silver halide based 'true colour holographic imaging', under a microscope. A thin layer of ultrafine grains of silver halide crystals of around 10 nm average diameter, dispersed in a colloid and coated on a substrate is used as the recording media. The significance of this method so far, is in its ability to produce 'true colour' three-dimensional images of specimen. The recordings have an appreciable depth, permitting the observer to scan through the image under a microscope, as one might with a real specimen sample. Current methods could perform ' True colour holographic imaging' directly under a microscope. The recording methodology has the potential for deeper complex and scattering media imaging, using very small pulses of appropriate laser wavelengths. The methodology, using novel nanosize panchromatic recording media consisting of dispersed fine nano grain crystals, could potentially revolutionise related medical imaging techniques. Future development of digital media will allow it to be utilized in this manner.

  4. [Clinical interpretation of high sensitivity troponin T].

    PubMed

    Alquézar Arbé, Aitor; Santaló Bel, Miguel; Sionis, Alessandro

    2015-09-21

    Determination of cardiac troponin (cTn) is necessary for the diagnosis of acute myocardial infarction without ST segment elevation. However Tnc can be released in other clinical situations. The development of high-sensitive cTn T assays (hs-cTnT) improves the management of patients with suspected acute coronary syndrome. Here, we provide an overview of the diverse causes of hs-cTnT elevation and recommend strategies for the clinical interpretation of the test result. PMID:25620025

  5. High-sensitivity silicon nanowire phototransistors

    NASA Astrophysics Data System (ADS)

    Tan, Siew Li; Zhao, Xingyan; Dan, Yaping

    2014-08-01

    Silicon nanowires (SiNWs) have emerged as a promising material for high-sensitivity photodetection in the UV, visible and near-infrared spectral ranges. In this work, we demonstrate novel planar SiNW phototransistors on silicon-oninsulator (SOI) substrate using CMOS-compatible processes. The device consists of a bipolar transistor structure with an optically-injected base region. The electronic and optical properties of the SiNW phototransistors are investigated. Preliminary simulation and experimental results show that nanowire geometry, doping densities and surface states have considerable effects on the device performance, and that a device with optimized parameters can potentially outperform conventional Si photodetectors.

  6. Photodetector having high speed and sensitivity

    DOEpatents

    Morse, Jeffrey D.; Mariella, Jr., Raymond P.

    1991-01-01

    The present invention provides a photodetector having an advantageous combination of sensitivity and speed; it has a high sensitivity while retaining high speed. In a preferred embodiment, visible light is detected, but in some embodiments, x-rays can be detected, and in other embodiments infrared can be detected. The present invention comprises a photodetector having an active layer, and a recombination layer. The active layer has a surface exposed to light to be detected, and comprises a semiconductor, having a bandgap graded so that carriers formed due to interaction of the active layer with the incident radiation tend to be swept away from the exposed surface. The graded semiconductor material in the active layer preferably comprises Al.sub.1-x Ga.sub.x As. An additional sub-layer of graded In.sub.1-y Ga.sub.y As may be included between the Al.sub.1-x Ga.sub.x As layer and the recombination layer. The recombination layer comprises a semiconductor material having a short recombination time such as a defective GaAs layer grown in a low temperature process. The recombination layer is positioned adjacent to the active layer so that carriers from the active layer tend to be swept into the recombination layer. In an embodiment, the photodetector may comprise one or more additional layers stacked below the active and recombination layers. These additional layers may include another active layer and another recombination layer to absorb radiation not absorbed while passing through the first layers. A photodetector having a stacked configuration may have enhanced sensitivity and responsiveness at selected wavelengths such as infrared.

  7. High-sensitivity 25-micron microbolometer FPAs

    NASA Astrophysics Data System (ADS)

    Murphy, Daniel F.; Ray, Michael; Wyles, Richard; Asbrock, James F.; Lum, Nancy A.; Wyles, Jessica; Hewitt, C.; Kennedy, Adam; Van Lue, David; Anderson, John S.; Bradley, Daryl; Chin, Richard; Kostrzewa, Thomas

    2002-08-01

    Raytheon Infrared Operations (RIO) has achieved a significant technical breakthrough in uncooled FPAs by reducing the pixel size by a factor of two while maintaining state-of-the-art sensitivity. Raytheon has produced the first high-quality 320x240 microbolometer FPAs with 25 micrometers pitch pixels. The 320 x240 FPAs have a sensitivity that is comparable to microbolometer FPAs with 50 micrometers pixels. The average NETD value for these FPAs is about 35 mK with an f/1 aperture and operating at 30 Hz frame rates. Good pixel operability and excellent image quality have been demonstrated. Pixel operability is greater than 99% on some FPAs, and uncorrected responsivity nonuniformity is less than 4% (sigma/mean). The microbolometer detectors also have a relatively fast thermal time constant of approximately 10 msec. This state-of-the-art performance has been achieved as a result of an advanced micromachining fabrication process. The process allows maximization of both the thermal isolation and the optical fill-factor. The reduction in pixel size offers several potential benefits for IR systems. For a given system resolution (IFOV) requirement, the 25 micrometers pixels allow a factor of two reduction in both the focal length and aperture size of the sensor optics. The pixel size reduction facilitates a significant FPA cost reduction since the number of die printed on a wafer can be increased. The pixel size reduction has enabled the development of a large-format 640x480 FPA array. Raytheon has produced arrays with very good sensitivity, operability, and excellent image quality. These FPAs are applicable to wide-field-of-view, long range surveillance and targeting missions. Raytheon is also developing a high performance 160x128 FPA that is designed for applications where miniaturization and temperature invariance are required as well as low cost and low power.

  8. High Sensitivity Imprint Measurements on Nike Laser

    NASA Astrophysics Data System (ADS)

    Karasik, Max

    2005-10-01

    Hydrodynamic instability seeded by laser non-uniformity (laser imprint) is an important factor in performance of direct-drive ICF targets. Most of the imprint occurs during the initial low-intensity (``foot'') part of the pulse, necessary to compress the target to achieve high gain. Experiments are carried out on Nike KrF laser with induced spatial incoherence (ISI) smoothing. The amount of imprint is varied by changing the uniformity the foot of the pulse. The resulting Raleigh-Taylor (RT) amplified areal mass non-uniformity is measured by face-on x-ray radiography using Bragg reflection from a curved crystal coupled to an x-ray streak camera. The streak camera was recently retrofitted with a new high sensitivity CCD camera. The sensitivity of the CCD has enabled it to be fiberoptically coupled directly to the streak camera output, without an image intensifier and lens coupling. This gave an increased overall spatial resolution as well as lower noise. Because of the strong short wavelength component of RT amplified imprint, the increased resolution and lower noise resulted in much lower noise floor in the measurement. Experimental results are compared with 2D simulations using FAST hydrocode for a range of foot uniformities and intensities. Work supported by the U. S. DOE/NNSA.

  9. High Sensitivity VLBI Science with Arecibo

    NASA Astrophysics Data System (ADS)

    Doeleman, Sheperd

    2007-12-01

    Modern VLBI instrumentation bears little resemblence to the systems that were in use just 5 years ago. By making use of industry driven trends, VLBI has moved from recording on magnetic tape to hard disk drive systems, and has replaced analog filterbanks with digital signal processing on FPGAs. The results are significantly increased recording bandwidths at a small fraction of the cost of previous VLBI systems. When this instrumentation is deployed on the largest radio telescopes, thermal noise levels down to 1 micro Jy/beam can be achieved. The collecting area of Arecibo, in particular, lowers detection thresholds to the point where a range of high sensitivity science projects can be addressed. Among these are studies of Ultra Luminous Infrared Galaxies (ULIGs), central images of Gravitational Lens systems, late time imaging of GRB afterglow structure, and pulsar astrometry and proper motion studies. This talk will briefly touch on enabling technologies and then focus on the ongoing and potential research enabled with Arecibo-anchored VLBI arrays. The Ultra High Sensitivity VLBI program at MIT Haystack Observatory is funded through a grant from the NSF AST division.

  10. Highly Sensitive Electro-Optic Modulators

    SciTech Connect

    DeVore, Peter S

    2015-10-26

    There are very important diagnostic and communication applications that receive faint electrical signals to be transmitted over long distances for capture. Optical links reduce bandwidth and distance restrictions of metal transmission lines; however, such signals are only weakly imprinted onto the optical carrier, resulting in low fidelity transmission. Increasing signal fidelity often necessitates insertion of radio-frequency (RF) amplifiers before the electro-optic modulator, but (especially at high frequencies) RF amplification results in large irreversible distortions. We have investigated the feasibility of a Sensitive and Linear Modulation by Optical Nonlinearity (SALMON) modulator to supersede RF-amplified modulators. SALMON uses cross-phase modulation, a manifestation of the Kerr effect, to enhance the modulation depth of an RF-modulated optical wave. This ultrafast process has the potential to result in less irreversible distortions as compared to a RF-amplified modulator due to the broadband nature of the Kerr effect. Here, we prove that a SALMON modulator is a feasible alternative to an RFamplified modulator, by demonstrating a sensitivity enhancement factor greater than 20 and significantly reduced distortion.

  11. High speed curved position sensitive detector

    DOEpatents

    Hendricks, Robert W.; Wilson, Jack W.

    1989-01-01

    A high speed curved position sensitive porportional counter detector for use in x-ray diffraction, the detection of 5-20 keV photons and the like. The detector employs a planar anode assembly of a plurality of parallel metallic wires. This anode assembly is supported between two cathode planes, with at least one of these cathode planes having a serpentine resistive path in the form of a meander having legs generally perpendicular to the anode wires. This meander is produced by special microelectronic fabrication techniques whereby the meander "wire" fans outwardly at the cathode ends to produce the curved aspect of the detector, and the legs of the meander are small in cross-section and very closely spaced whereby a spatial resolution of about 50 .mu.m can be achieved. All of the other performance characteristics are about as good or better than conventional position sensitive proportional counter type detectors. Count rates of up to 40,000 counts per second with 0.5 .mu.s shaping time constants are achieved.

  12. Highly sensitive silicon microreactor for catalyst testing

    SciTech Connect

    Henriksen, Toke R.; Hansen, Ole; Olsen, Jakob L.; Vesborg, Peter; Chorkendorff, Ib

    2009-12-15

    A novel microfabricated chemical reactor for highly sensitive measurements of catalytic activity and surface kinetics is presented. The reactor is fabricated in a silicon chip and is intended for gas-phase reactions at pressures ranging from 0.1 to 5.0 bar. A high sensitivity is obtained by directing the entire gas flow through the catalyst bed to a mass spectrometer, thus ensuring that nearly all reaction products are present in the analyzed gas flow. Although the device can be employed for testing a wide range of catalysts, the primary aim of the design is to allow characterization of model catalysts which can only be obtained in small quantities. Such measurements are of significant fundamental interest but are challenging because of the low surface areas involved. The relationship between the reaction zone gas flow and the pressure in the reaction zone is investigated experimentally. A corresponding theoretical model is presented, and the gas flow through an on-chip flow-limiting capillary is predicted to be in the intermediate regime. The experimental data for the gas flow are found to be in good agreement with the theoretical model. At typical experimental conditions, the total gas flow through the reaction zone is around 3x10{sup 14} molecules s{sup -1}, corresponding to a gas residence time in the reaction zone of about 11 s. To demonstrate the operation of the microreactor, CO oxidation on low-area platinum thin film circles is employed as a test reaction. Using temperature ramping, it is found that platinum catalysts with areas as small as 15 {mu}m{sup 2} are conveniently characterized with the device.

  13. Demonstration of high sensitivity laser ranging system

    NASA Astrophysics Data System (ADS)

    Millar, Pamela S.; Christian, Kent D.; Field, Christopher T.

    1994-01-01

    We report on a high sensitivity semiconductor laser ranging system developed for the Gravity and Magnetic Earth Surveyor (GAMES) for measuring variations in the planet's gravity field. The GAMES laser ranging instrument (LRI) consists of a pair of co-orbiting satellites, one which contains the laser transmitter and receiver and one with a passive retro-reflector mounted in an drag-stabilized housing. The LRI will range up to 200 km in space to the retro-reflector satellite. As the spacecraft pair pass over the spatial variations in the gravity field, they experience along-track accelerations which change their relative velocity. These time displaced velocity changes are sensed by the LRI with a resolution of 20-50 microns/sec. In addition, the pair may at any given time be drifting together or apart at a rate of up to 1 m/sec, introducing a Doppler shift into the ranging signals. An AlGaAs laser transmitter intensity modulated at 2 GHz and 10 MHz is used as fine and medium ranging channels. Range is measured by comparing phase difference between the transmit and received signals at each frequency. A separate laser modulated with a digital code, not reported in this paper, will be used for coarse ranging to unambiguously determine the distance up to 200 km.

  14. High sensitivity flow cytometry of membrane vesicles.

    PubMed

    Stoner, Samuel A; Duggan, Erika; Condello, Danilo; Guerrero, Abraham; Turk, James R; Narayanan, Padma K; Nolan, John P

    2016-02-01

    Extracellular vesicles (EVs) are attracting attention as vehicles for inter-cellular signaling that may have value as diagnostic or therapeutic targets. EVs are released by many cell types and by different mechanisms, resulting in phenotypic heterogeneity that makes them a challenge to study. Flow cytometry is a popular tool for characterizing heterogeneous mixtures of particles such as cell types within blood, but the small size of EVs makes them difficult to measure using conventional flow cytometry. To address this limitation, a high sensitivity flow cytometer was constructed and EV measurement approaches that allowed them to enumerate and estimate the size of individual EVs, as well as measure the presence of surface markers to identify phenotypic subsets of EVs. Several fluorescent membrane probes were evaluated and it was found that the voltage sensing dye di-8-ANEPPS could produce vesicle fluorescence in proportion to vesicle surface area, allowing for accurate measurements of EV number and size. Fluorescence-labeled annexin V and anti-CD61 antibody was used to measure the abundance of these surface markers on EVs in rat plasma. It was shown that treatment of platelet rich plasma with calcium ionophore resulted in an increase in the fraction of annexin V and CD61-positive EVs. Vesicle flow cytometry using fluorescence-based detection of EVs has the potential to realize the potential of cell-derived membrane vesicles as functional biomarkers for a variety of applications. © 2015 International Society for Advancement of Cytometry. PMID:26484737

  15. Highly sensitive direct conversion ultrasound interferometer

    NASA Astrophysics Data System (ADS)

    Svitelskiy, Oleksiy; Grossmann, John; Suslov, Alexey

    2015-03-01

    Being invented more than fifty years ago, the ultrasonic pulse-echo technique has proven itself as a valuable and indispensable non-destructive tool to explore elastic properties of materials in engineering and scientific tasks. We propose a new design for the instrument based on mass-produced integral microchips. In our design the radiofrequency echo-pulse signal is processed by AD8302 RF gain and phase detector (www.analog.com).Its phase output is linearly proportional to the phase difference between the exciting and response signals. The gain output is proportional to the log of the ratio of amplitudes of the received to the exciting signals. To exclude the non-linear fragments and to enable exploring large phase changes, we employ parallel connection of two detectors, fed by in-phase and quadrature signals respectively. The instrument allowed us exploring phase transitions with precision of ΔV / V ~10-7 (V is the ultrasound speed). The high sensitivity of the logarithmic amplifiers embedded into AD8302 requires good grounding and screening of the receiving circuitry.

  16. High Sensitivity, High Frequency and High Time Resolution Decimetric Spectroscope

    NASA Astrophysics Data System (ADS)

    Sawant, H. S.; Rosa, R. R.

    1990-11-01

    RESUMEN. Se ha desarrollado el primer espectroscopio decimetrico latino americano operando en una banda de 100 MHz con alta resoluci6n de fre- cuencia (100 KHz) y tiempo (10 ms), alrededor de cualquier centro de frecuencia en el intervalo de 2000-200 MHz. El prop6sito de esta nota es describir investigaciones solares y no solares que se planean, progra ma de investigaci6n y la situaci6n actual de desarrollo de este espectroscopio. ABSTRACT. First Latin American Decimetric Spectroscope operating over a band of 100 MHz with high resolution in frequency (100 KHz) and time (10 ms), around any center frequency in the range of 2000-200 MHz is being developed. The purpose of this note is to describe planned solar, and non-solar, research programmes and present status of development of this spectroscope. Keq wo : INSTRUMENTS - SPECTROSCOPY

  17. Simultaneous determination of amino acid and monoamine neurotransmitters in PC12 cells and rats models of Parkinson's disease using a sensitizing derivatization reagent by UHPLC-MS/MS.

    PubMed

    Zhao, Xian-En; Zhu, Shuyun; Yang, Hongmei; You, Jinmao; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2015-07-15

    Multi-analytes simultaneous monitoring of amino acid and monoamine neurotransmitters (NTs) has important scientific significance for their related pathology, physiology and drug screening. In this work, in virtue of a mass spectrometry sensitizing reagent 10-ethyl-acridone-3-sulfonyl chloride (EASC) as derivatization reagent, an Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous determination of six amino acid NTs, two monoamine ones and its one metabolite. The simple and rapid derivatization reaction was innovatively combined with plasma preparation by using EASC acetonitrile solution as protein precipitant. This interesting combination brought the advantages of speediness, simpleness and high-throughput in a cost-effective way. Under the optimized conditions, LODs (0.004-3.80nM) and LOQs (0.014-13.3nM) of EASC derivatized-NTs were calculated and found to be significantly lower than those of direct UHPLC-MS/MS detection about 11.5-275.0 and 14.4-371.4 times, respectively. Moreover, EASC derivatization significantly improved chromatographic resolution and matrix effect when compared with direct UPLC-MS/MS detection method without derivatization. Meanwhile, it also brought acceptable precision (3.0-13.0%, peak area CVs%), accuracy (86.4-112.9%), recovery (88.3-107.8%) and stability (3.8-8.5%, peak area CVs%) results. This method was successfully applied for the antiparkinsonian effect evaluation of levodopa and Ginsenoside Rg1 using PC12 cells and rats models by measuring multiple NTs. This provided a new method for the NTs related studies in the future. PMID:26021847

  18. A case of high noise sensitivity

    NASA Astrophysics Data System (ADS)

    Murata, M.; Sakamoto, H.

    1995-10-01

    A case of noise sensitivity with a five-year follow-up period is reported. The patient was a 34-year-old single man who was diagnosed as having psychosomatic disorder triggered by two stressful life events in rapid succession with secondary hypersensitivity to noise. Hypersensitivity to light and cold also developed later in the clinical course. The auditory threshold was within the normal range. The discomfort threshold as a measure of the noise sensitivity secondary to mental illness was measured repeatedly using test tone of audiometry. The discomfort threshold varied depending upon his mental status, ranging from 40-50 dB in the comparatively poorer mental state to 70-95 dB in the relatively good mental state. The features of noise sensitivity, including that secondary to mental illness, are discussed.

  19. High sensitivity leak detection method and apparatus

    DOEpatents

    Myneni, G.R.

    1994-09-06

    An improved leak detection method is provided that utilizes the cyclic adsorption and desorption of accumulated helium on a non-porous metallic surface. The method provides reliable leak detection at superfluid helium temperatures. The zero drift that is associated with residual gas analyzers in common leak detectors is virtually eliminated by utilizing a time integration technique. The sensitivity of the apparatus of this disclosure is capable of detecting leaks as small as 1 [times] 10[sup [minus]18] atm cc sec[sup [minus]1]. 2 figs.

  20. High sensitivity leak detection method and apparatus

    DOEpatents

    Myneni, Ganapatic R.

    1994-01-01

    An improved leak detection method is provided that utilizes the cyclic adsorption and desorption of accumulated helium on a non-porous metallic surface. The method provides reliable leak detection at superfluid helium temperatures. The zero drift that is associated with residual gas analyzers in common leak detectors is virtually eliminated by utilizing a time integration technique. The sensitivity of the apparatus of this disclosure is capable of detecting leaks as small as 1.times.10.sup.-18 atm cc sec.sup.-1.

  1. High-sensitivity photoacoustic leak testing.

    PubMed

    Huang, Eric; Dowling, David R; Whelan, Timothy; Spiesberger, John L

    2003-10-01

    The photoacoustic effect may be exploited for the detection and localization of gas leaks from otherwise sealed components. The technique involves filling the test component with a tracer gas, and radiating the component to produce photoacoustic sound from any leak site where tracer gas is present. This paper describes demonstration experiments utilizing 10.6-micro radiation from a carbon-dioxide laser and sulfur hexafluoride as a tracer gas for photoacoustic leak testing at leak rates between 6 x 10(-5) cm3/s (1 cm3 in 4.6 h) and 5 x 10(-9) cm3/s (1 cm3 in 6.3 years). The technique may reach or exceed the capabilities of the most sensitive commercial leak test systems using helium mass-spectrometers. In addition, comparison of the measured results to a simple scaling law suggests that tracer gas cloud geometry influences the photoacoustic signal amplitude. PMID:14587593

  2. High-Sensitivity GaN Microchemical Sensors

    NASA Technical Reports Server (NTRS)

    Son, Kyung-ah; Yang, Baohua; Liao, Anna; Moon, Jeongsun; Prokopuk, Nicholas

    2009-01-01

    Systematic studies have been performed on the sensitivity of GaN HEMT (high electron mobility transistor) sensors using various gate electrode designs and operational parameters. The results here show that a higher sensitivity can be achieved with a larger W/L ratio (W = gate width, L = gate length) at a given D (D = source-drain distance), and multi-finger gate electrodes offer a higher sensitivity than a one-finger gate electrode. In terms of operating conditions, sensor sensitivity is strongly dependent on transconductance of the sensor. The highest sensitivity can be achieved at the gate voltage where the slope of the transconductance curve is the largest. This work provides critical information about how the gate electrode of a GaN HEMT, which has been identified as the most sensitive among GaN microsensors, needs to be designed, and what operation parameters should be used for high sensitivity detection.

  3. Linearization strategies for high sensitivity magnetoresistive sensors

    NASA Astrophysics Data System (ADS)

    Silva, Ana V.; Leitao, Diana C.; Valadeiro, João; Amaral, José; Freitas, Paulo P.; Cardoso, Susana

    2015-10-01

    Ultrasensitive magnetic field sensors envisaged for applications on biomedical imaging require the detection of low-intensity and low-frequency signals. Therefore linear magnetic sensors with enhanced sensitivity low noise levels and improved field detection at low operating frequencies are necessary. Suitable devices can be designed using magnetoresistive sensors, with room temperature operation, adjustable detected field range, CMOS compatibility and cost-effective production. The advent of spintronics set the path to the technological revolution boosted by the storage industry, in particular by the development of read heads using magnetoresistive devices. New multilayered structures were engineered to yield devices with linear output. We present a detailed study of the key factors influencing MR sensor performance (materials, geometries and layout strategies) with focus on different linearization strategies available. Furthermore strategies to improve sensor detection levels are also addressed with best reported values of ˜40 pT/√Hz at 30 Hz, representing a step forward the low field detection at room temperature.

  4. Eugenic metal-free sensitizers with double anchors for high performance dye-sensitized solar cells.

    PubMed

    Hung, Wei-I; Liao, You-Ya; Lee, Ting-Hui; Ting, Yu-Chien; Ni, Jen-Shyang; Kao, Wei-Siang; Lin, Jiann T; Wei, Tzu-Chien; Yen, Yung-Sheng

    2015-02-01

    A series of new phenothiazine-based dyes (HL5-HL7) with double acceptors/anchors have been synthesized and used as the sensitizers for highly efficient dye-sensitized solar cells (DSSCs). Among them, the HL7-based cell exhibits the best efficiency of 8.32% exceeding the N719-based cell (7.35%) by ∼13%. PMID:25555237

  5. High-sensitivity spectroscopy with diode lasers

    NASA Astrophysics Data System (ADS)

    Fox, Richard W.; Robinson, H. G.; Zibrov, A. S.; Mackie, N.; Marquardt, John H.; Magyar, J.; Hollberg, Leo W.

    1993-04-01

    Linewidth reduction of an extended cavity diode laser at 657 nm was accomplished by negative feedback to an intra-cavity ADP crystal. High resolution (170 kHz wide) saturated absorption signals were recorded of the calcium intercombination line which is of interest for a frequency standard. The spectrum of the red 62p3/2 - 92s1/2 cesium line in a magneto-optical cell trap was also investigated.

  6. High sensitivity background absorption measurements in semiconductors

    NASA Astrophysics Data System (ADS)

    Giannini, Nathan; Silva, Junior R.; Wang, Chengao; Albrecht, Alexander R.; Melgaard, Seth D.; Sheik-Bahae, Mansoor

    2015-03-01

    Laser cooling in InGaP|GaAs double heterostructures (DHS) has been a sought after goal. Even though very high external quantum efficiency (EQE) has been achieved, background absorption has remained a bottleneck in achieving net cooling. The purpose of this study is to gain more insight into the source of the background absorption for InGaP|GaAs DHS as well as GaAs|AlGaAs DBRs by employing an excite-probe thermal Z-scan measurement.

  7. Quantification of patulin in fruit leathers by ultra-high-performance liquid chromatography-photodiode array (UPLC-PDA).

    PubMed

    Maragos, Chris M; Busman, Mark; Ma, Liang; Bobell, John

    2015-01-01

    Patulin is a mycotoxin commonly found in certain fruit and fruit products. For this reason many countries have established regulatory limits pertaining to, in particular, apple juice and apple products. Fruit leathers are produced by dehydrating fruit puree, leaving a sweet product that has a leathery texture. A recent report in the literature described the detection of patulin at substantial levels in fruit leathers. To investigate this further, an ultra-high-performance liquid chromatography-photodiode array (UPLC-PDA) method was developed for the sensitive detection of patulin in fruit leathers. Investigations were also made of the suitability of direct analysis in real time-mass spectrometry (DART-MS) for detection of patulin from the surface of fruit leathers. Results indicated DART-MS was insufficiently sensitive for quantification from the surface of home-style apple leathers, although patulin spiked onto the surface of leather or peel could be detected. The UPLC-PDA method was used to determine the fate of patulin during the preparation of home-made fruit leathers. Interestingly, when a home-style process was used, the patulin was not destroyed, but rather increased in concentration as the puree was dehydrated. The UPLC-PDA method was also used to screen for patulin in commercial fruit leathers. Of the 36 products tested, 14 were above the limit of detection (3.5 μg kg(-1)) and nine were above the limit of quantification (12 μg kg(-1)). Positive samples were confirmed by UPLC-MS/MS. Only one sample was found above the US regulatory limit for single-strength apple juice products (50 μg kg(-1)). These results suggest patulin can be concentrated during preparation and can be found in fruit leathers. The limited survey suggests that patulin is fairly prevalent in such commercial products, but that the levels are usually low. PMID:25832782

  8. Fabrication of sensitive high Tc bolometers

    NASA Technical Reports Server (NTRS)

    Nahum, Michael; Verghese, S.; Hu, Qing; Richards, Paul L.; Char, K.; Newman, N.; Sachtjen, Scott A.

    1990-01-01

    The rapid change of resistance with temperature of high quality films of high T sub c superconductors can be used to make resistance thermometers with very low temperature noise. Measurements on c-axis yttrium barium copper oxide (YBCO) films have given a spectral intensity of temperature noise less than 4 times 10(exp -8) K/Hz(exp 1/2) at 10 Hz. Consequently, the opportunity exists to make useful bolometric infrared detectors that operate near 90 K which can be cooled with liquid nitrogen. The fabrication and measurement of two bolometer architectures are discussed. The first is a conventional bolometer which consists of a 3000 A thick YBCO film deposited in situ by laser ablation on top of a 500 A thick SrTiO3 thickness and diced into 1x1 mm(exp 2) bolometer chips. Gold black smoke was used as the radiation absorber. The voltage noise was less than the amplifier noise when the film was current biased. Optical measurements gave an NEP of 5 times 10(exp -11) W/Hz(exp 1/2) at 10 Hz. The second architecture is that of an antenna-coupled microbolometer which consists of a small (5x10 cubic microns) YBCO film deposited directly on a bulk substrate with a low thermal conductance (YSZ) and an impedance matched planar lithographed spiral or log-periodic antenna. This structure is produced by standard photolithographic techniques. Measurements gave an electrical NEP of 4.7 times 10(exp -12) W/Hz(exp 1/2) at 10 kHz. Measurements of the optical efficiency are in progress. The measured performance of both bolometers will be compared to other detectors operating at or above liquid nitrogen temperatures so as to identify potential applications.

  9. High-throughput LC-MS/MS based simultaneous determination of polyamines including N-acetylated forms in human saliva and the diagnostic approach to breast cancer patients.

    PubMed

    Tsutsui, Haruhito; Mochizuki, Toshiki; Inoue, Koichi; Toyama, Tatsuya; Yoshimoto, Nobuyasu; Endo, Yumi; Todoroki, Kenichiro; Min, Jun Zhe; Toyo'oka, Toshimasa

    2013-12-17

    The determination of polyamines and their N-acetylated forms was performed by ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The polyamines efficiently reacted with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) in 0.1 M borax (pH 9.3) at 60 °C for 30 min. The resulting derivatives were analyzed by electrospray ionization (ESI)-MS and sensitively detected by selected reaction monitoring (SRM). Furthermore, a rapid separation of the polyamine derivatives within 10 min was performed by UPLC using an antipressurized column packed with 1.7-μm octadecylsilyl (ODS) silica gel. The limits of detection (S/N = 3) on the SRM chromatograms were at the attomole level (9-43 amol). This procedure was used to successfully determine 11 polyamines, including their N-acetylated forms, in the saliva of patients with primary and relapsed breast cancer and healthy volunteers. The level of several polyamines (Ac-PUT, Ac-SPD, Ac-SPM, DAc-SPD, and DAc-SPM) increases in breast cancer patients. Furthermore, the levels of three polyamines (Ac-SPM, DAc-SPD, and DAc-SPM) were significantly higher only in the relapsed patients. The present method proved highly sensitive and is characterized by specificity and feasibility for sample analysis. Consequently, the proposed method is useful for the noninvasive salivary diagnosis of cancer patients and could be applied to determine polyamines in several specimens of biological nature. PMID:24274257

  10. [Simultaneous determination of ten antibiotics in pharmaceutical wastewater using ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Qiu, Panzi; Guo, Xinyan; Wang, Na; Kong, Xiangji; He, Hua

    2015-07-01

    A simultaneous analytical method was established for ten selected antibiotics from three categories in pharmaceutical wastewater with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The water samples were enriched and cleaned-up by solid phase extraction cartridges. The types of solid phase extraction cartridges and eluents were optimized by comparing the recoveries of the analytes in water samples under different conditions. The target compounds were separated on an Agilent C18 column (75 mmx 2.1 mm, 2.7 μm) with the mobile phases of acetonitrile and 0.2% (v/v) formic acid aqueous solution, and then determined by electrospray ionization mass spectrometry (ESI-MS). The results showed that the calibration curves were linear in the range of 0.1-1000 μg/L (r2>0.995). The limits of detection (LODs, S/N≥3) and the limits of quantification (LOQs, S/N≥10) of the ten compounds were 0.07-4.37 ng/L and 0.22-14.55 ng/L, respectively. The recovery experiments were performed with samples spiked in the range of 0.002-40 μg/L. The recoveries of the target compounds were in the range of 50.4%-114.1% (RSDs≤9.89%, n=3). Based on this analytical method, the raw and treated sewage samples from a pharmaceutical manufacturer wastewater treatment plant in Jiangsu Province were analyzed. Three compounds were detected in the samples from different sewage treatment units in the range of 0.46-1033.60 μg/L. It shows that the method is accurate, reliable, highly sensitive and can be used to analyze the water samples of pharmaceutical wastewater treatment plant containing aminoglycosides, spiramycin and fluoroquinolones antibiotics. PMID:26672201

  11. Ultra-high performance liquid chromatography-electrospray tandem mass spectrometry for the analysis of antibiotic residues in environmental waters.

    PubMed

    Xue, Qiang; Qi, Yanjie; Liu, Fei

    2015-11-01

    An optimized solid-phase extraction (SPE) and ultra-high performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS) method was developed for the effective analysis of 35 antibiotics including sulfonamides (SAs), quinolones (QLs), tetracyclines (TCs), macrolides (MALs), lincomycin (LIN), and chloramphenicol (CAP). The addition of 0.1% formic acid to the mobile phase was favorable for the formation of [M + H](+) and the enhancement in the detection signals, but using ammonium formate decreased [M + H](+) with a corresponding reduction in the response of CAP. The optimal pH range for the SPE was 4.5 ∼ 5.0 with 6 mL aqueous ammonia/methanol (5/95, v/v) as the optimized eluent. An internal standard (IS) was selected for each type of analytes based on similarities in classification and retention time. The detection was completed in less than 10 min and was excellent with method detection limits (MDL) of 0.29 ∼ 4.03 ng/L. The recoveries of the antibiotics in samples from ultrapure water and groundwater were 67.13 ∼ 93.00% and 68.91 ∼ 92.67%, respectively. The antibiotics in samples collected from wastewater, surface water, and groundwater were also effectively detected. This newly developed method has the advantages of short detection times, small sample consumption, excellent reproducibility, and high sensitivity. This provides a reliable and promising technique for the simultaneous detection and monitoring of various residual antibiotics in aqueous environmental samples. PMID:26104902

  12. Approach to the Highly Sensitized Kidney Transplant Candidate.

    PubMed

    Keith, Douglas S; Vranic, Gayle M

    2016-04-01

    For patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist. PMID:26915916

  13. Simultaneous quantification of seven plasma metabolites of sulfur mustard by ultra high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Chunzheng; Chen, Jia; Liu, Qin; Xie, Jianwei; Li, Hua

    2013-02-15

    Sulfur mustard (SM) is a hazardous chemical warfare agent that has been used in several military conflicts. SM is also considered as a major threat to civilians because of its existing stockpiles and easy production. Analysis of exposure biomarkers in biological samples collected from suspected victims is a useful tool for early diagnosis of SM poisoning. In this study, a sensitive and rapid quantitative method with ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for simultaneous determination of seven SM plasma biomarkers, including its oxidative, hydrolysis and ?-lyase metabolites. A simple one-step protein precipitation with acetonitrile-methanol (4:1) was used for sample preparation. A full validation was conducted with respect to specificity, linearity, recovery, matrix effect, precision, accuracy and stability. The lower limits of quantification for the seven metabolites ranged from 0.01?gL(-1) to 5?gL(-1). The intraday relative standard deviation was less than 7.0%, and the interday deviation was less than 9.1%. The recoveries varied in the range from 82.8% to 118%. This method has been successfully applied to a toxicokinetic study for obtaining the plasma profiles of seven metabolites in SM-exposed rats, following a single subcutaneous dose of 3.3mgkg(-1). All the targeted compounds were detected in rat plasma. bis-?-Chloroethyl sulfoxide (SMO), thiodiglycol (TDG), thiodiglycol sulfoxide (TDGO), 1,1'-sulfonylbis-[2-S-(N-acetylcysteinyl)ethane (SBSNAE), 1,1'-sulfonylbis-[2-(methylsulfinyl)ethane] (SBMSE) and 1-methylsulfinyl-2-[2-(methylthio)ethylsulfonyl]ethane (MSMTESE) were found to be the major metabolites in rat plasma. The time windows for the detection of these metabolites were varied in the range of 5min to 48h after exposure. The method provides a useful tool for short-term diagnosis of SM poisoning. PMID:23369883

  14. Comparative pharmacokinetics of a proliposome formulation of Ginkgo biloba extract and Ginaton in rats by a sensitive ultra performance liquid chromatography-tandem mass spectrometry method.

    PubMed

    Zheng, Bin; Xing, Gaoyang; Bi, Ye; Yan, Guodong; Wang, Jing; Cheng, Yingkun; Liu, Yan; Ashraf, Muhammad Aqeel; Xie, Jing

    2016-01-01

    As a novel oral drug delivery system, proliposome was applied to improve the solubility of active components of Ginkgo biloba extract (GbE). There are currently few reports focusing on the pharmacokinetic characteristics of proliposome of GbE (GbP). A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of active components of GbP and a commercial tablet product (Ginaton) in rat plasma was developed and successfully validated. The method was applied to the comparative pharmacokinetic evaluation of GbP and Ginaton in rat plasma. The results indicated that GbP has a significant effect on absorption, elimination and bioavailability of flavonoids and terpenoid lactones in comparison with Ginaton. The obtained results would be helpful for evaluating the absorption mechanism in the gastrointestinal tract in pharmacokinetic level and guiding the development of the novel oral drug delivery system. PMID:26858539

  15. [Determination of 12 flavonoids in tobacco leaves using ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Li, Yong; Lin, Qian; Pang, Tao; Shi, Junli

    2015-07-01

    Flavonoids are very important secondary metabolites for tobacco plants. They are also considered as important flavor precursors for cigarettes. A method of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of 12 flavonoids in tobacco leaves. The developed method determined 10 more flavonoids compared to the traditional method. A solution of methanol-water-chloroform (5:2:2, v/v/v) was used to extract the flavonoids from tobacco leaves and remove the pigment. Instrument analysis using the UPLC-MS/MS was completed in 13 min. The method validation was performed, and the results showed that the linear correlation coefficients (r2) of all the 12 flavonoids were more than 0.99. The limits of detection and the limits of quantification were in the range of 0.3-100 μg/L and 1.2-400 μg/L, respectively. Intra-day and Inter-day reproducibilities were in the range of 3.5%-7.4% and 5.2%-11.4%, respectively. The recoveries were 81.2%-111.9%. The established method was successfully used to analyze the flavonoids of tobacco leaves of 11 varieties. Significant concentration differences of the flavonoids were found among the determined varieties. Furthermore, significant positive correlation among the flavonoids with similar chemical structures (aglycones and their related glycosides, glycosides with the same aglycone, and similar aglycones) was found using the acquired data. PMID:26672204

  16. Highly sensitive suspended-gate ion sensitive transistor for the detection of pH

    NASA Astrophysics Data System (ADS)

    Bendriaa, F.; Le Bihan, F.; Salaun, A. C.; Mohammed-Brahim, T.; Bonnaud, O.

    2005-07-01

    This paper presents a new device for the pH detection. It is based on a suspended polysilicon gate field effect transistor (SGFET). The sensitive layer is made of silicon nitride as for ISFET technology. The suspended bridge, used as gate electrode, is formed with doped polysilicon covered with silicon nitride layers for electrical insulation. The layers are deposited by Low Pressure Chemical Vapor Deposition (LPCVD). Surface micro-technology allows to obtain a small height (0.5μm) suspended-bridge. In this case, the solution penetrates under the gate. The high field effect in the gap between the gate and the channel is enough to change the charges distribution. Very high pH sensitivity, greater than 200 mV/pH, is found with this new structure and it is much higher than the usual Nernstian sensitivity of ISFETs. The device concept, electrical characteristics, and the effect of the thickness of the gap between the bridge and the sensitive layer on the pH sensitivity are discussed in this study.

  17. Near-infrared squaraine co-sensitizer for high-efficiency dye-sensitized solar cells.

    PubMed

    Rao, G Hanumantha; Venkateswararao, A; Giribabu, L; Han, Liyuan; Bedja, Idriss; Gupta, Ravindra Kumar; Islam, Ashraful; Singh, Surya Prakash

    2016-06-01

    A combination of squaraine-based dyes (SPSQ1 and SPSQ2) and a ruthenium-based dye (N3) were chosen as co-sensitizers to construct efficient dye-sensitized solar cells. The co-sensitization of squaraine dyes with N3 enhanced their light-harvesting properties as a result of the broad spectral coverage in the region 350-800 nm. The co-sensitized solar cells based on SPSQ2 + N3 showed the highest short circuit current density of 17.10 mA cm(-2), an open circuit voltage of 0.66 V and a fill factor of 0.73, resulting in the highest power conversion efficiency of 8.2%, which is higher than that of the dye-sensitized solar cells based on the individual SPSQ1 and SPSQ2 dyes. The high power conversion efficiency of SPSQ2 + N3 was ascribed to its good light-harvesting properties, which resulted from its broader incident photon current conversion spectrum than that of the individual dyes. The high electron life time and electron recombination, which were the main causes of the higher efficiency of the device, were successfully analysed and correlated using transient absorption spectrometry and intensity-modulated photovoltage spectrometry. PMID:27167491

  18. Analytical Glycobiology at High Sensitivity: Current Approaches and Directions

    PubMed Central

    Novotny, Milos V.; Alley, William R.; Mann, Benjamin F.

    2013-01-01

    This review summarizes the analytical advances made during the last several years in the structural and quantitative determinations of glycoproteins in complex biological mixtures. The main analytical techniques used in the fields of glycomics and glycoproteomics involve different modes of mass spectrometry and their combinations with capillary separation methods such as microcolumn liquid chromatography and capillary electrophoresis. The needs for high-sensitivity measurements have been emphasized in the oligosaccharide profiling used in the field of biomarker discovery through MALDI mass spectrometry. High-sensitivity profiling of both glycans and glycopeptides from biological fluids and tissue extracts has been aided significantly through lectin preconcentration and the uses of affinity chromatography. PMID:22945852

  19. Instrumentation for high-efficiency, high-sensitivity actinide analysis

    SciTech Connect

    Olivares, J.; Chamberlin, E.; Murrell, M.; Kahr, M.; Duan, Y.

    1996-04-01

    This is the final report of a 3-year project. We have developed a high-efficiency thermal ionization source that provides one to two orders of magnitude improvement in sample utilization efficiency in comparison with the traditional filament-type ion source currently used in thermal ionization mass spectrometry. This improved sample utilization efficiency results in a proportional increase in sample throughput and proportional decrease in analysis time. Coupling this source with a quadrupole mass spectrometer results in an instrument system for high-efficiency actinide analysis and other applications. In addition to its high efficiency, the sample used in this source can be much smaller than that in previous tube-type sources. The compact structure of the cavity makes it more applicable to any type of mass spectrometer and the whole instrument is small and transportable.

  20. A high sensitivity nanomaterial based SAW humidity sensor

    NASA Astrophysics Data System (ADS)

    Wu, Tsung-Tsong; Chen, Yung-Yu; Chou, Tai-Hsu

    2008-04-01

    In this paper, a highly sensitive humidity sensor is reported. The humidity sensor is configured by a 128YX-LiNbO3 based surface acoustic wave (SAW) resonator whose operating frequency is at 145 MHz. A dual delay line configuration is realized to eliminate external temperature fluctuations. Moreover, for nanostructured materials possessing high surface-to-volume ratio, large penetration depth and fast charge diffusion rate, camphor sulfonic acid doped polyaniline (PANI) nanofibres are synthesized by the interfacial polymerization method and further deposited on the SAW resonator as selective coating to enhance sensitivity. The humidity sensor is used to measure various relative humidities in the range 5-90% at room temperature. Results show that the PANI nanofibre based SAW humidity sensor exhibits excellent sensitivity and short-term repeatability.

  1. High-sensitivity, high-speed continuous imaging system

    DOEpatents

    Watson, Scott A; Bender, III, Howard A

    2014-11-18

    A continuous imaging system for recording low levels of light typically extending over small distances with high-frame rates and with a large number of frames is described. Photodiode pixels disposed in an array having a chosen geometry, each pixel having a dedicated amplifier, analog-to-digital convertor, and memory, provide parallel operation of the system. When combined with a plurality of scintillators responsive to a selected source of radiation, in a scintillator array, the light from each scintillator being directed to a single corresponding photodiode in close proximity or lens-coupled thereto, embodiments of the present imaging system may provide images of x-ray, gamma ray, proton, and neutron sources with high efficiency.

  2. HIGHLY SENSITIVE BIOASSAYS FOR EVALUATING AIRBORNE MUTAGENS INDOORS

    EPA Science Inventory

    The standard mutagenicity bioassays that are readily applied to the valuation of outdoor air samples collected by high volume samplers are not efficiently sensitive to measure the mutagenicity of low volume air samples collected indoors. wo microsuspension mutation assays using v...

  3. Microelectromechanical Resonant Accelerometer Designed with a High Sensitivity

    PubMed Central

    Zhang, Jing; Su, Yan; Shi, Qin; Qiu, An-Ping

    2015-01-01

    This paper describes the design and experimental evaluation of a silicon micro-machined resonant accelerometer (SMRA). This type of accelerometer works on the principle that a proof mass under acceleration applies force to two double-ended tuning fork (DETF) resonators, and the frequency output of two DETFs exhibits a differential shift. The dies of an SMRA are fabricated using silicon-on-insulator (SOI) processing and wafer-level vacuum packaging. This research aims to design a high-sensitivity SMRA because a high sensitivity allows for the acceleration signal to be easily demodulated by frequency counting techniques and decreases the noise level. This study applies the energy-consumed concept and the Nelder-Mead algorithm in the SMRA to address the design issues and further increase its sensitivity. Using this novel method, the sensitivity of the SMRA has been increased by 66.1%, which attributes to both the re-designed DETF and the reduced energy loss on the micro-lever. The results of both the closed-form and finite-element analyses are described and are in agreement with one another. A resonant frequency of approximately 22 kHz, a frequency sensitivity of over 250 Hz per g, a one-hour bias stability of 55 μg, a bias repeatability (1σ) of 48 μg and the bias-instability of 4.8 μg have been achieved. PMID:26633425

  4. The increased shock sensitivity of PBX 9502 at high temperature

    NASA Astrophysics Data System (ADS)

    Rae, Philip; Baca, Eva; Cartelli, Angelo

    2013-06-01

    It has been shown previously that the shock sensitivity of TATB based PBXs can be significantly increased at elevated temperature. In fact, some researchers have reported that at 250°C the Pop plot for LX-17 (a TATB based composition) overlays the Pop plot for room temperature PBX 9501 (an HMX based composition). The current study made use of the modified LANL small-scale gap test to investigate the shock sensitivity as a function of temperature. The modified gap test inputs an almost planar shock into the acceptor explosive rather than the more usual highly divergent one. This important change not only makes the geometry less sensitive to machining and assembly imperfections than a divergent version, but also allows accurate computer simulation using models calibrated to 1D Pop plot data. In these tests, samples of PBX 9502 were held at temperatures of 180, 200, 230 & 260°C for 30 minutes prior to firing the donor booster. As expected a significant increase in sensitivity was observed, but the material was not as sensitive as PBX 9501 even at 260°C. The method of performing these more complex high temperature gap tests and the accompanying computer modeling of the results will also be presented.

  5. Antibody-free ultra-high performance liquid chromatography/tandem mass spectrometry measurement of angiotensin I and II using magnetic epitope-imprinted polymers.

    PubMed

    Tan, Lei; Yu, Zerong; Zhou, Xiaoming; Xing, Da; Luo, Xiaoyan; Peng, Rongfei; Tang, Youwen

    2015-09-11

    The major challenges in measuring plasma renin activity (PRA) stem from the complexity of biological matrix, as well as from the instability and low circulating concentration of angiotensin. In this study, an ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) based technique has been developed for the measurement of angiotensin using magnetically imprinted polymers for simultaneous enrichment of the precursor peptide angiotensin II (Ang II) and the upstream peptide precursor angiotensin I (Ang I). This technique involved surface graft imprinting in aqueous solutions using vinyl-modified nano-iron oxide as solid supports, the specificity determinant of Ang I and Ang II as the epitope, and methacrylic acid and N-t-butylacrylamide as functional monomers. The vinyl-modified nano-iron oxide acted as a magnetic separation media, and the molecularly imprinted shell provided analyte selectivity for the recognition of Ang I and Ang II. Selective enrichment of Ang I and Ang II was accomplished by the magnetically imprinted polymers, followed by a magnetic separation procedure and subsequent quantification by UPLC-MS/MS in the positive ionization mode with multiple reaction monitoring. Through the latter protocol, a low limit of detection could be realized, viz. 0.07ng/mL and 0.06ng/mL for Ang I and II, respectively, which was thoroughly validated for accuracy and reproducibility through analyzing Ang I and Ang II in human plasma samples. PMID:26256923

  6. Sensitivity of high-frequency Rayleigh-wave data revisited

    USGS Publications Warehouse

    Xia, J.; Miller, R.D.; Ivanov, J.

    2007-01-01

    Rayleigh-wave phase velocity of a layered earth model is a function of frequency and four groups of earth properties: P-wave velocity, S-wave velocity (Vs), density, and thickness of layers. Analysis of the Jacobian matrix (or the difference method) provides a measure of dispersion curve sensitivity to earth properties. Vs is the dominant influence for the fundamental mode (Xia et al., 1999) and higher modes (Xia et al., 2003) of dispersion curves in a high frequency range (>2 Hz) followed by layer thickness. These characteristics are the foundation of determining S-wave velocities by inversion of Rayleigh-wave data. More applications of surface-wave techniques show an anomalous velocity layer such as a high-velocity layer (HVL) or a low-velocity layer (LVL) commonly exists in near-surface materials. Spatial location (depth) of an anomalous layer is usually the most important information that surface-wave techniques are asked to provide. Understanding and correctly defining the sensitivity of high-frequency Rayleigh-wave data due to depth of an anomalous velocity layer are crucial in applying surface-wave techniques to obtain a Vs profile and/or determine the depth of an anomalous layer. Because depth is not a direct earth property of a layered model, changes in depth will result in changes in other properties. Modeling results show that sensitivity at a given depth calculated by the difference method is dependent on the Vs difference (contrast) between an anomalous layer and surrounding layers. The larger the contrast is, the higher the sensitivity due to depth of the layer. Therefore, the Vs contrast is a dominant contributor to sensitivity of Rayleigh-wave data due to depth of an anomalous layer. Modeling results also suggest that the most sensitive depth for an HVL is at about the middle of the depth to the half-space, but for an LVL it is near the ground surface. ?? 2007 Society of Exploration Geophysicists.

  7. NK sensitivity of neuroblastoma cells determined by a highly sensitive coupled luminescent method

    SciTech Connect

    Ogbomo, Henry; Hahn, Anke; Geiler, Janina; Michaelis, Martin; Doerr, Hans Wilhelm; Cinatl, Jindrich . E-mail: Cinatl@em.uni-frankfurt.de

    2006-01-06

    The measurement of natural killer (NK) cells toxicity against tumor or virus-infected cells especially in cases with small blood samples requires highly sensitive methods. Here, a coupled luminescent method (CLM) based on glyceraldehyde-3-phosphate dehydrogenase release from injured target cells was used to evaluate the cytotoxicity of interleukin-2 activated NK cells against neuroblastoma cell lines. In contrast to most other methods, CLM does not require the pretreatment of target cells with labeling substances which could be toxic or radioactive. The effective killing of tumor cells was achieved by low effector/target ratios ranging from 0.5:1 to 4:1. CLM provides highly sensitive, safe, and fast procedure for measurement of NK cell activity with small blood samples such as those obtained from pediatric patients.

  8. Highly Mass-Sensitive Thin Film Plate Acoustic Resonators (FPAR)

    PubMed Central

    Arapan, Lilia; Alexieva, Gergana; Avramov, Ivan D.; Radeva, Ekaterina; Strashilov, Vesseline; Katardjiev, Ilia; Yantchev, Ventsislav

    2011-01-01

    The mass sensitivity of thin aluminum nitride (AlN) film S0 Lamb wave resonators is theoretically and experimentally studied. Theoretical predictions based on modal and finite elements method analysis are experimentally verified. Here, two-port 888 MHz synchronous FPARs are micromachined and subsequently coated with hexamethyl-disiloxane(HMDSO)-plasma-polymerized thin films of various thicknesses. Systematic data on frequency shift and insertion loss versus film thickness are presented. FPARs demonstrate high mass-loading sensitivity as well as good tolerance towards the HMDSO viscous losses. Initial measurements in gas phase environment are further presented. PMID:22163994

  9. Porous silicon ring resonator for compact, high sensitivity biosensing applications

    SciTech Connect

    Rodriguez, Gilberto A.; Hu, Shuren; Weiss, Sharon M.

    2015-01-01

    A ring resonator is patterned on a porous silicon slab waveguide to produce a compact, high quality factor biosensor with a large internal surface area available for enhanced recognition of biological and chemical molecules. The porous nature of the ring resonator allows molecules to directly interact with the guided mode. Quality factors near 10,000 were measured for porous silicon ring resonators with a radius of 25 μm. A bulk detection sensitivity of 380 nm/RIU was measured upon exposure to salt water solutions. Specific detection of nucleic acid molecules was demonstrated with a surface detection sensitivity of 4 pm/nM.

  10. Porous silicon ring resonator for compact, high sensitivity biosensing applications

    DOE PAGESBeta

    Rodriguez, Gilberto A.; Hu, Shuren; Weiss, Sharon M.

    2015-01-01

    A ring resonator is patterned on a porous silicon slab waveguide to produce a compact, high quality factor biosensor with a large internal surface area available for enhanced recognition of biological and chemical molecules. The porous nature of the ring resonator allows molecules to directly interact with the guided mode. Quality factors near 10,000 were measured for porous silicon ring resonators with a radius of 25 ?m. A bulk detection sensitivity of 380 nm/RIU was measured upon exposure to salt water solutions. Specific detection of nucleic acid molecules was demonstrated with a surface detection sensitivity of 4 pm/nM.

  11. High-sensitivity stress-sensitive differential amplifier with gain control and temperature compensation

    NASA Astrophysics Data System (ADS)

    Li, Jingjing; Yue, Ruifeng; Liu, Li-Tian

    2001-10-01

    An essential issue of almost all sensors using piezoresistive effect of silicon is the sensing of the stress induced by external cause such as pressure for pressure sensor, inertial force for inertial sensor, etc. Traditional piezoresistor array need relatively large area, exhibits low sensitivity, and need complex circuit for (delta) R/R to current or voltage measurement transaction. Using Stress-Sensitive Differential Amplifier, or SSDA, is an effective solution to the above-mentioned problems. SSDA exhibits relatively high sensitivity and low power dissipation. But, although it's temperature coefficient is lower compared to piezoresistor stress - sensing element, temperature compensation is still imperative. In this paper, the principles of SSDA are presented. A new SSDA circuit is designed. Using such circuit the sensitivity can be greatly increased, and such an increase need no any extra cost in circuit area, power dissipation, circuit complexity, etc. A new technic for the SSDA's gain control is developed, which makes the setting of the sensors' dynamic range simple; A temperature compensation circuit is also designed and integrated with the SSDA.

  12. A novel high-sensitivity FBG pressure sensor

    NASA Astrophysics Data System (ADS)

    Yao, Zhenhua; Fu, Tao; Leng, Jinsong

    2007-07-01

    A novel pressure sensor based on FBG is designed in this paper. Not only in normal environment, also does it accurately work in water and petrol where other conventional sensors can not work normally. In this paper, the principle of the novel sensor is introduced, and two experiments are further performed: One is keeping the sensor flatly in the gastight silo whose pressure is supplied by an air compressing engine, and the other one is keeping the sensor in liquid. The analysis of the result data demonstrates that the sensor possesses high sensitivity, high linearity, high precision and repeatability. Its experimental linearity and sensitivity approach 0.99858 and 5.35×10 -3MPa -1, respectively. It is also discussed using the sensor to measure the volume in tank.

  13. High-sensitivity linear piezoresistive transduction for nanomechanical beam resonators.

    PubMed

    Sansa, Marc; Fernández-Regúlez, Marta; Llobet, Jordi; San Paulo, Álvaro; Pérez-Murano, Francesc

    2014-01-01

    Highly sensitive conversion of motion into readable electrical signals is a crucial and challenging issue for nanomechanical resonators. Efficient transduction is particularly difficult to realize in devices of low dimensionality, such as beam resonators based on carbon nanotubes or silicon nanowires, where mechanical vibrations combine very high frequencies with miniscule amplitudes. Here we describe an enhanced piezoresistive transduction mechanism based on the asymmetry of the beam shape at rest. We show that this mechanism enables highly sensitive linear detection of the vibration of low-resistivity silicon beams without the need of exceptionally large piezoresistive coefficients. The general application of this effect is demonstrated by detecting multiple-order modes of silicon nanowire resonators made by either top-down or bottom-up fabrication methods. These results reveal a promising approach for practical applications of the simplest mechanical resonators, facilitating its manufacturability by very large-scale integration technologies. PMID:25000256

  14. High sensitivity glucose sensor based on optical heterodyne phase detection

    NASA Astrophysics Data System (ADS)

    Lin, Jiun-You; Chen, Kun-Huang; Chen, Jing-Heng; Liao, Yu-Cheng; Lin, Yu-Hsien

    2009-07-01

    Measurements of glucose concentration are important parts of biochemical analyses. Based on the principles of the common-path heterodyne interferometry, we develop a high sensitivity optical sensor for measuring glucose concentration. A heterodyne light beam after transmitted through a glucose solution passes through some polarization components for interference. The phase difference determined with heterodyne interferometric technique of the interference signal is greatly enhanced as a result of proper azimuth angles of some polarization components, and a high sensitivity measurement of glucose concentration can be achieved. The feasibility of the measuring method was demonstrated by our experimental results. This optical sensor should bear the merits of high accuracy, short sample medium length, and simpler operational endeavor.

  15. Sensitivity of HAWC to high-mass dark matter annihilations

    NASA Astrophysics Data System (ADS)

    Abeysekara, A. U.; Alfaro, R.; Alvarez, C.; Álvarez, J. D.; Arceo, R.; Arteaga-Velázquez, J. C.; Ayala Solares, H. A.; Barber, A. S.; Baughman, B. M.; Bautista-Elivar, N.; Becerra Gonzalez, J.; Belmont, E.; BenZvi, S. Y.; Berley, D.; Bonilla Rosales, M.; Braun, J.; Caballero-Lopez, R. A.; Caballero-Mora, K. S.; Carramiñana, A.; Castillo, M.; Cotti, U.; Cotzomi, J.; de la Fuente, E.; De León, C.; DeYoung, T.; Diaz Hernandez, R.; Diaz-Cruz, L.; Díaz-Vélez, J. C.; Dingus, B. L.; DuVernois, M. A.; Ellsworth, R. W.; Fiorino, D. W.; Fraija, N.; Galindo, A.; Garfias, F.; González, M. M.; Goodman, J. A.; Grabski, V.; Gussert, M.; Hampel-Arias, Z.; Harding, J. P.; Hui, C. M.; Hüntemeyer, P.; Imran, A.; Iriarte, A.; Karn, P.; Kieda, D.; Kunde, G. J.; Lara, A.; Lauer, R. J.; Lee, W. H.; Lennarz, D.; León Vargas, H.; Linares, E. C.; Linnemann, J. T.; Longo, M.; Luna-Garcia, R.; Marinelli, A.; Martinez, H.; Martinez, O.; Martínez-Castro, J.; Matthews, J. A. J.; McEnery, J.; Mendoza Torres, E.; Miranda-Romagnoli, P.; Moreno, E.; Mostafá, M.; Nellen, L.; Newbold, M.; Noriega-Papaqui, R.; Oceguera-Becerra, T.; Patricelli, B.; Pelayo, R.; Pérez-Pérez, E. G.; Pretz, J.; Rivière, C.; Rosa-González, D.; Ryan, J.; Salazar, H.; Salesa, F.; Sanchez, F. E.; Sandoval, A.; Schneider, M.; Silich, S.; Sinnis, G.; Smith, A. J.; Sparks Woodle, K.; Springer, R. W.; Taboada, I.; Toale, P. A.; Tollefson, K.; Torres, I.; Ukwatta, T. N.; Villaseñor, L.; Weisgarber, T.; Westerhoff, S.; Wisher, I. G.; Wood, J.; Yodh, G. B.; Younk, P. W.; Zaborov, D.; Zepeda, A.; Zhou, H.; Abazajian, K. N.; Milagro Collaboration

    2014-12-01

    The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19° North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi-TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from nonluminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross sections below thermal. HAWC should also be sensitive to nonthermal cross sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.

  16. Crocodylus niloticus (Crocodilia) is highly sensitive to water surface waves.

    PubMed

    Grap, Nadja J; Monzel, Anna S; Kohl, Tobias; Bleckmann, Horst

    2015-10-01

    Crocodiles show oriented responses to water surface wave stimuli but up to now behavioral thresholds are missing. This study determines the behavioral thresholds of crocodilians to water surface waves. Nile crocodiles (Crocodylus niloticus) were conditioned to respond to single-frequency water surface wave stimuli (duration 1150 ms, frequency 15, 30, 40, 60 and 80 Hz), produced by blowing air onto the water surface. Our study shows that C. niloticus is highly sensitive to capillary water surface waves. Threshold values decreased with increasing frequency and ranged between 10.3 μm (15 Hz) and 0.5 μm (80 Hz) peak-to-peak wave amplitude. For the frequencies 15 Hz and 30 Hz the sensitivity of one spectacled caiman (Caiman crocodilus) to water surface waves was also tested. Threshold values were 12.8 μm (15 Hz) down to 1.76 μm (30 Hz), i.e. close to the threshold values of C. niloticus. The surface wave sensitivity of crocodiles is similar to the surface wave sensitivity of semi-aquatic insects and fishing spiders but does not match the sensitivity of surface-feeding fishes which is higher by one to two orders of magnitude. PMID:26153334

  17. Organometallic carboxylate resists for extreme ultraviolet with high sensitivity

    NASA Astrophysics Data System (ADS)

    Passarelli, James; Murphy, Michael; Re, Ryan Del; Sortland, Miriam; Hotalen, Jodi; Dousharm, Levi; Fallica, Roberto; Ekinci, Yasin; Neisser, Mark; Freedman, Daniel A.; Brainard, Robert L.

    2015-10-01

    We have developed organometallic carboxylate compounds [RnM)] capable of acting as negative-tone extreme ultraviolet (EUV) resists. The most sensitive of these resists contain antimony, three R-groups and two carboxylate groups, and carboxylate groups with polymerizable olefins (e.g., acrylate, methacrylate, or styrenecarboxylate). Evidence suggests that high sensitivity is achieved through the polymerization of olefins in the exposed region. We have performed a systematic sensitivity study of the molecules of the type RnM) where we have studied seven R groups, four main group metals (M), and three polymerizable carboxylate groups (O2CR?). The sensitivity of these resists was evaluated using Emax or dose to maximum resist thickness after exposure and development. We found that the greatest predictor of sensitivity of the RnSb) resists is their level of polymerizable olefins. We mathematically define the polymerizable olefin loading (POL) as the ratio of the number of olefins versus the number of nonhydrogen atoms. Linear and log plots of Emax versus POL for a variety of molecules of the type R3Sb) lend insight into the behavior of these resists.

  18. Highly efficient photocathodes for dye-sensitized tandem solar cells.

    PubMed

    Nattestad, A; Mozer, A J; Fischer, M K R; Cheng, Y-B; Mishra, A; Bäuerle, P; Bach, U

    2010-01-01

    Thin-film dye-sensitized solar cells (DSCs) based on mesoporous semiconductor electrodes are low-cost alternatives to conventional silicon devices. High-efficiency DSCs typically operate as photoanodes (n-DSCs), where photocurrents result from dye-sensitized electron injection into n-type semiconductors. Dye-sensitized photocathodes (p-DSCs) operate in an inverse mode, where dye-excitation is followed by rapid electron transfer from a p-type semiconductor to the dye (dye-sensitized hole injection). Such p-DSCs and n-DSCs can be combined to construct tandem solar cells (pn-DSCs) with a theoretical efficiency limitation well beyond that of single-junction DSCs (ref. 4). Nevertheless, the efficiencies of such tandem pn-DSCs have so far been hampered by the poor performance of the available p-DSCs (refs 3, 5-15). Here we show for the first time that p-DSCs can convert absorbed photons to electrons with yields of up to 96%, resulting in a sevenfold increase in energy conversion efficiency compared with previously reported photocathodes. The donor-acceptor dyes, studied as photocathodic sensitizers, comprise a variable-length oligothiophene bridge, which provides control over the spatial separation of the photogenerated charge carriers. As a result, charge recombination is decelerated by several orders of magnitude and tandem pn-DSCs can be constructed that exceed the efficiency of their individual components. PMID:19946281

  19. High-sensitivity three-mode optomechanical transducer

    SciTech Connect

    Zhao, C.; Fang, Q.; Susmithan, S.; Miao, H.; Ju, L.; Fan, Y.; Blair, D.; Hosken, D. J.; Munch, J.; Veitch, P. J.; Slagmolen, B. J. J.

    2011-12-15

    Three-mode optomechanical interactions have been predicted to allow the creation of very high sensitivity transducers in which very strong optical self-cooling and strong optomechanical quantum entanglement are predicted. Strong coupling is achieved by engineering a transducer in which both the pump laser and a single signal sideband frequency are resonantly enhanced. Here we demonstrate that very high sensitivity can be achieved in a very simple system consisting of a Fabry-Perot cavity with CO{sub 2} laser thermal tuning. We demonstrate a displacement sensitivity of {approx}1x10{sup -17} m/{radical}(Hz), which is sufficient to observe a thermally excited acoustic mode in a 5.6 kg sapphire mirror with a signal-to-noise ratio of more than 20 dB. It is shown that a measurement sensitivity of {approx}2x10{sup -20} m/{radical}(Hz) limited by the quantum shot noise is achievable with optimization of the cavity parameters.

  20. Development of high-sensitivity SWIR APD receivers

    NASA Astrophysics Data System (ADS)

    Bai, Xiaogang; Yuan, Ping; Chang, James; Sudharsanan, Rengarajan; Krainak, Michael; Yang, Guangning; Sun, Xiaoli; Lu, Wei

    2013-06-01

    Emerging short wavelength infrared (SWIR) LIght Detection And Ranging (LIDAR) and long range laser rangefinder systems, require large optical aperture avalanche photodiodes (APDs) receivers with high sensitivity and high bandwidth. A large optical aperture is critical to increase the optical coupling efficiency and extend the LIDAR sensing range of the above systems. Both APD excess noise and transimpedance amplifier (TIA) noise need to be reduced in order to achieve high receiver sensitivity. The dark current and capacitance of large area APDs increase with APD aperture and thus limit the sensitivity and bandwidth of receivers. Spectrolab has been developing low excess noise InAlAs/InGaAs APDs with impact ionization engineering (I2E) designs for many years and has demonstrated APDs with optical gain over 100 utilizing multiple period I2E structures in the APD multiplier. These high gain I2E APDs have an excess noise factor less than 0.15. With an optical aperture of 200 μm, low excess noise multiple periods I2E APDs have capacitances about 1.7 pF. In addition, optical gains of InAlAs based APDs show very little temperature dependence and will enable APD photoreceivers without thermal electric cooling.

  1. High-sensitivity acoustic sensors from nanofibre webs

    NASA Astrophysics Data System (ADS)

    Lang, Chenhong; Fang, Jian; Shao, Hao; Ding, Xin; Lin, Tong

    2016-03-01

    Considerable interest has been devoted to converting mechanical energy into electricity using polymer nanofibres. In particular, piezoelectric nanofibres produced by electrospinning have shown remarkable mechanical energy-to-electricity conversion ability. However, there is little data for the acoustic-to-electric conversion of electrospun nanofibres. Here we show that electrospun piezoelectric nanofibre webs have a strong acoustic-to-electric conversion ability. Using poly(vinylidene fluoride) as a model polymer and a sensor device that transfers sound directly to the nanofibre layer, we show that the sensor devices can detect low-frequency sound with a sensitivity as high as 266 mV Pa-1. They can precisely distinguish sound waves in low to middle frequency region. These features make them especially suitable for noise detection. Our nanofibre device has more than five times higher sensitivity than a commercial piezoelectric poly(vinylidene fluoride) film device. Electrospun piezoelectric nanofibres may be useful for developing high-performance acoustic sensors.

  2. Compact Tb doped fiber optic current sensor with high sensitivity.

    PubMed

    Huang, Duanni; Srinivasan, Sudharsanan; Bowers, John E

    2015-11-16

    A highly sensitive fiber optic current sensor using terbium doped fiber is presented. The Verdet constant of the terbium doped fiber at 1300nm is found to be 19.5μrad/A using both a polarimetric and interferometric type sensor. Measurements on a Sagnac-loop sensor using 10cm of terbium doped fiber placed inside a solenoid show over 40dB of open loop dynamic range as well as a minimum detectable current of 0.1mA. Extrapolations of our measurements show that in a practical setup with Tb fiber wrapped around a current carrying wire, the optimal configuration is a 0.5m piece of Tb fiber with a noise limit of 22mA/√Hz. This sensor is promising for current sensing applications that require high sensitivity and small size, weight, and power. PMID:26698480

  3. Development of High Sensitivity Nuclear Emulsion and Fine Grained Emulsion

    NASA Astrophysics Data System (ADS)

    Kawahara, H.; Asada, T.; Naka, T.; Naganawa, N.; Kuwabara, K.; Nakamura, M.

    2014-08-01

    Nuclear emulsion is a particle detector having high spacial resolution and angular resolution. It became useful for large statistics experiment thanks to the development of automatic scanning system. In 2010, a facility for emulsion production was introduced and R&D of nuclear emulsion began at Nagoya university. In this paper, we present results of development of the high sensitivity emulsion and fine grained emulsion for dark matter search experiment. Improvement of sensitivity is achieved by raising density of silver halide crystals and doping well-adjusted amount of chemicals. Production of fine grained emulsion was difficult because of unexpected crystal condensation. By mixing polyvinyl alcohol (PVA) to gelatin as a binder, we succeeded in making a stable fine grained emulsion.

  4. Sensitivity to Envelope Interaural Time Differences at High Modulation Rates

    PubMed Central

    Bleeck, Stefan; McAlpine, David

    2015-01-01

    Sensitivity to interaural time differences (ITDs) conveyed in the temporal fine structure of low-frequency tones and the modulated envelopes of high-frequency sounds are considered comparable, particularly for envelopes shaped to transmit similar fidelity of temporal information normally present for low-frequency sounds. Nevertheless, discrimination performance for envelope modulation rates above a few hundred Hertz is reported to be poor—to the point of discrimination thresholds being unattainable—compared with the much higher (>1,000 Hz) limit for low-frequency ITD sensitivity, suggesting the presence of a low-pass filter in the envelope domain. Further, performance for identical modulation rates appears to decline with increasing carrier frequency, supporting the view that the low-pass characteristics observed for envelope ITD processing is carrier-frequency dependent. Here, we assessed listeners’ sensitivity to ITDs conveyed in pure tones and in the modulated envelopes of high-frequency tones. ITD discrimination for the modulated high-frequency tones was measured as a function of both modulation rate and carrier frequency. Some well-trained listeners appear able to discriminate ITDs extremely well, even at modulation rates well beyond 500 Hz, for 4-kHz carriers. For one listener, thresholds were even obtained for a modulation rate of 800 Hz. The highest modulation rate for which thresholds could be obtained declined with increasing carrier frequency for all listeners. At 10 kHz, the highest modulation rate at which thresholds could be obtained was 600 Hz. The upper limit of sensitivity to ITDs conveyed in the envelope of high-frequency modulated sounds appears to be higher than previously considered. PMID:26721926

  5. Structural Glycomic Analyses at High Sensitivity: A Decade of Progress

    PubMed Central

    Alley, William R.; Novotny, Milos V.

    2014-01-01

    The field of glycomics has recently advanced in response to the urgent need for structural characterization and quantification of complex carbohydrates in biologically and medically important applications. The recent success of analytical glycobiology at high sensitivity reflects numerous advances in biomolecular mass spectrometry and its instrumentation, capillary and microchip separation techniques, and microchemical manipulations of carbohydrate reactivity. The multimethodological approach appears to be necessary to gain an in-depth understanding of very complex glycomes in different biological systems. PMID:23560930

  6. Horizontal film balance having wide range and high sensitivity

    DOEpatents

    Abraham, B.M.; Miyano, K.; Ketterson, J.B.

    1981-03-05

    A thin-film, horizontal balance instrument is provided for measuring surface tension (surface energy) of thin films suspended on a liquid substrate. The balance includes a support bearing and an optical feedback arrangement for wide-range, high sensitivity measurements. The force on the instrument is balanced by an electromagnet, the current through the magnet providing a measure of the force applied to the instrument. A novel float construction is also disclosed.

  7. Horizontal film balance having wide range and high sensitivity

    DOEpatents

    Abraham, Bernard M.; Miyano, Kenjiro; Ketterson, John B.

    1983-01-01

    A thin-film, horizontal balance instrument is provided for measuring surface tension (surface energy) of thin films suspended on a liquid substrate. The balance includes a support bearing and an optical feedback arrangement for wide-range, high sensitivity measurements. The force on the instrument is balanced by an electromagnet, the current through the magnet providing a measure of the force applied to the instrument. A novel float construction is also disclosed.

  8. Horizontal film balance having wide range and high sensitivity

    DOEpatents

    Abraham, B.M.; Miyano, K.; Ketterson, J.B.

    1983-11-08

    A thin-film, horizontal balance instrument is provided for measuring surface tension (surface energy) of thin films suspended on a liquid substrate. The balance includes a support bearing and an optical feedback arrangement for wide-range, high sensitivity measurements. The force on the instrument is balanced by an electromagnet, the current through the magnet providing a measure of the force applied to the instrument. A novel float construction is also disclosed. 5 figs.

  9. High-sensitivity active pixel sensor with variable threshold photodetector

    NASA Astrophysics Data System (ADS)

    Jo, Sung-Hyun; Bae, Myunghan; Choi, Byoung-Soo; Lyu, Hong-Kun; Shin, Jang-Kyoo

    2015-05-01

    A novel high-sensitivity active pixel sensor (APS) with a variable threshold photodetector has been presented and for the first time, a simple SPICE model for the variable threshold photodetector is presented. Its SPICE model is in good agreement with measurements and is more simpler than the conventional model. The proposed APS has a gate/body-tied PMOSFET-type photodetector with an overlapping control gate that makes it possible to control the sensitivity of the proposed APS. It is a hybrid device composed of a metal-oxide-semiconductor field-effect transistor (MOSFET), a lateral bipolar junction transistor (BJT) and a vertical BJT. Using sufficient overlapping control gate bias to operate the MOSFET in inversion mode, the variable threshold photodetector allows for increasing the photocurrent gain by 105 at low light intensities when the control gate bias is -3 V. Thus, the proposed APS with a variable threshold photodetector has better low-light-level sensitivity than the conventional APS operating mode, and it has a variable sensitivity which is determined by the control gate bias. The proposed sensor has been fabricated by using 0.35 μm 2-poly 4-metal standard complementary MOS (CMOS) process and its characteristics have been evaluated.

  10. Pulsed Discharge Helium Ionization Detector for Highly Sensitive Aquametry.

    PubMed

    Mowry, Curtis D; Pimentel, Adam S; Sparks, Elizabeth S; Moorman, Matthew W; Achyuthan, Komandoor E; Manginell, Ronald P

    2016-01-01

    Trace moisture quantitation is crucial in medical, civilian and military applications. Current aquametry technologies are limited by the sample volume, reactivity, or interferences, and/or instrument size, weight, power, cost, and complexity. We report for the first time on the use of a pulsed discharge helium ionization detector (PDHID-D2) (∼196 cm(3)) for the sensitive (limit of detection, 0.047 ng; 26 ppm), linear (r(2) >0.99), and rapid (< 2 min) quantitation of water using a small (0.2 - 5.0 μL) volume of liquid or gas. The relative humidity sensitivity was 0.22% (61.4 ppmv) with a limit of detection of less than 1 ng moisture with gaseous samples. The sensitivity was 10 to 100 to fold superior to competing technologies without the disadvantages inherent to these technologies. The PDHID-D2, due to its small footprint and low power requirement, has good size, weight, and power-portability (SWAPP) factors. The relatively low cost (∼$5000) and commercial availability of the PDHID-D2 makes our technique applicable to highly sensitive aquametry. PMID:26860562

  11. A novel high-sensitivity electrostatic biased electric field sensor

    NASA Astrophysics Data System (ADS)

    Huang, Jing'ao; Wu, Xiaoming; Wang, Xiaohong; Yan, Xiaojun; Lin, Liwei

    2015-09-01

    In this paper, an electric field sensor (EFS) with high sensitivity is proposed for low-frequency weak-strength ac electric field (E-field) measurements. The EFS is based on a piezoelectric cantilever biased by a strong electrostatic field. The electrostatic bias can enhance the electric field force of a weak ac E-field, thus the cantilever can oscillate in a weak ac E-field and the device sensitivity improves. Theoretical analyses have been established and suggest that a stronger strength of electrostatic field bias would produce a higher sensitivity improvement. In the experiment, a demonstrated sensor consisting of a polyvinylidene fluoride (PVDF) piezoelectric cantilever and a polytetrafluoroethylene (PTFE) electret was built and tested. Instead of extra voltage sources, the PTFE electret was charged to provide the electrostatic field, allowing the EFS a low energy consumption and a simple electric circuit design. The experiment results show good agreement with the simulation. The sensitivity of the cantilever E-field sensor reached 0.84 mV (kV/m)-1 when the surface potential of the electret was  -770 V.

  12. High sensitive volumetric imaging of renal microcirculation in vivo using ultrahigh sensitive optical microangiography

    NASA Astrophysics Data System (ADS)

    Zhi, Zhongwei; Jung, Yeongri; Jia, Yali; An, Lin; Wang, Ruikang K.

    2011-03-01

    We present a non-invasive, label-free imaging technique called Ultrahigh Sensitive Optical Microangiography (UHSOMAG) for high sensitive volumetric imaging of renal microcirculation. The UHS-OMAG imaging system is based on spectral domain optical coherence tomography (SD-OCT), which uses a 47000 A-line scan rate CCD camera to perform an imaging speed of 150 frames per second that takes only ~7 seconds to acquire a 3D image. The technique, capable of measuring slow blood flow down to 4 um/s, is sensitive enough to image capillary networks, such as peritubular capillaries and glomerulus within renal cortex. We show superior performance of UHS-OMAG in providing depthresolved volumetric images of rich renal microcirculation. We monitored the dynamics of renal microvasculature during renal ischemia and reperfusion. Obvious reduction of renal microvascular density due to renal ischemia was visualized and quantitatively analyzed. This technique can be helpful for the assessment of chronic kidney disease (CKD) which relates to abnormal microvasculature.

  13. High sensitivity, homogeneous particle-based immunoassay for thyrotropin (Multipact).

    PubMed

    Wilkins, T A; Brouwers, G; Mareschal, J C; Cambiaso, C L

    1988-09-01

    We describe the first homogeneous, nonradioactive, high-sensitivity assay for human thyrotropin (TSH). The assay is based on particle immunoassay techniques, wherein 800-nm particles form the basis for the immunochemistry, delivery, and the detection technologies, respectively. Our assay also is the first to involve the use of fragmented monoclonal antibodies (to eliminate serum interferences) covalently coupled to particles without loss of their binding properties. Assays are performed in a semiautomated mode with use of a new modular system (Multipact). Equilibrium is reached in less than 2 h. Precision profile, sensitivity, and clinical studies indicate that the assay is accurate, has good precision at low concentrations, and that detection-limit characteristics compare well with those of a leading commercial high-sensitivity immunoradiometric assay (IRMA) for TSH. Dilution characteristics were satisfactory down to the assay's detection limit for a range of clinical samples. Correlation studies vs a reference IRMA method yielded the regression equation, present method = 0.976 (IRMA) + 0.002 milli-int. unit/L (r = 0.98), for 223 samples with TSH concentrations in the range 0 to 30 milli-int. units/L. For 40 samples with TSH less than or equal to 1.0 milli-int. unit/L it was: present method = 0.94 (IRMA) + 0.005 milli-int. unit/L (r = 0.96). PMID:3416423

  14. High-sensitive scanning laser magneto-optical imaging system.

    PubMed

    Murakami, Hironaru; Tonouchi, Masayoshi

    2010-01-01

    A high-sensitive scanning laser magneto-optical (MO) imaging system has been developed. The system is mainly composed of a laser source, galvano meters, and a high-sensitive differential optical-detector. Preliminary evaluation of system performance by using a Faraday indicator with a Faraday rotation coefficient of 3.47 x 10(-5) rad/microm Oe shows a magnetic sensitivity of about 5 microT, without any need for accumulation or averaging processing. Using the developed MO system we have succeeded in the fast and quantitative imaging of a rotationally symmetric magnetic field distribution around an YBa(2)Cu(3)O(7-delta) (YBCO) strip line applied with dc-biased current, and also succeeded in the detection of quantized fine signals corresponding to magnetic flux quantum generation in a superconducting loop of an YBCO Josephson vortex flow transistor. Thus, the developed system enables us not only to do fast imaging and local signal detection but also to directly evaluate both the strength and direction of a magnetic signal. PMID:20113101

  15. A high-sensitivity small animal SPECT system

    NASA Astrophysics Data System (ADS)

    Mitchell, Gregory S.; Cherry, Simon R.

    2009-03-01

    Medical imaging using single gamma-ray-emitting radionuclides typically makes use of parallel hole collimators or pinholes in order to achieve good spatial resolution. However, a tradeoff in sensitivity is inherent in the use of a collimator, and modern preclinical single photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma rays, often less than 0.1%. A system for small animal SPECT imaging which uses no collimators could potentially achieve very high sensitivityseveral tens of percentwith reasonably sized detectors. This would allow two significant improvements in preclinical studies: images could be obtained more rapidly, allowing higher throughput for screening applications, or for dynamic processes to be observed with very good time resolution; and images could be obtained with less radioactive tracer, making possible the in vivo imaging of low-capacity receptor systems, aiding research into new tracer compounds, and reducing the cost and easing the regulatory burden of an experiment. Of course, a system with no collimator will not be able to approach the submillimeter spatial resolutions produced by the most advanced pinhole and collimated systems, but a high-sensitivity system with resolution of order 1 cm could nonetheless find significant and new use in the many molecular imaging applications which do not require good spatial resolutionfor example, screening applications for drug development or new imaging agents. Rather than as an alternative to high-resolution SPECT systems, the high-sensitivity system is proposed as a radiotracer alternative to optical imaging for small animals. We have developed a prototype system for mouse imaging applications. The scanner consists of two large, thin, closely spaced scintillation detectors. Simulation studies indicate that a FWHM spatial resolution of 7 mm is possible. In an in vivo mouse imaging study using the 99mTc labeled tracer MAG-3, the sensitivity of the system is measured to be 40%. Simple projection images created by analytically combining the two detectors' data show sufficient resolution to observe the dynamic distribution of the radiotracer in the mouse.

  16. Polymer-Particle Pressure-Sensitive Paint with High Photostability

    PubMed Central

    Matsuda, Yu; Uchida, Kenta; Egami, Yasuhiro; Yamaguchi, Hiroki; Niimi, Tomohide

    2016-01-01

    We propose a novel fast-responding and paintable pressure-sensitive paint (PSP) based on polymer particles, i.e. polymer-particle (pp-)PSP. As a fast-responding PSP, polymer-ceramic (PC-)PSP is widely studied. Since PC-PSP generally consists of titanium (IV) oxide (TiO2) particles, a large reduction in the luminescent intensity will occur due to the photocatalytic action of TiO2. We propose the usage of polymer particles instead of TiO2 particles to prevent the reduction in the luminescent intensity. Here, we fabricate pp-PSP based on the polystyrene particle with a diameter of 1 μm, and investigate the pressure- and temperature-sensitives, the response time, and the photostability. The performances of pp-PSP are compared with those of PC-PSP, indicating the high photostability with the other characteristics comparable to PC-PSP. PMID:27092511

  17. Highly Sensitive Measurements of 222Rn Diffusion and Emanation

    SciTech Connect

    Zuzel, Grzegorz

    2005-09-08

    Highly sensitive techniques for determination of the 222Rn emanation from solids and diffusion through different membranes are presented. 222Rn and its daughters are measured via the alpha decays in special proportional counters at the absolute sensitivity of {approx}30 {mu}Bq. Radon diffusion can be measured at the level of {approx}10-13 cm2/s. Several samples were examined, e.g. stainless steel, teflon, various gaskets (emanation and diffusion measurements) and tanks. A combination of measurements of the 222Rn diffusion and emanation of thin nylon foils (used in the Borexino experiment) allowed the determination of 226Ra in the materials of interest at the level of {approx}10-12 g/g 238U-equivalent.

  18. Polymer-Particle Pressure-Sensitive Paint with High Photostability.

    PubMed

    Matsuda, Yu; Uchida, Kenta; Egami, Yasuhiro; Yamaguchi, Hiroki; Niimi, Tomohide

    2016-01-01

    We propose a novel fast-responding and paintable pressure-sensitive paint (PSP) based on polymer particles, i.e. polymer-particle (pp-)PSP. As a fast-responding PSP, polymer-ceramic (PC-)PSP is widely studied. Since PC-PSP generally consists of titanium (IV) oxide (TiO₂) particles, a large reduction in the luminescent intensity will occur due to the photocatalytic action of TiO₂. We propose the usage of polymer particles instead of TiO₂ particles to prevent the reduction in the luminescent intensity. Here, we fabricate pp-PSP based on the polystyrene particle with a diameter of 1 μm, and investigate the pressure- and temperature-sensitives, the response time, and the photostability. The performances of pp-PSP are compared with those of PC-PSP, indicating the high photostability with the other characteristics comparable to PC-PSP. PMID:27092511

  19. A CMOS In-Pixel CTIA High Sensitivity Fluorescence Imager.

    PubMed

    Murari, Kartikeya; Etienne-Cummings, Ralph; Thakor, Nitish; Cauwenberghs, Gert

    2011-10-01

    Traditionally, charge coupled device (CCD) based image sensors have held sway over the field of biomedical imaging. Complementary metal oxide semiconductor (CMOS) based imagers so far lack sensitivity leading to poor low-light imaging. Certain applications including our work on animal-mountable systems for imaging in awake and unrestrained rodents require the high sensitivity and image quality of CCDs and the low power consumption, flexibility and compactness of CMOS imagers. We present a 132×124 high sensitivity imager array with a 20.1 μm pixel pitch fabricated in a standard 0.5 μ CMOS process. The chip incorporates n-well/p-sub photodiodes, capacitive transimpedance amplifier (CTIA) based in-pixel amplification, pixel scanners and delta differencing circuits. The 5-transistor all-nMOS pixel interfaces with peripheral pMOS transistors for column-parallel CTIA. At 70 fps, the array has a minimum detectable signal of 4 nW/cm(2) at a wavelength of 450 nm while consuming 718 μA from a 3.3 V supply. Peak signal to noise ratio (SNR) was 44 dB at an incident intensity of 1 μW/cm(2). Implementing 4×4 binning allowed the frame rate to be increased to 675 fps. Alternately, sensitivity could be increased to detect about 0.8 nW/cm(2) while maintaining 70 fps. The chip was used to image single cell fluorescence at 28 fps with an average SNR of 32 dB. For comparison, a cooled CCD camera imaged the same cell at 20 fps with an average SNR of 33.2 dB under the same illumination while consuming over a watt. PMID:23136624

  20. High Sensitivity MEMS Strain Sensor: Design and Simulation

    PubMed Central

    Mohammed, Ahmed A. S.; Moussa, Walied A.; Lou, Edmond

    2008-01-01

    In this article, we report on the new design of a miniaturized strain microsensor. The proposed sensor utilizes the piezoresistive properties of doped single crystal silicon. Employing the Micro Electro Mechanical Systems (MEMS) technology, high sensor sensitivities and resolutions have been achieved. The current sensor design employs different levels of signal amplifications. These amplifications include geometric, material and electronic levels. The sensor and the electronic circuits can be integrated on a single chip, and packaged as a small functional unit. The sensor converts input strain to resistance change, which can be transformed to bridge imbalance voltage. An analog output that demonstrates high sensitivity (0.03mV/με), high absolute resolution (1με) and low power consumption (100μA) with a maximum range of ±4000με has been reported. These performance characteristics have been achieved with high signal stability over a wide temperature range (±50°C), which introduces the proposed MEMS strain sensor as a strong candidate for wireless strain sensing applications under harsh environmental conditions. Moreover, this sensor has been designed, verified and can be easily modified to measure other values such as force, torque…etc. In this work, the sensor design is achieved using Finite Element Method (FEM) with the application of the piezoresistivity theory. This design process and the microfabrication process flow to prototype the design have been presented.

  1. High-sensitivity converters of a TV type

    NASA Astrophysics Data System (ADS)

    Venediktov, M. D.; Krutyakov, Yu. A.; Plotnikov, M. I.

    1999-06-01

    Three principles of building high sensitive (low-level) converters of a TV-type are well known. They are based on the following: (1) usage of electron-optical image converters (IC) as input image amplifiers and its converting into a TV signal by commercial TV cameras (Fig. 1a); (2) location in a single vacuum volume of a receiving input part of IC with a diode silicon substrate -- a storage target -- in which a photoelectric image is being amplified (amplification factor is 100 . . . 300) and then is read out by an electron beam with the energy corresponding with the condition (sigma) less than 1 ((sigma) -- secondary electron emission coefficient). The converter developed on the base of this principal has got the name of superkremnikon (a super silicon-imaging device) (Fig. 1b); (3) location in a single vacuum volume of a receiving part of IC, amplification microchannel plate (MCP) with amplification factor 100 . . . 1000 and a CCD with amplification equal to 100 (Fig. 1c). One should take into account the following disadvantages of the above-mentioned devices of a TV-type: (1) not high linear resolution of an input image, caused by multiple conversion of an input image - - (2.2 . . . 3.5)(DOT)102 lines in the middle of a target; (2) inadequately high sensitivity, defined basically by optical losses. Limiting sensitivity within the visible range has been realized at superkremnikon (10-7 lx) coupled with an input IC through fiber-optical communication; (4) high cost of the converters, which is limiting their wide practical application for the purposes of medical diagnostics and non- destructive control. The alternative principle of building the high sensitive converters of a TV-type, based on a new method of energy radiation image conversion within a wide spectral range into an electrical (including TV) signal is proposed. In the frames of the new method the MCP is operating at the same time as a receiver, an amplifier and a two-sided storage target on reading out. A conventional image of the converter is given.

  2. Mechanoreceptors in calanoid copepods: designed for high sensitivity.

    PubMed

    Weatherby, T M; Lenz, P H

    2000-01-01

    The mechanoreceptors of the first antennae of Pleuromamma xiphias, a mesopelagic calanoid copepod, are critical for the detection of potential threats. These receptors exceed the physiological performance of other crustacean mechanoreceptors in sensitivity to water velocities as well as in frequency response. A study of these receptors was initiated to elucidate structure-function relationships. Morphologically, the receptors resemble the arthropod scolopidial organs by the presence of a scolopale tube. However, the rigidity of the copepod receptors greatly exceeds those described for crustaceans and other arthropods. The scolopale tube completely encloses the distal dendrites and it is firmly anchored to the cuticle. Microtubules are organized in register and arise from microtubule subfibers associated with crescent-shaped rods which extend from the basal body region to the setal socket. The distal dendrites are filled with a large number of cross-linked microtubules. Termination of the distal dendrites inside the lumen of the setae is gradual with a firm anchoring to the cuticle. A likely mechanism for mechanotransduction would involve a linkage between individual microtubules and mechano-gated channels in the dendritic membrane. The rigidity probably contributes to the high frequency sensitivity, and termination of the dendrite inside the seta increases the overall sensitivity of these receptors. PMID:18088933

  3. Highly stretchable and sensitive unidirectional strain sensor via laser carbonization.

    PubMed

    Rahimi, Rahim; Ochoa, Manuel; Yu, Wuyang; Ziaie, Babak

    2015-03-01

    In this paper, we present a simple and low-cost technique for fabricating highly stretchable (up to 100% strain) and sensitive (gauge factor of up to 20 000) strain sensors. Our technique is based on transfer and embedment of carbonized patterns created through selective laser pyrolization of thermoset polymers, such as polyimide, into elastomeric substrates (e.g., PDMS or Ecoflex). Embedded carbonized materials are composed of partially aligned graphene and carbon nanotube (CNT) particles and show a sharp directional anisotropy, which enables the fabrication of extremely robust, highly stretchable, and unidirectional strain sensors. Raman spectrum of pyrolized carbon regions reveal that under optimal laser settings, one can obtain highly porous carbon nano/microparticles with sheet resistances as low as 60 Ω/□. Using this technique, we fabricate an instrumented latex glove capable of measuring finger motion in real-time. PMID:25686021

  4. Highly strain-sensitive magnetostrictive tunnel magnetoresistance junctions

    NASA Astrophysics Data System (ADS)

    Tavassolizadeh, Ali; Hayes, Patrick; Rott, Karsten; Reiss, Günter; Quandt, Eckhard; Meyners, Dirk

    2015-06-01

    Tunnel magnetoresistance (TMR) junctions with CoFeB/MgO/CoFeB layers are promising for strain sensing applications due to their high TMR effect and magnetostrictive sense layer (CoFeB). TMR junctions available even in submicron dimensions can serve as strain sensors for microelectromechanical systems devices. Upon stress application, the magnetization configuration of such junctions changes due to the inverse magnetostriction effect resulting in strain-sensitive tunnel resistance. Here, strain sensitivity of round-shaped junctions with diameters of 11.3 μm, 19.2 μm, 30.5 μm, and 41.8 μm were investigated on macroscopic cantilevers using a four-point bending apparatus. This investigation mainly focuses on changes in hard-axis TMR loops caused by the stress-induced anisotropy. A macrospin model is proposed, supported by micromagnetic simulations, which describes the complete rotation of the sense layer magnetization within TMR loops of junctions, exposed to high stress. Below 0.2‰ tensile strain, a representative junction with 30.5 μm diameter exhibits a very large gauge factor of 2150. For such high gauge factor a bias field H = - 3.2 kA / m is applied in an angle equal to 3 π / 2 toward the pinned magnetization of the reference layer. The strain sensitivity strongly depends on the bias field. Applying stress along π / 4 against the induced magnetocrystalline anisotropy, both compressive and tensile strain can be identified by a unique sensor. More importantly, a configuration with a gauge factor of 400 at zero bias field is developed which results in a straightforward and compact measuring setup.

  5. High-sensitivity piezoelectric perovskites for magnetoelectric composites

    NASA Astrophysics Data System (ADS)

    Amorín, Harvey; Algueró, Miguel; Del Campo, Rubén; Vila, Eladio; Ramos, Pablo; Dollé, Mickael; Romaguera-Barcelay, Yonny; Pérez De La Cruz, Javier; Castro, Alicia

    2015-02-01

    A highly topical set of perovskite oxides are high-sensitivity piezoelectric ones, among which Pb(Zr,Ti)O3 at the morphotropic phase boundary (MPB) between ferroelectric rhombohedral and tetragonal polymorphic phases is reckoned a case study. Piezoelectric ceramics are used in a wide range of mature, electromechanical transduction technologies like piezoelectric sensors, actuators and ultrasound generation, to name only a few examples, and more recently for demonstrating novel applications like magnetoelectric composites. In this case, piezoelectric perovskites are combined with magnetostrictive materials to provide magnetoelectricity as a product property of the piezoelectricity and piezomagnetism of the component phases. Interfaces play a key issue, for they control the mechanical coupling between the piezoresponsive phases. We present here main results of our investigation on the suitability of the high sensitivity MPB piezoelectric perovskite BiScO3-PbTiO3 in combination with ferrimagnetic spinel oxides for magnetoelectric composites. Emphasis has been put on the processing at low temperature to control reactions and interdiffusion between the two oxides. The role of the grain size effects is extensively addressed.

  6. The Georgia Tech High Sensitivity Microwave Measurement System

    NASA Technical Reports Server (NTRS)

    Deboer, David R.; Steffes, Paul G.

    1996-01-01

    As observations and models of the planets become increasingly more accurate and sophisticated, the need for highly accurate laboratory measurements of the microwave properties of the component gases present in their atmospheres become ever more critical. This paper describes the system that has been developed at Georgia Tech to make these measurements at wavelengths ranging from 13.3 cm to 1.38 cm with a sensitivity of 0.05 dB/km at the longest wavelength and 0.6 db/km at the shortest wavelength.

  7. High sensitivity charge amplifier for ion beam uniformity monitor

    DOEpatents

    Johnson, Gary W.

    2001-01-01

    An ion beam uniformity monitor for very low beam currents using a high-sensitivity charge amplifier with bias compensation. The ion beam monitor is used to assess the uniformity of a raster-scanned ion beam, such as used in an ion implanter, and utilizes four Faraday cups placed in the geometric corners of the target area. Current from each cup is integrated with respect to time, thus measuring accumulated dose, or charge, in Coulombs. By comparing the dose at each corner, a qualitative assessment of ion beam uniformity is made possible. With knowledge of the relative area of the Faraday cups, the ion flux and areal dose can also be obtained.

  8. High-Sensitivity C-Reactive Protein and Statin Initiation.

    PubMed

    Trpkovic, Andreja; Stanimirovic, Julijana; Rizzo, Manfredi; Resanovic, Ivana; Soskic, Sanja; Jevremovic, Danimir; Isenovic, Esma R

    2015-07-01

    The assessment of cardiovascular risk and treatment of cardiovascular diseases are major public health issues worldwide. Inflammation is now recognized as a key regulatory process that links multiple risk factors for atherosclerosis. The substantial number of patients having cardiovascular events lack commonly established risk factors. The utility of high-sensitivity C-reactive protein (hsCRP), a circulating biomarker related to inflammation, may provide additional information in risk prediction. This review will consider the impact of hsCRP level on initiation of statin therapy. PMID:25053677

  9. High-Sensitivity Measurement of Density by Magnetic Levitation.

    PubMed

    Nemiroski, Alex; Kumar, A A; Soh, Siowling; Harburg, Daniel V; Yu, Hai-Dong; Whitesides, George M

    2016-03-01

    This paper presents methods that use Magnetic Levitation (MagLev) to measure very small differences in density of solid diamagnetic objects suspended in a paramagnetic medium. Previous work in this field has shown that, while it is a convenient method, standard MagLev (i.e., where the direction of magnetization and gravitational force are parallel) cannot resolve differences in density <10(-4) g/cm(3) for macroscopic objects (>mm) because (i) objects close in density prevent each other from reaching an equilibrium height due to hard contact and excluded volume, and (ii) using weaker magnets or reducing the magnetic susceptibility of the medium destabilizes the magnetic trap. The present work investigates the use of weak magnetic gradients parallel to the faces of the magnets as a means of increasing the sensitivity of MagLev without destabilization. Configuring the MagLev device in a rotated state (i.e., where the direction of magnetization and gravitational force are perpendicular) relative to the standard configuration enables simple measurements along the axes with the highest sensitivity to changes in density. Manipulating the distance of separation between the magnets or the lengths of the magnets (along the axis of measurement) enables the sensitivity to be tuned. These modifications enable an improvement in the resolution up to 100-fold over the standard configuration, and measurements with resolution down to 10(-6) g/cm(3). Three examples of characterizing the small differences in density among samples of materials having ostensibly indistinguishable densities-Nylon spheres, PMMA spheres, and drug spheres-demonstrate the applicability of rotated Maglev to measuring the density of small (0.1-1 mm) objects with high sensitivity. This capability will be useful in materials science, separations, and quality control of manufactured objects. PMID:26815205

  10. ALMA: Millimeter/submillimeter Astronomy at high sensitivity and resolution

    NASA Astrophysics Data System (ADS)

    Wootten, Alwyn; Corder, Stuartt Alan; Iono, Daisuke; Testi, Leonardo

    2015-08-01

    Vigorous and transformative investigation of the millimeter/submillimeter sky at high sensitivity and high resolution has benefitted from the recent completion of the Atacama Large Millimeter/submillimeter Array (ALMA), an effort of 22 countries. ALMA, a versatile interferometric telescope at 5000m elevation in the Atacama Desert of northern Chile, is comprised of sixty-six precision telescopes which may be arrayed over a 16 km extent on the high Chajnantor plain. Owing to its large collecting area of over 6600m^2 and its commodious spectral grasp of 8 GHz of spectrum in dual polarizations within an 84-950 GHz range, ALMA provides astronomers with vastly improved spectroscopic sensitivity. Spatial resolutions of 30 milliarcsec were demonstrated recently, revealing rings within the HL Tau protoplanetary disk, the rotating structure of the asteroid Juno and the molecular structure of the z~3 lensed galaxy SDP.81. The astrometric accuracy even at this early stage of deployment is better than 3 milliarcsec, providing improved ephemerides for the encounter of the New Horizons spacecraft with the Pluto-Charon system. Very long baseline capability is expected to bring microarcsecond imaging to a worldwide array anchored by ALMA with potential for imaging nearby Black Holes on the scales of their Event Horizons.ALMA's huge collecting area has enabled detection of lines of C, N and CO and continuum for characterization of massive complexes near the Era of Recombination. ALMA's sensitivity and resolution have enabledmeasurement of molecular emission through cosmic time from numerous molecules characterizing galactic star-forming regions and tracing their kinematics near active nuclei, starbursts, interacting clouds and quiescent disks. ALMA's sensitivity, resolution and spectral grasp have enabled it to image molecules and dust characterizing circumstellar disks and embedded bodies in protostellar, transition and debris stages of development.ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), NSC and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ.

  11. High-sensitivity 25-μm microbolometer FPAs

    NASA Astrophysics Data System (ADS)

    Murphy, Daniel F.; Ray, Michael; Wyles, Richard; Asbrock, James F.; Lum, Nancy A.; Wyles, Jessica; Hewitt, C.; Kennedy, Adam; Van Lue, David; Anderson, John S.; Bradley, Daryl; Chin, Richard; Kostrzewa, Thomas

    2003-01-01

    Raytheon IR Operations (RIO) has achieved a significant technical breakthrough in uncooled FPAs by reducing the pixel size by a factor of two while maintaining state-of-the-art sensitivity. Raytheon has produced the first high-quality 320×240 microbolometer FPAs wiht 25μm pitch pixels. The 320×240 FPAs have a sensitivity that is comparable to microbolometer FPAs with 50μm pixels. The average NETD value for these FPAs is about 35 mK with an f/1 aperture and oepratin at 30 Hz frame rates. Good pixel operability and excellent image quality have been demonstrated. Pixel operability is greater than 99 percent on some FPAs, and uncorrected responsivity nonconformity is less than 4%. The microbolometer detectors also have a relatively fast thermal time constant of approximately 10 msec. This state-of-the-art performance has been acheived as a result of an advanced micromachining fabrication process. The process allwos maximization of both the thermal isolation and the optical fill-factor. The reduction in pixel size offers several potential benefits for IR systems. For a given system resolution requirement, the 25 μm pixels allow a factor of two reduction in both the focal length and aperture size of the sensor optics. The pixel size reduction facilitates a significant FPA cost reduction since the number of die printed on a wafer can be increased. The pixel size reduction has enabled the development of a large-format 640×480 FPA array. Raytheon has produced arrays with very good sensitivity, operability, and excellent image quality. These FPAs are applicable to wide-field-of-view, long range surveillance and targeting missions. Raytheon is also developing a high performance 160×128 FPA that is designed for applications where miniaturizaitno and temperature invariance are required as well as low cost and low power.

  12. Coumarin-bearing triarylamine sensitizers with high molar extinction coefficient for dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Zhong, Changjian; Gao, Jianrong; Cui, Yanhong; Li, Ting; Han, Liang

    2015-01-01

    Coumarin unit is introduced into triarylamine and three organic sensitizers are designed and synthesized with triarylamine bearing coumarin moiety as the electron donor, conjugated system containing thiophene unit as the π-bridge, and cyanoacetic acid moiety as the electron acceptor. The light-harvesting capabilities and photovoltaic performance of these dyes are investigated systematically with the comparison of different π-bridges. High molar extinction coefficients are observed in these triarylamine dyes and the photocurrent and photovoltage are increased with the introduction of another thiophene or benzene. Optimal photovoltaic performance (η = 6.24%, Voc = 690 mV, Jsc = 14.33 mA cm-2, and ff = 0.63) is observed in the DSSC based on dye with thiophene-phenyl unit as the π-conjugated bridge under 100 mW cm-2 simulated AM 1.5 G solar irradiation.

  13. Metal-free tetrathienoacene sensitizers for high-performance dye-sensitized solar cells.

    PubMed

    Zhou, Nanjia; Prabakaran, Kumaresan; Lee, Byunghong; Chang, Sheng Hsiung; Harutyunyan, Boris; Guo, Peijun; Butler, Melanie R; Timalsina, Amod; Bedzyk, Michael J; Ratner, Mark A; Vegiraju, Sureshraju; Yau, Shuehlin; Wu, Chun-Guey; Chang, Robert P H; Facchetti, Antonio; Chen, Ming-Chou; Marks, Tobin J

    2015-04-01

    A new series of metal-free organic chromophores (TPA-TTAR-A (1), TPA-T-TTAR-A (2), TPA-TTAR-T-A (3), and TPA-T-TTAR-T-A (4)) are synthesized for application in dye-sensitized solar cells (DSSC) based on a donor-π-bridge-acceptor (D-π-A) design. Here a simple triphenylamine (TPA) moiety serves as the electron donor, a cyanoacrylic acid as the electron acceptor and anchoring group, and a novel tetrathienoacene (TTA) as the π-bridge unit. Because of the extensively conjugated TTA π-bridge, these dyes exhibit high extinction coefficients (4.5-5.2 × 10(4) M(-1) cm(-1)). By strategically inserting a thiophene spacer on the donor or acceptor side of the molecules, the electronic structures of these TTA-based dyes can be readily tuned. Furthermore, addition of a thiophene spacer has a significant influence on the dye orientation and self-assembly modality on TiO2 surfaces. The insertion of a thiophene between the π-bridge and the cyanoacrylic acid anchoring group in TPA-TTAR-T-A (dye 3) promotes more vertical dye orientation and denser packing on TiO2 (molecular footprint = 79 Å(2)), thus enabling optimal dye loading. Using dye 3, a DSSC power conversion efficiency (PCE) of 10.1% with Voc = 0.833 V, Jsc = 16.5 mA/cm(2), and FF = 70.0% is achieved, among the highest reported to date for metal-free organic DSSC sensitizers using an I(-)/I3(-) redox shuttle. Photophysical measurements on dye-grafted TiO2 films reveal that the additional thiophene unit in dye 3 enhances the electron injection efficiency, in agreement with the high quantum efficiency. PMID:25768124

  14. Highly Sensitive Assay for Measurement of Arenavirus-cell Attachment.

    PubMed

    Klaus, Joseph P; Botten, Jason

    2016-01-01

    Arenaviruses are a family of enveloped RNA viruses that cause severe human disease. The first step in the arenavirus life cycle is attachment of viral particles to host cells. While virus-cell attachment can be measured through the use of virions labeled with biotin, radioactive isotopes, or fluorescent dyes, these approaches typically require high multiplicities of infection (MOI) to enable detection of bound virus. We describe a quantitative (q)RT-PCR-based assay that measures Junin virus strain Candid 1 attachment via quantitation of virion-packaged viral genomic RNA. This assay has several advantages including its extreme sensitivity and ability to measure attachment over a large dynamic range of MOIs without the need to purify or label input virus. Importantly, this approach can be easily tailored for use with other viruses through the use of virus-specific qRT-PCR reagents. Further, this assay can be modified to permit measurement of particle endocytosis and genome uncoating. In conclusion, we describe a simple, yet robust assay for highly sensitive measurement of arenavirus-cell attachment. PMID:26966937

  15. Quantum-dot-sensitized solar cell with unprecedentedly high photocurrent.

    PubMed

    Lee, Jin-Wook; Son, Dae-Yong; Ahn, Tae Kyu; Shin, Hee-Won; Kim, In Young; Hwang, Seong-Ju; Ko, Min Jae; Sul, Soohwan; Han, Hyouksoo; Park, Nam-Gyu

    2013-01-01

    The reported photocurrent density (J(SC)) of PbS quantum dot (QD)-sensitized solar cell was less than 19 mA/cm(2) despite the capability to generate 38 mA/cm(2), which results from inefficient electron injection and fast charge recombination. Here, we report on a PbS:Hg QD-sensitized solar cell with an unprecedentedly high J(SC) of 30 mA/cm(2). By Hg(2+) doping into PbS, J(SC) is almost doubled with improved stability. Femtosecond transient study confirms that the improved J(SC) is due to enhanced electron injection and suppressed charge recombination. EXAFS reveals that Pb-S bond is reinforced and structural disorder is reduced by interstitially incorporated Hg(2+), which is responsible for the enhanced electron injection, suppressed recombination and stability. Thanks to the extremely high J(SC), power conversion efficiency of 5.6% is demonstrated at one sun illumination. PMID:23308343

  16. Sturdy Positioning with High Sensitivity GPS Sensors Under Adverse Conditions

    PubMed Central

    Trajkovski, Klemen Kozmus; Sterle, Oskar; Stopar, Bojan

    2010-01-01

    High sensitivity GPS receivers have extended the use of GNSS navigation to environments which were previously deemed unsuitable for satellite signal reception. Under adverse conditions the signals become attenuated and reflected. High sensitivity receivers achieve signal reception by using a large number of correlators and an extended integration time. Processing the observation data in dynamic and rapidly changing conditions requires a careful and consistent treatment. Code-based autonomous solutions can cause major errors in the estimated position, due primarily to multipath effects. A custom procedure of autonomous GPS positioning has been developed, boosting the positioning performance through appropriate processing of code and Doppler observations. Besides the common positioning procedures, robust estimation methods have been used to minimise the effects of gross observation errors. In normal conditions, differential GNSS yields good results, however, under adverse conditions, it fails to improve significantly the receiver’s position. Therefore, a so-called conditional DGPS has been developed which determines the position differentially by using data from the strong signals only. These custom-developed procedures have been tested in different conditions in static and kinematic cases and the results have been compared to those processed by the receiver. PMID:22163657

  17. High-sensitivity acoustic sensors from nanofibre webs.

    PubMed

    Lang, Chenhong; Fang, Jian; Shao, Hao; Ding, Xin; Lin, Tong

    2016-01-01

    Considerable interest has been devoted to converting mechanical energy into electricity using polymer nanofibres. In particular, piezoelectric nanofibres produced by electrospinning have shown remarkable mechanical energy-to-electricity conversion ability. However, there is little data for the acoustic-to-electric conversion of electrospun nanofibres. Here we show that electrospun piezoelectric nanofibre webs have a strong acoustic-to-electric conversion ability. Using poly(vinylidene fluoride) as a model polymer and a sensor device that transfers sound directly to the nanofibre layer, we show that the sensor devices can detect low-frequency sound with a sensitivity as high as 266 mV Pa(-1). They can precisely distinguish sound waves in low to middle frequency region. These features make them especially suitable for noise detection. Our nanofibre device has more than five times higher sensitivity than a commercial piezoelectric poly(vinylidene fluoride) film device. Electrospun piezoelectric nanofibres may be useful for developing high-performance acoustic sensors. PMID:27005010

  18. Sturdy positioning with high sensitivity GPS sensors under adverse conditions.

    PubMed

    Trajkovski, Klemen Kozmus; Sterle, Oskar; Stopar, Bojan

    2010-01-01

    High sensitivity GPS receivers have extended the use of GNSS navigation to environments which were previously deemed unsuitable for satellite signal reception. Under adverse conditions the signals become attenuated and reflected. High sensitivity receivers achieve signal reception by using a large number of correlators and an extended integration time. Processing the observation data in dynamic and rapidly changing conditions requires a careful and consistent treatment. Code-based autonomous solutions can cause major errors in the estimated position, due primarily to multipath effects. A custom procedure of autonomous GPS positioning has been developed, boosting the positioning performance through appropriate processing of code and Doppler observations. Besides the common positioning procedures, robust estimation methods have been used to minimise the effects of gross observation errors. In normal conditions, differential GNSS yields good results, however, under adverse conditions, it fails to improve significantly the receiver's position. Therefore, a so-called conditional DGPS has been developed which determines the position differentially by using data from the strong signals only. These custom-developed procedures have been tested in different conditions in static and kinematic cases and the results have been compared to those processed by the receiver. PMID:22163657

  19. Sensitive and rapid method for amino acid quantitation in malaria biological samples using AccQ.Tag ultra performance liquid chromatography-electrospray ionization-MS/MS with multiple reaction monitoring.

    PubMed

    Armenta, Jenny M; Cortes, Diego F; Pisciotta, John M; Shuman, Joel L; Blakeslee, Kenneth; Rasoloson, Dominique; Ogunbiyi, Oluwatosin; Sullivan, David J; Shulaev, Vladimir

    2010-01-15

    An AccQ*Tag ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (AccQ*Tag-UPLC-ESI-MS/MS) method for fast, reproducible, and sensitive amino acid quantitation in biological samples, particularly, the malaria parasite Plasmodium falciparum is presented. The Waters Acquity TQD UPLC/MS system equipped with a photodiode array (PDA) detector was used for amino acid separation and detection. The method was developed and validated using amino acid standard mixtures containing acidic, neutral, and basic amino acids. For MS analysis, the optimum cone voltage implemented, based on direct infusion analysis of a few selected AccQ*Tag amino acids with multiple reaction monitoring, varied from 29 to 39 V, whereas the collision energy varied from 15 to 35 V. Calibration curves were built using both internal and external standardization. Typically, a linear response for all amino acids was observed at concentration ranges of 3 x 10(-3)-25 pmol/muL. For some amino acids, concentration limits of detection were as low as 1.65 fmol. The coefficients of variation for retention times were within the range of 0.08-1.08%. The coefficients of variation for amino acid quantitation, determined from triplicate UPLC-MS/MS runs, were below 8% on the average. The developed AccQ*Tag-UPLC-ESI-MS/MS method revealed good technical and biological reproducibility when applied to P. falciparum and human red blood cells samples. This study should provide a valuable insight into the performance of UPLC-ESI-MS/MS for amino acid quantitation using AccQ*Tag derivatization. PMID:20038084

  20. Design of a charge sensitive preamplifier on high resistivity silicon

    SciTech Connect

    Radeka, V.; Rehak, P.; Rescia, S.; Gatti, E.; Longoni, A.; Sampietro, M.; Holl, P.; Strueder, L.; Kemmer, J.

    1987-01-01

    A low noise, fast charge sensitive preamplifier was designed on high resistivity, detector grade silicon. It is built at the surface of a fully depleted region of n-type silicon. This allows the preamplifier to be placed very close to a detector anode. The preamplifier uses the classical input cascode configuration with a capacitor and a high value resistor in the feedback loop. The output stage of the preamplifier can drive a load up to 20pF. The power dissipation of the preamplifier is 13mW. The amplifying elements are ''Single Sided Gate JFETs'' developed especially for this application. Preamplifiers connected to a low capacitance anode of a drift type detector should achieve a rise time of 20ns and have an equivalent noise charge (ENC), after a suitable shaping, of less than 50 electrons. This performance translates to a position resolution better than 3..mu..m for silicon drift detectors. 6 refs., 9 figs.

  1. Sensitivity of high-order-harmonic generation to aromaticity

    NASA Astrophysics Data System (ADS)

    Alharbi, A. F.; Boguslavskiy, A. E.; Thir, N.; Schmidt, B. E.; Lgar, F.; Brabec, T.; Spanner, M.; Bhardwaj, V. R.

    2015-10-01

    The influence of cyclic electron delocalization associated with aromaticity on the high-order-harmonic generation (HHG) process is investigated in organic molecules. We show that the aromatic molecules benzene (C6H6 ) and furan (C4H4O ) produce high-order harmonics more efficiently than nonaromatic systems having the same ring structure. We also demonstrate that the relative strength of plateau harmonics is sensitive to the aromaticity in five-membered-ring molecules using furan, pyrrole (C4H4NH ), and thiophene (C4H4S ). Numerical time-dependent Schrdinger equation simulations of total orientation-averaged strong-field ionization yields show that the HHG from aromatic molecules comes predominantly from the two highest ? molecular orbitals, which contribute to the aromatic character of the systems.

  2. Ultra high resolution ultra high sensitive optical micro-angiography based on super continuum light source

    NASA Astrophysics Data System (ADS)

    An, Lin; Qin, Jia; Zhi, Zhongwei; Wang, Ruikang

    2011-03-01

    In this paper, we demonstrate for the first time utilizing a super continuum light source to achieve ultra high sensitive Optical Micro-Angiography (UHS-OMAG) system. The broad band light with central wavelength around 800nm, emitted from the super continuum light source, could provide a ~2μm coherence gate for the system. Based on a fast CMOS camera, we could successfully develop a high speed (~70 kHz line rate) Fourier Domain Optical coherence tomography system. Applying the ultra high sensitive OMAG algorithm onto the system, we could visualize blood vessel networks buried within the tissue bed in a high resolution and high sensitivity mode. The modality is performed on imaging the human finger nail fold and the mouse pinna to obtain both high resolution structure image and detailed blood perfusion map. The excellent performance shows a great potential of our system in future biological imaging application.

  3. High-Sensitivity Temperature-Independent Silicon Photonic Microfluidic Biosensors

    NASA Astrophysics Data System (ADS)

    Kim, Kangbaek

    Optical biosensors that can precisely quantify the presence of specific molecular species in real time without the need for labeling have seen increased use in the drug discovery industry and molecular biology in general. Of the many possible optical biosensors, the TM mode Si biosensor is shown to be very attractive in the sensing application because of large field amplitude on the surface and cost effective CMOS VLSI fabrication. Noise is the most fundamental factor that limits the performance of sensors in development of high-sensitivity biosensors, and noise reduction techniques require precise studies and analysis. One such example stems from thermal fluctuations. Generally SOI biosensors are vulnerable to ambient temperature fluctuations because of large thermo-optic coefficient of silicon (˜2x10 -4 RIU/K), typically requiring another reference ring and readout sequence to compensate temperature induced noise. To address this problem, we designed sensors with a novel TM-mode shallow-ridge waveguide that provides both large surface amplitude for bulk and surface sensing. With proper design, this also provides large optical confinement in the aqueous cladding that renders the device athermal using the negative thermo-optic coefficient of water (~ --1x10-4RIU/K), demonstrating cancellation of thermo-optic effects for aqueous solution operation near 300K. Additional limitations resulting from mechanical actuator fluctuations, stability of tunable lasers, and large 1/f noise of lasers and sensor electronics can limit biosensor performance. Here we also present a simple harmonic feedback readout technique that obviates the need for spectrometers and tunable lasers. This feedback technique reduces the impact of 1/f noise to enable high-sensitivity, and a DSP lock-in with 256 kHz sampling rate can provide down to micros time scale monitoring for fast transitions in biomolecular concentration with potential for small volume and low cost. In this dissertation, a novel high-sensitivity, athermal biosensor on a TM-mode SOI resonator was designed, fabricated, and evaluated. High-performance biosensing for bulk and surface detection limits of 1x10-7 RIU and 24 fg/mm2 was demonstrated.

  4. CHOOZ -- A High Sensitivity Reactor Neutrino Oscillation Experiment

    NASA Astrophysics Data System (ADS)

    Steinberg, Richard I.

    1996-05-01

    We describe the CHOOZ experiment, a high sensitivity long baseline search for neutrino vacuum oscillations being performed in France by a collaboration of four nations -- France, Italy, Russia, and the USA. The small-mass sensitivity limit of neutrino oscillation experiments is determined by the parameter L/E, where L is the source to detector distance and E is the mean neutrino energy. Reactor neutrinos have energies of a few MeV, about 1000 times lower than that of typical accelerator-produced neutrinos. Hence, the ? m^2 sensitivity of a one-kilometer-baseline reactor neutrino oscillation experiment is equivalent to that of a 1000 kilometer accelerator experiment -- about 110-3 eV^2. The CHOOZ experiment is shielded from cosmic rays by its location underground at a depth equivalent to 300 meters of water. The detector consists of a 6 m^3 gadolinium-loaded liquid scintillation detector actively shielded by 120 m^3 of unloaded liquid scintillator. The detector measures the interaction rate and energy spectrum of electron antineutrinos from the 8.4 GW (thermal) Chooz nuclear power plant situated at a distance of 1.0 km. The basic measurement is a comparison between the expected and observed antineutrino inverse beta decay event rates. The experimental goal is to search for neutrino oscillations in the ?e disappearance channel with values of ? m^2 > 110-3 eV^2 for large values of the mixing parameter sin^2 2?. Values of sin^2 2? down to about .08 will be detectable for favorable regions of ? m^2. Completion of the detector is expected early in 1996. Initial data may be available for this meeting.

  5. High sensitivity gas permeability measurement system for thin plastic films

    NASA Astrophysics Data System (ADS)

    Ranade, A.; D'Souza, N. A.; Wallace, R. M.; Gnade, B. E.

    2005-01-01

    We have developed a system to quantitatively measure the permeation of gases through thin flexible substrates with high sensitivity. The system consists of two chambers, a high pressure side and an ultrahigh vacuum (UHV) side, separated by the flexible sample to be analyzed. The system is calibrated using a combination of a National Institute of Standards and Technology traceable calibrated He leak and a variable aperture calibrated orifice. The base total pressure for the UHV side is 1-3×10-10Torr. The partial pressure of individual gases that we are studying is <10-10Torr. The sample to be measured is secured between the two chambers using two 2.75 conflat flanges, two copper gaskets, and two indium "O" rings. The key factors that impact sensitivity and quantification are (1) reducing the residual partial pressure of the gas of interest to as low a value as possible on the UHV side of the system, (2) sealing the plastic sample between the two chambers with no detectable gas leakage around the sample or from the outside, (3) supporting the plastic substrate so that it can withstand 700Torr pressure on the high pressure side, and (4) developing a calibration procedure that closely mimics the actual permeability measurement. The system allows us to measure permeation rates as low as 1×10-6g/m2-day for He, 1×10-6g/m2-day for O2, and 5×10-7g/m2-day for Ar.

  6. Sensitivity of once-shocked, weathered high explosives

    SciTech Connect

    Williams, K.L.; Harris, B.W.

    1998-07-01

    Effects caused by stimulating once-shocked, weathered high explosives (OSW-HE) are investigated. The sensitivity of OSW-HE to mechanical stimuli was determined using standard industry tests. Some initial results are given. Pieces of OSW-HE were collected from active and inactive firing sites and from an area surrounding a drop tower at Los Alamos where skid and spigot tests were done. Samples evaluated were cast explosives or plastic bonded explosive (PBX) formulations containing cyclotrimethylenetrinitramine (RDX), cyclotetramethylene tetranitramine (HMX), 2,4,6-trinitrotoluene (TNT), mock or inert HE [tris(beta-chloroethyl)phosphate (CEF)], barium nitrate, cyanuric acid, talc, and Kel-F. Once-shocked, weathered LX-10 Livermore explosive [HMX/Viton A, (95/5 wt %)], PBX 9011 [HMX/Estane, (90/10 wt %)], PBX 9404 [HMX/nitrocellulose, tris(beta-chloroethyl) phosphate, (94/3/3 wt %)], Composition B or cyclotol (TNT/RDX explosives), and PBX 9007 (90% RDX, 9.1% styrene, 0.5% dioctyl phthalate, and 0.45 resin) were subjected to the hammer test, the drop-weight impact sensitivity test, differential thermal analysis (DTA), the spark test, the Henkin`s critical temperature test, and the flame test. Samples were subjected to remote, wet cutting and drilling; remote, liquid-nitrogen-cooled grinding and crushing; and scanning electron microscope (SEM) surface analyses for morphological changes.

  7. High-sensitivity instrument for measuring atmospheric NO2.

    PubMed

    Matsumi, Y; Murakami, S; Kono, M; Takahashi, K; Koike, M; Kondo, Y

    2001-11-15

    We report on the development of a high-sensitivity detection system for measuring atmospheric NO2 using a laser-induced fluorescence (LIF) technique around 440 nm. A tunable broad-band optical parametric oscillator laser pumped by the third harmonic of a Nd:YAG laser is used as a fluorescence excitation source. The laser wavelength is tuned at peak and bottom wavelengths around 440 nm alternatively, and the difference signal at the two wavelengths is used to extract the NO2 concentration. This procedure can give a good selectivity for NO2 and avoid interferences of fluorescent or particulate species other than NO2 in the sample air. The NO2 instrument developed has a sensitivity of 30 pptv in 10 s and S/N = 2. The practical performance of the detection system is tested in the suburban area for 24 h. The intercomparisons between the LIF instrument and a photofragmentation chemiluminescence (PF-CL) instrument have been performed under laboratory conditions. The correlation between the two instruments is measured up to 1000 pptv. A good linear relationship between the LIF measurements and the PF-CL measurements is obtained. PMID:11816578

  8. Kinetics of Highly Sensitive Troponin T after Cardiac Surgery.

    PubMed

    Omar, Amr S; Sudarsanan, Suraj; Hanoura, Samy; Osman, Hany; Sivadasan, Praveen C; Shouman, Yasser; Tuli, Alejandro Kohn; Singh, Rajvir; Al Khulaifi, Abdulaziz

    2015-01-01

    Perioperative myocardial infarction (PMI) confers a considerable risk in cardiac surgery settings; finding the ideal biomarker seems to be an ideal goal. Our aim was to assess the diagnostic accuracy of highly sensitive troponin T (hsTnT) in cardiac surgery settings and to define a diagnostic level for PMI diagnosis. This was a single-center prospective observational study analyzing data from all patients who underwent cardiac surgeries. The primary outcome was the diagnosis of PMI through a specific level. The secondary outcome measures were the lengths of mechanical ventilation (LOV), stay in the intensive care unit (LOSICU), and hospitalization. Based on the third universal definition of PMI, patients were divided into two groups: no PMI (Group I) and PMI (Group II). Data from 413 patients were analyzed. Nine patients fulfilled the diagnostic criteria of PMI, while 41 patients were identified with a 5-fold increase in their CK-MB (? 120 U/L). Using ROC analysis, a hsTnT level of 3,466 ng/L or above showed 90% sensitivity and 90% specificity for the diagnosis of PMI. Secondary outcome measures in patients with PMI were significantly prolonged. In conclusion, the hsTnT levels detected here paralleled those of CK-MB and a cut-off level of 3466 ng/L could be diagnostic of PMI. PMID:26539512

  9. High sensitivity, low profile neutron detector for safeguards measurements

    SciTech Connect

    Miley, H.S.; Abraham, J.R.; Thompson, R.C.; Sunberg, D.S.

    1993-12-01

    A neutron detector has been constructed and tested at Pacific Northwest Laboratory (PNL) for the purpose of making fast, high sensitivity measurements of neutron emitters in portal applications. The system is based upon glass fiber optic scintillators loaded with lithium-6 and operated to detect thermal neutrons. Due to their compact size. physical flexibility, freedom from microphonic pickup, and complete lack of environmental and safety concerns, these fibers are very suitable for some applications. The electronics needed for these fibers is somewhat more complex than for helium-3 proportional counters, but the entire electronics package (including the controlling computer) has been shrunk into a space of 20 {times} 25 {times} 2 cm. The prototype sensor is about 180 {times} 60 {times} 7 cm, but a final design now under construction measures 200 {times} 28 {times} 2.54 cm. The new, smaller detectors will be capable of ganging to achieve any needed sensitivity and will each weigh about 16 kg. The principles of operation of the fiber will be discussed as will the operational mode of the detector.

  10. A highly sensitive fiber Bragg grating diaphragm pressure transducer

    NASA Astrophysics Data System (ADS)

    Allwood, Gary; Wild, Graham; Lubansky, Alex; Hinckley, Steven

    2015-10-01

    In this work, a novel diaphragm based pressure transducer with high sensitivity is described, including the physical design structure, in-depth analysis of optical response to changes in pressure, and a discussion of practical implementation and limitations. A flat circular rubber membrane bonded to a cylinder forms the body of the transducer. A fiber Bragg grating bonded to the center of the diaphragm structure enables the fractional change in pressure to be determined by analyzing the change in Bragg wavelength of the reflected spectra. Extensive evaluation of the physical properties and optical characteristics of the transducer has been performed through experimentation, and modeling using small deformation theory. The results show the transducer has a sensitivity of 0.116 nm/kPa, across a range of 15 kPa. Ultra-low cost interrogation of the optical signal was achieved through the use of an optically mismatched Bragg grating acting as an edge filter to convert the spectral change into an intensity change. A numerical model of the intensity based interrogation was implemented in order to validate the experimental results. Utilizing this interrogation technique and housing both the sensing and reference Bragg gratings within the main body of the transducer means it is effectively temperature insensitive and easily connected to electronic systems.

  11. Kinetics of Highly Sensitive Troponin T after Cardiac Surgery

    PubMed Central

    Omar, Amr S.; Sudarsanan, Suraj; Hanoura, Samy; Osman, Hany; Sivadasan, Praveen C.; Shouman, Yasser; Tuli, Alejandro Kohn; Singh, Rajvir; Al Khulaifi, Abdulaziz

    2015-01-01

    Perioperative myocardial infarction (PMI) confers a considerable risk in cardiac surgery settings; finding the ideal biomarker seems to be an ideal goal. Our aim was to assess the diagnostic accuracy of highly sensitive troponin T (hsTnT) in cardiac surgery settings and to define a diagnostic level for PMI diagnosis. This was a single-center prospective observational study analyzing data from all patients who underwent cardiac surgeries. The primary outcome was the diagnosis of PMI through a specific level. The secondary outcome measures were the lengths of mechanical ventilation (LOV), stay in the intensive care unit (LOSICU), and hospitalization. Based on the third universal definition of PMI, patients were divided into two groups: no PMI (Group I) and PMI (Group II). Data from 413 patients were analyzed. Nine patients fulfilled the diagnostic criteria of PMI, while 41 patients were identified with a 5-fold increase in their CK-MB (≥120 U/L). Using ROC analysis, a hsTnT level of 3,466 ng/L or above showed 90% sensitivity and 90% specificity for the diagnosis of PMI. Secondary outcome measures in patients with PMI were significantly prolonged. In conclusion, the hsTnT levels detected here paralleled those of CK-MB and a cut-off level of 3466 ng/L could be diagnostic of PMI. PMID:26539512

  12. High sensitivity permeation measurement system for 'ultrabarrier' thin films

    SciTech Connect

    Zhang Xiaodong; Lewis, Jay S.; Wolter, Scott D.; Parker, Charles B.; Glass, Jeffrey T.

    2007-11-15

    The authors demonstrate a new technique for high sensitivity gas permeation measurements by integrating mass spectrometry with programed accumulation, detection, and evacuation of permeant. After passing through the film of interest, the gas permeant is captured and accumulated in an isolated ultrahigh vacuum (UHV) volume. The permeant is then allowed to enter an adjacent residual gas analyzer (RGA) and the resulting partial pressure increase is correlated with the steady state permeation rate. Calibrated results are given for helium and argon permeation through polymer films. The measured detection limits of the system are 1.8x10{sup -4} cm{sup 3}/m{sup 2} day for helium and 2.5x10{sup -4} cm{sup 3}/m{sup 2} day for argon. Both values are several orders of magnitude lower than what is available from commercial instruments or similar RGA-based instruments. Potential applications of this technique include measurement of oxygen and water vapor permeation with sensitivities required for assessment of ultrabarrier coatings.

  13. Luminescent Lanthanide Reporters for High-Sensitivity Novel Bioassays.

    SciTech Connect

    Anstey, Mitchell; Fruetel, Julia A.; Foster, Michael E.; Hayden, Carl C.; Buckley, Heather L.; Arnold, John

    2013-09-01

    Biological imaging and assay technologies rely on fluorescent organic dyes as reporters for a number of interesting targets and processes. However, limitations of organic dyes such as small Stokes shifts, spectral overlap of emission signals with native biological fluorescence background, and photobleaching have all inhibited the development of highly sensitive assays. To overcome the limitations of organic dyes for bioassays, we propose to develop lanthanide-based luminescent dyes and demonstrate them for molecular reporting applications. This relatively new family of dyes was selected for their attractive spectral and chemical properties. Luminescence is imparted by the lanthanide atom and allows for relatively simple chemical structures that can be tailored to the application. The photophysical properties offer unique features such as narrow and non-overlapping emission bands, long luminescent lifetimes, and long wavelength emission, which enable significant sensitivity improvements over organic dyes through spectral and temporal gating of the luminescent signal.Growth in this field has been hindered due to the necessary advanced synthetic chemistry techniques and access to experts in biological assay development. Our strategy for the development of a new lanthanide-based fluorescent reporter system is based on chelation of the lanthanide metal center using absorbing chromophores. Our first strategy involves %22Click%22 chemistry to develop 3-fold symmetric chelators and the other involves use of a new class of tetrapyrrole ligands called corroles. This two-pronged approach is geared towards the optimization of chromophores to enhance light output.

  14. High sensitivity tracking of CD-SEM performance: QSEM

    NASA Astrophysics Data System (ADS)

    Babin, S.; Huang, Jaffee; Yushmanov, P.

    2015-03-01

    The performance of CD-SEMs directly affects the measured values of critical dimensions (CDs) at the time of their measurement. Tracking the performance of CD-SEMs is necessary to establish trust in their results and provide guidance for preventive maintenance and tune-ups. When the measured CDs are out of specification in manufacturing, it is crucial to determine whether this is due to process variation or the metrology tool itself. Multiple methods that use linewidth measurements have been employed thus far; however, they suffer from linewidth variations on the wafer, as well as from variations of line edge and linewidth roughness. Here, we report a method that is capable of providing a quantitative extraction of the SEM performance based on advanced algorithms. The method is independent of linewidth, line edge roughness and linewidth roughness, and has high sensitivity. This software, QSEM, was developed to automatically evaluate image quality and assign a value to that quality. The image quality value is based on multiple factors such as noise, sharpness, analysis of histograms, and contrast. The sensitivity of the software was evaluated; a good correlation between image quality results and linewidth variation due to SEM performance was established. Using QSEM to analyze SEM images allows the performance of CDSEMs to be tracked for proper calibration and preventive maintenance, as well as to resolve the dispute between failure in the process or the metrology.

  15. Magnetic probe array with high sensitivity for fluctuating field.

    PubMed

    Kanamaru, Yuki; Gota, Hiroshi; Fujimoto, Kayoko; Ikeyama, Taeko; Asai, Tomohiko; Takahashi, Tsutomu; Nogi, Yasuyuki

    2007-03-01

    A magnetic probe array is constructed to measure precisely the spatial structure of a small fluctuating field included in a strong confinement field that varies with time. To exclude the effect of the confinement field, the magnetic probes consisting of figure-eight-wound coils are prepared. The spatial structure of the fluctuating field is obtained from a Fourier analysis of the probe signal. It is found that the probe array is more sensitive to the fluctuating field with a high mode number than that with a low mode number. An experimental demonstration of the present method is attempted using a field-reversed configuration plasma, where the fluctuating field with 0.1% of the confinement field is successfully detected. PMID:17411230

  16. Highly sensitive biological sensor based on photonic crystal fiber

    NASA Astrophysics Data System (ADS)

    Azzam, Shaimaa I. H.; Hameed, Mohamed F.; Obayya, S. S. A.

    2014-05-01

    A photonic crystal fiber (PCF) surface plasmon resonance (SPR) based sensor is proposed and analysed. The proposed sensor consists of microuidic slots enclosing a dodecagonal layer of air holes cladding and a central air hole. The sensor can perform analyte detection using both HEx 11 and HEy 11 modes with a relatively high sensitivities up to 4000 nm=RIU and 3000 nm=RIU and resolutions of 2.5×10-5 RIU-1 and 3.33×10-5 RIU-1 with HEx11 and HEy11, respectively, with regards to spectral interrogation which to our knowledge are higher than those reported in the literature. Moreover, the structure of the suggested sensor is simple with no fabrication complexities which makes it easy to fabricate with standard PCF fabrication technologies.

  17. Versatile, high-sensitivity faraday cup array for ion implanters

    DOEpatents

    Musket, Ronald G.; Patterson, Robert G.

    2003-01-01

    An improved Faraday cup array for determining the dose of ions delivered to a substrate during ion implantation and for monitoring the uniformity of the dose delivered to the substrate. The improved Faraday cup array incorporates a variable size ion beam aperture by changing only an insertable plate that defines the aperture without changing the position of the Faraday cups which are positioned for the operation of the largest ion beam aperture. The design enables the dose sensitivity range, typically 10.sup.11 -10.sup.18 ions/cm.sup.2 to be extended to below 10.sup.6 ions/cm.sup.2. The insertable plate/aperture arrangement is structurally simple and enables scaling to aperture areas between <1 cm.sup.2 and >750 cm.sup.2, and enables ultra-high vacuum (UHV) applications by incorporation of UHV-compatible materials.

  18. Simultaneous determination of cyromazine and dicyclanil in animal edible tissues using UPLC-MS/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyromazine and dicyclanil are used as insect growth regulators. This article describes an easy and innovative simultaneous extraction for residues of cyromazine and dicyclanil in food of animal origin and the confirmation procedure using an ultra-performance liquid chromatography-electrospray ioniz...

  19. Determination of ergot alkaloids from grains with UPLC-MS/MS.

    PubMed

    Kokkonen, Meri; Jestoi, Marika

    2010-08-01

    A simple and rapid method for determining six ergot alkaloids and four of their respective epimers was developed for rye and wheat. The analytes were extracted from the sample matrix with ACN/ammonium carbonate solution. The extract was purified with a commercial push-through SPE column (Mycosep 150 Ergot). After concentration and filtration steps, the final separation of the analytes was achieved with ultra-performance LC-MS/MS. The chromatographic separation of the ergot alkaloids was achieved in 4.5 min. The method performance proved satisfactory in the preliminary validation. The calculated LOQs were low ranging from 0.01 to 1.0 microg/kg for wheat and from 0.01 to 10.0 microg/kg for rye. At the concentration levels of 10, 50 and 200 microg/kg, the recoveries were between 80 and 120% in most cases and the within-day repeatability (expressed as RSD) ranged between 1.3 and 13.9%. Despite the cleanup of the samples, some matrix effect was observed in the MS, highlighting the necessity of using matrix-assisted standards. This is the first article to describe the application of the push-through columns and ultra-performance LC in the analysis of ergot alkaloids. PMID:20572264

  20. Rapid qualitative and quantitative analysis of proanthocyanidin oligomers and polymers by UPLC-MS/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proanthocyanidins (PAs) are a structurally complex and bioactive group of tannins. Detailed analysis of PA concentration, composition, and structure typically requires the use of one or more time-consuming analytical methods. For example, the commonly employed thiolysis and phloroglucinolysis method...

  1. Depletion of Urinary Zilpaterol Residues in Horses as Measured by ELISA and UPLC-MS/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three horses were dosed with dietary zilpaterol and the urine concentration measured from withdrawal day 0 to withdrawal day 21. The analyses were carried out using both enzyme linked immunosorbent assay (ELISA) and an ultra-performance liquid chromatography with triple-quadrupole-tandem mass spect...

  2. High-sensitivity diamond magnetometer with nanoscale resolution

    NASA Astrophysics Data System (ADS)

    Cappellaro, Paola

    2008-05-01

    The detection of weak magnetic fields with high spatial resolution is an important problem in diverse areas ranging from fundamental physics and material science to data storage and biomedical science. Here we describe a novel approach to magnetometry that takes advantage of recently developed techniques for coherent control of solid-state electronic spin quantum bits. To be specific, we investigate the use of spins associated with Nitrogen-Vacancy (NV) centers in diamond. Two key features distinguish our approach: the possibility to confine the sensing spins into a solid sample of nanometer dimensions that can be brought into direct proximity of a localized magnetic field source; and the potential of achieving high spin densities while maintaining good coherence properties, enabling the detection of sub-femtotesla magnetic fields. The resulting magnetic sensor, which can operate at room-temperature, ambient conditions, is projected to provide an unprecedented combination of ultra-high sensitivity and spatial resolution. As an example, we show that this could enable sensing of nanotesla magnetic fields with resolution well below 50 nanometers --allowing for the detection of a single nuclear spin's precession within one second. Finally, we describe first experiments toward the realization of these ideas.

  3. Instruments for highly sensitive investigations of volatiles and planetary solids

    NASA Astrophysics Data System (ADS)

    Tulej, M.; Riedo, A.; Meyer, S.; Neuland, M.; Iakovleva, M.; Abplanalp, D.; Wurz, P.

    2012-09-01

    Two miniature time-of-flight mass spectrometers, laser ablation/ionisation mass analyser (LMS) and a neutral gas mass spectrometer (NGMS), which were designed for chemical analysis of planetary solids and gaseous samples, respectively, will be introduced. LMS can perform full elemental and isotopic analysis of planetary materials (ablation mode) and can be used for detection of molecular compounds (desorption mode), which can be deposited on surfaces of planetary rocks. Current performance evaluations shows a high mass resolution m/Δm~500 and the effective dynamic range of higher than 8 decades. The limits of the detection for both, metallic and nonmetallic (e.g., B, C, S, P, Si) elements are at some tens of ppb. The LMS instrument can also perform analysis of isotopic abundances at least at per mill 1. Introduction accuracy and precision. The second instrument, NGMS, is designed for the investigation of planetary gas samples (volatiles, atmospheric gases, composition of exosphere) and allows for measurements with a mass resolution m/Δm ~ 1100 at an extended mass range, which is limited only by the available data acquisition memory. The repetition range of 10 kHz allows for highly sensitive studies with a high effective dynamic range of at least 7 decades.

  4. A new, sensitive, high resolution Raman detector based on ionization

    NASA Astrophysics Data System (ADS)

    Smith, B. W.; Omenetto, N.; Winefordner, J. D.

    1989-01-01

    A novel detection method for weak pulsed or cw Raman fluxes is described. The detector is based upon the production of Raman scatter with a tunable pulsed or cw dye laser, collecting a large fraction of the Raman scatter and transferring it efficiently into an ionization detector containing a metal (M) vapor, such as Li. The resonance ionization detector (RID) is simultaneously illuminated by a second dye laser. When the second laser is tuned to an excited state transition of the metal vapor M and when the first laser is at such a wavelength that the Raman scatter appears at the ground state absorption transition of the metal, then a current will be produced in the RID which is proportional to the Raman scatter intensity. Both the production and collection of this current can be made very efficient (approaching 100%) and should result in improved sensitivity compared to conventional dispersive or FT Raman techniques. The new approach should be much less sensitive to scatter, should have a spectral resolution better than 0.1 cm -1 and should allow Raman scatter measurements to be made at wavenumbers below 100 cm -1 and under certain conditions to 0.01 cm -1. The approach should be especially useful in highly scattering environments like Ag-sols in surface enhanced Raman and should be useful for detection of ultratrace levels of drugs and metabolites in biological fluids. The Raman-RID approach should also be useful for resonance Raman since laser scatter and molecular fluorescence should have minimal effects.

  5. Graphene nanomesh as highly sensitive chemiresistor gas sensor

    PubMed Central

    Paul, Rajat Kanti; Badhulika, Sushmee; Saucedo, Nuvia M.; Mulchandani, Ashok

    2016-01-01

    Graphene is a one atom thick carbon allotrope with all surface atoms that has attracted significant attention as a promising material as the conduction channel of a field-effect transistor and chemical field-effect transistor sensors. However, the zero bandgap of semimetal graphene still limits its application for these devices. In this work, ethanol-chemical vapor deposition (CVD) grown p-type semiconducting large-area monolayer graphene film was patterned into nanomesh by the combination of nanosphere lithography and reactive ion etching and evaluated as field-effect transistor and chemiresistor gas sensors. The resulting neck-width of the synthesized nanomesh was about ~20 nm comprised of the gap between polystyrene spheres that was formed during the reactive ion etching process. The neck-width and the periodicities of the graphene nanomesh could be easily controlled depending the duration/power of RIE and the size of PS nanospheres. The fabricated GNM transistor device exhibited promising electronic properties featuring high drive current and ION/IOFF ratio of about 6, significantly higher than its film counterpart. Similarly, when applied as chemiresistor gas sensor at room temperature, the graphene nanomesh sensor showed excellent sensitivity towards NO2 and NH3, significantly higher than their film counterparts. The ethanol-based graphene nanomesh sensors exhibited sensitivities of about 4.32%/ppm in NO2 and 0.71%/ppm in NH3 with limit of detections of 15 ppb and 160 ppb, respectively. Our demonstrated studies on controlling the neck width of the nanomesh would lead to further improvement of graphene-based transistors and sensors. PMID:22931286

  6. High-sensitivity (25-um pitch) microbolometer FPAs

    NASA Astrophysics Data System (ADS)

    Murphy, Daniel F.; Ray, Michael; Wyles, Richard; Asbrock, James F.; Lum, Nancy A.; Kennedy, Adam; Wyles, Jessica; Hewitt, C.; Graham, Glen E.; Horikiri, Tad; Anderson, John S.; Bradley, Daryl; Chin, Richard; Kostrzewa, Thomas

    2001-11-01

    RIO has achieved a significant technical breakthrough in uncooled FPAs by reducing the pixel size by a factor of two while maintaining state-of-the-art sensitivity. Raytheon has produced high-quality 320 by 240 micro bolometer FPAs with 25 micrometers pitch pixels. The 320 by 240 FPAs have a sensitivity that is comparable to micro bolometer FPAs with 50 micrometers pixels. The average NETD value for these FPAs is about 35 mK with an f/1 aperture and operating at 30 Hz frame rates. Good pixel operability and excellent image quality have been demonstrated. Pixel operability is greater than 99 percent on some FPAs, and uncorrected responsivity nonuniformity is less than 4 percent. The micro bolometer detectors also have a relatively fast thermal time constant of approximately 10 msec. This state-of-the-art performance has been achieved as a result of an advanced micromachining fabrication process. The process allows maximization of both the thermal isolation and the optical fill-factor. The reduction in pixel size offers several potential benefits for IR systems. For a given system resolution requirement, the 225 micrometers pixels allow a factor of two reduction in both the focal length and aperture size of the sensor optics. The pixel size reduction facilitates a significant FPA cost reduction since the number of die printed on a wafer can be increased. The pixel size reduction has enabled the development of a large-format 640 by 512 FPA array applicable to wide-field-of-view, long range surveillance and targeting missions, and a 160 by 128 array where applications for miniaturization and temperature invariance are required as well as low cost and low power.

  7. High-Speed Position-Sensitive Devices: Theory and Experiments

    NASA Astrophysics Data System (ADS)

    Dutta, Achyut Kumar

    Desirability for measurement of the correct high speed illuminated position becomes increasingly important in many applications. Using conventional position-sensitive devices (CPSDs), the illuminated-position can not be measured accurately. In search for measuring the fast illuminated -position, we are led to perform the study from two directions: (i) development of the new generalized model for one-dimensional (1-D) and two-dimensional (2-D) CPSDs to predict the performance characteristics in high-speed illuminated position measurement and (ii) proposing novel structures for the high-speed position-sensitive devices (HPSDs). The generalized models for 1-D and 2-D CPSD are derived based on the well known RC-transmission line approximation. The novelty of these generalized models lie in obtaining direct results for any kind of excitations, illuminated on CPSD. These model equations are used in analysis and prediction of dynamic performance of the very short-pulse (impulse-like) excitation of 0.2T_{rm c} for 1-D and 0.1T_{rm c} for 2-D CPSD, where T_{ rm c} represents the time-constant of PSD. Results show that 2-D CPSD is faster than 1-D CPSD having the same area, and for impulse-like excitation measurement using 2-D CPSD, the position resolution is more degraded in the near-electrode region than that of in the central region. The predicted results from models are consistent with the experimental results, performed using a-Si based CPSD. After this essential work on CPSD, study on HPSD is carried out proposing two novel structures. In the first, CPSD response-speed is improved using a mesh type resistive layer, a new structure for HPSD reducing junction capacitance. This concept making HPSD is verified, and compared with CPSD, fabricated using the same IC technology. Again, a theoretical based design strategy is proposed for investigating effects of the principle design parameters on device performances and to select the optimum design parameters for mesh-type PSD (MEPSD). Results indicate that MEPSD can be designed to operate one- to two-orders in magnitude faster than CPSD. In the second on study of HPSD, a novel structure consisting of matrix-structured photodetectors is proposed. This HPSD can detect illuminated position binarily. In the binary PSD (BPSD), each element is individually excited with illumination, and response-speed is dependent on speed of each element. For laboratory demonstration, an 8 x 8 matrix is chosen for the BPSD, fabricated using an a -Si technology and was verified the operation of newly proposed BPSD.

  8. High sensitivity dynamic spectral search for flare star radio

    NASA Technical Reports Server (NTRS)

    Abada-Simon, M.; Lecacheux, A.; Louarn, P.; Dulk, G. A.; Belkora, L.; Bookbinder, J. A.; Rosolen, C.

    1994-01-01

    We observed ten well-known flare stars with the Arcibo radio telescope at 1.4 GHz and 5 GHz, using a special observing technique to discriminate between real flares and radio freqeuncy interference. With a high sensitivity of 5.5 K/Jy at 1.4 GHz when averaged over a 50 MHz band, we are able to recognize flux enhancements as weak as approximately 6 mJy above the sky background variations. In about 85 hours of observation, about a dozen bursts were detected, only from AD Leo. All had flux densities lower than 70 mJy, which probably explains their lack of fine structures (except for the strongest one), such as were reported in the literature for stronger flares. Half of the bursts that we recorded are 100% circularly polarized, and half are not circularly polarized. Our results are a first attempt of reliable statistics on dMe flare rates at 1.4 GHz. The high brightness temperatures we infer for the observed bursts are interpreted in terms of coherent emission processes, either the cyclotron maser instability or plasma radiation. Efficiencies are comparable to those of solar or planetary radio emissions in the case of the cyclotron maser, and higher than the solar efficiency in the case of plasma radiation, with the caveat that there are great uncertainties in the coronal model and the source size.

  9. Comparing standard Bonner spheres and high-sensitivity Bonner cylinders.

    PubMed

    Lee, Kuo-Wei; Yuan, Ming-Chen; Jiang, Shiang-Huei; Sheu, Rong-Jiun

    2014-10-01

    Standard Bonner spheres and proposed high-sensitivity Bonner cylinders were calibrated in a neutron calibration room, using a (252)Cf source. The Bonner sphere system consists of 11 polyethylene (PE) spheres of various diameters and 4 extended spheres that comprise embedded metal shells. Similar to the design of Bonner spheres, a set of Bonner cylinders was assembled using a large cylindrical (3)He tube as the central probe, which was wrapped using various thicknesses of PE. A layer of lead was employed inside one of the PE cylinders to increase the detection efficiency of high-energy neutrons. The central neutron probe used in the Bonner cylinders exhibited an efficiency of ∼17.9 times higher than that of the Bonner spheres. However, compared with the Bonner spheres, the Bonner cylinders are not fully symmetric in their geometry, exhibiting angular dependence in their responses to incoming neutrons. Using a series of calculations and measurements, this study presents a systematic comparison between Bonner spheres and cylinders in terms of their response functions, detection efficiencies, angular dependences and spectrum unfolding. PMID:24366247

  10. Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks

    PubMed Central

    Arampatzis, Georgios; Katsoulakis, Markos A.; Pantazis, Yannis

    2015-01-01

    Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially) sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in “sloppy” systems. In particular, the computational acceleration is quantified by the ratio between the total number of parameters over the number of the sensitive parameters. PMID:26161544

  11. Highly sensitive and multiplexed platforms for allergy diagnostics

    NASA Astrophysics Data System (ADS)

    Monroe, Margo R.

    Allergy is a disorder of the immune system caused by an immune response to otherwise harmless environmental allergens. Currently 20% of the US population is allergic and 90% of pediatric patients and 60% of adult patients with asthma have allergies. These percentages have increased by 18.5% in the past decade, with predicted similar trends for the future. Here we design sensitive, multiplexed platforms to detect allergen-specific IgE using the Interferometric Reflectance Imaging Sensor (IRIS) for various clinical settings. A microarray platform for allergy diagnosis allows for testing of specific IgE sensitivity to a multitude of allergens, while requiring only small volumes of patient blood sample. However, conventional fluorescent microarray technology is limited by i) the variation of probe immobilization, which hinders the ability to make quantitative, assertive, and statistically relevant conclusions necessary in immunodiagnostics and ii) the use of fluorophore labels, which is not suitable for some clinical applications due to the tendency of fluorophores to stick to blood particulates and require daily calibration methods. This calibrated fluorescence enhancement (CaFE) method integrates the low magnification modality of IRIS with enhanced fluorescence sensing in order to directly correlate immobilized probe (major allergens) density to allergen-specific IgE in patient serum. However, this platform only operates in processed serum samples, which is not ideal for point of care testing. Thus, a high magnification modality of IRIS was adapted as an alternative allergy diagnostic platform to automatically discriminate and size single nanoparticles bound to specific IgE in unprocessed, characterized human blood and serum samples. These features make IRIS an ideal candidate for clinical and diagnostic applications, such a POC testing. The high magnification (nanoparticle counting) modality in conjunction with low magnification of IRIS in a combined instrument offers four significant advantages compared to existing sensing technologies: IRIS i) corrects for any variation in probe immobilization, ii) detects proteins from attomolar to nanomolar concentrations in unprocessed biological samples, iii) unambiguously discriminates nanoparticles tags on a robust and physically large sensor area, iv) detects protein targets with conjugated nanoparticle tags (~40nm diameter), which minimally affect assay kinetics compared to conventional microparticle tagging methods, and v) utilizes components that make the instrument inexpensive, robust, and portable. This platform was successfully validated on patient serum and whole blood samples with documented allergy profiles (ImmunoCAPRTM, ThermoFisher Scientific).

  12. Improvement of sensitivity in high-resolution Rutherford backscattering spectroscopy

    SciTech Connect

    Hashimoto, H.; Nakajima, K.; Suzuki, M.; Kimura, K.; Sasakawa, K.

    2011-06-15

    The sensitivity (limit of detection) of high-resolution Rutherford backscattering spectroscopy (HRBS) is mainly determined by the background noise of the spectrometer. There are two major origins of the background noise in HRBS, one is the stray ions scattered from the inner wall of the vacuum chamber of the spectrometer and the other is the dark noise of the microchannel plate (MCP) detector which is commonly used as a focal plane detector of the spectrometer in HRBS. In order to reject the stray ions, several barriers are installed inside the spectrometer and a thin Mylar foil is mounted in front of the detector. The dark noise of the MCP detector is rejected by the coincidence measurement with the secondary electrons emitted from the Mylar foil upon the ion passage. After these improvements, the background noise is reduced by a factor of 200 at a maximum. The detection limit can be improved down to 10 ppm for As in Si at a measurement time of 1 h under ideal conditions.

  13. Sensitivity study of high eccentricity orbits for Mars gravity recovery

    NASA Astrophysics Data System (ADS)

    He, Zhi-Zhou; Huang, Cheng-Li

    2015-01-01

    By linear perturbation theory, a sensitivity study is presented to calculate the contribution of the Mars gravity field to the orbital perturbations in velocity for spacecrafts in both low eccentricity Mars orbits and high eccentricity orbits (HEOs). In order to improve the solution of some low degree/order gravity coefficients, a method of choosing an appropriate semimajor axis is often used to calculate an expected orbital resonance, which will significantly amplify the magnitude of the position and velocity perturbations produced by certain gravity coefficients. We can then assess to what degree/order gravity coefficients can be recovered from the tracking data of the spacecraft. However, this existing method can only be applied to a low eccentricity orbit, and is not valid for an HEO. A new approach to choosing an appropriate semimajor axis is proposed here to analyze an orbital resonance. This approach can be applied to both low eccentricity orbits and HEOs. This small adjustment in the semimajor axis can improve the precision of gravity field coefficients and does not affect other scientific objectives.

  14. Design of high sensitivity detector for underwater communication system

    NASA Astrophysics Data System (ADS)

    Cheong, J. S.; Ong, J. S. L.; Ng, J. S.; Krysa, A. B.; Bastiman, F.; David, J. P. R.

    2013-11-01

    Al0.52In0.48P is the largest bandgap material in III-V non-nitride semiconductors that is lattice matched to a readily available substrate (GaAs). Having a bandgap narrower than that of GaN enables it to detect wavelengths around 480 nm. Such wavelengths have the best transmittance underwater and may be used as a carrier in underwater communication systems. We present an Al0.52In0.48P homo-junction Separate-Absorption-Multiplication-Avalanche-Photodiode (SAMAPD) as a high sensitivity detector for such an application. By increasing the neutral and space-charge region thicknesses, the peak response wavelength can be tuned to longer wavelengths with a narrower full-width-half-maximum (FWHM). The quantum efficiency of the detector reduces with FWHM and this is compensated by having an avalanche gain. At room temperature, the SAM-APD has a dark current of <20 pA for a 210 μm radius device up to 99.9% of breakdown voltage. The structure gives a narrow spectral FWHM of 22 nm with centre wavelength of 482 nm. An external quantum efficiency of 33% and 6410% at 482 nm is obtained at bias voltage of -19 V and -92.6 V respectively.

  15. High resolution, position sensitive detector for energetic particle beams

    NASA Astrophysics Data System (ADS)

    Marsh, E. P.; Strathman, M. D.; Reed, D. A.; Morse, D. H.; Pontau, A. E.; Odom, R. W.

    1993-05-01

    The performance and design of an imaging position sensitive, particle beam detector will be presented. The detector is minimally invasive, operates over a wide dynamic range (> 10 10), and exhibits high spatial resolution. The secondary electrons produced when a particle beam passes through a thin foil are imaged using stigmatic ion optics onto a two-dimensional imaging detector. Due to the low scattering cross section of the 6 nm carbon foil the detector is a minimal perturbation on the primary beam. A prototype detector with an image resolution of approximately 5 μm for a field of view of 1 mm has been reported [R.W. Odom, M.D. Strathman, S.E. Buttrill, Jr., and S.M. Bauman, Nucl. Instr. and Meth. B44 (1990) 465]. A higher resolution detector for imaging small beams (< 50 μm) with an image resolution of better than 0.5 μm has since been developed and its design is presented.

  16. High-sensitivity detection of negative ions in the stratosphere

    NASA Astrophysics Data System (ADS)

    McCrumb, J. L.; Arnold, F.

    1981-11-01

    High-sensitivity, in situ measurements of the negative ion composition of the stratosphere are presented which have led to the detection of previously unobserved ion species. The balloon-borne measurements were made by an instrument consisting of a cryogenically pumped quadrupole mass filter with single ion detection by a channel electron multiplier operating in a pulse-saturated ion counting mode, with an ion detection limit of about 1 ion/cu cm. Mass spectra taken during a daytime flight over southwestern France at a float altitude of 34 km reveal the presence of ions in the families NO3(-)(HNO3)(a) and HSO4(-)(H2SO4)(b)(HNO3)(c) at fractional ion count rates between 0.9 and 6.5%. Minor ions detected at count rates between 0.05 and 0.4% include those containing NO3(-) and HSO4(-) cores, as well as CN(-) and CO3 and CO3(-).H2O. Ligands identified for these molecules include HNO3 and H2SO4 and, tentatively, H2O, HCl, HNO2 and HOCl. An atmospheric nitric acid concentration of 7 x 10 to the 7th/cu cm is estimated on the basis of the NO3(-) and HNO3 species data.

  17. Highly sensitive tube-topology magnetoelectric magnetic sensors

    NASA Astrophysics Data System (ADS)

    Gillette, Scott Matthew

    Magnetoelectric (ME) composites have drawn increasing interest in recent years due to advancements in the technology resulting in enhanced ME coupling coefficients, stable room-temperature operation, sub-nanoTesla noise floor, low- and zero-biased operation, and fabrication of compact, miniaturized devices. Now, more than ever, practical use of ME devices in commercial magnetometry applications is feasible, while continued development of numerous other applications, such as voltage-tunable magnetic field generators, voltage-tunable inductors, and magnetically-tunable capacitors, bolster the overall usefulness of ME composites as a valuable technology. This dissertation focuses on development and characterization of tube-topology ME composites as magnetic field sensors. The novel topology is most notable for demonstrating high zero-external-bias sensitivity, low noise floor, low-frequency bandwidth, and self-powered, stable room temperature operation. Numerous characterization studies are included in this work where several devices are analyzed as a function of test-field, DC-bias field, geometry, material choice, and more. The overall conclusions drawn upon these results indicate strongly that the tube-topology ME magnetic field sensor holds promise to compete with existing hall-effect and flux-gate magnetometers. ME composites are at the tipping point of commercialization for use in magnetometry applications and are emerging as a valuable technology for use in numerous creative ways.

  18. High sensitivity metamaterial based bi-material terahertz sensor

    NASA Astrophysics Data System (ADS)

    Alves, Fabio; Grbovic, Dragoslav; Kearney, Brian; Karunasiri, Gamani

    2013-03-01

    We report on the fabrication of a microelectromechanical systems (MEMS) based bi-material terahertz (THz) detector integrated with a metamaterial structure to provide high absorption at 3.8 THz. The absorbing element of the sensor was designed with a resonant frequency that matches the quantum cascade laser illumination source, while simultaneously providing structural support, desired thermomechanical properties and optical read-out access. It consists of a periodic array of aluminum squares separated from a homogeneous aluminum (Al) ground plane by a silicon-rich silicon oxide (SiOx) layer. The absorbing element is connected to two Al/SiOx microcantilevers (legs), anchored to a silicon substrate, which acts as a heat sink, allowing the sensor to return to its unperturbed position when excitation is terminated. The metamaterial structure absorbs the incident THz radiation and transfers the heat to the legs where the significant difference between thermal expansion coefficients of Al and SiOx causes the structure to deform proportionally to the absorbed power. The amount of deformation is probed optically by measuring the displacement of a laser beam reflected on the Al ground plane of the metamaterial absorber. Measurement showed that the fabricated absorber has nearly 95% absorption at 3.8 THz. The responsivity and time constant were found to be 1.2 deg/μW and 0.65 s, respectively. The minimum detectable incident power including the readout noise is around 9 nW. The obtained high sensitivity and design flexibility indicate that sensor can be further tuned to achieve the required parameters for real time THz imaging applications.

  19. Development of an isotope labeling ultra-high performance liquid chromatography mass spectrometric method for quantification of acylglycines in human urine.

    PubMed

    Stanislaus, Avalyn; Guo, Kevin; Li, Liang

    2012-10-31

    Acylglycines play a crucial regulatory and detoxification role in the accumulation of the corresponding acyl CoA esters and are an important class of metabolites in the diagnoses of inborn errors of metabolism. Sensitive quantification of a large number of acylglycines not only improves diagnosis but also enables the discovery of potential new biomarkers of diseases. We report an ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS) method for quantifying acylglycines in human urine with high sensitivity. This method is based on the use of a newly developed isotope labeling reagent, p-dimethylaminophenacyl (DmPA) bromide, to label acylglycines to improve detection sensitivity. Eighteen acylglycines, namely acetylglycine, propionylglycine, isobutyrylglycine, butyrylglycine, 4-hydroxyphenylacetylglycine, 2-furoylglycine, tiglylglycine, 2-methybutyrylglycine, 3-methylcrotonylglycine, isovalerylglycine, valerylglycine, hexanoylglycine, phenylacetylglycine, phenylpropionylglycine, glutarylglycine, heptanoylglycine, octanoylglycine and suberylglycine, were measured. This method uses calibration standards prepared in surrogate matrix (un-derivatized urine) and stable-isotope labeled analytes as the internal standards. The analysis was carried out in the positive ion detection mode using multiple reaction monitoring (MRM) survey scans. The calibration curves were validated over the range of 1.0-500 nM. The method achieved a lower limit of quantitation (LLOQ) of 1-5 nM for all analytes, as measured by the standard derivations associated with calibration curves and confirmed in surrogate matrix; the signal-to-noise ratio at LLOQ ranged from 12.50 to 156.70. Both accuracy (% RE or relative error) and precision (% CV) were <15%. Matrix effects were minimized using the surrogate matrix. All eighteen analytes were stable in urine for at least 5h at room temperature, autosampler (4 °C) for 24 h, 7 weeks at -20 °C and after three freeze/thaw cycles. This surrogate matrix approach was validated using a standard addition experiment. As an example of applications, the endogenous concentrations of all eighteen analytes in urine samples of 20 healthy individuals collected in three consecutive days (i.e., 60 samples) were determined; there was no significant correlation found between the acylglycine profile and gender or body mass indices. PMID:23062437

  20. Stochastic sensitivity measure for mistuned high-performance turbines

    NASA Technical Reports Server (NTRS)

    Murthy, Durbha V.; Pierre, Christophe

    1992-01-01

    A stochastic measure of sensitivity is developed in order to predict the effects of small random blade mistuning on the dynamic aeroelastic response of turbomachinery blade assemblies. This sensitivity measure is based solely on the nominal system design (i.e., on tuned system information), which makes it extremely easy and inexpensive to calculate. The measure has the potential to become a valuable design tool that will enable designers to evaluate mistuning effects at a preliminary design stage and thus assess the need for a full mistuned rotor analysis. The predictive capability of the sensitivity measure is illustrated by examining the effects of mistuning on the aeroelastic modes of the first stage of the oxidizer turbopump in the Space Shuttle Main Engine. Results from a full analysis mistuned systems confirm that the simple stochastic sensitivity measure predicts consistently the drastic changes due to misturning and the localization of aeroelastic vibration to a few blades.

  1. High angular sensitivity thin film tin oxide sensor

    NASA Astrophysics Data System (ADS)

    Kaur, Davinder; Madaan, Divya; Sharma, V. K.; Kapoor, A.

    2016-05-01

    We present theoretical anlaysis of a thin film SnO2 (Tin Oxide) sensor for the measurement of variation in the refractive index of the bulk media. It is based on lossy mode resonance between the absorbing thin film lossy modes and the evanescent wave. Also the addition of low index dielectric matching layer between the prism and the lossy waveguiding layer future increase the angular sensitivity and produce an efficient refractive index sensor. The angular interrogation is done and obtained sensitivity is 110 degree/RIU. Theoretical analysis of the proposed sensor based on Fresnel reflection coefficients is presented. This enhanced sensitivity will further improve the monitoring of biomolecular interactions and the higher sensitivity of the proposed configurations makes it to be a much better option to be employed for biosensing applications.

  2. High sensitivity imaging Thomson scattering for low temperature plasma

    SciTech Connect

    Meiden, H. J. van der; Al, R. S.; Barth, C. J.; Donne, A. J. H.; Goedheer, W. J.; Groot, B. de; Koppers, W. R.; Pol, M. J. van de; Prins, P. R.; Shumack, A. E.; Smeets, P. H. M.; Vijvers, W. A. J.; Westerhout, J.; Wright, G. M.; Rooij, G. J. van; Engeln, R.; Kleyn, A. W.; Lopes Cardozo, N. J.; Schram, D. C.

    2008-01-15

    A highly sensitive imaging Thomson scattering system was developed for low temperature (0.1-10 eV) plasma applications at the Pilot-PSI linear plasma generator. The essential parts of the diagnostic are a neodymium doped yttrium aluminum garnet laser operating at the second harmonic (532 nm), a laser beam line with a unique stray light suppression system and a detection branch consisting of a Littrow spectrometer equipped with an efficient detector based on a ''Generation III'' image intensifier combined with an intensified charged coupled device camera. The system is capable of measuring electron density and temperature profiles of a plasma column of 30 mm in diameter with a spatial resolution of 0.6 mm and an observational error of 3% in the electron density (n{sub e}) and 6% in the electron temperature (T{sub e}) at n{sub e}=4x10{sup 19} m{sup -3}. This is achievable at an accumulated laser input energy of 11 J (from 30 laser pulses at 10 Hz repetition frequency). The stray light contribution is below 9x10{sup 17} m{sup -3} in electron density equivalents by the application of a unique stray light suppression system. The amount of laser energy that is required for a n{sub e} and T{sub e} measurement is 7x10{sup 20}/n{sub e} J, which means that single shot measurements are possible for n{sub e}>2x10{sup 21} m{sup -3}.

  3. Design of a High Sensitivity GNSS receiver for Lunar missions

    NASA Astrophysics Data System (ADS)

    Musumeci, Luciano; Dovis, Fabio; Silva, João S.; da Silva, Pedro F.; Lopes, Hugo D.

    2016-06-01

    This paper presents the design of a satellite navigation receiver architecture tailored for future Lunar exploration missions, demonstrating the feasibility of using Global Navigation Satellite Systems signals integrated with an orbital filter to achieve such a scope. It analyzes the performance of a navigation solution based on pseudorange and pseudorange rate measurements, generated through the processing of very weak signals of the Global Positioning System (GPS) L1/L5 and Galileo E1/E5 frequency bands. In critical scenarios (e.g. during manoeuvres) acceleration and attitude measurements from additional sensors complementing the GNSS measurements are integrated with the GNSS measurement to match the positioning requirement. A review of environment characteristics (dynamics, geometry and signal power) for the different phases of a reference Lunar mission is provided, focusing on the stringent requirements of the Descent, Approach and Hazard Detection and Avoidance phase. The design of High Sensitivity acquisition and tracking schemes is supported by an extensive simulation test campaign using a software receiver implementation and navigation results are validated by means of an end-to-end software simulator. Acquisition and tracking of GPS and Galileo signals of the L1/E1 and L5/E5a bands was successfully demonstrated for Carrier-to-Noise density ratios as low as 5-8 dB-Hz. The proposed navigation architecture provides acceptable performances during the considered critical phases, granting position and velocity errors below 61.4 m and 3.2 m/s, respectively, for the 99.7% of the mission time.

  4. The Subaru Coronagraphic Extreme AO High Speed and High Sensitivity Wavefront Sensors

    NASA Astrophysics Data System (ADS)

    Clergeon, Christophe; Guyon, O.; Martinache, F.; Veran, J.; Correia, C.; Garrel, V.; Jovanovic, N.

    2013-01-01

    The Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) system uses advanced coronagraphic technique for high contrast imaging of exoplanets and disks as close as 1 lambda/D from the host star. In addition to unusual optics, achieving high contrast at this small angular separation requires a wavefront sensing and control architecture which is optimized for exquisite control and calibration of low order aberrations. To complement the current near-IR wavefront control system driving a single MEMS type deformable mirror mounted on a tip-tilt mount, two high order and high sensitivity visible wavefront sensors have been integrated to SCEXAO: - a non modulated Pyramid wavefront sensor (CHEOPS) which is a sensitivity improvement over modulated Pyramid systems now used in high performant astronomical AO, - a non linear wavefront sensor designed in 2012 by Subaru Telescope with the collaboration of the NRC-CNRC which is expected to improve significantly the achieved sensitivity of low order aberations measurements. I will present the Cheops on sky results acquired during last SCEXAO run (November 2012) downstream the Subaru AO188 AO system and then introduce its primary laboratory performances comparison with the first built non linear curvature wavefront sensor.

  5. The Subaru Coronagraphic Extreme AO High Speed and High Sensitivity Wavefront Sensors

    NASA Astrophysics Data System (ADS)

    Clergeon, Christophe; Guyon, Olivier; Martinache, Frantz; Veran, Jean-Pierre; Gendron, Eric; Rousset, Grard; Correia, Carlos; Garrel, Vincent

    2013-12-01

    The Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) system uses advanced coronagraphic technique for high contrast imaging of exoplanets and disks as close as 1 lambda/D from the host star. In addition to unusual optics, achieving high contrast at this small angular separation requires a wavefront sensing and control architecture which is optimized for exquisite control and calibration of low order aberrations. To complement the current near-IR wavefront control system driving a single MEMS type deformable mirror mounted on a tip-tilt mount, two high order and high sensitivity visible wavefront sensors have been integrated to SCEXAO: - a non modulated Pyramid wavefront sensor (CHEOPS) which is a sensitivity improvement over modulated Pyramid systems now used in high performant astronomical AO, - a non linear wavefront sensor designed in 2012 by Subaru Telescope with the collaboration of the NRC-CNRC which is expected to improve significantly the achieved sensitivity of low order aberations measurements. I will present the CHEOPS last results measured downstream the Subaru AO188 system highlighting limits of our instrument and then introduce the primary laboratory images of the first built prototype of the non linear curvature wavefront sensor.

  6. Novel Ruthenium Sensitizers with a Phenothiazine Conjugated Bipyridyl Ligand for High-Efficiency Dye-Sensitized Solar Cells.

    PubMed

    She, Zhijie; Cheng, Yangyang; Zhang, Luoqiang; Li, Xiaoyu; Wu, Di; Guo, Qiang; Lan, Jingbo; Wang, Ruilin; You, Jingsong

    2015-12-23

    Two efficient ruthenium sensitizers with a phenothiazine-modified bipyridine as an ancillary ligand, coded SCZ-1 and SCZ-2, have been developed as dyes in dye-sensitized solar cells (DSSCs). Both sensitizers exhibit low-energy metal-to-ligand charge transfer (MLCT) bands centered at 539 nm with high molar extinction coefficients of 1.77 × 10(4) M(-1) cm(-1) for SCZ-1 and 1.66 × 10(4) M(-1) cm(-1) for SCZ-2, which are significantly higher than the corresponding value for the reference N719 (1.27 × 10(4) M(-1) cm(-1)), indicating that the light-harvesting capacity of ruthenium sensitizers can be reinforced by introducing phenothiazine moieties into the bipyridine ligand. Under AM 1.5G irradiation (100 mW cm(-2)), SCZ-1 and SCZ-2 sensitized DSSC devices show impressive power conversion efficiencies (PCE) up to 10.4% by using of iodide-based electrolytes, which exceeds that of N719 (9.9%) under the same conditions. Both of the open circuit voltage (VOC) and fill factor (FF) of SCZ-sensitized solar cells approximate to those of N719-sensitized cell. The relatively higher efficiencies of the SCZ-sensitized cells than that of N719-sensitized cell come from their higher short-circuit photocurrent density (JSC), which may be mainly attributed to the high absorption coefficient. The absorption spectrum and device efficiency of SCZ-1 are both quite close to those of SCZ-2, suggesting that the difference in alkyl chains on the N atom of phenothiazine is not a decisive factor in affecting the photovoltaic performance of dyes. PMID:26624527

  7. High-resolution melting analysis (HRMA): a highly sensitive inexpensive genotyping alternative for population studies.

    PubMed

    Smith, B L; Lu, C-P; Alvarado Bremer, J R

    2010-01-01

    High-resolution melting analysis (HRMA) is a highly sensitive closed-tube genotyping method used primarily in clinical studies. As the method is rapid, inexpensive and amenable to high throughput, we decided to investigate its applicability to population studies. Small amplicons and unlabelled probes were used to genotype the nuclear genes, lactate dehydrogenase-A (ldh-A), myosin light chain-2 (mlc-2), acidic ribosomal phosphoprotein P0 (ARP) and calmodulin (CaM) in populations of swordfish, Xiphias gladius. Results indicate that HRMA is a powerful genotyping tool to study wild populations. PMID:21565009

  8. Highly sensitive flexible pressure sensors with microstructured rubber dielectric layers

    NASA Astrophysics Data System (ADS)

    Mannsfeld, Stefan C. B.; Tee, Benjamin C.-K.; Stoltenberg, Randall M.; Chen, Christopher V. H.-H.; Barman, Soumendra; Muir, Beinn V. O.; Sokolov, Anatoliy N.; Reese, Colin; Bao, Zhenan

    2010-10-01

    The development of an electronic skin is critical to the realization of artificial intelligence that comes into direct contact with humans, and to biomedical applications such as prosthetic skin. To mimic the tactile sensing properties of natural skin, large arrays of pixel pressure sensors on a flexible and stretchable substrate are required. We demonstrate flexible, capacitive pressure sensors with unprecedented sensitivity and very short response times that can be inexpensively fabricated over large areas by microstructuring of thin films of the biocompatible elastomer polydimethylsiloxane. The pressure sensitivity of the microstructured films far surpassed that exhibited by unstructured elastomeric films of similar thickness, and is tunable by using different microstructures. The microstructured films were integrated into organic field-effect transistors as the dielectric layer, forming a new type of active sensor device with similarly excellent sensitivity and response times.

  9. A high-sensitivity push-pull magnetometer

    SciTech Connect

    Breschi, E.; Grujić, Z. D.; Knowles, P.; Weis, A.

    2014-01-13

    We describe our approach to atomic magnetometry based on the push-pull optical pumping technique. Cesium vapor is pumped and probed by a resonant laser beam whose circular polarization is modulated synchronously with the spin evolution dynamics induced by a static magnetic field. The magnetometer is operated in a phase-locked loop, and it has an intrinsic sensitivity below 20fT/√(Hz), using a room temperature paraffin-coated cell. We use the magnetometer to monitor magnetic field fluctuations with a sensitivity of 300fT/√(Hz)

  10. High Sensitivity SPECT for Small Animals and Plants

    SciTech Connect

    Mitchell, Gregory S.

    2015-02-28

    Imaging systems using single gamma-ray emitting radioisotopes typically implement collimators in order to form the images. However, a tradeoff in sensitivity is inherent in the use of collimators, and modern preclinical single-photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma-rays (<0.3%). We have built a collimator-less system, which can reach sensitivity of 40% for 99mTc imaging, while still producing images of sufficient spatial resolution for certain applications in thin objects such as mice, small plants, and well plates used for in vitro experiments.

  11. High-sensitivity photoacoustic detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Pushkarsky, Michael B.; Webber, Michael E.; MacDonald, Tyson; Patel, C. Kumar N.

    2004-12-01

    We report sensitive and selective detection of Diisopropyl methylphosphonate (DIMP) - a decomposition product of Sarin and a common surrogate for the nerve gases - in presence of several gases expected to be interferences in an urban setting. By employing photoacosutic spectroscopy with broadly tunable CO2 laser as a radiation source we demonstrate detection sensitivity for DIMP in the presence of these interferences of better than 0.5 ppb in 60 second long measurement time, which satisfies most current homeland and military security requirements and validates the photoacoustic spectroscopy as a powerful technology for nerve gas sensing instrumentation.

  12. Single Cell Proteomics with Ultra-High Sensitivity Mass Spectrometry

    SciTech Connect

    Frank, M

    2005-02-16

    This project was a joint LDRD project between PAT, CMS and NAI with the objective to develop an instrument that analyzes the biochemical composition of single cells in real-time using bioaerosol mass spectrometry (BAMS) combined with advanced laser desorption and ionization techniques. Applications include both biological defense, fundamental cell biology and biomedical research. BAMS analyzes the biochemical composition of single, micrometer-sized particles (such as bacterial cells or spores) that can be directly sampled from air or a suspension. BAMS is based on an earlier development of aerosol time of flight mass spectrometry (ATOFMS) by members of our collaboration [1,2]. Briefly, in ATOFMS and BAMS aerosol particles are sucked directly from the atmosphere into vacuum through a series of small orifices. As the particles approach the ion source region of the mass spectrometer, they cross and scatter light from two CW laser beams separated by a known distance. The timing of the two bursts of scattered light created by each ''tracked'' particle reveals the speed, location and size of the particle. This information then enables the firing of a high-intensity laser such that the resulting laser pulse desorbs and ionizes molecules from the tracked particle just as it reaches the center of the ion source region. The full spectrum of ions is then measured using a time-of-flight mass spectrometer. The ability to rapidly analyze individual particles is clearly applicable to the rapid detection of aerosolized biological warfare agents so long as agent particles can be made to produce mass spectra that are distinct from the spectra of harmless background particles. The pattern of ions formed is determined by the properties of the laser pulse, the particle, and, in aerosol matrix-assisted laser desorption/ionization (MALDI), also the MALDI matrix used. As a result, it is critical that the properties of the laser pulses used for desorption and ionization be carefully chosen. The work on this LDRD project was centered on demonstrating the usefulness of mass signatures obtained by BAMS for identification of biological agents and discrimination from background. To accomplish this goal this work also included a thorough study of the origins of the observed mass signatures (i.e. peak identification and dependence on bacterial growth conditions) and their dependence on laser parameters. Such a fundamental understanding of the mass signatures and their dependence on laser parameters is required for optimizing the desorption/ionization process and the bioaerosol mass spectrometer in order to increase the sensitivity and specificity of this method for practical CBNP applications.

  13. Development of High Temperature/High Sensitivity Novel Chemical Resistive Sensor

    SciTech Connect

    Chen, Chonglin; Nash, Patrick; Ma, Chunrui; Enriquez, Erik; Wang, Haibing; Xu, Xing; Bao, Shangyong; Collins, Gregory

    2013-08-13

    The research has been focused to design, fabricate, and develop high temperature/high sensitivity novel multifunctional chemical sensors for the selective detection of fossil energy gases used in power and fuel systems. By systematically studying the physical properties of the LnBaCo{sub 2}O{sub 5+d} (LBCO) [Ln=Pr or La] thin‐films, a new concept chemical sensor based high temperature chemical resistant change has been developed for the application for the next generation highly efficient and near zero emission power generation technologies. We also discovered that the superfast chemical dynamic behavior and an ultrafast surface exchange kinetics in the highly epitaxial LBCO thin films. Furthermore, our research indicates that hydrogen can superfast diffuse in the ordered oxygen vacancy structures in the highly epitaxial LBCO thin films, which suggest that the LBCO thin film not only can be an excellent candidate for the fabrication of high temperature ultra sensitive chemical sensors and control systems for power and fuel monitoring systems, but also can be an excellent candidate for the low temperature solid oxide fuel cell anode and cathode materials.

  14. High-sensitivity DPSK receiver for high-bandwidth free-space optical communication links.

    PubMed

    Juarez, Juan C; Young, David W; Sluz, Joseph E; Stotts, Larry B

    2011-05-23

    A high-sensitivity modem and high-dynamic range optical automatic gain controller (OAGC) have been developed to provide maximum link margin and to overcome the dynamic nature of free-space optical links. A sensitivity of -48.9 dBm (10 photons per bit) at 10 Gbps was achieved employing a return-to-zero differential phase shift keying based modem and a commercial Reed-Solomon forward error correction system. Low-noise optical gain was provided by an OAGC with a noise figure of 4.1 dB (including system required input loses) and a dynamic range of greater than 60 dB. PMID:21643335

  15. Sensitive, high-strain, high-rate bodily motion sensors based on graphene-rubber composites.

    PubMed

    Boland, Conor S; Khan, Umar; Backes, Claudia; O'Neill, Arlene; McCauley, Joe; Duane, Shane; Shanker, Ravi; Liu, Yang; Jurewicz, Izabela; Dalton, Alan B; Coleman, Jonathan N

    2014-09-23

    Monitoring of human bodily motion requires wearable sensors that can detect position, velocity and acceleration. They should be cheap, lightweight, mechanically compliant and display reasonable sensitivity at high strains and strain rates. No reported material has simultaneously demonstrated all the above requirements. Here we describe a simple method to infuse liquid-exfoliated graphene into natural rubber to create conducting composites. These materials are excellent strain sensors displaying 10(4)-fold increases in resistance and working at strains exceeding 800%. The sensitivity is reasonably high, with gauge factors of up to 35 observed. More importantly, these sensors can effectively track dynamic strain, working well at vibration frequencies of at least 160 Hz. At 60 Hz, we could monitor strains of at least 6% at strain rates exceeding 6000%/s. We have used these composites as bodily motion sensors, effectively monitoring joint and muscle motion as well and breathing and pulse. PMID:25100211

  16. SML resist processing for high-aspect-ratio and high-sensitivity electron beam lithography

    NASA Astrophysics Data System (ADS)

    Mohammad, Mohammad Ali; Dew, Steven K.; Stepanova, Maria

    2013-03-01

    A detailed process characterization of SML electron beam resist for high-aspect-ratio nanopatterning at high sensitivity is presented. SML contrast curves were generated for methyl isobutyl ketone (MIBK), MIBK/isopropyl alcohol (IPA) (1:3), IPA/water (7:3), n-amyl acetate, xylene, and xylene/methanol (3:1) developers. Using IPA/water developer, the sensitivity of SML was improved considerably and found to be comparable to benchmark polymethylmethacrylate (PMMA) resist without affecting the aspect ratio performance. Employing 30-keV exposures and ultrasonic IPA/water development, an aspect ratio of 9:1 in 50-nm half-pitch dense grating patterns was achieved representing a greater than two times improvement over PMMA. Through demonstration of 25-nm lift-off features, the pattern transfer performance of SML is also addressed.

  17. Single nanobeam optical sensor with a high Q-factor and high sensitivity.

    PubMed

    Kim, Sejeong; Kim, Hwi-Min; Lee, Yong-Hee

    2015-11-15

    The miniaturization of optical sensors is essential for the realization of compact, portable, and cost-effective devices. Photonic crystal-based optical sensors, which have an ultra-small mode volume and footprint, have demonstrated remarkable recent progress in achieving a high figure-of-merit (FOM) in a sensor. Here, we report an optical sensor with a high Q-factor and high sensitivity based on a photonic crystal nanobeam using the second lowest air band-edge mode. We calculated that a nanobeam (n=3.4) in a water environment (n=1.33) has refractive-index sensitivity of ~631 nm/RIU, while the quality factor is greater than 23,300. Accordingly, a theoretical FOM of the sensor corresponds to >9500. To the best of our knowledge, experimental refractive-index sensitivity of 461 nm/RIU is the highest value among photonic crystal single nanobeam geometry. The simple geometry of uniform air hole sizes and lattice constants in the proposed nanobeam sensor allows easy fabrication and mechanical stability. PMID:26565872

  18. A High-Sensitivity Current Sensor Utilizing CrNi Wire and Microfiber Coils

    PubMed Central

    Xie, Xiaodong; Li, Jie; Sun, Li-Peng; Shen, Xiang; Jin, Long; Guan, Bai-ou

    2014-01-01

    We obtain an extremely high current sensitivity by wrapping a section of microfiber on a thin-diameter chromium-nickel wire. Our detected current sensitivity is as high as 220.65 nm/A2 for a structure length of only 35 μm. Such sensitivity is two orders of magnitude higher than the counterparts reported in the literature. Analysis shows that a higher resistivity or/and a thinner diameter of the metal wire may produce higher sensitivity. The effects of varying the structure parameters on sensitivity are discussed. The presented structure has potential for low-current sensing or highly electrically-tunable filtering applications. PMID:24824372

  19. Improvement in the light sensitivity of the ultrahigh-speed high-sensitivity CCD with a microlens array

    NASA Astrophysics Data System (ADS)

    Hayashida, T.,; Yonai, J.; Kitamura, K.; Arai, T.; Kurita, T.; Tanioka, K.; Maruyama, H.; Etoh, T. Goji; Kitagawa, S.; Hatade, K.; Yamaguchi, T.; Takeuchi, H.; Iida, K.

    2008-02-01

    We are advancing the development of ultrahigh-speed, high-sensitivity CCDs for broadcast use that are capable of capturing smooth slow-motion videos in vivid colors even where lighting is limited, such as at professional baseball games played at night. We have already developed a 300,000 pixel, ultrahigh-speed CCD, and a single CCD color camera that has been used for sports broadcasts and science programs using this CCD. However, there are cases where even higher sensitivity is required, such as when using a telephoto lens during a baseball broadcast or a high-magnification microscope during science programs. This paper provides a summary of our experimental development aimed at further increasing the sensitivity of CCDs using the light-collecting effects of a microlens array.

  20. High-sensitivity and wide-directivity ultrasound detection using high Q polymer microring resonators

    NASA Astrophysics Data System (ADS)

    Ling, Tao; Chen, Sung-Liang; Guo, L. Jay

    2011-05-01

    Small size ultrahigh Q polymer microrings working at near visible wavelength have been experimentally demonstrated as ultralow noise ultrasound detectors with wide directivity at high frequencies (>20 MHz). By combining a resist reflow and a low bias continuous etching and passivation process in mold fabrication, imprinted polymer microrings with drastically improved sidewall smoothness were obtained. An ultralow noise-equivalent pressure of 21.4 Pa over 1-75 MHz range has been achieved using a fabricated detector of 60 μm diameter. The device's wide acceptance angle with high sensitivity considerably benefits ultrasound-related imaging.

  1. Thallium-201 myocardial imaging: comparison of the high sensitivity and high resolution collimators

    SciTech Connect

    Wynant, G.E.

    1981-03-01

    Thallium-201 myocardial images of 20 patients undergoing treadmill exercise were evaluated as to the ability of the high sensitivity collimator (HSC) to reveal perfusion defects compared to images obtained using the high resolution collimator (HRC). The study acquired 200,000 count images in the anterior, 45/sup 0/ left anterior oblique, and left lateral projections. Average acquisition times were: HSC 3.41 min, and HRC 6.08 min. Fifteen patients who had clearly visible perfusion defects using the HRC showed degraded definition or appreciable loss of definition of the same defects when using the HSC.

  2. Highly sensitive straightness measurement system using a ball-lens

    NASA Astrophysics Data System (ADS)

    Lee, Minho; Yang, Hyun-Ik; Cho, Nahm-Gyoo

    2016-01-01

    In this paper, a new and simple optical technique to accurately measure the straightness errors of a linear stage is proposed. To improve the performance, including the measurement sensitivity and resolution of the measurement system, and to simultaneously measure two-dimensional straightness errors (2D straightness errors), an optical system was designed using a laser, a retro-reflector, a ball-lens, and a two-dimensional position sensitive detector (2D PSD). The characteristics of the measurement system were analytically and experimentally investigated. A prototype measurement system was manufactured based on the investigated results, and the performances of this system have been tested. The measuring performance of the system was easily improved by about 12 times using the proposed technique and it can be further improved. It is shown that the proposed technique can easily and effectively improve the performance of a conventional straightness measurement system based on the geometric optical method using a PSD.

  3. Highly sensitive BTX detection using surface functionalized QCM sensor

    NASA Astrophysics Data System (ADS)

    Bozkurt, Asuman Aşıkoǧlu; Özdemir, Okan; Altındal, Ahmet

    2016-03-01

    A novel organic compound was designed and successfully synthesized for the fabrication of QCM based sensors to detect the low concentrations of BTX gases in indoor air. The effect of the long-range electron orbital delocalization on the BTX vapour sensing properties of azo-bridged Pcs based chemiresistor-type sensors have also been investigated in this work. The sensing behaviour of the film for the online detection of volatile organic solvent vapors was investigated by utilizing an AT-cut quartz crystal resonator. It was observed that the adsorption of the target molecules on the coating surface cause a reversible negative frequency shift of the resonator. Thus, a variety of solvent vapors can be detected by using the phthalocyanine film as sensitive coating, with sensitivity in the ppm range and response times in the order of several seconds depending on the molecular structure of the organic solvent.

  4. Adaptive interferometry for high sensitivity optical fiber sensing

    NASA Astrophysics Data System (ADS)

    Peigné, A.; Bortolozzo, U.; Residori, S.; Molin, S.; Dolfi, D.; Huignard, J.-P.

    2015-09-01

    We report on the use of an adaptive holographic interferometer, based on a liquid crystal light valve, to achieve phase shift measurements in an optical fiber. Owing to the physical mechanisms involved, the interferometer adapts itself to slow phase variations. As a consequence, it is possible to use a multimode fiber for sensing, which improves the sensitivity. Moreover, a distributed architecture relying on phase-OTDR principle is presented and a localization experiment is performed.

  5. Nitrogen detected TROSY at high field yields high resolution and sensitivity for protein NMR.

    PubMed

    Takeuchi, Koh; Arthanari, Haribabu; Shimada, Ichio; Wagner, Gerhard

    2015-12-01

    Detection of (15)N in multidimensional NMR experiments of proteins has sparsely been utilized because of the low gyromagnetic ratio (?) of nitrogen and the presumed low sensitivity of such experiments. Here we show that selecting the TROSY components of proton-attached (15)N nuclei (TROSY (15)NH) yields high quality spectra in high field magnets (>600MHz) by taking advantage of the slow (15)N transverse relaxation and compensating for the inherently low (15)N sensitivity. The (15)N TROSY transverse relaxation rates increase modestly with molecular weight but the TROSY gain in peak heights depends strongly on the magnetic field strength. Theoretical simulations predict that the narrowest line width for the TROSY (15)NH component can be obtained at 900MHz, but sensitivity reaches its maximum around 1.2GHz. Based on these considerations, a (15)N-detected 2D (1)H-(15)N TROSY-HSQC ((15)N-detected TROSY-HSQC) experiment was developed and high-quality 2D spectra were recorded at 800MHz in 2h for 1mM maltose-binding protein at 278K (?c~40ns). Unlike for (1)H detected TROSY, deuteration is not mandatory to benefit (15)N detected TROSY due to reduced dipolar broadening, which facilitates studies of proteins that cannot be deuterated, especially in cases where production requires eukaryotic expression systems. The option of recording (15)N TROSY of proteins expressed in H2O media also alleviates the problem of incomplete amide proton back exchange, which often hampers the detection of amide groups in the core of large molecular weight proteins that are expressed in D2O culture media and cannot be refolded for amide back exchange. These results illustrate the potential of (15)NH-detected TROSY experiments as a means to exploit the high resolution offered by high field magnets near and above 1GHz. PMID:26497830

  6. The strain-rate sensitivity of high-strength high-toughness steels.

    SciTech Connect

    Dilmore, M.F.; Crenshaw, Thomas B.; Boyce, Brad Lee

    2006-01-01

    The present study examines the strain-rate sensitivity of four high strength, high-toughness alloys at strain rates ranging from 0.0002 s-1 to 200 s-1: Aermet 100, a modified 4340, modified HP9-4-20, and a recently developed Eglin AFB steel alloy, ES-1c. A refined dynamic servohydraulic method was used to perform tensile tests over this entire range. Each of these alloys exhibit only modest strain-rate sensitivity. Specifically, the strain-rate sensitivity exponent m, is found to be in the range of 0.004-0.007 depending on the alloy. This corresponds to a {approx}10% increase in the yield strength over the 7-orders of magnitude change in strain-rate. Interestingly, while three of the alloys showed a concominant {approx}3-10% drop in their ductility with increasing strain-rate, the ES1-c alloy actually exhibited a 25% increase in ductility with increasing strain-rate. Fractography suggests the possibility that at higher strain-rates ES-1c evolves towards a more ductile dimple fracture mode associated with microvoid coalescence.

  7. High sensitivity gas sensor based on high-Q suspended polymer photonic crystal nanocavity

    SciTech Connect

    Clevenson, Hannah Desjardins, Pierre; Gan, Xuetao; Englund, Dirk

    2014-06-16

    We present high-sensitivity, multi-use optical gas sensors based on a one-dimensional photonic crystal cavity. These devices are implemented in versatile, flexible polymer materials which swell when in contact with a target gas, causing a measurable cavity length change. This change causes a shift in the cavity resonance, allowing precision measurements of gas concentration. We demonstrate suspended polymer nanocavity sensors and the recovery of sensors after the removal of stimulant gas from the system. With a measured quality factor exceeding 10{sup 4}, we show measurements of gas concentration as low as 600 parts per million (ppm) and an experimental sensitivity of 10 ppm; furthermore, we predict detection levels in the parts-per-billion range for a variety of gases.

  8. Highly sensitive voltammetric determination of lamotrigine at highly oriented pyrolytic graphite electrode.

    PubMed

    Saberi, Reyhaneh-Sadat; Shahrokhian, Saeed

    2012-04-01

    The electrochemical behavior of lamotrigine (LMT) at the pyrolytic graphite electrode (PGE) is investigated in detail by the means of cyclic voltammetry. During the electrochemical reduction of LMT, an irreversible cathodic peak appeared. Cyclic voltammetric studies indicated that the reduction process has an irreversible and adsorption-like behavior. The observed reduction peak is attributed to a two-electron process referring to the reduction of azo group. The electrode showed an excellent electrochemical activity toward the electro-reduction of LMT, leading to a significant improvement in sensitivity as compared to the glassy carbon electrode. The results of electrochemical impedance spectroscopy and cyclic voltammetry showed that edge-plane pyrolytic graphite electrode has excellent electrochemical response properties toward LMTs with respect to glassy carbon electrode modified with carbon nanotubes. High sensitivity, low detection limit and very good repeatability together with excellent recovery make the electrode as a powerful devise for accurate determination of LMT in pharmaceutical and biological samples. PMID:22137203

  9. Analysis of Cyberbullying Sensitivity Levels of High School Students and Their Perceived Social Support Levels

    ERIC Educational Resources Information Center

    Akturk, Ahmet Oguz

    2015-01-01

    Purpose: The purpose of this paper is to determine the cyberbullying sensitivity levels of high school students and their perceived social supports levels, and analyze the variables that predict cyberbullying sensitivity. In addition, whether cyberbullying sensitivity levels and social support levels differed according to gender was also

  10. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    SciTech Connect

    Iwai, J.; Friedman, R.; Tassinari, L.

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  11. Analysis of Cyberbullying Sensitivity Levels of High School Students and Their Perceived Social Support Levels

    ERIC Educational Resources Information Center

    Akturk, Ahmet Oguz

    2015-01-01

    Purpose: The purpose of this paper is to determine the cyberbullying sensitivity levels of high school students and their perceived social supports levels, and analyze the variables that predict cyberbullying sensitivity. In addition, whether cyberbullying sensitivity levels and social support levels differed according to gender was also…

  12. Screening and analyzing the potential bioactive components from reduning injection, using macrophage cell extraction and ultra-high performance liquid chromatography coupled with mass spectrometry.

    PubMed

    Li, Yonghui; Wang, Peixiang; Xiao, Wei; Zhao, Li; Wang, Zhenzhong; Yu, Li

    2013-01-01

    In this paper, a useful method for screening and analyzing the potential bioactive components from Reduning Injection was developed using macrophage cell extraction and ultra-high performance liquid chromatography coupled with Q-TOF/MS spectrometry. In addition, the protective effects on macrophage cell damage induced by LPS in vitro were also investigated. The results showed that chlorogenic acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid and 4, 5-dicaffeoylquinic acid significantly inhibited the prostaglandin E(2) (PGE(2)) release and reversed the interleukin-6 (IL-6) secretion of macrophages (p < 0.05). These data indicated that the method of macrophage cell extraction coupled with UPLC-MS technology is feasible, rapid and useful for screening and analyzing potential bioactive components from TCM injection. PMID:23336518

  13. High-performance and high-sensitivity applications of graphene transistors with self-assembled monolayers.

    PubMed

    Yeh, Chao-Hui; Kumar, Vinod; Moyano, David Ricardo; Wen, Shao-Hsuan; Parashar, Vyom; Hsiao, She-Hsin; Srivastava, Anchal; Saxena, Preeti S; Huang, Kun-Ping; Chang, Chien-Chung; Chiu, Po-Wen

    2016-03-15

    Charge impurities and polar molecules on the surface of dielectric substrates has long been a critical obstacle to using graphene for its niche applications that involve graphene's high mobility and high sensitivity nature. Self-assembled monolayers (SAMs) have been found to effectively reduce the impact of long-range scatterings induced by the external charges. Yet, demonstrations of scalable device applications using the SAMs technique remains missing due to the difficulties in the device fabrication arising from the strong surface tension of the modified dielectric environment. Here, we use patterned SAM arrays to build graphene electronic devices with transport channels confined on the modified areas. For high-mobility applications, both rigid and flexible radio-frequency graphene field-effect transistors (G-FETs) were demonstrated, with extrinsic cutoff frequency and maximum oscillation frequency enhanced by a factor of ~2 on SiO2/Si substrates. For high sensitivity applications, G-FETs were functionalized by monoclonal antibodies specific to cancer biomarker chondroitin sulfate proteoglycan 4, enabling its detection at a concentration of 0.01 fM, five orders of magnitude lower than that detectable by a conventional colorimetric assay. These devices can be very useful in the early diagnosis and monitoring of a malignant disease. PMID:26547427

  14. Highly sensitive method for diagnosis of subclinical B. ovis infection.

    PubMed

    Horta, Sara; Barreto, Maria C; Pepe, Ana; Campos, Joana; Oliva, Abel

    2014-10-01

    Babesia ovis is a tick-transmitted protozoa parasite that infects small ruminants causing fever, anaemia, hemoglobinuria, anorexia and, in acute cases, death. Common in tropical and sub-tropical areas, the presence of this parasite in sheep herds has an economic impact on industry and therefore sensitive methods for the diagnosis and disease eradication are required. To achieve this goal, a semi-nested PCR for B. ovis specific identification was developed and consequent reaction conditions and enzymes were optimized and tested with field samples. 300 blood samples from small ruminants and 39 ticks from Rhipicephalus genus were collected from different regions of Portugal. Afterwards, DNA extraction was performed and conventional and semi-nested PCR were accomplished for all samples. The results obtained from both methodologies were compared and the sensitivity was evaluated. Employing the semi-nested PCR it was possible to identify a higher number of positive cases among the evaluated samples than using the conventional PCR, namely 38/300 blood samples and 7/39 ticks. However, fragment amplification was only observed in 5 out of 300 blood samples and in none of the 39 ticks when a conventional PCR was employed. The validation of the results was achieved by sequencing the DNA fragments corresponding to the hypervariable v4 region of the 18S ribosomal RNA gene and performing an alignment with sequences already published on GenBank(®). The ticks collected in this study belong to the Rhipicephalus genus, although other species could be involved as a vector in the Babesia spread. The diagnostic assay here described is presently the most effective and sensitive method for detection of B. ovis in field blood samples and ticks, enabling the detection up to 1 parasite into 10(9) erythrocytes. PMID:25127159

  15. JAFFA: High sensitivity transcriptome-focused fusion gene detection.

    PubMed

    Davidson, Nadia M; Majewski, Ian J; Oshlack, Alicia

    2015-01-01

    Genomic instability is a hallmark of cancer and, as such, structural alterations and fusion genes are common events in the cancer landscape. RNA sequencing (RNA-Seq) is a powerful method for profiling cancers, but current methods for identifying fusion genes are optimised for short reads. JAFFA (https://github.com/Oshlack/JAFFA/wiki) is a sensitive fusion detection method that outperforms other methods with reads of 100 bp or greater. JAFFA compares a cancer transcriptome to the reference transcriptome, rather than the genome, where the cancer transcriptome is inferred using long reads directly or by de novo assembling short reads. PMID:26019724

  16. Super LOTIS a high sensitive optical counterpart search experiment

    SciTech Connect

    Park, H.S., Ables, E.; Band, D.L

    1997-11-17

    We are constructing a 0.6 meter telescope system to search for early time gamma-ray burst (GRB) optical counterparts. Super-LOTIS (Super-Livermore Optical Transient Imaging System) is an automated telescope system that has a 0.8 x 0.8{degree} field-of-view, is sensitive to M{sub v} {approximately} 19 and responds to a burst trigger within 5 min. This telescope will record images of the gamma-ray burst coordinates that is given by the GCN (GRB Coordinate Network). A measurement of GRB light curves at early times will greatly enhance our understanding of GRB physics.

  17. A low-power, high-sensitivity micromachined optical magnetometer

    NASA Astrophysics Data System (ADS)

    Mhaskar, R.; Knappe, S.; Kitching, J.

    2012-12-01

    We demonstrate an optical magnetometer based on a microfabricated 87Rb vapor cell in a micromachined silicon sensor head. The alkali atom density in the vapor cell is increased by heating the cell with light brought to the sensor through an optical fiber, and absorbed by colored filters attached to the cell windows. A second fiber-optically coupled beam optically pumps and interrogates the atoms. The magnetometer operates on 140 mW of heating power and achieves a sensitivity below 20 fT/√Hz throughout most of the frequency band from 15 Hz to 100 Hz. Such a sensor can measure magnetic fields from the human heart and brain.

  18. Patterns of Allergic Sensitization in High IgE Syndromes.

    PubMed

    Lawrence, Monica G

    2015-12-01

    Dramatic elevations in the serum IgE level are seen both in polygenic allergic diseases such as atopic dermatitis and food allergy, and in a growing list of monogenic primary immune deficiencies (PIDs). Although the IgE produced in patients with PID has generally been considered to be driven by dysregulated IL-4 production and thus lack antigen specificity, in fact allergen-specific IgE can be detected by skin and serum testing in many of these patients. However, perhaps not surprisingly given the distinct immunologic pathways involved, the patterns of allergic disease and atopic sensitization vary widely between syndromes, leading to strikingly different clinical phenotypes. PMID:26492876

  19. Advanced Cd(II) complexes as high efficiency co-sensitizers for enhanced dye-sensitized solar cell performance.

    PubMed

    Gao, Song; Fan, Rui Qing; Wang, Xin Ming; Qiang, Liang Sheng; Wei, Li Guo; Wang, Ping; Yang, Yu Lin; Wang, Yu Lei

    2015-11-01

    This work reports on two new complexes with the general formula [Cd3(IBA)3(Cl)2(HCOO)(H2O)]n (1) and {[Cd1.5(IBA)3(H2O)6]·3.5H2O}n (2), which can be synthesized by the reaction of Cd(II) with rigid linear ligand 4-HIBA containing imidazolyl and carboxylate functional groups [4-HIBA = 4-(1H-imidazol-1-yl)benzoic acid]. Single-crystal X-ray diffraction analyses indicate that complex 1 is a 2D "wave-like" layer structure constructed from trinuclear units and complex 2 is just a mononuclear structure. Surprisingly, both complexes 1 and 2 appear as a 3D supramolecular network via intermolecular hydrogen bonding interactions. What's more, due to their strong UV-visible absorption, 1 and 2 can be employed as co-sensitizers in combination with N719 to enhance dye-sensitized solar cell (DSSC) performance. Both of them could overcome the deficiency of the ruthenium complex N719 absorption in the region of ultraviolet and blue-violet, and the charge collection efficiency is also improved when 1 and 2 are used as co-sensitizers, which are all in favor of enhancing the performance. The DSSC devices using co-sensitizers of 1/N719 and 2/N719 show an overall conversion efficiency of 8.27% and 7.73% with a short circuit current density of 17.48 mA cm(-2) and 17.39 mA cm(-2), and an open circuit voltage of 0.75 V and 0.74 V, respectively. The overall conversion efficiency is 27.23% and 18.92% higher than that of a device solely sensitized by N719 (6.50%). Consequently, the prepared complexes are high efficiency co-sensitizers for enhancing the performance of N719 sensitized solar cells. PMID:26419745

  20. Nanostructured photoelectrochemical biosensor for highly sensitive detection of organophosphorous pesticides.

    PubMed

    Li, Xinyu; Zheng, Zhaozhu; Liu, Xuefeng; Zhao, Shenlong; Liu, Shaoqin

    2015-02-15

    A sensitive photoelectrochemical (PEC) biosensor for detection of organophosphorus pesticides (OPs) using the nanocomposite of CdSe@ZnS quantum dots (QDs) and graphene deposited on the ITO coated glass electrode as a photoactive electrode is presented. The integration of CdSe@ZnS/graphene nanocomposite with biomolecules acetylcholinesterase (AChE) as a biorecognition element yields a novel biosensing platform. Under visible light irradiation, the AChE-CdSe@ZnS/graphene nanocomposite can generate a stable photocurrent and the photocurrent is found to be inversely dependent on the concentration of OPs. Under the optimal experimental conditions, the photocurrents were proportional to the logarithm of paraoxon and dichlorvos within the concentration range of 10(-12)-10(-6) M. The detection limits (LOD) of the proposed biosensor for paraoxon and dichlorvos are as low as 10(-14) M and 10(-12) M. The photoelectrochemical biosensor shows good sensitivity, reproducibility, stability, and could be successfully applied to detection of OPs in real fruit samples. PMID:25173731

  1. Highly Sensitive Immunochromatographic Identification of Tetracycline Antibiotics in Milk

    PubMed Central

    Taranova, N. A.; Kruhlik, A. S.; Zvereva, E. A.; Shmanai, V. V.; Vashkevich, I. I.; Semyonov, D. A.; Eremin, S. A.; Zherdev, A. V.; Dzantiev, B. B.

    2015-01-01

    A rapid immunochromatographic assay was developed for the control of tetracycline (TC). The assay is based on the competition between immobilized TC-protein conjugate and TC in a tested sample for binding with polyclonal anti-TC antibodies conjugated to colloidal gold during the flow of the sample along a membrane strip with immobilized reactants. Conjugation of colloidal gold and the total immunoglobulin (IgG) fraction of polyclonal antibodies was used to increase the assay sensitivity to ensure low content of specific antibodies in the conjugate. This allowed effective inhibition of free TC and conjugate binding in the strip test zone. Photometric marker registration allows control of the reduction of binding, thereby enhancing detection sensitivity. The proposed assay allows TC to be detected at concentrations up to 20 ng/mL, exceeding the limit of detection of the known analogues, in a wide working range (more than two orders) of 60 pg/mL to 10 ng/mL, ensured through the use of polyclonal antibodies. The assay time is 10 min. The efficiency of the designed assay is shown to identify TC in milk; the degree of recovery of TC ranges from 90 to 112%. The precision of the concentrations measurements was no more than 10%. PMID:26689537

  2. Sensitivity analysis for high accuracy proximity effect correction

    NASA Astrophysics Data System (ADS)

    Thrun, Xaver; Browning, Clyde; Choi, Kang-Hoon; Figueiro, Thiago; Hohle, Christoph; Saib, Mohamed; Schiavone, Patrick; Bartha, Johann W.

    2015-10-01

    A sensitivity analysis (SA) algorithm was developed and tested to comprehend the influences of different test pattern sets on the calibration of a point spread function (PSF) model with complementary approaches. Variance-based SA is the method of choice. It allows attributing the variance of the output of a model to the sum of variance of each input of the model and their correlated factors.1 The objective of this development is increasing the accuracy of the resolved PSF model in the complementary technique through the optimization of test pattern sets. Inscale® from Aselta Nanographics is used to prepare the various pattern sets and to check the consequences of development. Fraunhofer IPMS-CNT exposed the prepared data and observed those to visualize the link of sensitivities between the PSF parameters and the test pattern. First, the SA can assess the influence of test pattern sets for the determination of PSF parameters, such as which PSF parameter is affected on the employments of certain pattern. Secondly, throughout the evaluation, the SA enhances the precision of PSF through the optimization of test patterns. Finally, the developed algorithm is able to appraise what ranges of proximity effect correction is crucial on which portion of a real application pattern in the electron beam exposure.

  3. An all-optical, high-sensitivity magnetic gradiometer

    NASA Astrophysics Data System (ADS)

    Affolderbach, C.; Sthler, M.; Knappe, S.; Wynands, R.

    Optical magnetometers have reached sensitivities that make them interesting candidates for the measurement of weak magnetic fields also outside physics laboratories. In order to overcome problems with stray magnetic fields a common solution with existing magnetometers is to operate a pair of them in a gradiometer configuration: one sensor measures the signal plus the stray fields, while the other one is mounted such that it is only influenced by the stray fields. In the difference signal the stray fields cancel. We have constructed such a gradiometer consisting of two sensors based on coherent population trapping (CPT) resonances in a thermal cesium vapor. Using a magnetic bias field the intrinsically scalar CPT magnetometer can be turned into a true vector magnetometer that is insensitive to magnetic fields perpendicular to a chosen measurement direction. We describe how to align and calibrate the gradiometer. Stray field suppression by more than two orders of magnitude has been achieved, limited by the sensitivity of the magnetometer. This makes possible the detection of picotesla flux density changes in a weakly shielded or even unshielded environment.

  4. High temperature probe sensor with high sensitivity based on Michelson interferometer

    NASA Astrophysics Data System (ADS)

    Zhao, Na; Fu, Haiwei; Shao, Min; Yan, Xu; Li, Huidong; Liu, Qinpeng; Gao, Hong; Liu, Yinggang; Qiao, Xueguang

    2015-05-01

    A novel Michelson interferometer based on a bi-taper is achieved. Such a device is fabricated by splicing a section of thin core fiber (TCF) at one end of single-mode fiber (SMF). Due to the fiber bi-taper at the splicing point of SMF and TCF, the light is coupled into the fiber core and cladding from lead in fiber core. The light will be reflected at the end of the fiber and then will be recoupled back into the lead out fiber core by the fiber bi-taper. While the light returns back to the lead out fiber, the intermodal interference will occur for the optical path difference between core mode and cladding mode. A high temperature sensitivity of 0.140 nm/°C is achieved from 30 to 800 °C, and the linearity is 99.9%. The configuration features the advantages of easy fabrication, a compact size, high sensitivity, wide sensing range and high mechanical strength, making it a good candidate for distant temperature sensing and oil prospecting.

  5. Research on test technology of high sensitivity and high frame rate of far ultraviolet spectroscopy

    NASA Astrophysics Data System (ADS)

    Sun, Guang-wei; Sun, Hong-sheng; Wang, Jia-peng; Gao, Shu-min

    2015-10-01

    Importance of ultraviolet calibration is growing fast as ultraviolet payloads are wildly used in national space plan. Calibration device for UV radiation celestial body simulator is established especially for the calibration of instantaneous radiation parameters and high-sensitivity radiation parameters. Parameters such as spectral radiance, spectral irradiance can be calibrated from 200 nm to 400 nm. The uncertainty of spectral radiance is 15% (k=2 and the uncertainty of spectral irradiance is 20% (k=2 .The calibration device is perspective for its application in national defense system.

  6. High-sensitivity, high-selectivity detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Pushkarsky, Michael B.; Webber, Michael E.; Macdonald, Tyson; Patel, C. Kumar N.

    2006-01-01

    We report high-sensitivity detection of chemical warfare agents (nerve gases) with very low probability of false positives (PFP). We demonstrate a detection threshold of 1.2ppb (7.7μg/m3 equivalent of Sarin) with a PFP of <1:106 in the presence of many interfering gases present in an urban environment through the detection of diisopropyl methylphosphonate, an accepted relatively harmless surrogate for the nerve agents. For the current measurement time of ˜60s, a PFP of 1:106 corresponds to one false alarm approximately every 23months. The demonstrated performance satisfies most current homeland and military security requirements.

  7. Novel Characteristics of Photodamage to PSII in a High-Light-Sensitive Symbiodinium Phylotype.

    PubMed

    Karim, Widiastuti; Seidi, Azadeh; Hill, Ross; Chow, Wah S; Minagawa, Jun; Hidaka, Michio; Takahashi, Shunichi

    2015-06-01

    Dinoflagellates from the genus Symbiodinium form symbiotic relationships with many marine invertebrates, including reef-building corals. Symbiodinium is genetically diverse, and acquiring suitable Symbiodinium phylotypes is crucial for the host to survive in habitat environments, such as high-light conditions. The sensitivity of Symbiodinium to high light differs among Symbiodinium phylotypes, but the mechanism that controls light sensitivity has not yet been fully resolved. In the present study using high-light-tolerant and -sensitive Symbiodinium phylotypes, we examined what determines sensitivity to high light. In growth experiments under different light intensities, Symbiodinium CS-164 (clade B1) and CCMP2459 (clade B2) were identified as high-light-tolerant and -sensitive phylotypes, respectively. Measurements of the maximum quantum yield of photosystem II (PSII) and the maximum photosynthetic oxygen production rate after high-light exposure demonstrated that CCMP2459 is more sensitive to photoinhibition of PSII than CS-164, and tends to lose maximum photosynthetic activity faster. Measurement of photodamage to PSII under light of different wavelength ranges demonstrated that PSII in both Symbiodinium phylotypes was significantly more sensitive to photodamage under shorter wavelength regions of light spectra (<470 nm). Importantly, PSII in CCMP2459, but not CS-164, was also sensitive to photodamage under the regions of light spectra around 470-550 and 630-710 nm, where photosynthetic antenna proteins of Symbiodinium have light absorption peaks. This finding indicates that the high-light-sensitive CCMP2459 has an extra component of photodamage to PSII, resulting in higher sensitivity to high light. Our results demonstrate that sensitivity of PSII to photodamage differs among Symbiodinium phylotypes and this determines their sensitivity to high light. PMID:25759327

  8. Carbon nanotube quantum dots as highly sensitive THz spectrometers

    NASA Astrophysics Data System (ADS)

    Rinzan, Mohamed; Jenkins, Greg; Drew, Dennis; Shafranjuk, Serhii; Barbara, Paola

    2012-02-01

    We show that carbon nanotube quantum dots (CNT-Dots) coupled to antennas are extremely sensitive, broad-band, terahertz quantum detectors. Their response is due to photon-assisted single-electron tunneling (PASET)[1], but cannot be fully understood with orthodox PASET models[2]. We consider intra-dot excitations and non-equilibrium cooling to explain the anomalous response. REFERENCES: [1] Y. Kawano, S. Toyokawa, T. Uchida and K. Ishibashi, THz photon assisted tunneling in carbon-nanotube quantum dots, Journal of Applied Physics 103, 034307 (2008). [2] P. K. Tien and J. P. Gordon, Multiphoton Process Observed in the Interaction of Microwave Fields with the Tunneling between Superconductor Films, Phys. Rev. 129, 647 (1963).

  9. A new compact, high sensitivity neutron imaging system

    SciTech Connect

    Caillaud, T.; Landoas, O.; Briat, M.; Rosse, B.; Thfoin, I.; Philippe, F.; Casner, A.; Bourgade, J. L.; Disdier, L.; Glebov, V. Yu.; Marshall, F. J.; Sangster, T. C.; Park, H. S.; Robey, H. F.; Amendt, P.

    2012-10-15

    We have developed a new small neutron imaging system (SNIS) diagnostic for the OMEGA laser facility. The SNIS uses a penumbral coded aperture and has been designed to record images from low yield (10{sup 9}-10{sup 10} neutrons) implosions such as those using deuterium as the fuel. This camera was tested at OMEGA in 2009 on a rugby hohlraum energetics experiment where it recorded an image at a yield of 1.4 Multiplication-Sign 10{sup 10}. The resolution of this image was 54 {mu}m and the camera was located only 4 meters from target chamber centre. We recently improved the instrument by adding a cooled CCD camera. The sensitivity of the new camera has been fully characterized using a linear accelerator and a {sup 60}Co {gamma}-ray source. The calibration showed that the signal-to-noise ratio could be improved by using raw binning detection.

  10. A new compact, high sensitivity neutron imaging systema)

    NASA Astrophysics Data System (ADS)

    Caillaud, T.; Landoas, O.; Briat, M.; Rossé, B.; Thfoin, I.; Philippe, F.; Casner, A.; Bourgade, J. L.; Disdier, L.; Glebov, V. Yu.; Marshall, F. J.; Sangster, T. C.; Park, H. S.; Robey, H. F.; Amendt, P.

    2012-10-01

    We have developed a new small neutron imaging system (SNIS) diagnostic for the OMEGA laser facility. The SNIS uses a penumbral coded aperture and has been designed to record images from low yield (109-1010 neutrons) implosions such as those using deuterium as the fuel. This camera was tested at OMEGA in 2009 on a rugby hohlraum energetics experiment where it recorded an image at a yield of 1.4 × 1010. The resolution of this image was 54 μm and the camera was located only 4 meters from target chamber centre. We recently improved the instrument by adding a cooled CCD camera. The sensitivity of the new camera has been fully characterized using a linear accelerator and a 60Co γ-ray source. The calibration showed that the signal-to-noise ratio could be improved by using raw binning detection.

  11. Recent Advances in High Sensitivity Nuclear Quadrupole Resonance

    NASA Astrophysics Data System (ADS)

    Edmonds, D. I.

    The field of nuclear quadrupole resonance has been transformed recently by the invention of double-resonance techniques which are applicable to powdered solids or frozen liquids. The spectra of light elements such as 2H, 14N, 170 and 23Na are now detected with ease and with a sensitivity such that 17O, or even 2H, may be measured in its natural abundance. The review describes four of these techniques, namely double resonance with level crossing (DRLC), double resonance with continuous coupling (DRCC), double resonance in the laboratory frame (DRLF) and double resonance with coupled multiplets (DRCM). The treatment relies on physical models where possible and is aimed at the practical experimenter who may not be a specialist in the thermodynamics of nuclear spin systems.

  12. Highly sensitive humidity sensing properties of carbon quantum dots films

    SciTech Connect

    Zhang, Xing; Ming, Hai; Liu, Ruihua; Han, Xiao; Kang, Zhenhui; Liu, Yang; Zhang, Yonglai; State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun 130012

    2013-02-15

    Graphical abstract: Display Omitted Highlights: ► A humidity sensing device was fabricated based on carbon quantum dots (CQDs) films. ► The conductivity of the CQDs films shows a linear and rapid response to atmosphere humidity. ► The humidity sensing property was due to the hydrogen bonds between the functional groups on CQDs. -- Abstract: We reported the fabrication of a humidity sensing device based on carbon quantum dots (CQDs) film. The conductivity of the CQDs film has a linear and rapid response to relative humidity, providing the opportunity for the fabrication of humidity sensing devices. The mechanism of our humidity sensor was proposed to be the formation of hydrogen bonds between carbon quantum dots and water molecules in the humidity environment, which significantly promote the electrons migration. In a control experiment, this hypothesis was confirmed by comparing the humidity sensitivity of candle soot (i.e. carbon nanoparticles) with and without oxygen containing groups on the surfaces.

  13. A new compact, high sensitivity neutron imaging system.

    PubMed

    Caillaud, T; Landoas, O; Briat, M; Ross, B; Thfoin, I; Philippe, F; Casner, A; Bourgade, J L; Disdier, L; Glebov, V Yu; Marshall, F J; Sangster, T C; Park, H S; Robey, H F; Amendt, P

    2012-10-01

    We have developed a new small neutron imaging system (SNIS) diagnostic for the OMEGA laser facility. The SNIS uses a penumbral coded aperture and has been designed to record images from low yield (10(9)-10(10) neutrons) implosions such as those using deuterium as the fuel. This camera was tested at OMEGA in 2009 on a rugby hohlraum energetics experiment where it recorded an image at a yield of 1.4 10(10). The resolution of this image was 54 ?m and the camera was located only 4 meters from target chamber centre. We recently improved the instrument by adding a cooled CCD camera. The sensitivity of the new camera has been fully characterized using a linear accelerator and a (60)Co ?-ray source. The calibration showed that the signal-to-noise ratio could be improved by using raw binning detection. PMID:23126952

  14. Genome-wide synteny through highly sensitive sequence alignment: Satsuma

    PubMed Central

    Grabherr, Manfred G.; Russell, Pamela; Meyer, Miriah; Mauceli, Evan; Alföldi, Jessica; Di Palma, Federica; Lindblad-Toh, Kerstin

    2010-01-01

    Motivation: Comparative genomics heavily relies on alignments of large and often complex DNA sequences. From an engineering perspective, the problem here is to provide maximum sensitivity (to find all there is to find), specificity (to only find real homology) and speed (to accommodate the billions of base pairs of vertebrate genomes). Results: Satsuma addresses all three issues through novel strategies: (i) cross-correlation, implemented via fast Fourier transform; (ii) a match scoring scheme that eliminates almost all false hits; and (iii) an asynchronous ‘battleship’-like search that allows for aligning two entire fish genomes (470 and 217 Mb) in 120 CPU hours using 15 processors on a single machine. Availability: Satsuma is part of the Spines software package, implemented in C++ on Linux. The latest version of Spines can be freely downloaded under the LGPL license from http://www.broadinstitute.org/science/programs/genome-biology/spines/ Contact: grabherr@broadinstitute.org PMID:20208069

  15. Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection

    PubMed Central

    Bale, Shyam Sundhar; Bhushan, Abhinav; Shen, Keyue; Seker, Erkin; Polyak, Boris

    2014-01-01

    There is a growing need for diagnostic technologies that provide laboratories with solutions that improve quality, enhance laboratory system productivity, and provide accurate detection of a broad range of infectious diseases and cancers. Recent advances in micro- and nanoscience and engineering, in particular in the areas of particles and microfluidic technologies, have advanced the “lab-on-a-chip” concept towards the development of a new generation of point-of-care diagnostic devices that could significantly enhance test sensitivity and speed. In this review, we will discuss many of the recent advances in microfluidics and particle technologies with an eye towards merging these two technologies for application in medical diagnostics. Although the potential diagnostic applications are virtually unlimited, the most important applications are foreseen in the areas of biomarker research, cancer diagnosis, and detection of infectious microorganisms. PMID:25378716

  16. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    SciTech Connect

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

    2008-09-15

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD{sub 10} dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-{alpha}, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 {+-} 14.0 nmol/min/g heart in ND versus 400.2 {+-} 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-{alpha}2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3 pathway.

  17. Highly sensitive glucose biosensor based on Au-Ni coaxial nanorod array having high aspect ratio.

    PubMed

    Hsu, Che-Wei; Wang, Gou-Jen

    2014-06-15

    An effective glucose biosensor requires a sufficient amount of GOx immobilizing on the electrode surface. An electrode of a 3D nanorod array, having a larger surface-to-volume ratio than a 2D nanostructure, can accommodate more GOx molecules to immobilize onto the surface of the nanorods. In this study, a highly sensitive Au-Ni coaxial nanorod array electrode fabricated through the integration of nano electroforming and immersion gold (IG) method for glucose detection was developed. The average diameter of the as-synthesized Ni nanorods and that of the Au-Ni nanorods were estimated to be 150 and 250 nm, respectively; both had a height of 30 μm. The aspect ratio was 120. Compared to that of a flat Au electrode, the effective sensing area was enhanced by 79.8 folds. Actual glucose detections demonstrated that the proposed Au-Ni coaxial nanorod array electrode could operate in a linear range of 27.5 μM-27.5mM with a detection limit of 5.5μM and a very high sensitivity of 769.6 μA mM(-1)cm(-2). Good selectivity of the proposed sensing device was verified by sequential injections of uric acid (UA) and ascorbic acid (AA). Long-term stability was examined through successive detections over a period of 30 days. PMID:24495482

  18. Development of highly sensitive sensor system for methane utilizing cataluminescence.

    PubMed

    Gong, Gu; Zhu, Hua

    2016-02-01

    A gaseous sensor system was developed for the detection of methane based on its cataluminescence emission. Cataluminescence characteristics and optimal conditions were studied in detail under optimized experimental conditions. Results showed that the methane cataluminescence sensor system could cover a linear detection range from 10 to 5800 ppm (R = 0.9963, n = 7) and the detection limit was about 7 ppm (S/N = 3), which was below the standard permitted concentration. Moreover, a linear discriminant analysis method was used to test the recognizable performance of the methane sensor. It was found that methane, ethane, propane and pentane could be distinguished clearly. Its methane sensing properties, including improved sensitivity, selectivity, stability and recognition demonstrated the TiO2 /SnO2 materials to be promising candidates for constructing a cataluminescence-based gas sensor that could be used for detecting explosive gas contaminants. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26014851

  19. Achieving tunable sensitivity in composite high-energy density materials

    NASA Astrophysics Data System (ADS)

    Rashkeev, Sergey; Tsyshevsky, Roman; Kuklja, Maija

    2015-06-01

    Laser irradiation provides a unique opportunity for selective, predictive, and controlled initiation of energetic materials. We propose a consistent micro-scale mechanism of photoexcitation at the interface, formed by a molecular energetic material and a metal oxide. A specific PETN-MgO model composite is used to illustrate and explain seemingly puzzling experiments on selective laser initiation of energetic materials, which reported that the presence of metal oxide additives triggered the photoinitiation by an unusually low energy. We suggest that PETN photodecomposition is catalyzed by oxygen vacancies (F0 centers) at the MgO surface. The proposed model suggests ways to tune sensitivity of energetic molecular materials to photoinitiation. Our quantum-chemical calculations suggest that the structural defects (e.g., oxygen vacancies) strongly interact with the molecular material (e.g., adsorbed energetic molecules) by inducing a charge transfer at the interface and hence play an imperative role in governing both energy absorption and energy release in the system. Our approach and conclusions provide a solid basis for novel design of energetic interfaces with desired properties and offers a new perspective in the field of explosive materials and devices.

  20. On-line parameter estimation using a high sensitivity estimator

    NASA Technical Reports Server (NTRS)

    Mishne, D.; Bryson, A. E., Jr.

    1978-01-01

    An on-line parameter identification method is presented. The method is based on a recursive formulation of the maximum likelihood method, with a significant modification on the gains of the state estimator. In the conventional maximum likelihood method, the Kalman gains are used in the state estimator. This produces unbiased, minimum variance parameter estimates in the presence of process noise and measurement noise, but it also slows the convergence rate when the identification is done on-line. Here we suggest choosing the gains to maximize a measure of the sensitivities of the state estimates to parameter variations. One such criterion is to minimize the trace of the inverse information matrix. This increases the convergence rate significantly. After one or two time constants, the gains are switched to the Kalman values to assure unbiased, minimum-variance estimates. The state estimate will initially be nonoptimal, and may not be adequate for control purposes. In this case, a parallel Kalman filter which uses the identifier's parameter estimates can be used. This method is applied here for the identification of a simple first-order system, and for the identification of short-period stability derivatives of an F-8 aircraft from simulated data.

  1. High sensitivity capacitive MEMS microphone with spring supported diaphragm

    NASA Astrophysics Data System (ADS)

    Mohamad, Norizan; Iovenitti, Pio; Vinay, Thurai

    2007-12-01

    Capacitive microphones (condenser microphones) work on a principle of variable capacitance and voltage by the movement of its electrically charged diaphragm and back plate in response to sound pressure. There has been considerable research carried out to increase the sensing performance of microphones while reducing their size to cater for various modern applications such as mobile communication and hearing aid devices. This paper reviews the development and current performance of several condenser MEMS microphone designs, and introduces a microphone with spring supported diaphragm to further improve condenser microphone performance. The numerical analysis using Coventor FEM software shows that this new microphone design has a higher mechanical sensitivity compared to the existing edge clamped flat diaphragm condenser MEMS microphone. The spring supported diaphragm is shown to have a flat frequency response up to 7 kHz and more stable under the variations of the diaphragm residual stress. The microphone is designed to be easily fabricated using the existing silicon fabrication technology and the stability against the residual stress increases its reproducibility.

  2. Highly sensitive Taqman PCR detection of Puumala hantavirus.

    PubMed

    Garin, D; Peyrefitte, C; Crance, J M; Le Faou, A; Jouan, A; Bouloy, M

    2001-07-01

    An increasing number of clinical cases of Hantavirus infections have been reported from various regions in Asia, Europe and North America. Hantaviruses (family Bunyaviridae, genus Hantavirus) are enveloped and possess a single-stranded trisegmented RNA genome of negative polarity. Rodents or insectivores are natural hosts of hantaviruses and transmit the virus to humans chiefly by aerosolisation. These viruses are the causative agents of haemorrhagic fever with renal and pulmonary syndromes. In the northeast of France, Puumala hantavirus causes, every year, more than 150 mild forms of haemorrhagic fever with a renal syndrome known as nephropathia epidemica. Serological tests may lack sensitivity for diagnosing early stages of infection and virus isolation is limited because it grows poorly in cell culture. Since reverse transcription (RT)-PCR amplification is an efficient method for detecting viral genomes in patient specimens, we developed an assay using a Taqman probe and compared it with the classical RT-PCR amplification. To achieve this goal, a Puumala strain was grown in Vero E6 cells and RNA extracted from the culture supernatant. We found that the semi-nested RT-PCR detected a minimal amount of 300 TCID(50) mL(-1), while the Taqman PCR allowed detection of less than 10 TCID(50) mL(-1 )and provided a quantitative analysis. PMID:11489422

  3. Highly sensitive homogenous chemiluminescence immunoassay using gold nanoparticles as label

    NASA Astrophysics Data System (ADS)

    Luo, Jing; Cui, Xiang; Liu, Wei; Li, Baoxin

    2014-10-01

    Homogeneous immunoassay is becoming more and more attractive for modern medical diagnosis because it is superior to heterogeneous immunoassay in sample and reagent consumption, analysis time, portability and disposability. Herein, a universal platform for homogeneous immunoassay, using human immunoglobulin G (IgG) as a model analyte, has been developed. This assay relies upon the catalytic activity of gold nanoparticles (AuNPs) on luminol-AgNO3 chemiluminescence (CL) reaction. The immunoreaction of antigen and antibody can induce the aggregation of antibody-functionalized AuNPs, and after aggregation the catalytic activity of AuNPs on luminol-AgNO3 CL reaction is greatly enhanced. Without any separation steps, a CL signal is generated upon addition of a trigger solution, and the CL intensity is directly correlated to the quantity of IgG. The detection limit of IgG was estimated to be as low as 3 pg/mL, and the sensitivity was better than that of the reported AuNPs-based CL immunoassay for IgG.

  4. Highly sensitive self-complementary DNA nanoswitches triggered by polyelectrolytes

    NASA Astrophysics Data System (ADS)

    Wu, Jincai; Yu, Feng; Zhang, Zheng; Chen, Yong; Du, Jie; Maruyama, Atsushi

    2015-12-01

    Dimerization of two homologous strands of genomic DNA/RNA is an essential feature of retroviral replication. Herein we show that a cationic comb-type copolymer (CCC), poly(l-lysine)-graft-dextran, accelerates the dimerization of self-complementary stem-loop DNA, frequently found in functional DNA/RNA molecules, such as aptamers. Furthermore, an anionic polymer poly(sodium vinylsulfonate) (PVS) dissociates CCC from the duplex shortly within a few seconds. Then single stem-loop DNA spontaneously transforms from its dimer. Thus we can easily control the dimer and stem-loop DNA by switching on/off CCC activity. Both polyelectrolytes and DNA concentrations are in the nanomole per liter range. The polyelectrolyte-assisted transconformation and sequences design strategy ensures the reversible state control with rapid response and effective switching under physiologically relevant conditions. A further application of this sensitive assembly is to construct an aptamer-type drug delivery system, bind or release functional molecules responding to its transconformation.Dimerization of two homologous strands of genomic DNA/RNA is an essential feature of retroviral replication. Herein we show that a cationic comb-type copolymer (CCC), poly(l-lysine)-graft-dextran, accelerates the dimerization of self-complementary stem-loop DNA, frequently found in functional DNA/RNA molecules, such as aptamers. Furthermore, an anionic polymer poly(sodium vinylsulfonate) (PVS) dissociates CCC from the duplex shortly within a few seconds. Then single stem-loop DNA spontaneously transforms from its dimer. Thus we can easily control the dimer and stem-loop DNA by switching on/off CCC activity. Both polyelectrolytes and DNA concentrations are in the nanomole per liter range. The polyelectrolyte-assisted transconformation and sequences design strategy ensures the reversible state control with rapid response and effective switching under physiologically relevant conditions. A further application of this sensitive assembly is to construct an aptamer-type drug delivery system, bind or release functional molecules responding to its transconformation. Electronic supplementary information (ESI) available: I. Sequences of DIS25, DIS25-2a and DIS25-3a. II. Structural formula of poly(l-lysine)-graft-dextran (PLL-g-Dex). 1H-NMR spectra of PLL-g-Dex in D2O. III. Gel electrophoretic analysis of dimerization of DIS25 with various N/P ratios. IV. The effect of polyelectrolyte on the fluorescence polarity of TAMRA-labeled duplex. V. UV absorption/Tm profiles of DIS25. VI. Arrhenius plots for spontaneous dissociation of the DIS25 dimer and PLL-g-Dex-assisted dimerization of DIS25.VII. Switching between double stem-loop DIS42 and extended multiplex drived by PLL-g-Dex and PVS. See DOI: 10.1039/c5nr05193b

  5. High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

    PubMed Central

    Hahn, Juliane; Seeber, Frank; Kolodziej, Herbert; Ignatius, Ralf; Laue, Michael; Aebischer, Toni; Klotz, Christian

    2013-01-01

    Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment failure rates of up to 20 percent reflect the compelling need for alternative treatment options. Here, we investigated whether orlistat, a drug approved to treat obesity, represents a potential therapeutic agent against giardiasis. We compared the growth inhibitory effects of orlistat and MTZ on a long-term in vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14-03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The giardiacidal concentration of the drugs and their combined in vitro efficacy was determined by median-effect analysis. Morphological changes after treatment were analysed by light and electron microscopy. Orlistat inhibited the in vitro growth of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7 (IC5024h = 2.8 µM) being more sensitive than WB-C6 (IC5024h = 6.2 µM). The effect was significantly more potent compared to MTZ (IC5024h = 4.3 µM and 11.0 µM, respectively) and led to specific undulated morphological alterations on the parasite surface. The giardiacidal concentration of orlistat was >14 µM for 14-03/F7 and >43 µM for WB-C6, respectively. Importantly, the combination of both drugs revealed no interaction on their inhibitory effects. We demonstrate that orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills parasites at concentrations achievable in the gut by approved treatment regimens for obesity. We therefore propose to investigate orlistat in controlled clinical studies as a new drug in giardiasis. PMID:23977083

  6. Highly sensitive phototransistor based on GaSe nanosheets

    NASA Astrophysics Data System (ADS)

    Huang, Hai; Wang, Peng; Gao, Yanqing; Wang, Xudong; Lin, Tie; Wang, Jianlu; Liao, Lei; Sun, Jinglan; Meng, Xiangjian; Huang, Zhiming; Chen, Xiaoshuang; Chu, Junhao

    2015-10-01

    Phototransistors based on two dimensional semiconductors have drawn increasing attention in recent years. GaSe is a typical semiconductor with a layered structure. In this work, the ultrathin GaSe nanosheets were exfoliated from commercially available crystals using a micromechanical cleavage technique. Then, the nanosheets were used to fabricate field effect transistors (FETs) on Si/SiO2 substrates with interdigitated electrodes. The electrical and optoelectronic properties of the FET were characterized. The phototransistor based on a GaSe nanosheet had a high photoresponsivity (˜2200 mA/W) and a high Iphoto/Idark (photoresponse current over dark current) ratio of almost 103.

  7. Highly sensitive vacuum ion pump current measurement system

    DOEpatents

    Hansknecht, John Christopher

    2006-02-21

    A vacuum system comprising: 1) an ion pump; 2) power supply; 3) a high voltage DC--DC converter drawing power from the power supply and powering the vacuum pump; 4) a feedback network comprising an ammeter circuit including an operational amplifier and a series of relay controlled scaling resistors of different resistance for detecting circuit feedback; 5) an optional power block section intermediate the power supply and the high voltage DC--DC converter; and 6) a microprocessor receiving feedback information from the feedback network, controlling which of the scaling resistors should be in the circuit and manipulating data from the feedback network to provide accurate vacuum measurement to an operator.

  8. UNCERTAINTY AND SENSITIVITY ANALYSES FOR VERY HIGH ORDER MODELS

    EPA Science Inventory

    While there may in many cases be high potential for exposure of humans and ecosystems to chemicals released from a source, the degree to which this potential is realized is often uncertain. Conceptually, uncertainties are divided among parameters, model, and modeler during simula...

  9. Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice.

    PubMed

    Le Bouter, Sabrina; Rodriguez, Marianne; Guigal-Stephan, Nolwen; Courtade-Gaïani, Sophie; Xuereb, Laura; de Montrion, Catherine; Croixmarie, Vincent; Umbdenstock, Thierry; Boursier-Neyret, Claire; Lonchampt, Michel; Brun, Manuel; Dacquet, Catherine; Ktorza, Alain; Lockhart, Brian-Paul; Galizzi, Jean-Pierre

    2010-01-01

    Rosiglitazone (RSG), developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d) with untreated non-diabetic littermates (db/+). For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT) and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs) and free fatty acids (FFAs)) in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues. PMID:20953342

  10. PCF Based Sensor with High Sensitivity, High Birefringence and Low Confinement Losses for Liquid Analyte Sensing Applications.

    PubMed

    Ademgil, Huseyin; Haxha, Shyqyri

    2015-01-01

    In this paper, we report a design of high sensitivity Photonic Crystal Fiber (PCF) sensor with high birefringence and low confinement losses for liquid analyte sensing applications. The proposed PCF structures are designed with supplementary elliptical air holes in the core region vertically-shaped V-PCF and horizontally-shaped H-PCF. The full vectorial Finite Element Method (FEM) simulations performed to examine the sensitivity, the confinement losses, the effective refractive index and the modal birefringence features of the proposed elliptical air hole PCF structures. We show that the proposed PCF structures exhibit high relative sensitivity, high birefringence and low confinement losses simultaneously for various analytes. PMID:26694408

  11. PCF Based Sensor with High Sensitivity, High Birefringence and Low Confinement Losses for Liquid Analyte Sensing Applications

    PubMed Central

    Ademgil, Huseyin; Haxha, Shyqyri

    2015-01-01

    In this paper, we report a design of high sensitivity Photonic Crystal Fiber (PCF) sensor with high birefringence and low confinement losses for liquid analyte sensing applications. The proposed PCF structures are designed with supplementary elliptical air holes in the core region vertically-shaped V-PCF and horizontally-shaped H-PCF. The full vectorial Finite Element Method (FEM) simulations performed to examine the sensitivity, the confinement losses, the effective refractive index and the modal birefringence features of the proposed elliptical air hole PCF structures. We show that the proposed PCF structures exhibit high relative sensitivity, high birefringence and low confinement losses simultaneously for various analytes. PMID:26694408

  12. The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions

    PubMed Central

    Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L

    2014-01-01

    Background Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. Methods This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Results Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). Conclusions As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits. PMID:25161824

  13. Highly sensitive multichannel spectrometer for subpicosecond spectroscopy in the midinfrared.

    PubMed

    Hamm, P; Wiemann, S; Zurek, M; Zinth, W

    1994-10-15

    A spectrometer system is presented for time-resolved probing in the midinfrared between 5 and 11 microm with a temporal resolution of better than 400 fs. Multichannel detection with HgCdTe detector arrays consisting of ten elements in combination with a high repetition rate permits one to record weak absorbance changes with an accuracy of 0.1 mOD. PMID:19855608

  14. Silicon nanowire structures as high-sensitive pH-sensors

    NASA Astrophysics Data System (ADS)

    Belostotskaya, S. O.; Chuyko, O. V.; Kuznetsov, A. E.; Kuznetsov, E. V.; Rybachek, E. N.

    2012-02-01

    Sensitive elements for pH-sensors created on silicon nanostructures were researched. Silicon nanostructures have been used as ion-sensitive field effect transistor (ISFET) for the measurement of solution pH. Silicon nanostructures have been fabricated by "top-down" approach and have been studied as pH sensitive elements. Nanowires have the higher sensitivity. It was shown, that sensitive element, which is made of "one-dimensional" silicon nanostructure have bigger pH-sensitivity as compared with "two-dimensional" structure. Integrated element formed from two p- and n-type nanowire ISFET ("inverter") can be used as high sensitivity sensor for local relative change [H+] concentration in very small volume.

  15. Differential Sensitivity Theory applied to the MESA code for high pressure interactions

    NASA Astrophysics Data System (ADS)

    Maudlin, P. J.; Henninger, R. J.; Harstad, E. N.

    A technique called Differential Sensitivity Theory (DST) is applied to the system of equations solved by the MESA hydrocode. DST uses adjoint techniques to determine exact sensitivity derivatives, i.e., if R is a calculational result of interest (response R) and alpha(sub i) is a calculational input (parameter alpha(sub i)), then (partial derivative)R/(partial derivative)alpha(sub i) is defined as the sensitivity. The advantage of using DST is that for an n-parameter problem all n sensitivities can be obtained by integrating the solutions from only two calculations, a MESA calculation and its corresponding adjoint calculation using an Adjoint Continuum Mechanics code (ACM). This work describes the derivation and solution of the appropriate set of adjoint and sensitivity equations for the purpose of computing sensitivities for high-rate two-dimensional, multi-component, high deformation problems. As an example, results are presented for a flyer plate problem.

  16. Differential Sensitivity Theory applied to the MESA code for high pressure interactions

    SciTech Connect

    Maudlin, P.J.; Henninger, R.J.; Harstad, E.N.

    1993-07-01

    A technique called Differential Sensitivity Theory (DST) is applied to the system of equations solved by the MESA hydrocode. DST uses adjoint techniques to determine exact sensitivity derivatives, i.e., if R is a calculational result of interest (response R) and {alpha}{sub i} is a calculational input (parameter {alpha}{sub i}), then {partial_derivative}R/{partial_derivative}{alpha}{sub i} is defined as the sensitivity. The advantage of using DST is that for an n-parameter problem all n sensitivities can be obtained by integrating the solutions from only two calculations, a MESA calculation and its corresponding adjoint calculation using an Adjoint Continuum Mechanics code (ACM). This work describes the derivation and solution of the appropriate set of adjoint and sensitivity equations for the purpose of computing sensitivities for high-rate two-dimensional, multi-component, high deformation problems. As an example, results are presented for a flyer plate problem.

  17. Dynamics and sensitivity analysis of high frequency conduction block

    PubMed Central

    Ackermann, D. Michael; Bhadra, Niloy; Gerges, Meana; Thomas, Peter J.

    2012-01-01

    The local delivery of extracellular high frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction, and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: 1) That depolarizing currents promote conduction block via inactivation of sodium channels, and 2) that the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in a conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high frequency stimuli of arbitrary amplitude are incapable of inducing conduction block. PMID:22056338

  18. Porous tungsten oxide nanoflakes for highly alcohol sensitive performance.

    PubMed

    Xiao, J; Liu, P; Liang, Y; Li, H B; Yang, G W

    2012-11-21

    Porous tungsten oxide (WO(3)) nanoflakes have been synthesized by a simple and green approach in an ambient environment. As a precursor solution a polycrystalline hydrated tungstite (H(2)WO(4)H(2)O) nanoparticles colloid was first prepared by pulsed-laser ablation of a tungsten target in water. The H(2)WO(4)H(2)O nanoflakes were produced by 72 h aging treatment at room temperature. Finally, porous WO(3) nanoflakes were synthesized by annealing at 800 C for 4 h. Considering the large surface-to-volume ratio of porous nanoflakes, a porous WO(3) nanoflake gas sensor was fabricated, which exhibits an excellent sensor response performance to alcohol concentrations in the range of 20 to 600 ppm under low working temperature. This high response was attributed to the highly crystalline and porous flake-like morphology, which leads to effective adsorption and desorption, and provides more active sites for the gas molecules' reaction. These findings showed that the porous tungsten oxide nanoflake has great potential in gas-sensing performance. PMID:23069859

  19. Birth Weight, Current Anthropometric Markers, and High Sensitivity C-Reactive Protein in Brazilian School Children

    PubMed Central

    Pellanda, Lucia Campos

    2015-01-01

    Studies have shown associations of birth weight with increased concentrations of high sensitivity C-reactive protein. This study assessed the relationship between birth weight, anthropometric and metabolic parameters during childhood, and high sensitivity C-reactive protein. A total of 612 Brazilian school children aged 5–13 years were included in the study. High sensitivity C-reactive protein was measured by particle-enhanced immunonephelometry. Nutritional status was assessed by body mass index, waist circumference, and skinfolds. Total cholesterol and fractions, triglycerides, and glucose were measured by enzymatic methods. Insulin sensitivity was determined by the homeostasis model assessment method. Statistical analysis included chi-square test, General Linear Model, and General Linear Model for Gamma Distribution. Body mass index, waist circumference, and skinfolds were directly associated with birth weight (P < 0.001, P = 0.001, and P = 0.015, resp.). Large for gestational age children showed higher high sensitivity C-reactive protein levels (P < 0.001) than small for gestational age. High birth weight is associated with higher levels of high sensitivity C-reactive protein, body mass index, waist circumference, and skinfolds. Large for gestational age altered high sensitivity C-reactive protein and promoted additional risk factor for atherosclerosis in these school children, independent of current nutritional status. PMID:25874126

  20. Method for rapid, high sensitivity tritiated water extraction

    SciTech Connect

    Failor, R.; Belovodsky, L.; Gaevoy, V.; Golubev, A.

    1997-04-20

    We have developed a thermal vacuum desorption process to rapidly extract water from environmental samples for tritium analysis. Thermal vacuum desorption allows for extraction of the moisture from the sample within a few hours in a form and quantity suitable for liquid scintillation counting and allows detection of tritium at the levels of <2 Bq/L of milk, <0.5 Bq/gm of vegetation, and < 0.5 Bq/gin of soil. We developed a prototype unit that can process batches of twenty or more samples within 24 hours. Early data shows that a high percentage of water is extracted reproducibly without enrichment or depletion of the tritium content. The quench coefficient of the extracted water is low allowing for accurate, direct liquid scintillation counting. Excellent comparison has been observed with results using freeze-dry lypholization as the water extraction method.

  1. High Magnetic Field Shielding for Sensitive Devices Relevant to ITER

    NASA Astrophysics Data System (ADS)

    Xia, Zhiwei; Li, Wei; Li, Bo; Yang, Qingwei; Lu, Jie

    2014-06-01

    High magnetic field shielding has been increasingly important for engineering design in recent years. In this report, a cylindric shield made from soft iron is studied using FEM (finite element method) analysis and compared with experiments. The residual fields inside the shield are calculated and measured in both parallel and perpendicular fields up to 2000 Gs. The calculated results are compared with the experiments, and the input B-H curve is modified for a better conformity. The results indicate that the covers could greatly improve the shielding performance of the cylindric shield in our research. The comparison result shows that a proper B-H curve, which can well describe the material properties, is very important in FEM analysis and should be selected carefully.

  2. (abstract) A Miniature, High-Sensitivity, Electron-Tunneling Accelerometer

    NASA Technical Reports Server (NTRS)

    Gabrielson, Thomas B.; Rockstad, Howard K.; Tang, Tony K.

    1994-01-01

    A prototype low-noise accelerometer has been fabricated with an electron-tunneling transducer. By measuring the tunneling current between an electrode on the proof mass and a feedback-controlled monitor electrode, very small accelerations can be detected with high responsivity. This particular prototype (10x10x1.5 mm) was designed for underwater acoustic measurement from a few hertz to 1 kHz. The measured responsivity below the fundamental device resonance at 100 Hz is roughly 1500 volts per m/s(sup 2) with a measured noise spectral density of 10(sup -6) m/s(sup 2) per root hertz or less between 30 and 300 Hz. The noise floor is controlled primarily by 1/f noise in the tunneling current although the noise floor reaches the theoretical molecular-agitation limit at 100 hertz. The responsivity and directivity of the device were measured in a standard gradient-hydrophone calibrator; the noise floor was determined in a vacuum-ionization chamber assembled from commercial off-the-shelf components; and the detailed dynamics of the proof-mass motion were examined using a heterodyne laser interferometer that was scanned across the surface and synchronously detected with respect to the excitation.

  3. BCN nanotubes as highly sensitive torsional electromechanical transducers.

    PubMed

    Garel, Jonathan; Zhao, Chong; Popovitz-Biro, Ronit; Golberg, Dmitri; Wang, Wenlong; Joselevich, Ernesto

    2014-11-12

    Owing to their mechanically tunable electronic properties, carbon nanotubes (CNTs) have been widely studied as potential components for nanoelectromechanical systems (NEMS); however, the mechanical properties of multiwall CNTs are often limited by the weak shear interactions between the graphitic layers. Boron nitride nanotubes (BNNTs) exhibit a strong interlayer mechanical coupling, but their high electrical resistance limits their use as electromechanical transducers. Can the outstanding mechanical properties of BNNTs be combined with the electromechanical properties of CNTs in one hybrid structure? Here, we report the first experimental study of boron carbonitride nanotube (BCNNT) mechanics and electromechanics. We found that the hybrid BCNNTs are up to five times torsionally stiffer and stronger than CNTs, thereby retaining to a large extent the ultrahigh torsional stiffness of BNNTs. At the same time, we show that the electrical response of BCNNTs to torsion is 1 to 2 orders of magnitude higher than that of CNTs. These results demonstrate that BCNNTs could be especially attractive building blocks for NEMS. PMID:25275220

  4. Enhanced Laboratory Sensitivity to Variation of the Fine-Structure Constant using Highly Charged Ions

    SciTech Connect

    Berengut, J. C.; Dzuba, V. A.; Flambaum, V. V.

    2010-09-17

    We study atomic systems that are in the frequency range of optical atomic clocks and have enhanced sensitivity to potential time variation of the fine-structure constant {alpha}. The high sensitivity is due to coherent contributions from three factors: high nuclear charge Z, high ionization degree, and significant differences in the configuration composition of the states involved. Configuration crossing keeps the frequencies in the optical range despite the large ionization energies. We discuss a few promising examples that have the largest {alpha} sensitivities seen in atomic systems.

  5. Draft Genome Sequence of Streptomyces fradiae ATCC 19609, a Strain Highly Sensitive to Antibiotics

    PubMed Central

    Klimina, Ksenia M.; Vatlin, Aleksey A.; Zakharevich, Natalia V.; Kasianov, Artem S.

    2014-01-01

    We report here a sequence of the genome of the Streptomyces fradiae ATCC 19609 strain, initially isolated from the soil, which produces tylosin. S. fradiae is highly sensitive to different classes of antibiotics, compared to the sensitivities of other bacteria. We have identified 9 groups of genes directly or indirectly involved in the resistome formation. PMID:25477406

  6. Reward Sensitivity and Substance Abuse in Middle School and High School Students

    ERIC Educational Resources Information Center

    Genovese, Jeremy E. C.; Wallace, Deborah

    2007-01-01

    In this study, the authors investigated the relation between reward and punishment sensitivity and adolescent substance use. The sample (N = 216; 130 girls, 85 boys) was drawn from high school and middle school students enrolled in a Midwestern suburban school district. Participants completed a substance use questionnaire and the Sensitivity to

  7. A highly sensitive colorimetric metalloimmunoassay based on copper-mediated etching of gold nanorods.

    PubMed

    Cheng, Fangbin; Chen, Zhaopeng; Zhang, Zhiyang; Chen, Lingxin

    2016-03-01

    A highly sensitive colorimetric metalloimmunoassay with a detection limit of 0.15 ng ml(-1) for human IgG based on copper-mediated etching of gold nanorods was proposed. The assay is more sensitive than traditional ELISA, electrochemical metalloimmunoassay and HRP mimic nanomaterial tag-based immunoassay. PMID:26911421

  8. Reward Sensitivity and Substance Abuse in Middle School and High School Students

    ERIC Educational Resources Information Center

    Genovese, Jeremy E. C.; Wallace, Deborah

    2007-01-01

    In this study, the authors investigated the relation between reward and punishment sensitivity and adolescent substance use. The sample (N = 216; 130 girls, 85 boys) was drawn from high school and middle school students enrolled in a Midwestern suburban school district. Participants completed a substance use questionnaire and the Sensitivity to…

  9. Draft Genome Sequence of Streptomyces fradiae ATCC 19609, a Strain Highly Sensitive to Antibiotics.

    PubMed

    Bekker, Olga B; Klimina, Ksenia M; Vatlin, Aleksey A; Zakharevich, Natalia V; Kasianov, Artem S; Danilenko, Valery N

    2014-01-01

    We report here a sequence of the genome of the Streptomyces fradiae ATCC 19609 strain, initially isolated from the soil, which produces tylosin. S. fradiae is highly sensitive to different classes of antibiotics, compared to the sensitivities of other bacteria. We have identified 9 groups of genes directly or indirectly involved in the resistome formation. PMID:25477406

  10. Hypoxia-sensitive reporter system for high-throughput screening.

    PubMed

    Tsujita, Tadayuki; Kawaguchi, Shin-ichi; Dan, Takashi; Baird, Liam; Miyata, Toshio; Yamamoto, Masayuki

    2015-01-01

    The induction of anti-hypoxic stress enzymes and proteins has the potential to be a potent therapeutic strategy to prevent the progression of ischemic heart, kidney or brain diseases. To realize this idea, small chemical compounds, which mimic hypoxic conditions by activating the PHD-HIF-α system, have been developed. However, to date, none of these compounds were identified by monitoring the transcriptional activation of hypoxia-inducible factors (HIFs). Thus, to facilitate the discovery of potent inducers of HIF-α, we have developed an effective high-throughput screening (HTS) system to directly monitor the output of HIF-α transcription. We generated a HIF-α-dependent reporter system that responds to hypoxic stimuli in a concentration- and time-dependent manner. This system was developed through multiple optimization steps, resulting in the generation of a construct that consists of the secretion-type luciferase gene (Metridia luciferase, MLuc) under the transcriptional regulation of an enhancer containing 7 copies of 40-bp hypoxia responsive element (HRE) upstream of a mini-TATA promoter. This construct was stably integrated into the human neuroblastoma cell line, SK-N-BE(2)c, to generate a reporter system, named SKN:HRE-MLuc. To improve this system and to increase its suitability for the HTS platform, we incorporated the next generation luciferase, Nano luciferase (NLuc), whose longer half-life provides us with flexibility for the use of this reporter. We thus generated a stably transformed clone with NLuc, named SKN:HRE-NLuc, and found that it showed significantly improved reporter activity compared to SKN:HRE-MLuc. In this study, we have successfully developed the SKN:HRE-NLuc screening system as an efficient platform for future HTS. PMID:25746387

  11. Confidence Level and Sensitivity Limits in High Contrast Imaging

    SciTech Connect

    Marois, C

    2007-11-07

    In long adaptive optics corrected exposures, exoplanet detections are currently limited by speckle noise originating from the telescope and instrument optics, and it is expected that such noise will also limit future high-contrast imaging instruments for both ground and space-based telescopes. Previous theoretical analysis have shown that the time intensity variations of a single speckle follows a modified Rician. It is first demonstrated here that for a circular pupil this temporal intensity distribution also represents the speckle spatial intensity distribution at a fix separation from the point spread function center; this fact is demonstrated using numerical simulations for coronagraphic and non-coronagraphic data. The real statistical distribution of the noise needs to be taken into account explicitly when selecting a detection threshold appropriate for some desired confidence level. In this paper, a technique is described to obtain the pixel intensity distribution of an image and its corresponding confidence level as a function of the detection threshold. Using numerical simulations, it is shown that in the presence of speckles noise, a detection threshold up to three times higher is required to obtain a confidence level equivalent to that at 5{sigma} for Gaussian noise. The technique is then tested using TRIDENT CFHT and angular differential imaging NIRI Gemini adaptive optics data. It is found that the angular differential imaging technique produces quasi-Gaussian residuals, a remarkable result compared to classical adaptive optic imaging. A power-law is finally derived to predict the 1-3 x 10{sup -7} confidence level detection threshold when averaging a partially correlated non-Gaussian noise.

  12. Confidence Level and Sensitivity Limits in High Contrast Imaging

    SciTech Connect

    Marois, C; LaFreniere, D; Macintosh, B; Doyon, R

    2008-06-02

    In long adaptive optics corrected exposures, exoplanet detections are currently limited by speckle noise originating from the telescope and instrument optics, and it is expected that such noise will also limit future high-contrast imaging instruments for both ground and space-based telescopes. Previous theoretical analysis have shown that the time intensity variations of a single speckle follows a modified Rician. It is first demonstrated here that for a circular pupil this temporal intensity distribution also represents the speckle spatial intensity distribution at a fix separation from the point spread function center; this fact is demonstrated using numerical simulations for coronagraphic and non-coronagraphic data. The real statistical distribution of the noise needs to be taken into account explicitly when selecting a detection threshold appropriate for some desired confidence level. In this paper, a technique is described to obtain the pixel intensity distribution of an image and its corresponding confidence level as a function of the detection threshold. Using numerical simulations, it is shown that in the presence of speckles noise, a detection threshold up to three times higher is required to obtain a confidence level equivalent to that at 5{sigma} for Gaussian noise. The technique is then tested using TRIDENT CFHT and angular differential imaging NIRI Gemini adaptive optics data. It is found that the angular differential imaging technique produces quasi-Gaussian residuals, a remarkable result compared to classical adaptive optic imaging. A power-law is finally derived to predict the 1-3 x 10{sup -7} confidence level detection threshold when averaging a partially correlated non-Gaussian noise.

  13. Confidence Level and Sensitivity Limits in High-Contrast Imaging

    NASA Astrophysics Data System (ADS)

    Marois, Christian; Lafrenière, David; Macintosh, Bruce; Doyon, René

    2008-01-01

    In long adaptive optics corrected exposures, exoplanet detections are currently limited by speckle noise originating from the telescope and instrument optics, and it is expected that such noise will also limit future high-contrast imaging instruments for both ground- and space-based telescopes. Previous theoretical analyses have shown that the time intensity variations of a single speckle follow a modified Rician. It is first demonstrated here that for a circular pupil, this temporal intensity distribution also represents the speckle spatial intensity distribution at a fixed separation from the point-spread function center; this fact is demonstrated using numerical simulations for coronagraphic and noncoronagraphic data. The real statistical distribution of the noise needs to be taken into account explicitly when selecting a detection threshold appropriate for some desired confidence level (CL). In this paper, a technique is described to obtain the pixel intensity distribution of an image and its corresponding CL as a function of the detection threshold. Using numerical simulations, it is shown that in the presence of speckle noise, a detection threshold up to 3 times higher is required to obtain a CL equivalent to that at 5 σ for Gaussian noise. The technique is then tested on data acquired by simultaneous spectral differential imaging with TRIDENT and by angular differential imaging with NIRI. It is found that the angular differential imaging technique produces quasi-Gaussian residuals, a remarkable result compared to classical adaptive optic imaging. Finally, a power law is derived to predict the 1 - 3 × 10-7 CL detection threshold when averaging a partially correlated non-Gaussian noise. Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT), which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii. Also based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Particle Physics and Astronomy Research Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), CNPq (Brazil), and CONICET (Argentina).

  14. High-sensitivity strain sensor based on in-fiber improved Fabry-Perot interferometer.

    PubMed

    Liu, Shen; Wang, Yiping; Liao, Changrui; Wang, Guanjun; Li, Zhengyong; Wang, Qiao; Zhou, Jiangtao; Yang, Kaiming; Zhong, Xiaoyong; Zhao, Jing; Tang, Jian

    2014-04-01

    We demonstrated a high-sensitivity strain sensor based on an in-fiber Fabry-Perot interferometer (FPI) with an air cavity, which was created by splicing together two sections of standard single-mode fibers. The sensitivity of this strain sensor was enhanced to 6.0  pm/με by improving the cavity length of the FPI by means of repeating arc discharges for reshaping the air cavity. Moreover, such a strain sensor has a very low temperature sensitivity of 1.1  pm/°C, which reduces the cross sensitivity between tensile strain and temperature. PMID:24686690

  15. Chemometric analysis of urine fingerprints acquired by liquid chromatography-mass spectrometry and capillary electrophoresis: application to the schistosomiasis mouse model.

    PubMed

    Garcia-Perez, Isabel; Earll, Marc E; Angulo, Santiago; Barbas, Coral; Legido-Quigley, Cristina

    2010-07-01

    Urine fingerprints from Schistosoma mansoni infected and control animals were acquired with ultra performance liquid chromatography-MS (UPLC-MS) and compared with the urine fingerprints obtained by CE by applying the same set of multivariate analysis tools. Principal component analysis of the aligned data provided a time trajectory where the infection was observed after 30 days with UPLC-MS and CE. Two main markers describing infected and control, respectively - phenyl acetyl glycine (PAG) and hippurate - were selected to illustrate the use of orthogonal partial least-square discriminant analysis in determining the discriminatory confidence. PAG was found to be significantly related to the disease (high covariance and correlation), whereas hippurate was found to be nonsignificant as an indicator. Orthogonal partial least-square discriminant analysis models were validated for sensitivity and specificity. Multivariate data analysis derived from two different detection systems showed that CE-UV and UPLC-MS found equivalent results. This work gives additional mechanistic insight into the progress of the S. mansoni infection; the biochemical role and specificity of PAG as a biomarker is yet to be determined. PMID:20575107

  16. A highly sensitive high-throughput luminescence assay for malonyl-CoA decarboxylase.

    PubMed

    Lo, Mei-Chu; Wang, Minghan; Kim, Ki Won; Busby, James; Yamane, Harvey; Zondlo, James; Yuan, Chester; Young, Stephen W; Xiao, Shou-Hua

    2008-05-01

    Malonyl-CoA decarboxylase (MCD) catalyzes the conversion of malonyl-CoA to acetyl-CoA and thereby regulates malonyl-CoA levels in cells. Malonyl-CoA is a potent inhibitor of mitochondrial carnitine palmitoyltransferase-1, a key enzyme involved in the mitochondrial uptake of fatty acids for oxidation. Abnormally high rates of fatty acid oxidation contribute to ischemic damage. Inhibition of MCD leads to increased malonyl-CoA and therefore decreases fatty acid oxidation, representing a novel approach for the treatment of ischemic heart injury. The commonly used MCD assay monitors the production of NADH fluorometrically, which is not ideal for library screening due to potential fluorescent interference by certain compounds. Here we report a luminescence assay for MCD activity. This assay is less susceptible to fluorescent interference by compounds. Furthermore, it is 150-fold more sensitive, with a detection limit of 20 nM acetyl-CoA, compared to 3 muM in the fluorescence assay. This assay is also amenable to automation for high-throughput screening and yields excellent assay statistics (Z' > 0.8). In addition, it can be applied to the screening for inhibitors of any other enzymes that generate acetyl-CoA. PMID:18294446

  17. Development and validation of sensitive LC-MS/MS assays for quantification of HP-β-CD in human plasma and CSF

    PubMed Central

    Jiang, Hui; Sidhu, Rohini; Fujiwara, Hideji; De Meulder, Marc; de Vries, Ronald; Gong, Yong; Kao, Mark; Porter, Forbes D.; Yanjanin, Nicole M.; Carillo-Carasco, Nuria; Xu, Xin; Ottinger, Elizabeth; Woolery, Myra; Ory, Daniel S.; Jiang, Xuntian

    2014-01-01

    2-Hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used excipient for drug formulation, has emerged as an investigational new drug for the treatment of Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the pharmacokinetics (PKs) of HP-β-CD required for clinical trials has been challenging owing to the dispersity of the HP-β-CD. To support a phase 1 clinical trial for ICV delivery of HP-β-CD in NPC1 patients, novel methods for quantification of HP-β-CD in human plasma and cerebrospinal fluid (CSF) using LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D-LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC-MS/MS) assay. In both assays, protein precipitation and “dilute and shoot” procedures were used to process plasma and CSF, respectively. The assays were fully validated and in close agreement, and allowed determination of PK parameters for HP-β-CD. The LC-MS/MS methods are ∼100-fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP-β-CD in human plasma and CSF samples to support the phase 1 clinical trial of HP-β-CD in NPC1 patients. PMID:24868096

  18. HIGH SENSITIVITY FOURIER TRANSFORM NMR. INTERMOLECULAR INTERACTIONS BETWEEN ENVIRONMENTAL TOXIC SUBSTANCES AND BIOLOGICAL MACROMOLECULES

    EPA Science Inventory

    This project explored the feasibility of developing new techniques for evaluation of the effects of environmental toxic materials on complex biopolymer systems using high sensitivity Fourier transform nuclear magnetic resonance (nmr) spectroscopy. Commercial instrumentation avail...

  19. Hybrid nanostructures for high-sensitivity luminescence nanothermometry in the second biological window.

    PubMed

    Cerón, Elizabeth Navarro; Ortgies, Dirk H; Del Rosal, Blanca; Ren, Fuqiang; Benayas, Antonio; Vetrone, Fiorenzo; Ma, Dongling; Sanz-Rodríguez, Francisco; Solé, José García; Jaque, Daniel; Rodríguez, Emma Martín

    2015-08-26

    Hybrid nanostructures containing neodymium-doped nanoparticles and infrared-emitting quantum dots constitute highly sensitive luminescent thermometers operating in the second biological window. They demonstrate that accurate subtissue fluorescence thermal sensing is possible. PMID:26174612

  20. Temperature insensitive hysteresis free highly sensitive polymer optical fiber Bragg grating humidity sensor.

    PubMed

    Woyessa, Getinet; Nielsen, Kristian; Stefani, Alessio; Markos, Christos; Bang, Ole

    2016-01-25

    The effect of humidity on annealing of poly (methyl methacrylate) (PMMA) based microstructured polymer optical fiber Bragg gratings (mPOFBGs) and the resulting humidity responsivity are investigated. Typically annealing of PMMA POFs is done in an oven without humidity control around 80C and therefore at low humidity. We demonstrate that annealing at high humidity and high temperature improves the performances of mPOFBGs in terms of stability and sensitivity to humidity. PMMA POFBGs that are not annealed or annealed at low humidity level will have a low and highly temperature dependent sensitivity and a high hysteresis in the humidity response, in particular when operated at high temperature. PMMA mPOFBGs annealed at high humidity show higher and more linear humidity sensitivity with negligible hysteresis. We also report how annealing at high humidity can blue-shift the FBG wavelength more than 230 nm without loss in the grating strength. PMID:26832503

  1. Tenfold improved sensitivity using high refractive-index substrates for surface plasmon sensing

    SciTech Connect

    Micheletto, Ruggero; Hamamoto, Katsumi; Fujii, Takashi; Kawakami, Yoichi

    2008-10-27

    Surface plasmon resonance sensors exploit the high sensitivity to local perturbations of plasma waves in a thin metal layer. These devices have a wide range of applications as biomedical, environmental, industrial, and homeland security. We concentrate on the theoretical aspects of the sensing principle. By calculations at various indexes of refraction we proved that using substrate material of higher index, sensitivity and dynamics range improve conspicuously. Finally, we show experimental data taken using a special transparent ceramic material of exceptionally high index of refraction n=2.04. Tests demonstrate sensitivity about one order of magnitude better than those obtained with conventional BK7 glass.

  2. High-throughput, Highly Sensitive Analyses of Bacterial Morphogenesis Using Ultra Performance Liquid Chromatography.

    PubMed

    Desmarais, Samantha M; Tropini, Carolina; Miguel, Amanda; Cava, Felipe; Monds, Russell D; de Pedro, Miguel A; Huang, Kerwyn Casey

    2015-12-25

    The bacterial cell wall is a network of glycan strands cross-linked by short peptides (peptidoglycan); it is responsible for the mechanical integrity of the cell and shape determination. Liquid chromatography can be used to measure the abundance of the muropeptide subunits composing the cell wall. Characteristics such as the degree of cross-linking and average glycan strand length are known to vary across species. However, a systematic comparison among strains of a given species has yet to be undertaken, making it difficult to assess the origins of variability in peptidoglycan composition. We present a protocol for muropeptide analysis using ultra performance liquid chromatography (UPLC) and demonstrate that UPLC achieves resolution comparable with that of HPLC while requiring orders of magnitude less injection volume and a fraction of the elution time. We also developed a software platform to automate the identification and quantification of chromatographic peaks, which we demonstrate has improved accuracy relative to other software. This combined experimental and computational methodology revealed that peptidoglycan composition was approximately maintained across strains from three Gram-negative species despite taxonomical and morphological differences. Peptidoglycan composition and density were maintained after we systematically altered cell size in Escherichia coli using the antibiotic A22, indicating that cell shape is largely decoupled from the biochemistry of peptidoglycan synthesis. High-throughput, sensitive UPLC combined with our automated software for chromatographic analysis will accelerate the discovery of peptidoglycan composition and the molecular mechanisms of cell wall structure determination. PMID:26468288

  3. Ultra-long high-sensitivity Φ-OTDR for high spatial resolution intrusion detection of pipelines.

    PubMed

    Peng, Fei; Wu, Han; Jia, Xin-Hong; Rao, Yun-Jiang; Wang, Zi-Nan; Peng, Zheng-Pu

    2014-06-01

    An ultra-long phase-sensitive optical time domain reflectometry (Φ-OTDR) that can achieve high-sensitivity intrusion detection over 131.5km fiber with high spatial resolution of 8m is presented, which is the longest Φ-OTDR reported to date, to the best of our knowledge. It is found that the combination of distributed Raman amplification with heterodyne detection can extend the sensing distance and enhances the sensitivity substantially, leading to the realization of ultra-long Φ-OTDR with high sensitivity and spatial resolution. Furthermore, the feasibility of applying such an ultra-long Φ-OTDR to pipeline security monitoring is demonstrated and the features of intrusion signal can be extracted with improved SNR by using the wavelet detrending/denoising method proposed. PMID:24921572

  4. High-sensitivity ultrasonic phase-shifted fiber Bragg grating balanced sensing system.

    PubMed

    Wu, Qi; Okabe, Yoji

    2012-12-17

    A high-sensitivity ultrasonic sensing system is proposed and demonstrated. In this system, a phase-shifted fiber Bragg grating (PS-FBG) is used as a sensor to achieve broadband and highly sensitive detection. The PS-FBG modulates the output of a tunable laser to detect the ultrasonic strain directly. Balanced photo-detector (BPD) is used for eliminating the DC component and further amplifying the AC component in the detected signal. Another major function of the BPD is to reject laser intensity noise. As a result, the minimum detectable strain is limited by the BPD's noise and laser frequency noise. The sensitivity of the system is 9 nε/Hz(1/2). Because of its high sensitivity, this system has the potential to be used in acousto-ultrasonic testing without amplifying the input signal and in practical acoustic emission detection. PMID:23263070

  5. Coupled Aerodynamic and Structural Sensitivity Analysis of a High-Speed Civil Transport

    NASA Technical Reports Server (NTRS)

    Mason, B. H.; Walsh, J. L.

    2001-01-01

    An objective of the High Performance Computing and Communication Program at the NASA Langley Research Center is to demonstrate multidisciplinary shape and sizing optimization of a complete aerospace vehicle configuration by using high-fidelity, finite-element structural analysis and computational fluid dynamics aerodynamic analysis. In a previous study, a multi-disciplinary analysis system for a high-speed civil transport was formulated to integrate a set of existing discipline analysis codes, some of them computationally intensive, This paper is an extension of the previous study, in which the sensitivity analysis for the coupled aerodynamic and structural analysis problem is formulated and implemented. Uncoupled stress sensitivities computed with a constant load vector in a commercial finite element analysis code are compared to coupled aeroelastic sensitivities computed by finite differences. The computational expense of these sensitivity calculation methods is discussed.

  6. Fano resonance-based highly sensitive, compact temperature sensor on thin film lithium niobate.

    PubMed

    Qiu, Wentao; Ndao, Abdoulaye; Vila, Venancio Calero; Salut, Roland; Courjal, Nadège; Baida, Fadi Issam; Bernal, Maria-Pilar

    2016-03-15

    In this Letter, we report a Fano resonance-based highly sensitive and compact temperature sensor fabricated on thin film lithium niobate (TFLN) Suzuki phase lattice (SPL) photonic crystal. The experimental sensitivity is estimated to be 0.77 nm/°C with a photonic crystal size of only 25  μm×24  μm. This sensitivity is 38 times larger than the intrinsic one of lithium niobate which is 0.02 nm/°C. The demonstrated sharp and high extinction ratio characteristics of the Fano lineshape resonance could be an excellent candidate in developing a high sensitivity temperature sensor, electric field sensor, etc. PMID:26977645

  7. Sensitivity of the High Altitude Water Cherenkov Experiment to observe Gamma-Ray Bursts

    NASA Astrophysics Data System (ADS)

    González, M. M.

    Ground based telescopes have marginally observed very high energy emission (>100GeV) from gamma-ray bursts(GRB). For instance, Milagrito observed GRB970417a with a significance of 3.7 sigmas over the background. Milagro have not yet observed TeV emission from a GRB with its triggered and untriggered searches or GeV emission with a triggered search using its scalers. These results suggest the need of new observatories with higher sensitivity to transient sources. The HAWC (High Altitute Water Cherenkov) observatory is proposed as a combination of the Milagro tecnology with a very high altitude (>4000m over see level) site. The expected HAWC sensitivity for GRBs is at least >10 times the Milagro sensitivity. In this work HAWC sensitivity for GRBs is discussed for different detector configurations such as altitude, distance between PMTs, depth under water of PMTs, number of PMTs required for a trigger, etc.

  8. High-sensitivity temperature sensor based on a droplet-like fiber circle.

    PubMed

    Xie, Jianglei; Xu, Ben; Li, Yi; Kang, Juan; Shen, Changyu; Wang, Jianfeng; Jin, Yongxing; Liu, Honglin; Ni, Kai; Dong, Xinyong; Zhao, Chunliu; Jin, Shangzhong

    2014-06-20

    A low-cost yet high-sensitivity temperature fiber sensor is proposed and demonstrated in this paper. A single-mode fiber with coating is simply bent in a droplet-like circle with a radius of several millimeters. The strong bending induces mode interferences between the silica core mode and the excited modes propagating in the polymer coating. Many resonant dips were observed in the transmission spectra and are found to shift to a shorter wavelength with the increase of environmental temperature. Our linear fitting result of the experimental data shows that the proposed sensor presents high temperature sensitivity up to -3.102  nm/°C, which is even comparable with sensors based on selective liquid-filled photonic crystal fibers. Such high temperature sensitivity results from the large thermo-optical coefficient difference between the silica core and the polymer coating. The influence of a circle radius to the sensitivities is also discussed. PMID:24979444

  9. Highly sensitive electronic whiskers based on patterned carbon nanotube and silver nanoparticle composite films

    PubMed Central

    Takei, Kuniharu; Yu, Zhibin; Zheng, Maxwell; Ota, Hiroki; Takahashi, Toshitake; Javey, Ali

    2014-01-01

    Mammalian whiskers present an important class of tactile sensors that complement the functionalities of skin for detecting wind with high sensitivity and navigation around local obstacles. Here, we report electronic whiskers based on highly tunable composite films of carbon nanotubes and silver nanoparticles that are patterned on high-aspect-ratio elastic fibers. The nanotubes form a conductive network matrix with excellent bendability, and nanoparticle loading enhances the conductivity and endows the composite with high strain sensitivity. The resistivity of the composites is highly sensitive to strain with a pressure sensitivity of up to ∼8%/Pa for the whiskers, which is >10× higher than all previously reported capacitive or resistive pressure sensors. It is notable that the resistivity and sensitivity of the composite films can be readily modulated by a few orders of magnitude by changing the composition ratio of the components, thereby allowing for exploration of whisker sensors with excellent performance. Systems consisting of whisker arrays are fabricated, and as a proof of concept, real-time two- and three-dimensional gas-flow mapping is demonstrated. The ultrahigh sensitivity and ease of fabrication of the demonstrated whiskers may enable a wide range of applications in advanced robotics and human–machine interfacing. PMID:24449857

  10. Combined liver and kidney transplantation in a highly sensitized and positively cross-matched patient.

    PubMed

    Alqurashi, Salem; Alsayyari, Abdullah A; Abdullah, Khalid; Alwan, Abduljalil; Hajeer, Ali H

    2011-07-01

    Combined liver kidney transplantation (CLKT) has been used on many occasions and proved to be a successful event for both liver and kidney in highly sensitized patients. Our aim was to review the immunological and other laboratory results of a CLKT in a highly sensitized patient. CLKT was used to treat a highly sensitized, 42-year-old female. She was suffering from end-stage liver disease due to hepatitis C virus (HCV) infection and renal disease due to diabetic nephropathy. Cross-matching, panel reactive assay (PRA) and routine laboratory tests for liver and renal function were carried out before and after the CLKT. Prior to the CLKT, the patient was highly sensitized with human leukocytes antigens (anti-HLA) class I antibodies (>90%). Patient was offered CLKT from a deceased donor. She had donor-specific antibodies, class I and II. Both T and B CDC cross-matches (XM) were positive pre-transplant and eight hours post-transplant. Both cross-match and PRA results became completely negative six days post CKLT. Almost 30 months post CLKT, her renal function is normal and negative for class I and II PRA. Liver graft appears to be protective for renal graft when they are combined even in highly sensitized patients. CLKT is very useful in overcoming sensitization in addition to treating end-stage liver and renal diseases. PMID:21743223

  11. Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis.

    PubMed

    Masillo, A; Valmaggia, L R; Saba, R; Brandizzi, M; Lindau, J F; Solfanelli, A; Curto, M; Narilli, F; Telesforo, L; Kotzalidis, G D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

    2016-01-01

    A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals. PMID:25711287

  12. Structure-function analysis identifies highly sensitive strigolactone receptors in Striga.

    PubMed

    Toh, Shigeo; Holbrook-Smith, Duncan; Stogios, Peter J; Onopriyenko, Olena; Lumba, Shelley; Tsuchiya, Yuichiro; Savchenko, Alexei; McCourt, Peter

    2015-10-01

    Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels. PMID:26450211

  13. Highly Sensitive Electrochemical Determination of Alfatoxin B1 Using Quantum Dots-Assembled Amplification Labels

    PubMed Central

    Zeng, Xiaoqun; Gao, Huiju; Pan, Daodong; Sun, Yangying; Cao, Jinxuan; Wu, Zhen; Pan, Zhenyu

    2015-01-01

    A competitive electrochemical immunoassay for highly sensitive detection of AFB1 is demonstrated using layer-by-layer (LBL) assembled quantum dots (QDs) as labels. To investigate the effects of the higher sensitivity of square wave voltammetric stripping (SWV) and of the LBL technique on the proposed immunoassays, the proposed assay was compared to electrochemical (EC) and fluorescent immunoassays, which did not use LBL technology. Peanut samples were analyzed using the three immunoassays. The limits of detection (LODs) were 0.018, 0.046 and 0.212 ng/mL, respectively, while the sensitivities were 0.308, 1.011 and 4.594 ng/mL, respectively. The proposed electrochemical immunoassay displayed a significant improvement in sensitivity, thereby providing a simple and sensitive alternative strategy for determining AFB1 levels in peanut samples. PMID:26307990

  14. Highly Sensitive Electrochemical Determination of Alfatoxin B1 Using Quantum Dots-Assembled Amplification Labels.

    PubMed

    Zeng, Xiaoqun; Gao, Huiju; Pan, Daodong; Sun, Yangying; Cao, Jinxuan; Wu, Zhen; Pan, Zhenyu

    2015-01-01

    A competitive electrochemical immunoassay for highly sensitive detection of AFB1 is demonstrated using layer-by-layer (LBL) assembled quantum dots (QDs) as labels. To investigate the effects of the higher sensitivity of square wave voltammetric stripping (SWV) and of the LBL technique on the proposed immunoassays, the proposed assay was compared to electrochemical (EC) and fluorescent immunoassays, which did not use LBL technology. Peanut samples were analyzed using the three immunoassays. The limits of detection (LODs) were 0.018, 0.046 and 0.212 ng/mL, respectively, while the sensitivities were 0.308, 1.011 and 4.594 ng/mL, respectively. The proposed electrochemical immunoassay displayed a significant improvement in sensitivity, thereby providing a simple and sensitive alternative strategy for determining AFB1 levels in peanut samples. PMID:26307990

  15. High-performance aqueous/organic dye-sensitized solar cells based on sensitizers containing triethylene oxide methyl ether.

    PubMed

    Lin, Ryan Yeh-Yung; Wu, Feng-Ling; Li, Chun-Ting; Chen, Pei-Yu; Ho, Kuo-Chuan; Lin, Jiann T

    2015-08-10

    Metal-free dyes (EO1 to EO4) containing the hydrophilic triethylene oxide methyl ether (TEOME) unit in the spacer have been synthesized and used in dye-sensitized solar cells (DSSCs). Efficient lithium-ion trapping by TEOME results in improved open-circuit voltage (VOC ), leading to excellent conversion efficiency of the cells, ranging from 9.02 to 9.98 % with I(-) /I3 (-) electrolyte in acetonitrile under AM 1.5 illumination. The TEOME unit also enhances the wettability of the dye molecules for application in aqueous-based DSSCs. Aqueous-based DSSCs with a dual TEMPO/iodide electrolyte exhibit high VOC values (0.80-0.88 V) and very promising cell performances of up to 5.97 %. PMID:26098636

  16. Is sensitivity to reward associated with the malleability of implicit inclinations toward high-fat food?

    PubMed

    Ashby, Casey R; Stritzke, Werner G K

    2013-08-01

    Two experiments examined the effect of positive and negative priming on implicit approach and avoidance inclinations toward high-fat food stimuli in participants high or low in reward sensitivity, using personalized unipolar variants of the Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K. Schwartz, 1998, "Measuring individual differences in implicit cognition: The Implicit Association Test," Journal of Personality and Social Psychology, Vol. 74, pp. 1464-1480). Participants high in reward sensitivity showed an automatic processing bias that is characterized by a dual vulnerability of being particularly susceptible to priming of the rewarding aspects of high-fat foods, while being unaffected by priming of the negative aspects of those foods. In contrast, participants low in reward sensitivity generally showed no facilitation of implicit-approach inclinations following positive priming, but consistently showed facilitation of implicit-avoidance inclinations following negative priming. These results are consistent with the revised reinforcement sensitivity theory ( J. A. Gray & N. McNaughton, 2000, The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system, 2nd ed., New York, NY, Oxford University Press.) and suggest that the systems mediating reward sensitivity and punishment sensitivity are not orthogonal, as predicted by the separable subsystems hypothesis, but can be interdependent, as predicted by the joint subsystems hypothesis. PMID:23527505

  17. Longevity Tests of High-Sensitivity BD-PND Bubble Dosimeters

    SciTech Connect

    Radev, R; Carlberg, E

    2002-07-09

    Medium- and very-high-sensitivity neutron bubble dosimeters (BD-PNDs) made by Bubble Technology Industries (BTI) were used to study the life span of such dosimeters in a standard setup with a {sup 252}Cf source. Although data on the longevity of bubble dosimeters with low and medium sensitivity exist, such data for dosimeters with high and very high sensitivity are not readily available. The manufacturer guarantees optimum dosimeter performance for 3 months after receipt. However, it is important to know the change in the dosimeters' characteristics with time, especially after the first 3 months. The long-term performance of four sets of very high sensitivity and one set of medium-sensitivity bubble dosimeters was examined for periods of up to 13 months. During that time, the detectors were exposed and reset more than 20 times. Although departures from initial detection sensitivity were observed in several cases, the detectors indicated a significantly longer life span than stated in the manufacturer's warranty. In addition, the change in the number of bubbles and in evaluated neutron dose as a function of the time from the end of exposure until the dosimeters were read was investigated.

  18. High-sensitivity and high-Q-factor glass photonic crystal cavity and its applications as sensors.

    PubMed

    Siraji, Ashfaqul Anwar; Zhao, Yang

    2015-04-01

    We investigate the properties of a planar photonic crystal cavity on glass and its applications as sensors. An airbridged twofold defect cavity on Schott glass background and Gorilla glass substrate has been designed for high Q-factor up to 4459. The average sensitivity of the cavity resonance to background refractive index is 388nm/Refractive Index Unit. The resonant wavelength is sensitive to background temperature by 18.5pm/C. The designed sensors show much higher sensitivity than those based on waveguide interferometers or photonic bandgap structures without cavity resonance. The results are also useful for experimental studies of glass photonic devices. PMID:25831371

  19. Sensitivity of downward longwave surface radiation to humidity and clouds at a high elevation site

    NASA Astrophysics Data System (ADS)

    Chen, Y.; Naud, C. M.; Rangwala, I.; Miller, J. R.

    2013-12-01

    This study investigates why some high elevation regions can experience greater rates of warming than their lower elevation surroundings. We focus on the combined effects of specific humidity (q) and clouds on the surface downward longwave radiation (DLR). Using 6-years of ground-based observations at two nearby high-elevation sites in the San Juan Mountains in southwestern Colorado, we investigate the sensitivity of DLR to changes in q. We find that the sensitivity of DLR to changes in q is much greater when the atmosphere is dry, and these conditions tend to occur at higher elevations during winter. In addition, we use satellite-derived cloud properties to examine how the sensitivity is affected by changes in cloud cover and optical thickness. Although DLR increases with increasing cloud cover, both a simple regression and a neural network analysis indicate that clouds have a small effect on the sensitivity of DLR to q, mostly a reduction that increases with increasing q. Changes in cloud fraction have a larger impact on DLR for large cloud fractions, but have less impact on changes in DLR than changes in humidity. In the limit of overcast clouds, DLR is sensitive to changes in optical thickness only when clouds are optically thin, otherwise the sensitivity of DLR to optical thickness is negligible. We discuss differences between nighttime and daytime sensitivities at two nearby sites, as well as the generality of our results.

  20. Suppression of Sensitivity to Drugs and Antibiotics by High External Cation Concentrations in Fission Yeast

    PubMed Central

    Shabro, Aidin; Sunnerhagen, Per

    2015-01-01

    Background Potassium ion homeostasis plays an important role in regulating membrane potential and therefore resistance to cations, antibiotics and chemotherapeutic agents in Schizosaccharomyces pombe and other yeasts. However, the precise relationship between drug resistance in S. pombe and external potassium concentrations (particularly in its natural habitats) remains unclear. S. pombe can tolerate a wide range of external potassium concentrations which in turn affect plasma membrane polarization. We thus hypothesized that high external potassium concentrations suppress the sensitivity of this yeast to various drugs. Methods We have investigated the effect of external KCl concentrations on the sensitivity of S. pombe cells to a wide range of antibiotics, antimicrobial agents and chemotherapeutic drugs. We employed survival assays, immunoblotting and microscopy for these studies. Results We demonstrate that KCl, and to a lesser extent NaCl and RbCl can suppress the sensitivity of S. pombe to a wide range of antibiotics. Ammonium chloride and potassium hydrogen sulphate also suppressed drug sensitivity. This effect appears to depend in part on changes to membrane polarization and membrane transport proteins. Interestingly, we have found little relationship between the suppressive effect of KCl on sensitivity and the structure, polarity or solubility of the various compounds investigated. Conclusions High concentrations of external potassium and other cations suppress sensitivity to a wide range of drugs in S. pombe. Potassium-rich environments may thus provide S. pombe a competitive advantage in nature. Modulating potassium ion homeostasis may sensitize pathogenic fungi to antifungal agents. PMID:25793410

  1. A highly sensitive humidity sensor based on a nanofibrous membrane coated quartz crystal microbalance.

    PubMed

    Wang, Xianfeng; Ding, Bin; Yu, Jianyong; Wang, Moran; Pan, Fukui

    2010-02-01

    A novel humidity sensor was fabricated by electrospinning deposition of nanofibrous polyelectrolyte membranes as sensitive coatings on a quartz crystal microbalance (QCM). The results of sensing experiments indicated that the response of the sensors increased by more than two orders of magnitude with increasing relative humidity (RH) from 6 to 95% at room temperature, exhibiting high sensitivity, and that, in the range of 20-95% RH, the Log(Deltaf) showed good linearity. The sensitivity of fibrous composite polyacrylic acid (PAA)/poly(vinyl alcohol) (PVA) membranes was two times higher than that of the corresponding flat films at 95% RH. Compared with fibrous PAA/PVA membranes, the nanofibrous PAA membranes exhibited remarkably enhanced humidity sensitivity due to their high PAA content and large specific surface area caused by the formation of ultrathin nanowebs among electrospun fibers. Additionally, the resultant sensors exhibited a good reversible behavior and good long term stability. PMID:20023313

  2. High sensitivity molecular detection with enzyme-linked immuno-sorbent assay (ELISA)-type immunosensing

    NASA Astrophysics Data System (ADS)

    Pita, Marcos; Cui, Lili; Gaikwad, Ravi M.; Katz, Evgeny; Sokolov, Igor

    2008-09-01

    Here we describe an immunosensing method, which is designed for high sensitivity sensing of various substances utilizing specificity of antigen-antibody (ELISA-type) interaction. The building up of the nanostructured sensing interface and the immunointeraction at the surface were characterized by atomic force microscopy. The proposed design makes potentially feasible attaining ultimate single-molecule sensitivity upon optimization of the system. The first non-optimized prototype described here has already demonstrated sensitivity to the presence of dinitrophenyl (DNP) in concentrations as low as 10 pM, which is 100 times better than reported limits of detection of DNP with a traditional enzyme-linked immuno-sorbent assay setup.

  3. High sensitivity phase retrieval method in grating-based x-ray phase contrast imaging

    SciTech Connect

    Wu, Zhao; Gao, Kun; Chen, Jian; Wang, Dajiang; Wang, Shenghao; Chen, Heng; Bao, Yuan; Shao, Qigang; Wang, Zhili; Zhang, Kai; Zhu, Peiping; Wu, Ziyu

    2015-02-15

    Purpose: Grating-based x-ray phase contrast imaging is considered as one of the most promising techniques for future medical imaging. Many different methods have been developed to retrieve phase signal, among which the phase stepping (PS) method is widely used. However, further practical implementations are hindered, due to its complex scanning mode and high radiation dose. In contrast, the reverse projection (RP) method is a novel fast and low dose extraction approach. In this contribution, the authors present a quantitative analysis of the noise properties of the refraction signals retrieved by the two methods and compare their sensitivities. Methods: Using the error propagation formula, the authors analyze theoretically the signal-to-noise ratios (SNRs) of the refraction images retrieved by the two methods. Then, the sensitivities of the two extraction methods are compared under an identical exposure dose. Numerical experiments are performed to validate the theoretical results and provide some quantitative insight. Results: The SNRs of the two methods are both dependent on the system parameters, but in different ways. Comparison between their sensitivities reveals that for the refraction signal, the RP method possesses a higher sensitivity, especially in the case of high visibility and/or at the edge of the object. Conclusions: Compared with the PS method, the RP method has a superior sensitivity and provides refraction images with a higher SNR. Therefore, one can obtain highly sensitive refraction images in grating-based phase contrast imaging. This is very important for future preclinical and clinical implementations.

  4. Image quality and dose efficiency of high energy phase sensitive x-ray imaging: Phantom studies

    PubMed Central

    Wong, Molly Donovan; Wu, Xizeng; Liu, Hong

    2014-01-01

    The goal of this preliminary study was to perform an image quality comparison of high energy phase sensitive imaging with low energy conventional imaging at similar radiation doses. The comparison was performed with the following phantoms: American College of Radiology (ACR), contrast-detail (CD), acrylic edge and tissue-equivalent. Visual comparison of the phantom images indicated comparable or improved image quality for all phantoms. Quantitative comparisons were performed through ACR and CD observer studies, both of which indicated higher image quality in the high energy phase sensitive images. The results of this study demonstrate the ability of high energy phase sensitive imaging to overcome existing challenges with the clinical implementation of phase contrast imaging and improve the image quality for a similar radiation dose as compared to conventional imaging near typical mammography energies. In addition, the results illustrate the capability of phase sensitive imaging to sustain the image quality improvement at high x-ray energies and for – breast – simulating phantoms, both of which indicate the potential to benefit fields such as mammography. Future studies will continue to investigate the potential for dose reduction and image quality improvement provided by high energy phase sensitive contrast imaging. PMID:24865208

  5. A four-pixel matched collimator for high-sensitivity SPECT imaging

    NASA Astrophysics Data System (ADS)

    Suzuki, Atsuro; Takeuchi, Wataru; Ishitsu, Takafumi; Tsuchiya, Katsutoshi; Ueno, Yuichiro; Kobashi, Keiji

    2013-04-01

    We propose a wide aperture parallel-hole collimator that we call a 4-pixel matched collimator (4-PMC) for high-sensitivity SPECT imaging. The hole size of the 4-PMC is matched to four detector pixels; that is, there are four (2 × 2) pixels per collimator hole. By contrast, a 1-pixel matched collimator (1-PMC) is defined as a collimator whose hole size is matched to one detector pixel. We evaluated four types of collimator (high-resolution collimator versions and high-sensitivity collimator versions of both 4-PMC and 1-PMC) by simulation. SPECT images of a cylindrical phantom with cold spots in the noise-free condition demonstrated that the 4-PMC provided a higher-contrast image than the 1-PMC for the same collimator version. In addition, SPECT images at the noise level corresponding to a human cerebral blood flow study suggested that the high-sensitivity version of the 4-PMC provided the highest contrast image among the four collimator types. In conclusion, the high-sensitivity SPECT system using the 4-PMC can improve the trade-off between spatial resolution and sensitivity and will consequently provide improved image contrast for clinical studies of the human brain compared with the SPECT system using the 1-PMC.

  6. The fluctuation of high-order aberration's sensitivity in ArF immersion lithography

    NASA Astrophysics Data System (ADS)

    Zhang, Fei; Li, Yanqui

    2006-01-01

    To achieve smaller and smaller feature sizes in the semiconductor industry, extreme demands are placed on the lithographic optics, specifically the projection lens. Higher numerical aperture (NA) is adopted to obtain higher resolution. However, higher NA scales the impact of geometrical aberrations on lithography performance. Thus, a detailed understanding of the effect of geometrical aberrations on the lithographic process is indispensable. In this paper, we consider some of the surprising phenomena that occur at such high NA. We discuss the impact of flare, polarization state and MSD on higher-order aberration's sensitivity using ArF immersion lithography to print elbow pattern exposed features in photo resist on 65nm node. The higher-order aberration's sensitivity is analyzed when the annular illumination (NA=1.2, sigma out=0.76, sigma in=0.52) is employed. The 3rd, 5th, 7th, 9th geometrical aberrations according to the Fringe convention are discussed. The sensitivities to individual geometrical aberrations are calculated by introducing a fixed amount of aberration for each Zernike coefficient with all other aberrations being zero. On 65nm node, with annular illumination, the high-order aberration's sensitivity is calculated respectively according to the variation of flare, polarization state, and MSD. The results show that flare, polarization state, and MSD can contribute to the high-order aberration's sensitivity. The aberration sensitivities are increasing with the MSD and flare's value rising. The aberration sensitivities can be decreased when the horizontal linear polarized light is adopted. The merits of adjusting polarization state to choke back the aberration sensitivities are presented.

  7. Ultra high vacuum pumping system and high sensitivity helium leak detector

    DOEpatents

    Myneni, G.R.

    1997-12-30

    An improved helium leak detection method and apparatus are disclosed which increase the leak detection sensitivity to 10{sup {minus}13} atm cc/s. The leak detection sensitivity is improved over conventional leak detectors by completely eliminating the use of o-rings, equipping the system with oil-free pumping systems, and by introducing measured flows of nitrogen at the entrances of both the turbo pump and backing pump to keep the system free of helium background. The addition of dry nitrogen flows to the system reduces back streaming of atmospheric helium through the pumping system as a result of the limited compression ratios of the pumps for helium. 2 figs.

  8. Ultra high vacuum pumping system and high sensitivity helium leak detector

    DOEpatents

    Myneni, Ganapati Rao

    1997-01-01

    An improved helium leak detection method and apparatus are disclosed which increase the leak detection sensitivity to 10.sup.-13 atm cc s.sup.-1. The leak detection sensitivity is improved over conventional leak detectors by completely eliminating the use of o-rings, equipping the system with oil-free pumping systems, and by introducing measured flows of nitrogen at the entrances of both the turbo pump and backing pump to keep the system free of helium background. The addition of dry nitrogen flows to the system reduces backstreaming of atmospheric helium through the pumping system as a result of the limited compression ratios of the pumps for helium.

  9. Evaluation of a High-Sensitivity GPS Receiver for Kinematics Application in Regions with High Shading

    NASA Astrophysics Data System (ADS)

    Suhandri, H. F.; Becker, D.; Kleusberg, A.

    2009-04-01

    GPS positioning has been very much improved with high-sensitivity GPS (HSGPS) receivers. This kind of receiver can track the signal until 20-25dB below the level of conventional receivers. Obviously, no problem occurs when GPS technology is used for air and ocean vehicles navigation; sufficient and/or redundant signals can be easily acquired due to good hemispherical signal reception. A problem arises whenever signals cannot be traced anymore, if not enough satellites are available or if there is very weak signal reception in forest areas or between buildings. Those situations cannot be avoided or eliminated in land vehicle navigation. The HSGPS technology tries to solve those problems by tracking signals below the normal signal threshold of non-HSGPS receivers. This paper discusses the two factors of availability and accuracy in the context of navigation with HSGPS receivers. In order to investigate these issues some scenarios of receivers-placing will be examined which represent various receiver environments: good hemispherical signal reception, strong signal shading environment and indoor environment. The signal availability and accuracy are investigated during observation sessions of several hours by comparing the measurements of the HSGPS receiver with the measurements of a conventional, non-HSGPS receiver. As expected, the non-HSGPS receiver yields the same level of availability as the HSGPS receiver in an environment with good hemispherical signal reception. When both receivers are located in an environment with significant signal shading, the percentage of availability will significantly decay for the non-HSGPS receiver whereas the availability of the HSGPS receiver is much less reduced. However the results from the HSGPS receiver in this case are at a significantly reduced accuracy level. The accuracy level is assessed by using three parameters: i) the difference between the C/A code and the carrier phase in order to investigate how big the multipath and other disturbance effects are, ii) investigation of the carrier phase accuracy by using triple-difference, iii) comparison of the signal-to-noise ratio with satellite elevation. After analyzing the availability and accuracy for both receivers, data processing has been done by using static and kinematic methods. Both are based on post processing methods calculating the baselines from double-difference carrier phase and code measurements.

  10. Highly sensitive glucose sensors based on enzyme-modified whole-graphene solution-gated transistors

    PubMed Central

    Zhang, Meng; Liao, Caizhi; Mak, Chun Hin; You, Peng; Mak, Chee Leung; Yan, Feng

    2015-01-01

    Noninvasive glucose detections are convenient techniques for the diagnosis of diabetes mellitus, which require high performance glucose sensors. However, conventional electrochemical glucose sensors are not sensitive enough for these applications. Here, highly sensitive glucose sensors are successfully realized based on whole-graphene solution-gated transistors with the graphene gate electrodes modified with an enzyme glucose oxidase. The sensitivity of the devices is dramatically improved by co-modifying the graphene gates with Pt nanoparticles due to the enhanced electrocatalytic activity of the electrodes. The sensing mechanism is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate. The optimized glucose sensors show the detection limits down to 0.5 μM and good selectivity, which are sensitive enough for non-invasive glucose detections in body fluids. The devices show the transconductances two orders of magnitude higher than that of a conventional silicon field effect transistor, which is the main reason for their high sensitivity. Moreover, the devices can be conveniently fabricated with low cost. Therefore, the whole-graphene solution-gated transistors are a high-performance sensing platform for not only glucose detections but also many other types of biosensors that may find practical applications in the near future. PMID:25655666

  11. The Design and Optimization of a Highly Sensitive and Overload-Resistant Piezoresistive Pressure Sensor.

    PubMed

    Meng, Xiawei; Zhao, Yulong

    2016-01-01

    A piezoresistive pressure sensor with a beam-membrane-dual-island structure is developed for micro-pressure monitoring in the field of aviation, which requires great sensitivity and overload resistance capacity. The design, fabrication, and test of the sensor are presented in this paper. By analyzing the stress distribution of sensitive elements using the finite element method, a novel structure incorporating sensitive beams with a traditional bossed diaphragm is built up. The proposed structure proved to be advantageous in terms of high sensitivity and high overload resistance compared with the conventional bossed diaphragm and flat diaphragm structures. Curve fittings of surface stress and deflection based on ANSYS simulation results are performed to establish the sensor equations. Fabricated on an n-type single crystal silicon wafer, the sensor chips are wire-bonded to a printed circuit board (PCB) and packaged for experiments. The static and dynamic characteristics are tested and discussed. Experimental results show that the sensor has a sensitivity as high as 17.339 μV/V/Pa in the range of 500 Pa at room temperature, and a high overload resistance of 200 times overpressure. Due to the excellent performance, the sensor can be applied in measuring micro-pressure lower than 500 Pa. PMID:27005627

  12. The Design and Optimization of a Highly Sensitive and Overload-Resistant Piezoresistive Pressure Sensor

    PubMed Central

    Meng, Xiawei; Zhao, Yulong

    2016-01-01

    A piezoresistive pressure sensor with a beam-membrane-dual-island structure is developed for micro-pressure monitoring in the field of aviation, which requires great sensitivity and overload resistance capacity. The design, fabrication, and test of the sensor are presented in this paper. By analyzing the stress distribution of sensitive elements using the finite element method, a novel structure incorporating sensitive beams with a traditional bossed diaphragm is built up. The proposed structure proved to be advantageous in terms of high sensitivity and high overload resistance compared with the conventional bossed diaphragm and flat diaphragm structures. Curve fittings of surface stress and deflection based on ANSYS simulation results are performed to establish the sensor equations. Fabricated on an n-type single crystal silicon wafer, the sensor chips are wire-bonded to a printed circuit board (PCB) and packaged for experiments. The static and dynamic characteristics are tested and discussed. Experimental results show that the sensor has a sensitivity as high as 17.339 μV/V/Pa in the range of 500 Pa at room temperature, and a high overload resistance of 200 times overpressure. Due to the excellent performance, the sensor can be applied in measuring micro-pressure lower than 500 Pa. PMID:27005627

  13. Highly sensitive glucose sensors based on enzyme-modified whole-graphene solution-gated transistors.

    PubMed

    Zhang, Meng; Liao, Caizhi; Mak, Chun Hin; You, Peng; Mak, Chee Leung; Yan, Feng

    2015-01-01

    Noninvasive glucose detections are convenient techniques for the diagnosis of diabetes mellitus, which require high performance glucose sensors. However, conventional electrochemical glucose sensors are not sensitive enough for these applications. Here, highly sensitive glucose sensors are successfully realized based on whole-graphene solution-gated transistors with the graphene gate electrodes modified with an enzyme glucose oxidase. The sensitivity of the devices is dramatically improved by co-modifying the graphene gates with Pt nanoparticles due to the enhanced electrocatalytic activity of the electrodes. The sensing mechanism is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate. The optimized glucose sensors show the detection limits down to 0.5 μM and good selectivity, which are sensitive enough for non-invasive glucose detections in body fluids. The devices show the transconductances two orders of magnitude higher than that of a conventional silicon field effect transistor, which is the main reason for their high sensitivity. Moreover, the devices can be conveniently fabricated with low cost. Therefore, the whole-graphene solution-gated transistors are a high-performance sensing platform for not only glucose detections but also many other types of biosensors that may find practical applications in the near future. PMID:25655666

  14. High degree gravitational sensitivity from Mars orbiters for the GMM-1 gravity model

    NASA Technical Reports Server (NTRS)

    Lerch, F. J.; Smith, D. E.; Chan, J. C.; Patel, G. B.; Chinn, D. S.

    1994-01-01

    Orbital sensitivity of the gravity field for high degree terms (greater than 30) is analyzed on satellites employed in a Goddard Mars Model GMM-1, complete in spherical harmonics through degree and order 50. The model is obtained from S-band Doppler data on Mariner 9 (M9), Viking Orbiter 1 (VO1), and Viking Orbiter 2 (VO2) spacecraft, which were tracked by the NASA Deep Space Network on seven different highly eccentric orbits. The main sensitivity of the high degree terms is obtained from the VO1 and VO2 low orbits (300 km periapsis altitude), where significant spectral sensitivity is seen for all degrees out through degree 50. The velocity perturbations show a dominant effect at periapsis and significant effects out beyond the semi-latus rectum covering over 180 degrees of the orbital groundtrack for the low altitude orbits. Because of the wideband of periapsis motion covering nearly 180 degrees in w and +39 degrees in latitude coverage, the VO1 300 km periapsis altitude orbit with inclination of 39 degrees gave the dominant sensitivity in the GMM-1 solution for the high degree terms. Although the VO2 low periapsis orbit has a smaller band of periapsis mapping coverage, it strongly complements the VO1 orbit sensitivity for the GMM-1 solution with Doppler tracking coverage over a different inclination of 80 degrees.

  15. Highly sensitive glucose sensors based on enzyme-modified whole-graphene solution-gated transistors

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Liao, Caizhi; Mak, Chun Hin; You, Peng; Mak, Chee Leung; Yan, Feng

    2015-02-01

    Noninvasive glucose detections are convenient techniques for the diagnosis of diabetes mellitus, which require high performance glucose sensors. However, conventional electrochemical glucose sensors are not sensitive enough for these applications. Here, highly sensitive glucose sensors are successfully realized based on whole-graphene solution-gated transistors with the graphene gate electrodes modified with an enzyme glucose oxidase. The sensitivity of the devices is dramatically improved by co-modifying the graphene gates with Pt nanoparticles due to the enhanced electrocatalytic activity of the electrodes. The sensing mechanism is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate. The optimized glucose sensors show the detection limits down to 0.5 μM and good selectivity, which are sensitive enough for non-invasive glucose detections in body fluids. The devices show the transconductances two orders of magnitude higher than that of a conventional silicon field effect transistor, which is the main reason for their high sensitivity. Moreover, the devices can be conveniently fabricated with low cost. Therefore, the whole-graphene solution-gated transistors are a high-performance sensing platform for not only glucose detections but also many other types of biosensors that may find practical applications in the near future.

  16. Highly Sensitive and Reproducible SERS Performance from Uniform Film Assembled by Magnetic Noble Metal Composite Microspheres.

    PubMed

    Niu, Chunyu; Zou, Bingfang; Wang, Yongqiang; Cheng, Lin; Zheng, Haihong; Zhou, Shaomin

    2016-01-26

    To realize highly sensitive and reproducible SERS performance, a new route was put forward to construct uniform SERS film by using magnetic composite microspheres. In the experiment, monodisperse Fe3O4@SiO2@Ag microspheres with hierarchical surface were developed and used as building block of SERS substrate, which not only realized fast capturing analyte through dispersion and collection under external magnet but also could be built into uniform film through magnetically induced self-assembly. By using R6G as probe molecule, the as-obtained uniform film exhibited great improvement on SERS performance in both sensitivity and reproducibility when compared with nonuniform film, demonstrating the perfect integration of high sensitivity of hierarchal noble metal microspheres and high reproducibility of ordered microspheres array. Furthermore, the as-obtained product was used to detect pesticide thiram and also exhibited excellent SERS performance for trace detection. PMID:26731200

  17. A highly sensitive mean-reverting process in finance and the Euler-Maruyama approximations

    NASA Astrophysics Data System (ADS)

    Wu, Fuke; Mao, Xuerong; Chen, Kan

    2008-12-01

    Empirical studies show that the most successful continuous-time models of the short-term rate in capturing the dynamics are those that allow the volatility of interest changes to be highly sensitive to the level of the rate. However, from the mathematics, the high sensitivity to the level implies that the coefficients do not satisfy the linear growth condition, so we can not examine its properties by traditional techniques. This paper overcomes the mathematical difficulties due to the nonlinear growth and examines its analytical properties and the convergence of numerical solutions in probability. The convergence result can be used to justify the method within Monte Carlo simulations that compute the expected payoff of financial productsE For illustration, we apply our results compute the value of a bond with interest rate given by the highly sensitive mean-reverting process as well as the value of a single barrier call option with the asset price governed by this process.

  18. Design and Synthesis of an MOF Thermometer with High Sensitivity in the Physiological Temperature Range.

    PubMed

    Zhao, Dian; Rao, Xingtang; Yu, Jiancan; Cui, Yuanjing; Yang, Yu; Qian, Guodong

    2015-12-01

    An important result of research on mixed-lanthanide metal-organic frameworks (M'LnMOFs) is the realization of highly sensitive ratiometric luminescent thermometers. Here, we report the design and synthesis of the new M'LnMOF Tb0.80Eu0.20BPDA with high relative sensitivity in the physiological temperature regime (298-318 K). The emission intensity and luminescence lifetime were investigated and compared to those of existing materials. It was found that the temperature-dependent luminescence properties of Tb0.80Eu0.20BPDA are strongly associated with the distribution of the energy levels of the ligand. Such a property can be useful in the design of highly sensitive M'LnMOF thermometers. PMID:26575207

  19. High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors.

    PubMed

    March, Carmen; Garca, Jos V; Snchez, Angel; Arnau, Antonio; Jimnez, Yolanda; Garca, Pablo; Mancls, Juan J; Montoya, Angel

    2014-10-01

    In spite of being widely used for in liquid biosensing applications, sensitivity improvement of conventional (5-20MHz) quartz crystal microbalance (QCM) sensors remains an unsolved challenging task. With the help of a new electronic characterization approach based on phase change measurements at a constant fixed frequency, a highly sensitive and versatile high fundamental frequency (HFF) QCM immunosensor has successfully been developed and tested for its use in pesticide (carbaryl and thiabendazole) analysis. The analytical performance of several immunosensors was compared in competitive immunoassays taking carbaryl insecticide as the model analyte. The highest sensitivity was exhibited by the 100MHz HFF-QCM carbaryl immunosensor. When results were compared with those reported for 9MHz QCM, analytical parameters clearly showed an improvement of one order of magnitude for sensitivity (estimated as the I50 value) and two orders of magnitude for the limit of detection (LOD): 30?gl(-1) vs 0.66?gL(-1)I50 value and 11?gL(-1) vs 0.14?gL(-1) LOD, for 9 and 100MHz, respectively. For the fungicide thiabendazole, I50 value was roughly the same as that previously reported for SPR under the same biochemical conditions, whereas LOD improved by a factor of 2. The analytical performance achieved by high frequency QCM immunosensors surpassed those of conventional QCM and SPR, closely approaching the most sensitive ELISAs. The developed 100MHz QCM immunosensor strongly improves sensitivity in biosensing, and therefore can be considered as a very promising new analytical tool for in liquid applications where highly sensitive detection is required. PMID:25461131

  20. Effects of intrinsic magnetostriction on tube-topology magnetoelectric sensors with high magnetic field sensitivity

    SciTech Connect

    Gillette, Scott M.; Fitchorov, Trifon; Obi, Ogheneyunume; Chen, Yajie Harris, Vincent G.; Jiang, Liping; Hao, Hongbo; Wu, Shuangxia

    2014-05-07

    Three quasi-one-dimensional magnetoelectric (ME) magnetic field sensors, each with a different magnetostrictive wire material, were investigated in terms of sensitivity and noise floor. Magnetostrictive Galfenol, iron-cobalt-vanadium, and iron-nickel wires were examined. Sensitivity profiles, hysteresis effects, and noise floor measurements for both optimally biased and zero-biased conditions are presented. The FeNi wire (FN) exhibits high sensitivity (5.36 mV/Oe) at bias fields below 22 Oe and an optimal bias of 10 Oe, whereas FeGa wire (FG) exhibits higher sensitivity (6.89 mW/Oe) at bias fields >22 Oe. The sensor of FeCoV wire (FC) presents relatively low sensitivity (2.12 mV/Oe), due to low magnetostrictive coefficient. Each ME tube-topology sensor demonstrates relatively high sensitivity at zero bias field, which results from a magnetic shape anisotropy and internal strain of the thin magnetostrictive wire.

  1. Highly Sensitive and Selective Ethanol Sensor Fabricated with In-Doped 3DOM ZnO.

    PubMed

    Wang, Zhihua; Tian, Ziwei; Han, Dongmei; Gu, Fubo

    2016-03-01

    ZnO is an important n-type semiconductor sensing material. Currently, much attention has been attracted to finding an effective method to prepare ZnO nanomaterials with high sensing sensitivity and excellent selectivity. A three-dimensionally ordered macroporous (3DOM) ZnO nanostructure with a large surface area is beneficial to gas and electron transfer, which can enhance the gas sensitivity of ZnO. Indium (In) doping is an effective way to improve the sensing properties of ZnO. In this paper, In-doped 3DOM ZnO with enhanced sensitivity and selectivity has been synthesized by using a colloidal crystal templating method. The 3DOM ZnO with 5 at. % of In-doping exhibits the highest sensitivity (∼88) to 100 ppm ethanol at 250 °C, which is approximately 3 times higher than that of pure 3DOM ZnO. The huge improvement to the sensitivity to ethanol was attributed to the increase in the surface area and the electron carrier concentration. The doping by In introduces more electrons into the matrix, which is helpful for increasing the amount of adsorbed oxygen, leading to high sensitivity. The In-doped 3DOM ZnO is a promising material for a new type of ethanol sensor. PMID:26844815

  2. Optical Transitions in Highly Charged Californium Ions with High Sensitivity to Variation of the Fine-Structure Constant

    NASA Astrophysics Data System (ADS)

    Berengut, J. C.; Dzuba, V. A.; Flambaum, V. V.; Ong, A.

    2012-08-01

    We study electronic transitions in highly charged Cf ions that are within the frequency range of optical lasers and have very high sensitivity to potential variations in the fine-structure constant, α. The transitions are in the optical range despite the large ionization energies because they lie on the level crossing of the 5f and 6p valence orbitals in the thallium isoelectronic sequence. Cf16+ is a particularly rich ion, having several narrow lines with properties that minimize certain systematic effects. Cf16+ has very large nuclear charge and large ionization energy, resulting in the largest α sensitivity seen in atomic systems. The lines include positive and negative shifters.

  3. High-resolution, high sensitivity detectors for molecular imaging with radionuclides: The coded aperture option

    NASA Astrophysics Data System (ADS)

    Cusanno, F.; Cisbani, E.; Colilli, S.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lo Meo, S.; Lucentini, M.; Magliozzi, M. L.; Santavenere, F.; Lanza, R. C.; Majewski, S.; Cinti, M. N.; Pani, R.; Pellegrini, R.; Orsini Cancelli, V.; De Notaristefani, F.; Bollini, D.; Navarria, F.; Moschini, G.

    2006-12-01

    Molecular imaging with radionuclides is a very sensitive technique because it allows to obtain images with nanomolar or picomolar concentrations. This has generated a rapid growth of interest in radionuclide imaging of small animals. Indeed radiolabeling of small molecules, antibodies, peptides and probes for gene expression enables molecular imaging in vivo, but only if a suitable imaging system is used. Detecting small tumors in humans is another important application of such techniques. In single gamma imaging, there is always a well known tradeoff between spatial resolution and sensitivity due to unavoidable collimation requirements. Limitation of the sensitivity due to collimation is well known and affects the performance of imaging systems, especially if only radiopharmaceuticals with limited uptake are available. In many cases coded aperture collimation can provide a solution, if the near field artifact effect can be eliminated or limited. At least this is the case for "small volumes" imaging, involving small animals. In this paper 3D-laminography simulations and preliminary measurements with coded aperture collimation are presented. Different masks have been designed for different applications showing the advantages of the technique in terms of sensitivity and spatial resolution. The limitations of the technique are also discussed.

  4. High open circuit voltages of solar cells based on quantum dot and dye hybrid-sensitization

    SciTech Connect

    Zhao, Yujie; Zhao, Wanyu; Chen, Jingkuo; Li, Huayang; Fu, Wuyou E-mail: fuwy56@163.com; Sun, Guang; Cao, Jianliang; Zhang, Zhanying; Bala, Hari E-mail: fuwy56@163.com; College of Chemistry and Chemical Engineering, Inner Mongolia University for the Nationalities, Tongliao 028043

    2014-01-06

    A type of solar cell based on quantum dot (QD) and dye hybrid-sensitized mesoporous TiO{sub 2} film electrode was designed and reported. The electrode was consisted of a TiO{sub 2} nanoparticle (NP) thin film layer sensitized with CdS quantum dot (QD) and an amorphous TiO{sub 2} coated TiO{sub 2} NP thin film layer that sensitized with C106 dye. The amorphous TiO{sub 2} layer was obtained by TiCl{sub 4} post-treatment to improve the properties of solar cells. Research showed that the solar cells fabricated with as-prepared hybrid-sensitized electrode exhibited excellent photovoltaic performances and a fairly high open circuit voltage of 796 mV was achieved.

  5. Highly sensitive bending sensor based on multimode-multimode-coreoffset fiber structure

    NASA Astrophysics Data System (ADS)

    Qi, Yanhui; Ma, Lin; Sun, Jiang; Kang, Zexin; Bai, Yunlong; Jian, Shuisheng

    2015-12-01

    In this paper, we present a simple fiber optic bending sensor based on the multimode-multimode structure combining with the core-offset fiber structure. The multimode-multimode structure is composed of no core fiber (NCF) with hundreds of micrometers in length as a micro-lens for mode conversion, and single mode fiber (SMF) which can be seen as a section of special multimode fiber (MMF) when considered the cladding modes. The transmission spectrum in the experiment agrees well with the numerical model. The sensitivity of the structure can be achieved as high as 11.104 nm/m-1 in the measuring range. Meanwhile, the sensitivity of the neighboring resonance wavelength around 1546 nm exhibits approximately the same sensitivity which is 10.579 nm/m-1. Besides, the strain sensitivity is about -0.927 pm/με within the measuring strain range.

  6. High-Sensitivity X-ray Polarimetry with Amorphous Silicon Active-Matrix Pixel Proportional Counters

    NASA Technical Reports Server (NTRS)

    Black, J. K.; Deines-Jones, P.; Jahoda, K.; Ready, S. E.; Street, R. A.

    2003-01-01

    Photoelectric X-ray polarimeters based on pixel micropattern gas detectors (MPGDs) offer order-of-magnitude improvement in sensitivity over more traditional techniques based on X-ray scattering. This new technique places some of the most interesting astronomical observations within reach of even a small, dedicated mission. The most sensitive instrument would be a photoelectric polarimeter at the focus of 2 a very large mirror, such as the planned XEUS. Our efforts are focused on a smaller pathfinder mission, which would achieve its greatest sensitivity with large-area, low-background, collimated polarimeters. We have recently demonstrated a MPGD polarimeter using amorphous silicon thin-film transistor (TFT) readout suitable for the focal plane of an X-ray telescope. All the technologies used in the demonstration polarimeter are scalable to the areas required for a high-sensitivity collimated polarimeter. Leywords: X-ray polarimetry, particle tracking, proportional counter, GEM, pixel readout

  7. High open circuit voltages of solar cells based on quantum dot and dye hybrid-sensitization

    NASA Astrophysics Data System (ADS)

    Zhao, Yujie; Bala, Hari; Zhao, Wanyu; Chen, Jingkuo; Li, Huayang; Fu, Wuyou; Sun, Guang; Cao, Jianliang; Zhang, Zhanying

    2014-01-01

    A type of solar cell based on quantum dot (QD) and dye hybrid-sensitized mesoporous TiO2 film electrode was designed and reported. The electrode was consisted of a TiO2 nanoparticle (NP) thin film layer sensitized with CdS quantum dot (QD) and an amorphous TiO2 coated TiO2 NP thin film layer that sensitized with C106 dye. The amorphous TiO2 layer was obtained by TiCl4 post-treatment to improve the properties of solar cells. Research showed that the solar cells fabricated with as-prepared hybrid-sensitized electrode exhibited excellent photovoltaic performances and a fairly high open circuit voltage of 796 mV was achieved.

  8. Highly Sensitive Colorimetric Detection of Ochratoxin A by a Label-Free Aptamer and Gold Nanoparticles

    PubMed Central

    Luan, Yunxia; Chen, Jiayi; Li, Cheng; Xie, Gang; Fu, Hailong; Ma, Zhihong; Lu, Anxiang

    2015-01-01

    A label-free aptamer-based assay for the highly sensitive and specific detection of Ochratoxin A (OTA) was developed using a cationic polymer and gold nanoparticles (AuNPs). The OTA aptamer was used as a recognition element for the colorimetric detection of OTA based on the aggregation of AuNPs by the cationic polymer. By spectroscopic quantitative analysis, the colorimetric assay could detect OTA down to 0.009 ng/mL with high selectivity in the presence of other interfering toxins. This study offers a new alternative in visual detection methods that is rapid and sensitive for OTA detection. PMID:26690477

  9. Real-Time, Single-Step Bioassay Using Nanoplasmonic Resonator With Ultra-High Sensitivity

    NASA Technical Reports Server (NTRS)

    Zhang, Xiang (Inventor); Ellman, Jonathan A. (Inventor); Chen, Fanqing Frank (Inventor); Su, Kai-Hang (Inventor); Wei, Qi-Huo (Inventor); Sun, Cheng (Inventor)

    2014-01-01

    A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

  10. A Hybrid LPG/CFBG for Highly Sensitive Refractive Index Measurements

    PubMed Central

    Sun, An; Wu, Zhishen

    2012-01-01

    A simple and high sensitive method employing a hybrid long period grating (LPG)/chirped fiber Bragg grating (CFBG) for refractive index (RI) measurements is proposed and investigated experimentally. The wide wavelength range of backward cladding modes are excited through the coupling and recoupling between LPG and CFBG. Experimental results indicate that the recoupled cladding modes between LPG and CFBG and core mode are modulated by the surrounding RI and highly sensitive RI measurements can be achieved by simply measuring the reflected intensity changes of the recoupled cladding modes and core mode. PMID:22969347

  11. Real-time, single-step bioassay using nanoplasmonic resonator with ultra-high sensitivity

    DOEpatents

    Zhang, Xiang; Ellman, Jonathan A; Chen, Fanqing Frank; Su, Kai-Hang; Wei, Qi-Huo; Sun, Cheng

    2014-04-01

    A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

  12. Formation of High-Purity Indium Oxide Nanoparticles and Their Application to Sensitive Detection of Ammonia.

    PubMed

    Bhardwaj, Sanjeev K; Bhardwaj, Neha; Kukkar, Manil; Sharma, Amit L; Kim, Ki-Hyun; Deep, Akash

    2015-01-01

    High-purity In₂O₃ nanoparticles were recovered from scrap indium tin oxide substrates in a stepwise process involving acidic leaching, liquid-liquid extraction with a phosphine oxide extractant, and combustion of the organic phase. The morphological and structural parameters of the recovered nanoparticles were investigated to support the formation of the desired products. These In₂O₃ nanoparticles were used for sensitive sensing of ammonia gas using a four-probe electrode device. The proposed sensor offered very quick response time (around 10 s) and highly sensitive detection of ammonia (at a detection limit of 1 ppm). PMID:26694415

  13. Submicrometer resolution far field high sensitivity Kerr microscopy for in-plane magnetization detection.

    PubMed

    Wang, C H; Yang, Z

    2009-07-01

    We report that a far field magneto-optical system designed for detecting the off-plane magnetization in polar configuration can also detect the in-plane magnetization, while preserving the high sensitivity by using symmetric illumination and photoelastic modulation, even though the optical axis of the system is vertical to the sample surface. The spatial resolution can reach 500 nm at 514 nm in wavelength. The in-plane sensitivity can be eliminated by using an aperture to remove the off-axis obliquely incident light generated by the high numerical aperture objective lens that focuses the laser beam onto the sample surface. PMID:19655943

  14. Formation of High-Purity Indium Oxide Nanoparticles and Their Application to Sensitive Detection of Ammonia

    PubMed Central

    Bhardwaj, Sanjeev K.; Bhardwaj, Neha; Kukkar, Manil; Sharma, Amit L.; Kim, Ki-Hyun; Deep, Akash

    2015-01-01

    High-purity In2O3 nanoparticles were recovered from scrap indium tin oxide substrates in a stepwise process involving acidic leaching, liquid-liquid extraction with a phosphine oxide extractant, and combustion of the organic phase. The morphological and structural parameters of the recovered nanoparticles were investigated to support the formation of the desired products. These In2O3 nanoparticles were used for sensitive sensing of ammonia gas using a four-probe electrode device. The proposed sensor offered very quick response time (around 10 s) and highly sensitive detection of ammonia (at a detection limit of 1 ppm). PMID:26694415

  15. Localized brain differences in Arc expression between mice showing low vs. high propensity to ethanol sensitization.

    PubMed

    Nona, Christina N; Lam, Marcus; Nobrega, José N

    2016-03-01

    Behavioral sensitization to ethanol (EtOH) manifests as a progressive and enduring increase in locomotor activity with repeated drug exposure. However, not all mice sensitize to EtOH and the neuronal mechanisms mediating vulnerability and resistance to EtOH sensitization remain unclear. We examined regional brain expression of the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) in order to identify brain areas in which neuroplastic changes may contribute to the development and expression of EtOH sensitization. Male DBA/2J mice received 5 biweekly injections of EtOH (2.2g/kg, i.p.) or saline (SAL). They were categorized as high- (HS) or low-sensitized (LS) on the basis of final locomotor activity scores. In both LS and HS mice sacrificed after the last sensitization injection, Arc expression was decreased throughout the brain in comparison to SAL animals. A similar pattern was seen in mice sacrificed after an EtOH challenge two weeks after the last sensitization injection. However in this cohort, Arc expression was significantly increased in the central amygdala (CeA) in LS mice and in SAL mice receiving EtOH for the first time. No significant increases in Arc expression were seen in brains of sensitized (HS) animals. These results indicate an acute EtOH challenge results in different patterns of Arc expression in brains of LS, HS, and SAL mice. The dramatic increases in Arc expression in the CeA in LS and SAL mice showing little or no behavioral activation suggests that neural activity in this region may serve to inhibit the stimulant effects of EtOH. The observation that HS mice do not show increases in Arc expression with an EtOH challenge suggests the possibility that increased tolerance to the Arc-inducing effects of EtOH may be a factor in behavioral sensitization. PMID:26708208

  16. Engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens.

    PubMed

    Seo, Youngmin; Kim, Ji-eun; Jeong, Yoon; Lee, Kwan Hong; Hwang, Jangsun; Hong, Jongwook; Park, Hansoo; Choi, Jonghoon

    2016-01-28

    Many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. Given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Vaccinia virus) is highly desirable. Here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capturing antibodies against four different high-risk pathogens for simple and rapid isolation, and (2) genetically engineered apoferritin nanoparticles conjugated with multiple quantum dots and detection antibodies against four different high-risk pathogens for signal amplification. For each high-risk pathogen, we demonstrated at least 10-fold increase in sensitivity compared to traditional lateral flow devices that utilize enzyme-based detection methods. Multiplexed detection of high-risk pathogens in a sample was also successful by using the nanoconstructs harboring the dye molecules with fluorescence at different wavelengths. We ultimately envision the use of this novel nanoprobe detection platform in future applications that require highly sensitive on-site detection of high-risk pathogens. PMID:26462853

  17. Engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens

    NASA Astrophysics Data System (ADS)

    Seo, Youngmin; Kim, Ji-Eun; Jeong, Yoon; Lee, Kwan Hong; Hwang, Jangsun; Hong, Jongwook; Park, Hansoo; Choi, Jonghoon

    2016-01-01

    Many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. Given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Vaccinia virus) is highly desirable. Here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capturing antibodies against four different high-risk pathogens for simple and rapid isolation, and (2) genetically engineered apoferritin nanoparticles conjugated with multiple quantum dots and detection antibodies against four different high-risk pathogens for signal amplification. For each high-risk pathogen, we demonstrated at least 10-fold increase in sensitivity compared to traditional lateral flow devices that utilize enzyme-based detection methods. Multiplexed detection of high-risk pathogens in a sample was also successful by using the nanoconstructs harboring the dye molecules with fluorescence at different wavelengths. We ultimately envision the use of this novel nanoprobe detection platform in future applications that require highly sensitive on-site detection of high-risk pathogens.

  18. Indoor allergen exposure, sensitization, and development of asthma in a high-risk birth cohort.

    PubMed

    Carlsten, Chris; Dimich-Ward, Helen; Becker, Allan B; Ferguson, Alexander; Chan, Henry W; DyBuncio, Anne; Chan-Yeung, Moira

    2010-06-01

    Contradictory findings have been observed for the association of house dust mite (HDM), cat, and dog allergen exposure with sensitization and asthma. We sought to determine the relationship between exposures to these allergens, at various points during early childhood, and specific sensitization and asthma at age 7 in a high-risk birth cohort. As part of a multi-faceted Canadian intervention program for the primary prevention of asthma in high-risk infants, children were assessed by pediatric allergists at age 7 for asthma and underwent allergy skin prick testing. House dust samples were analyzed for HDM, cat, and dog allergen levels at several time points during years 1 and 7 of life. Multiple logistic regression analyses were carried out for the combined cohort and separately for the control and intervention groups. Exposure to a higher level of HDM allergen in year 1 or year 7 was associated with a higher risk of year 7 sensitization to HDM but not asthma. Exposure to higher levels of cat allergen in year 1 or year 7 did not affect the risk of year 7 sensitization to cat or asthma. Dog ownership, or exposure to higher levels of dog allergen in year 1 or year 7, did not affect the risk of year 7 sensitization to dog; however, year 7 dog allergen exposure (intervention group only) or ownership was associated with increased year 7 asthma risk. Our findings suggest that in high-risk children, there are allergen-specific associations of exposure with sensitization and with asthma; early life-elevated HDM exposure was associated with risk of sensitization but not asthma while the opposite was true for dog exposure. PMID:20337962

  19. High sensitivity refractive index sensor based on adiabatic tapered optical fiber deposited with nanofilm by ALD.

    PubMed

    Zhu, Shan; Pang, Fufei; Huang, Sujuan; Zou, Fang; Dong, Yanhua; Wang, Tingyun

    2015-06-01

    Atomic layer deposition (ALD) technology is introduced to fabricate a high sensitivity refractive index sensor based on an adiabatic tapered optical fiber. Different thickness of Al2O3 nanofilm is coated around fiber taper precisely and uniformly under different deposition cycles. Attributed to the high refractive index of the Al2O3 nanofilm, an asymmetry Fabry-Perot like interferometer is constructed along the fiber taper. Based on the ray-optic analysis, total internal reflection happens on the nanofilm-surrounding interface. With the ambient refractive index changing, the phase delay induced by the Goos-Hänchen shift is changed. Correspondingly, the transmission resonant spectrum shifts, which can be utilized for realizing high sensitivity sensor. The high sensitivity sensor with 6008 nm/RIU is demonstrated by depositing 3000 layers Al2O3 nanofilm as the ambient refractive index is close to 1.33. This high sensitivity refractive index sensor is expected to have wide applications in biochemical sensors. PMID:26072758

  20. The nature and nurture of high IQ: an extended sensitive period for intellectual development.

    PubMed

    Brant, Angela M; Munakata, Yuko; Boomsma, Dorret I; Defries, John C; Haworth, Claire M A; Keller, Matthew C; Martin, Nicholas G; McGue, Matthew; Petrill, Stephen A; Plomin, Robert; Wadsworth, Sally J; Wright, Margaret J; Hewitt, John K

    2013-08-01

    IQ predicts many measures of life success, as well as trajectories of brain development. Prolonged cortical thickening observed in individuals with high IQ might reflect an extended period of synaptogenesis and high environmental sensitivity or plasticity. We tested this hypothesis by examining the timing of changes in the magnitude of genetic and environmental influences on IQ as a function of IQ score. We found that individuals with high IQ show high environmental influence on IQ into adolescence (resembling younger children), whereas individuals with low IQ show high heritability of IQ in adolescence (resembling adults), a pattern consistent with an extended sensitive period for intellectual development in more-intelligent individuals. The pattern held across a cross-sectional sample of almost 11,000 twin pairs and a longitudinal sample of twins, biological siblings, and adoptive siblings. PMID:23818653