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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 rapid and highly sensitive UPLC-MS-MS method for the quantification of zolpidem tartrate in human EDTA plasma and its application to pharmacokinetic study.

    PubMed

    Reddy, Dendhi Chandrapal; Bapuji, Akula Tukaram; Rao, Vepakomma Suryanarayana; Himabindu, Vurimindi; Ravinder, Sreedasyam

    2012-07-01

    A rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the quantification of zolpidem in human EDTA plasma using ondansetron (IS) as an internal standard. The analyte and IS were extracted from human plasma using ethyl acetate and separated on a C18 column (Inertsil-ODS, 5 µm, 4.6 × 50 mm) interfaced with a triple quadrupole tandem mass spectrometer. The mobile phase, which consisted of a mixture of methanol and 20 mM ammonium formate (pH 5.00 ± 0.05; 75:25 v/v), was injected at a flow rate of 0.40 mL/min. The retention times of zolpidem and IS were approximately 1.76 and 1.22. The LC run time was 3 min. The electrospray ionization source was operated in positive ion mode. Multiple reaction monitoring used the [M + H](+) ions m/z 308.13 → 235.21 for zolpidem and m/z 294.02 → 170.09 for the ondansetron, respectively. Five freeze-thaw cycles was established at -20 and -70°C.The linearity of the response/concentration curve was established in human EDTA plasma over the concentration range 0.10-149.83 ng/mL. The lower detection limit [(signal-to-noise (S/N) > 3] was 0.04 ng/mL and the lower limit of quantification (S/N > 10) was 0.10 ng/mL. This LC-MS-MS method was validated with intra-batch and inter-batch precision of 0.52-8.66.The intra-batch and inter-batch accuracy was 96.66-106.11. Recovery of zolpidem in human plasma was 87.00% and IS recovery was 81.60%. The primary pharmacokinetic parameters were T(max) (h) = (1.25 ± 0.725), C(max) (ng/mL) (127.80 ± 34.081), AUC(0→t), = (665.37 ± 320.982) and AUC(0→∞), 686.03 ± 342.952, respectively. PMID:22689921

  3. Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2′-deoxyguanosine by UPLC-MS/MS Analysis

    PubMed Central

    Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

    2016-01-01

    Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7−5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC. PMID:27585556

  4. Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2'-deoxyguanosine by UPLC-MS/MS Analysis.

    PubMed

    Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

    2016-01-01

    Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7-5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC. PMID:27585556

  5. 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. PMID:26869341

  6. Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma.

    PubMed

    Jacobs, Bart A W; Rosing, Hilde; de Vries, Niels; Meulendijks, Didier; Henricks, Linda M; Schellens, Jan H M; Beijnen, Jos H

    2016-07-15

    Quantification of the endogenous dihydropyrimidine dehydrogenase (DPD) substrate uracil (U) and the reaction product dihydrouracil (UH2) in plasma might be suitable for identification of patients at risk of fluoropyrimidine-induced toxicity as a result of DPD deficiency. In this paper, we describe the development and validation of a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantification of U and UH2 in human plasma. Analytes were extracted by protein precipitation, chromatographically separated on an Acquity UPLC(®) HSS T3 column with gradient elution and analyzed with a tandem mass spectrometer equipped with an electrospray ionization source. U was quantified in the negative ion mode and UH2 in the positive ion mode. Stable isotopes for U and UH2 were used as internal standards. Total chromatographic run time was 5min. Validated concentration ranges for U and UH2 were from 1 to 100ng/mL and 10 to 1000ng/mL, respectively. Inter-assay bias and inter-assay precision for U were within ±2.8% and ≤12.4%. For UH2, inter-assay bias and inter-assay precision were within ±2.9% and ≤7.2%. Adequate stability of U and UH2 in dry extract, final extract, stock solution and plasma was demonstrated. Stability of U and UH2 in whole blood was only satisfactory when stored up to 4hours at 2-8°C, but not at ambient temperatures. An accurate, precise and sensitive UPLC-MS/MS assay for quantification of U and UH2 in plasma was developed. This assay is now applied to support clinical studies with fluoropyrimidine drugs. PMID:27179185

  7. 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

  8. 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

  9. Development and validation of sensitive and rapid UPLC-MS/MS method for quantitative determination of daclatasvir in human plasma: Application to a bioequivalence study.

    PubMed

    Rezk, Mamdouh R; Bendas, Ehab R; Basalious, Emad B; Karim, Iman A

    2016-09-01

    A rapid and sensitive UPLC-MS/MS method was developed and validated for determination of daclatasvir (DAC) in human plasma using sofosbuvir (SOF) as an internal standard (IS). The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Precipitation with acetonitrile was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC HSS C18 (50×2.1mm, 1.8μm) column by pumping 10mM ammonium formate (pH 3.5) and acetonitrile in an isocratic mode at a flow rate of 0.30ml/min. Method validation was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 5-4000ng/ml for DAC. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1.2min made it possible to analyze more than 500 human plasma samples per day. The wider range of quantification of DAC allowed the applicability of the developed method for its determination in a bioequivalence study in human volunteers. PMID:27232152

  10. Determination of opiates and cocaine in urine by high pH mobile phase reversed phase UPLC-MS/MS.

    PubMed

    Berg, Thomas; Lundanes, Elsa; Christophersen, Asbjørg S; Strand, Dag Helge

    2009-02-01

    A fast and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of opiates (morphine, codeine, 6-monoacetylmorphine (6-MAM), pholcodine, oxycodone, ethylmorphine), cocaine and benzoylecgonine in urine has been developed and validated. Sample preparation was performed by solid phase extraction (SPE) on a mixed mode cation exchange (MCX) cartridge. For optimized chromatographic performance with repeatable retention times, narrow and symmetrical peaks, and focusing of all analytes at the column inlet at gradient start, a basic mobile phase consisting of 5mM ammonium bicarbonate, pH 10.2, and methanol (MeOH) was chosen. Positive electrospray ionization (ESI(+)) MS/MS detection was performed with a minimum of two multiple reaction monitoring (MRM) transitions for each analyte. Deuterium labelled-internal standards were used for six of the analytes. Between-assay retention time repeatabilities (n=10 series, 225 injections in total) had relative standard deviation (RSD) values within 0.1-0.6%. Limit of detection (LOD) and limit of quantification (LOQ) values were in the range 0.003-0.05 microM (0.001-0.02 microg/mL) and 0.01-0.16 microM (0.003-0.06 microg/mL), respectively. The RSD values of the between-assay repeatabilities of concentrations were

  11. 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

  12. Development and validation of a selective, sensitive and stability indicating UPLC-MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance.

    PubMed

    A, Vijaya Bhaskar Reddy; Yusop, Zulkifli; Jaafar, Jafariah; Aris, Azmi B; Majid, Zaiton A; Umar, Khalid; Talib, Juhaizah

    2016-09-01

    In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm×2.1mm, 1.7μm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp-I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis. PMID:27262107

  13. Novel and sensitive UPLC-MS/MS method for quantification of sofosbuvir in human plasma: application to a bioequivalence study.

    PubMed

    Rezk, Mamdouh R; Basalious, Emad B; Amin, Mohammed E

    2016-09-01

    A novel and sensitive LC-MS/MS method was developed and validated for determination of sofosbuvir (SF) using eplerenone as an internal standard. The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Extraction with tert-butyl methyl ether was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column by pumping 0.1% formic acid and acetonitrile in an isocratic mode at a flow rate of 0.35 mL/min. Method validation was performed as per the US Food and Drug Administration guidelines and the standard curves were found to be linear in the range of 0.25-3500 ng/mL for SF. The intra- and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1 min made it possible to analyze more than 500 human plasma samples per day. A very low quantification limit of SF allowed the applicability of the developed method for determination of SF in a bioequivalence study in human volunteers. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26821881

  14. 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

  15. 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

  16. [Simultaneous determination of 11 mycotoxins in malt by isotope internal standard-UPLC-MS/MS].

    PubMed

    Wang, Sha; Kong, Wei-jun; Yang, Mei-hua

    2016-01-01

    A suitable ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of 11 mycotoxins with isotope internal standard in malt. The mycotoxins in malt were extracted and purified by one-step ultrasonic extraction procedure using acetonitrile/water/acetic acid (80 : 19 : 1), and then detected and confirmed by UPLC-MS/MS, and quantified by isotope labeled AFB1 ([13C17]-AFB1) and ZEN ([13C18]-ZEN) internal standards. Rapid separation of the 11 mycotoxins was successfully achieved on a Phenomenex Kinetex C18 column (100 mm x 2.1 mm, 2.6 μm) with gradient elution using the mobile phase of methanol containing 0.1% formic acid and 2 mmol x L(-1) ammonium acetate in water. Simultaneous acquisition was performed in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI) source operated in both positive and negative ionization modes. The established method provided a good linearity for the 11 mycotoxins within their respective linear ranges with correlation coefficients all higher than 0.999 1. The average recoveries ranged from 75.0% to 117.0% with relative standard deviations (RSDs) below 5.1%. The limits of detection (LODs) and quantitation (LOQs) ranged from 0.05 to 30 μg x kg(-1) and 0.15 to 87.5 μg x kg(-1), respectively, which were below the maximum residue levels (MRLs) set by the European Union. Twenty malt samples were analyzed and nine samples were detected with mycotoxins, which were confirmed according to the same fragment ions found in positive samples and the standards at the same retention time. This study has demonstrated that the one-step extraction procedure of mycotoxins from complex matrices coupled to UPLC-MS/MS method is simple, quick, accurate and sensitive for quantitative and qualitative analysis of multiple mycotoxins in malt. PMID:27405171

  17. 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 μm, 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

  18. Development and validation of a simple and sensitive method for quantification of levodopa and carbidopa in rat and monkey plasma using derivatization and UPLC-MS/MS.

    PubMed

    Junnotula, Venkatraman; Licea-Perez, Hermes

    2013-05-01

    A simple, selective, and sensitive quantitative method has been developed for the simultaneous determination of levodopa and carbidopa in rat and monkey plasma by protein precipitation using acetonitrile containing the derivatizing reagent, flourescamine. Derivatized products of levodopa and carbidopa were separated on a BEH C18 column (2.1 mm × 50 mm; 1.7 μm particle size) using ultra high performance liquid chromatography (UHPLC) without any further purification. Tandem mass spectrometry (MS/MS) was used for detection. The method was validated over the concentration range of 5-5000 ng/mL and 3-3000 ng/mL for levodopa and carbidopa, respectively in rat and monkey plasma. Due to the poor stability of the investigated analytes in biological matrices, a mixture of sodium metabisulfite and hydrazine dihydrochloride was used as a stabilizer. This method was successfully utilized to support pharmacokinetic studies in both species. The results from assay validations and incurred samples re-analysis show that the method is selective, sensitive and robust. To our knowledge, this is the first UHPLC-MS/MS based method that utilizes derivatization with fluorescamine and provides adequate sensitivity for both levodopa and carbidopa with 50 μL of sample and a run time of 3.5 min. PMID:23548675

  19. Development and Validation of an UPLC-MS/MS Method for Simultaneous Determination of Ibuprofen and Promethazine in Tablets Stored on Board the International Space Station

    NASA Technical Reports Server (NTRS)

    Wu, L.; Chow, D. S.-L.; Daniels, V. R.

    2016-01-01

    Therapeutic efficacy and safety of pharmaceuticals remain a critical issue for successful NASA medical operations of long-term space missions on International Space Station (ISS). Medications stored aboard the ISS are subjected to unique environmental factors for extended time periods that may cause physicochemical degradation or alterations in the integrity of formulations that include the active pharmaceutical ingredient (API) and the chemical matrix of the formulation. Degradation of API and adjuvants, in addition to alterations of the chemical matrix of the formulation, can decrease potency and bioavailability and increase the risk due to toxicity of degraded medications. UPLC-MS/MS analysis is efficient and highly sensitive to quantify API content and MS analysis enables the elucidation of the structures of degradation products for each formulation. Therefore the aim of this project was to develop and validate a rapid, specific, and sensitive UPLC-MS/MS assay for the simultaneous determination of ibuprofen and promethazine in tablets stored aboard the ISS.

  20. 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

  1. 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. PMID:26753970

  2. A quantitative determination of fluorochloridone in rat plasma by UPLC-MS/MS method: application to a pharmacokinetic study.

    PubMed

    Liu, Shihong; Shi, Jingmin; Fan, Junpei; Sun, Jie; Zhang, Suhui; Hu, Yue; Wei, Li; Wu, Chunhua; Chang, Xiuli; Tang, Liming; Zhou, Zhijun

    2016-08-01

    A precise, high-throughput and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the determination of fluorochloridone (FLC) in rat plasma. The extraction of analytes from plasma samples was carried out by protein precipitation procedure using acetonitrile prior to UPLC-MS/MS analysis. Verapamil was proved as a proper internal standard (IS) among many candidates. The chromatographic separation based on UPLC was well optimized. Multiple reaction monitoring in positive electrospray ionization was used with the optimized MS transitions at: m/z 312.0 → 292.0 for FLC and m/z 456.4 → 165.2 for IS. This method was well validated with good linear response (r(2)  > 0.998) observed over the investigated range of 3-3000 ng/mL and with satisfactory stability. This method was also characterized with adequate intra- and inter-day precision and accuracy (within 12%) in the quality control samples, and with high selectivity and less matrix effect observed. Total running time was only 1.5 min. This method has been successfully applied to a pilot FLC pharmacokinetic study after oral administration. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26663256

  3. 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 1.95 ng/mL. LAZ and internal standard diadzein (IS) were separated using ACQUITY UPLC(®) BEH C18 column. Gradient elution was used at a flow rate of 0.45 mL/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 (100 μL) 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 1.95-250 ng/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 5 mg/kg. PMID

  4. Determination of rivaroxaban, apixaban and edoxaban in rat plasma by UPLC-MS/MS method.

    PubMed

    Zhang, Wan-Li; Lou, Dan; Zhang, Dong-Tao; Zhang, Yin; Huang, Huan-Jie

    2016-08-01

    To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of rivaroxaban, apixaban and edoxaban in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm × 50 mm, 1.7 μm) using gradient elution with a mobile phase of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 436.1 → 145.1 for rivaroxaban, m/z 460.0 → 443.1 for apixaban, m/z 548.2 → 366.1 for edoxaban and m/z 285.2 → 193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 1.0-200 ng/mL for rivaroxaban, 1.0-100 ng/mL for apixaban and 1.0-500 ng/mL for edoxaban. Total time for each chromatograph was 3.5 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations <10.5 % and the accuracy values ranged from -9.9 to 11.3 %. The method was successfully applied to a pharmacokinetic study of rivaroxaban, apixaban and edoxaban in rats. PMID:27116356

  5. 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

  6. 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

  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

  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. Coumarin and furanocoumarin quantitation in citrus peel via ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS).

    PubMed

    Dugrand, Audray; Olry, Alexandre; Duval, Thibault; Hehn, Alain; Froelicher, Yann; Bourgaud, Frédéric

    2013-11-13

    Coumarins and furanocoumarins are secondary metabolites commonly found in citrus plants. These molecules are allelochemical compounds in plants that have controversial effects on humans, such as phototoxicity and the commonly described interactions with drugs, referred to as the "grapefruit juice effect". Thus, it is important to develop a reliable method to identify and quantitate the coumarins and furanocoumarins in citrus extracts. For this purpose, we herein describe an ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS)-based method. We first developed a rapid UPLC method (20 min) to separate the isomers of each furanocoumarin. A subsequent single ion monitoring MS detection method was performed to distinguish between the molecules, which were possibly coeluting but had different molecular weights. The method was successfully used to separate and quantitate 6 coumarins and 21 furanocoumarins in variable amounts within peel extracts (flavedo and albedo) of 6 varieties of Citrus (sweet orange, lemon, grapefruit, bergamot, pummelo, and clementine). This method combines high selectivity and sensitivity in a rapid analysis and is useful for fingerprinting Citrus species via their coumarin and furanocoumarin contents. PMID:24117278

  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. 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

  13. 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

  14. [Metabolites and metabolic pathways of mesaconitine in rat liver microsomal investigated by using UPLC-MS/MS method in vitro].

    PubMed

    Bi, Yun-Feng; Liu, Shu; Zhang, Rui-Xing; Song, Feng-Rui; Liu, Zhi-Qiang

    2013-12-01

    Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes. PMID:24689241

  15. 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

  16. 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

  17. 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 μm) 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

  18. 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

  19. Photocatalytic degradation of hexazinone and its determination in water via UPLC-MS/MS.

    PubMed

    Mei, Mei; Du, Zhenxia; Xu, Ruifen; Chen, Yun; Zhang, Haojie; Qu, Shuping

    2012-06-30

    Degradation of hexazinone has been investigated by means of photocatalysis of mixed-phase crystal nano-TiO(2). Influences of adsorption, amount of nano-TiO(2), pH and irradiation time on the photocatalytic process are studied. Results show that hexazinone is totally degraded within 40min of irradiation under pH neutral conditions. This compares favorably with Degussa P25 TiO(2) when conducted under the same experimental conditions. Preliminary photocatalytic kinetic information for hexazinone degradation is proposed. First order kinetics is obtained for the adsorption and photocatalytic degradation reactions, which fit the Langmuir-Hinshelwood model. A rapid, sensitive and accurate UPLC-MS/MS technique is developed and utilized to determine the level of hexazinone in water in support of the degradation kinetics study. The results indicate a limit of detection (LOD) at 0.05μg/l and the recoveries between 90.2 and 98.5% with relative standard deviations (RSD) lower than 12%. A LC-MS/MS technique is used to trace the degradation process. Complete degradation is achieved into final products including nontoxic water, carbon dioxide and urea. A probable pathway for the total photocatalytic degradation of hexazinone is proposed. PMID:22551636

  20. Rapid determination of eight oxoisoaporphine alkaloids in Rhizoma Menispermi by the optimal homogenate extraction followed by UPLC-MS/MS.

    PubMed

    Wei, Jinxia; Jiang, Zhen; Cui, Zhi; Guo, Xingjie

    2015-07-01

    The objective of this study was to develop a rapid and reliable homogenate extraction (HGE) and ultra high-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for simultaneous analysis of eight bioactive oxoisoaporphine alkaloids (including two new alkaloids) in Rhizoma Menispermi. HGE was optimized by response surface methodology (RSM) to obtain the maximum extraction efficiency of eight alkaloids. Separation was achieved on a Waters ACQUITY UPLC® BEH C18 column (50 × 2.1 mm(2), 1.7 μm) using gradient elution with a mobile phase consisting of acetonitrile and 0.2% formic acid in water. Quantification was performed with multiple reaction monitoring (MRM) mode using positive ESI as an interface. This is the first report of the simultaneous analysis of eight oxoisoaporphine alkaloids in Rhizoma Menispermi using a UPLC-MS/MS method; this analysis afforded good linearity, precision, and accuracy. Then, the method was successfully applied to determine the alkaloids in Rhizoma Menispermi from different sources. PMID:25948242

  1. 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...

  2. 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...

  3. A UPLC-MS/MS Method for Therapeutic Drug Monitoring of Etonogestrel

    PubMed Central

    Thomas, Tiffany; Petrie, Kelsey; Shim, Joonho; Abildskov, Kirsten M.; Westhoff, Carolyn L.; Cremers, Serge

    2013-01-01

    Introduction Etonogestrel is a progestin used in the contraceptive vaginal ring NuvaRing and the subdermal implant Implanon. A sensitive method for measuring etonogestrel is useful for further investigating the progestin’s pharmacokinetics with these alternative contraceptive formulations as well as generating important information about possible continued efficacy or potential failure to remove the subdermal implant. Methods Standards and serum samples were spiked with D8 progesterone (internal standard) and subsequently extracted with dichloromethane, dried, and reconstituted in 25% methanol with formic acid. Etonogestrel was analyzed by positive electrospray ionization in multiple reaction monitoring mode with a run time of 5.5 minutes using a C18 BEH column. The mobile phase was a gradient of water:acetonitrile, with 0.1% formic acid. The method was applied successfully to study the pharmacokinetics of etonogestrel during vaginal ring use. The method was also used in routine patient care to assess etonogestrel levels. Results The method is linear from 50pg/ml to 2000pg/ml. The limit of detection and quantification (LOD and LOQ) are 25 and 50pg/ml respectively. There was no observed ionization suppression within the linear range of the assay and the average recovery was 87%. Serum etonogestrel levels of n=3 subjects were all within the linear range of the assay for a total study period of 42 days after insertion of the ring. Of n=20 patients with non-palpable subdermal implants, n=13 had etonogestrel levels > 25 pg/mL, while n=7 had levels < 25 pg/mL. Conclusions We developed a rapid, sensitive, and robust UPLC-MS/MS method for the quantification of etonogestrel in serum that is useful to study the progestin’s pharmacokinetics and inform physicians about successful implantation or potential failure to remove a subdermal device. PMID:24081205

  4. 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

  5. Inhibition of the isoprenoid biosynthesis pathway; detection of intermediates by UPLC-MS/MS.

    PubMed

    Henneman, Linda; van Cruchten, Arno G; Kulik, Willem; Waterham, Hans R

    2011-04-01

    The isoprenoid biosynthesis pathway provides the cell with a variety of compounds which are involved in multiple cellular processes. Inhibition of this pathway with statins and bisphosphonates is widely applied in the treatment of hypercholesterolemia and metabolic bone disease, respectively. In addition, since isoprenylation of proteins is an important therapeutic target in cancer research there is interest in interfering with isoprenoid biosynthesis, for which new inhibitors to block farnesylation and geranylgeranylation of small GTPases are being developed. We recently developed a sensitive method using UPLC-MS/MS that allows the direct detection and quantification of all intermediates of the mevalonate pathway from MVA to GGPP which can be used to verify the specificity of inhibitors of the isoprenoid biosynthesis pathway. We here investigated the specificity of several inhibitors of the isoprenoid biosynthesis pathway in HepG2 cells, fibroblasts and lymphoblasts. The nitrogen-containing bisphosphonates pamidronate and zoledronate specifically inhibit farnesyl pyrophosphate synthase indicated by the accumulation of IPP/DMAPP. However, zaragozic acid A, a squalene synthase inhibitor, causes an increase of MVA in addition to the expected increase of FPP. Analysis of isoprenoid intermediate profiles after incubation with 6-fluoromevalonate showed a very nonspecific result with an increase in MVA, MVAP, MVAPP and IPP/DMAPP. These results show that inhibitors of a particular enzyme of the isoprenoid biosynthesis pathway can have additional effects on other enzymes of the pathway either direct or indirect through accumulation of isoprenoid intermediates. Our method can be used to test new inhibitors and their effect on overall isoprenoid biosynthesis. PMID:21237288

  6. Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS.

    PubMed

    Wang, Xianqin; Wang, Shuanghu; Ma, Jianshe; Ye, Tao; Lu, Mengrou; Fan, Miao; Deng, Mingjie; Hu, Lufeng; Gao, Zhimou

    2015-11-10

    Berberrubine is an isoquinoline alkaloid isolated from Berberis vulgaris L, and it is readily derived from berberine. In this study, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of berberrubine in rat plasma and mouse tissue has been developed. Magnoflorine was employed as an internal standard (IS), and liquid-liquid extraction by ethyl acetate was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1mm×100mm, 1.7μm) 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 322.0→307.0 for berberrubine and m/z 342.8→298.2 for IS. Calibration plots were linear in the range of 2-2000ng/mL for berberrubine in rat plasma and mouse tissue. Mean recoveries of berberrubine in rat plasma ranged from 79.6% to 84.8%. Intra-day and inter-day precision were less than 11%. The accuracy ranged from 93.6% to 106.8%. The method has also been successfully applied in pharmacokinetics and tissue distribution study of berberrubine. The absolute bioavailability of berberrubine was determined to be 31.6%. The results also show that berberrubine is rapidly absorbed and widely distributed in various tissues. The level of berberrubine in liver is highest, and followed by kidney, spleen and heart. Furthermore, the concentration of berberrubine in various tissues could also be predicted by a BP-ANN model. PMID:26279368

  7. 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

  8. 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

  9. 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

  10. Evaluation of a rapid method for the simultaneous quantification of ribavirin, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS.

    PubMed

    Shi, Xiaojun; Zhu, Dedong; Lou, Jie; Zhu, Bo; Hu, Ai-rong; Gan, Dongmei

    2015-10-01

    A rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ribavirin, sofosbuvir and its metabolite GS-331007 in rat plasma was established. The analytes and the internal standard (midazolam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 245.1→113.1 for ribavirin, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 326.2→291.1 for midazolam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 5-1000ng/mL for ribavirin, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.0% and the accuracy values ranged from -10.6% to 11.6%. The method was successfully applied to a pharmacokinetic study of ribavirin, sofosbuvir and GS-331007 in rats. PMID:26363369

  11. Simultaneous determination of ledipasvir, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

    PubMed

    Pan, Chenwei; Chen, Yongping; Chen, Weilai; Zhou, Guangyao; Jin, Lingxiang; Zheng, Yi; Lin, Wei; Pan, Zhenzhen

    2016-01-01

    In this work, a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ledipasvir, sofosbuvir and its metabolite GS-331007 in rat plasma was developed. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 889.8→130.1 for ledipasvir, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 2-500ng/mL for ledipasvir, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatography was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<10.2% and the accuracy values ranged from -9.8% to 11.2%. The method was successfully applied to a pharmacokinetic study of ledipasvir, sofosbuvir and GS-331007 in rats. PMID:26684720

  12. Simultaneous determination of nintedanib and its metabolite by UPLC-MS/MS in rat plasma and its application to a pharmacokinetic study.

    PubMed

    Lin, Dan; Qiao, Li-man; Zhang, Yu-niao; Liu, Yuan; Liu, Xin-she

    2016-01-01

    To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of concentration of nintedanib and its metabolite BIBF 1202 in rat plasma. The nintedanib and its metabolite and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm×50 mm, 1.7 μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.30 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z540.3→113.1 for nintedanib, m/z526.3→113.0 for BIBF 1202 and m/z285.3→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated for 1.0-200 ng/mL for nintedanib and 0.5-100 ng/mL for BIBF 1202 using 100 μL of plasma sample. Total time for each chromatograph was 3.0 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.8% and the accuracy values ranged from -11.9% to 10.4%. The method was successfully applied to a pharmacokinetic study of nintedanib and BIBF 1202 in rats after oral administration of nintedanib. PMID:26355771

  13. Simultaneous quantification of vortioxetine, carvedilol and its active metabolite 4-hydroxyphenyl carvedilol in rat plasma by UPLC-MS/MS: Application to their pharmacokinetic interaction study.

    PubMed

    Huang, Yi; Zheng, Shuangli; Pan, Yongyang; Li, Tao; Xu, Zhi-Sheng; Shao, Meng-Meng

    2016-09-01

    To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of vortioxetine, carvedilol and its metabolite 4-hydroxyphenyl carvedilol in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 299.2→150.1 for vortioxetine, m/z 407.2→100.3 for carvedilol, m/z 423.2→100.1 for 4-hydroxyphenyl carvedilol and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 0.5-100ng/mL for vortioxetine, 0.5-1000ng/mL for carvedilol and 0.1-50ng/mL for 4-hydroxyphenyl carvedilol. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<11.6% and the accuracy values ranged from -12.2% to 11.3%. The analytical method was successfully applied to a pharmacokinetic interaction study of vortioxetine and carvedilol after oral administration vortioxetine and carvedilol in rats. Results suggested that the co-administration of vortioxetine and carvedilol results in a significant drug interaction in rats. PMID:27262994

  14. Development and validation of an UPLC-MS/MS method for the quantification of ethoxzolamide in plasma and bioequivalent buffers: Applications to absorption, brain distribution, and pharmacokinetic studies

    PubMed Central

    Gao, Song; Zhao, Jing; Yin, Taijun; Ma, Yong; Xu, Beibei; Moore, Anthony N.; Dash, Pramod K.; Hu, Ming

    2015-01-01

    The purpose of this study is to develop and validate an UPLC-MS/MS method to quantify ethoxzolamide in plasma (EZ) and apply the method to absorption, brain distribution, as well as pharmacokinetic studies. A C18 column was used with 0.1% of formic acid in acetonitrile and 0.1% of formic acid in water as the mobile phases to resolve EZ. The mass analysis was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode. The results show that the linear range of EZ is 4.88–10,000.00 nM. The intra-day variance is less than 12.43 % and the accuracy is between 88.88–08.00 %. The inter-day variance is less than 12.87 % and accuracy is between 89.27–115.89 %. Protein precipitation was performed using methanol to extract EZ from plasma and brain tissues. Only 40 µL of plasma is needed for analysis due to the high sensitivity of this method, which could be completed in less than three minutes. This method was used to study the pharmacokinetics of EZ in SD rats, and the transport of EZ in Caco-2 and MDCK-MDR1 overexpressing cell culture models. Our data show that EZ is not a substrate for p-glycoprotein (P-gp) and its entry into the brain may not limited by the blood-brain barrier. PMID:25706567

  15. 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

  16. UPLC-MS/MS determination of voriconazole in human plasma and its application to a pharmacokinetic study.

    PubMed

    Wang, Zhe; Huang, Cheng-ke; Sun, Wei; Xiao, Cui; Wang, Zeng-shou

    2015-02-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine voriconazole in human plasma. Sample preparation was accomplished through a simple one-step protein precipitation with methanol. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using an isocratic mobile phase system composed of acetonitrile and water containing 1% formic acid (45:55, v/v) at a flow rate of 0.50 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 351.0 → 281.5 and m/z 237.1 → 194.2 were used to quantify voriconazole and carbamazepine (internal standard), respectively. The linearity of this method was found to be within the concentration range of 2.0-1000 ng/mL with a lower limit of quantification of 2.0 ng/mL. Only 1.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after oral administration of 200 mg voriconazole to 20 Chinese healthy male volunteers. PMID:24925071

  17. Determination and validation of hupehenine in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study.

    PubMed

    Wen, Congcong; Wang, Shuanghu; Huang, Xueli; Liu, Zezheng; Lin, Yingying; Yang, Suping; Ma, Jianshe; Zhou, Yunfang; Wang, Xianqin

    2015-12-01

    In this work, a sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of hupehenine in rat plasma was developed and validated. After addition of imperialine 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 × 100 mm, 1.7 µm) 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 reaction monitoring mode was used for quantification using target fragment ions m/z 416.3 → 98.0 for hupehenine, and m/z 430.3 → 138.2 for IS. Calibration plots were linear throughout the range 2-2000 ng/mL for hupehenine in rat plasma. Mean recoveries of hupehenine in rat plasma ranged from 92.5 to 97.3%. Relative standard deviations of intra-day and inter-day precision were both <6%. The accuracy of the method was between 92.7 and 107.4%. The method was successfully applied to a pharmacokinetic study of hupehenine after either oral or intravenous administration. For the first time, the bioavailability of hupehenine was reported as 13.4%. PMID:26033449

  18. 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.

  19. Determination of Apremilast in Rat Plasma by UPLC-MS-MS and Its Application to a Pharmacokinetic Study.

    PubMed

    Chen, Lian-Guo; Wang, Zhe; Wang, Shujun; Li, Tao; Pan, Yongyang; Lai, Xixi

    2016-09-01

    A rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was developed and validated for the determination and pharmacokinetic investigation of apremilast in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.0 min, and the elution of apremilast was at 1.27 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 461.3 → 257.1 for apremilast and m/z 237.2 → 194.2 for carbamazepine (internal standard). The calibration curve was linear over the range of 0.1-100 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The mean recovery of apremilast in plasma was in the range of 83.2-87.5%. Both intraday and interday precision were <9.6%. This method was successfully applied in the pharmacokinetic study after oral administration of 6.0 mg/kg apremilast in rats. PMID:27165568

  20. Simultaneous detection and comparative pharmacokinetics of amoxicillin, clavulanic acid and prednisolone in cows' milk by UPLC-MS/MS.

    PubMed

    Liu, Yuan; Zhu, Kui; Wang, Jianfen; Huang, Xiaoyong; Wang, Guanlin; Li, Congying; Cao, Jie; Ding, Shuangyang

    2016-01-01

    Amoxicillin (AMOX), clavulanic acid (CLAV) and prednisolone (PSL) are widely used in combination for the treatment of mastitis in lactating dairy cows. However, no method has been reported to detect these three chemicals in milk in a single assay. In the present work, a reliable and sensitive UPLC-MS/MS method was developed and validated for simultaneous determination of AMOX, CLAV and PSL in cow's milk. The analytes were determined by a positive and negative ionization electrospray mass spectrometer via multiple reaction monitoring. The linear ranges of AMOX, CLAV and PSL were from 2 to 1000ng/mL, 20-1000ng/mL and 1-1000ng/mL, respectively, with the correlation coefficients greater than 0.999. The limits of quantification (LOQs) were 2ng/mL (AMOX), 20ng/mL (CLAV) and 1ng/mL (PSL). Recoveries of the analytes of interest in milk samples were in the ranges of 84.2-101.4%. The intra-day and inter-day precisions ranged from 1.8% to 11.9%. This method was successfully applied to investigate the pharmacokinetics of AMOX, CLAV and PSL in milk from healthy and mastitic cows. The elimination times of AMOX and PSL in mastitic cows were longer than that in healthy cows, but the elimination times of CLAV did not show significant difference. PMID:26638031

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

    PubMed

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

    2013-05-01

    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. PMID:23529861

  2. Simultaneous Determination of Aliskiren Hemifumarate, Amlodipine Besylate and Hydrochlorothiazide in Spiked Human Plasma Using UPLC-MS/MS.

    PubMed

    Ebeid, Walid M; Elkady, Ehab F; El-Zaher, Asmaa A; El-Bagary, Ramzia I; Patonay, Gabor

    2015-08-01

    A sensitive UPLC-MS/MS method was developed and validated for simultaneous estimation of aliskiren hemifumarate (ALS), amlodipine besylate (AML) and hydrochlorothiazide (HCZ) in spiked human plasma using valsartan as an internal standard (IS). Liquid-liquid extraction was used for purification and pre-concentration of analytes. The mobile phase consisted of 0.1% formic acid in ammonium acetate buffer (0.02 M, pH 3.5) and methanol (25:75, v/v), flowing through XBridge BEH (50 × 2.1 mm ID, 5 µm) C18 column, at a flow rate of 0.6 mL min(-1). Multiple reaction monitoring (MRM) transitions were measured using an electrospray source in the positive ion mode for ALS and AML, whereas HCZ and IS were measured in negative ion mode. Validation of the method was performed as per US-FDA guidelines with linearity in the range of 2.0-400.0, 0.3-25.0 and 5.0-400.0 ng mL(-1) for ALS, AML and HCZ, respectively. In human plasma, ALS, AML and HCZ were stable for at least 1 month at -70 ± 5°C and for at least 6 h at ambient temperature. After extraction from plasma, the reconstituted samples of ALS, AML and HCZ were stable in the autosampler at ambient temperature for 6 h. The LC-MS/MS method is suitable for bioequivalence and pharmacokinetic studies of this combination. PMID:25575509

  3. 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

  4. 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

  5. Determination of pseudoprotodioscin in rat plasma by UPLC-MS/MS: Assay development and application to pharmacokinetic study.

    PubMed

    Liao, Min; Chen, Xiao; Chen, Jiefeng; Liu, Mengping; Wang, Junyi; Chen, Zuanguang; Xie, Zhiyong; Yao, Meicun

    2016-07-15

    An original and sensitive ultraperformance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for the determination of pseudoprotodioscin (PPD) in rat plasma was developed and validated. Digitoxin was applied as an internal standard. Plasma samples were processed by acetonitrile-mediated plasma protein precipitation and chromatographed using a step gradient program on a C18 column (2.1×50mm i.d., 1.7μm). The mobile phase was comprised of acetonitrile and 0.1mmolL(-1) aqueous lithium acetate mixed with 0.03% formic acid at the flow rate of 0.2mLmin(-1). Multiple reaction monitoring (MRM) transitions were performed for detection and lithium adduct ions were employed with a significant improvement of the response of the analytes in electrospray positive ionization mode. The concentration range of calibration curve was linear over the range 2-5000ngmL(-1). The intra- and inter-day precisions were all less than 11.5% and accuracies were within the range of 94.1-103.5%, and the analytes exhibited no severe matrix effect. The validated method was successfully applied in the pharmacokinetics of PPD after intragastric (50mgkg(-1)) and intravenous (4mgkg(-1)) administration in rats. PPD showed rapid excretion and with bioavailability of simply about 5.7% in rats. PMID:26012509

  6. An UPLC-MS/MS method for the quantitation of vortioxetine in rat plasma: Application to a pharmacokinetic study.

    PubMed

    Gu, Er-min; Huang, Chengke; Liang, Bingqing; Yuan, Lingjing; Lan, Tian; Hu, Guoxin; Zhou, Hongyu

    2015-08-01

    In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of vortioxetine in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 0.05-20ng/mL (R(2)>0.997) with a lower limit of quantification (0.05ng/mL). The extraction recovery was in the range of 78.3-88.4% for vortioxetine and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.5% and accuracy was from -11.2% to 9.5%. No notable matrix effect and astaticism was observed for vortioxetine. The method has been successfully applied to a pharmacokinetic study of vortioxetine in rats for the first time, which provides the basis for the further development and application of vortioxetine. PMID:26094207

  7. 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

  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 4.88-10000 nM, 39-5000 nM, 48.8-6250 nM and 48.8-6250 nM, respectively (R(2)>0.99). In case of SN-38 glucuronide, the standard curves were linear in the concentration range of 6.25-2000 nM, 4.88-1250 nM, 9.8-1250 nM and 9.8-1250 nM 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 25 nM 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 20 μl 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

  9. 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...

  10. 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

  11. Evidence of non-extractable florfenicol residues: development and validation of a confirmatory method for total florfenicol content in kidney by UPLC-MS/MS.

    PubMed

    Faulkner, Dermot; Cantley, Margaret; Walker, Matthew; Crooks, Steven; Kennedy, David; Elliott, Christopher

    2016-06-01

    The parent compound florfenicol (FF) is a broad-spectrum antibacterial compound licensed in the UK for use in cattle, pigs and the aquaculture industry. The analysis of porcine tissues in this study demonstrates that significant amounts of solvent non-extractable FF-related residues are present in incurred tissues (kidney and muscle) from treated animals. The results indicate that methods based on solvent extraction alone may carry a significant risk of reporting false-negative results. The use of a strong acid hydrolysis step prior to solvent extraction of tissue samples is necessary for an accurate estimate of the total tissue FF content. A robust and sensitive method for the determination of total FF residue content in kidney samples by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated. This method covers the synthetic amphenicol drug FF and its metabolites, measured as the marker residue florfenicol amine (FFA) as per Commission Regulation (EU) No. 37/2010. Non-extractable and intermediate metabolites are converted to the hydrolysis product FFA, and then partitioned into ethyl acetate. Extracts are solvent exchanged prior to a dispersive solid-phase extraction step, then analysed using an alkaline reverse-phase gradient separation by UPLC-MS/MS. The method was validated around the maximum residue levels (MRLs) set out in Regulation (EU) No. 37/2010 for bovine kidney in accordance with Commission Decision No. 2002/657/EC. The following method performance characteristics were assessed during a single laboratory validation study: selectivity, specificity, sensitivity, linearity, matrix effects, accuracy and precision (decision limit (CCα) and detection capability (CCβ) were determined). PMID:27053017

  12. Seasonal and Species Variation of the Hepatotoxin Indospicine in Australian Indigofera Legumes As Measured by UPLC-MS/MS.

    PubMed

    Tan, Eddie T T; Materne, Christopher M; Silcock, Richard G; D'Arcy, Bruce R; Al Jassim, Rafat; Fletcher, Mary T

    2016-08-31

    Livestock industries have maintained a keen interest in pasture legumes because of the high protein content and nutritive value. Leguminous Indigofera plant species have been considered as having high feeding values to be utilized as pasture, but the occurrence of the toxic constituent indospicine in some species has restricted this utility. Indospicine has caused both primary and secondary hepatotoxicosis and also reproductive losses, but has only previously been determined in a small number of Indigofera species. This paper validates a high-throughput ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine the indospicine content of various Indigofera species found in Australian pasture. Twelve species of Indigofera together with Indigastrum parviflorum plants were collected and analyzed. Of the 84 samples analyzed, *I. spicata (the asterisk indicates a naturalized species) contained the highest indospicine level (1003 ± 328 mg/kg DM, n = 4) followed by I. linnaei (755 ± 490 mg/kg DM, n = 51). Indospicine was not detected in 9 of the remaining 11 species and at only low levels (<10 mg/kg DM) in 2 of 8 I. colutea specimens and in 1 of 5 I. linifolia specimens. Indospicine concentrations were below quantitation levels for other Indigofera spp. (I. adesmiifolia, I. georgei, I. hirsuta, I. leucotricha, *I. oblongifolia, I. australis, and I. trita) and Indigastrum parviflorum. One of the more significant findings to emerge from this study is that the indospicine content of I. linnaei is highly variable (from 159 to 2128 mg/kg DM, n = 51) and differs across both regions and seasons. Its first regrowth after spring rain has a higher (p < 0.01) indospicine content than growth following more substantial summer rain. The species collected include the predominant Indigofera in Australia pasture, and of these, only *I. spicata and I. linnaei contain high enough levels of indospicine to pose a potential toxic threat to grazing

  13. Identification of a ligand for tumor necrosis factor receptor from Chinese herbs by combination of surface plasmon resonance biosensor and UPLC-MS.

    PubMed

    Cao, Yan; Li, Ying-Hua; Lv, Di-Ya; Chen, Xiao-Fei; Chen, Lang-Dong; Zhu, Zhen-Yu; Chai, Yi-Feng; Zhang, Jun-Ping

    2016-07-01

    Identification of bioactive compounds directly from complex herbal extracts is a key issue in the study of Chinese herbs. The present study describes the establishment and application of a sensitive, efficient, and convenient method based on surface plasmon resonance (SPR) biosensors for screening active ingredients targeting tumor necrosis factor receptor type 1 (TNF-R1) from Chinese herbs. Concentration-adjusted herbal extracts were subjected to SPR binding assay, and a remarkable response signal was observed in Rheum officinale extract. Then, the TNF-R1-bound ingredients were recovered, enriched, and analyzed by UPLC-QTOF/MS. As a result, physcion-8-O-β-D-monoglucoside (PMG) was identified as a bioactive compound, and the affinity constant of PMG to TNF-R1 was determined by SPR affinity analysis (K D  = 376 nM). Pharmacological assays revealed that PMG inhibited TNF-α-induced cytotoxicity and apoptosis in L929 cells via TNF-R1. Although PMG was a trace component in the chemical constituents of the R. officinale extract, it had considerable anti-inflammatory activities. It was found for the first time that PMG was a ligand for TNF receptor from herbal medicines. The proposed SPR-based screening method may prove to be an effective solution to analyzing bioactive components of Chinese herbs and other complex drug systems. Graphical abstract Scheme of the method based on SPR biosensor for screening and recovering active ingredients from complex herbal extracts and UPLC-MS for identifying them. Scheme of the method based on SPR biosensor for screening and recovering active ingredients from complex herbal extracts and UPLC-MS for identifying them. PMID:27225174

  14. Photodegradation assessment of ciprofloxacin, moxifloxacin, norfloxacin and ofloxacin in the presence of excipients from tablets by UPLC-MS/MS and DSC

    PubMed Central

    2013-01-01

    Background Ciprofloxacin (CIP), moxifloxacin (MOX), norfloxacin (NOR) and ofloxacin (OFL), are the antibacterial synthetic drugs, belonging to the fluoroquinolones group. Fluoroquinolones are compounds susceptible to photodegradation process, which may lead to reduction of their antibacterial activity and to induce phototoxicity as a side effect. This paper describes a simple, sensitive UPLC-MS/MS method for the determination of CIP, MOX, NOR and OFL in the presence of photodegradation products. Results Chromatographic separations were carried out using the Acquity UPLC BEH C18 column; (2.1 × 100 mm, 1.7 μm particle size). The column was maintained at 40°C, and the following gradient was used: 0 min, 95% of eluent A and 5% of eluent B; 10 min, 0% of eluent A and 100% of eluent B, at a flow rate of 0.3 mL min-1. Eluent A: 0.1% (v/v) formic acid in water; eluent B: 0.1% (v/v) formic acid in acetonitrile. The method was validated and all the validation parameters were in the ranges acceptable by the guidelines for analytical method validation. The photodegradation of examined fluoroquinolones in solid phase in the presence of excipients followed kinetic of the first order reaction and depended upon the type of analyzed drugs and coexisting substances. Photodegradation process of analyzed drugs was confirmed by differential scanning calorimetry. In addition, the identification of degradation products was carried out by mass spectrometry. Conclusion The developed UPLC-MS/MS method enables the determination of CIP, MOX, NOR and OFL in the presence of photodegradation products and identification of photodegradation products. PMID:23899303

  15. Simultaneous determination of loganin, morroniside, catalpol and acteoside in normal and chronic kidney disease rat plasma by UPLC-MS for investigating the pharmacokinetics of Rehmannia glutinosa and Cornus officinalis Sieb drug pair extract.

    PubMed

    Zhao, Min; Tao, Jinhua; Qian, Dawei; Liu, Pei; Shang, Er-xin; Jiang, Shu; Guo, Jianming; Su, Shu-lan; Duan, Jin-ao; Du, Leyue

    2016-01-15

    A sensitive and rapid method for determination of loganin, morroniside, catalpol and acteoside in rat plasma after oral administration of Rehmannia glutinosa Libosch and Cornus officinalis Sieb drug pair based on ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS). Chromatographic separation was achieved using an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the mobile phase A and B. Loganin, morroniside, catalpol, acteoside and the internal standard (chloramphenicol) were detected by selected reaction monitoring in the negative ion mode with the mass transition of m/z 451.0→179.0 (morroniside), m/z 435.0→227.0 (loganin), m/z 407.1→199.1 (catalpol), m/z 623.2→161.0 (acteoside) and m/z 320.8→151.9 (chloramphenicol), respectively. All calibration curves showed good linearity (r>0.991). The precision was evaluated by intra-day and inter-day assays and the RSD% were all within 9.58%. The recovery ranged from 67.62 to 80.14%. The method was successfully applied to pharmacokinetic study of the analytes in normal and doxorubicin-induced chronic kidney disease rat plasma. PMID:26720701

  16. Development and validation of an UPLC-MS/MS method for the quantification of ethoxzolamide in blood, brain tissue, and bioequivalent buffers: applications to absorption, brain distribution, and pharmacokinetic studies.

    PubMed

    Gao, Song; Zhao, Jing; Yin, Taijun; Ma, Yong; Xu, Beibei; Moore, Anthony N; Dash, Pramod K; Hu, Ming

    2015-04-01

    The purpose of this study is to develop and validate an UPLC-MS/MS method to quantify ethoxzolamide in plasma (EZ) and apply the method to absorption, brain distribution, as well as pharmacokinetic studies. A C₁₈ column was used with 0.1% of formic acid in acetonitrile and 0.1% of formic acid in water as the mobile phases to resolve EZ. The mass analysis was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode. The results show that the linear range of EZ is 4.88-10,000.00 nM. The intra-day variance is less than 12.43% and the accuracy is between 88.88 and 108.00%. The inter-day variance is less than 12.87% and accuracy is between 89.27 and 115.89%. Protein precipitation was performed using methanol to extract EZ from plasma and brain tissues. Only 40 μL of plasma is needed for analysis due to the high sensitivity of this method, which could be completed in less than three minutes. This method was used to study the pharmacokinetics of EZ in SD rats, and the transport of EZ in Caco-2 and MDCK-MDR1 overexpressing cell culture models. Our data show that EZ is not a substrate for p-glycoprotein (P-gp) and its entry into the brain may not limited by the blood-brain barrier. PMID:25706567

  17. 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

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

    PubMed

    Li, Yanshen; Liu, Kaili; Beier, Ross C; Cao, Xingyuan; Shen, Jianzhong; Zhang, Suxia

    2014-10-01

    This report presents a UPLC-MS/MS method for determination of mequindox (MEQ), quinocetone (QCT) and their 11 metabolites in chicken and pork samples. Following extraction process with acetonitrile-ethyl acetate, acidulation, and re-extraction with ethyl acetate in turn, target analytes were further purified using C18 solid phase extraction (SPE) cartridges for UPLC-MS/MS analysis. Validation was processed with mean recoveries from 69.1% to 113.3% with intra-day relative standard deviation (RSD) <14.7%, inter-day RSD <19.2%, and limit of detection between 0.05 and 1.0 μg/kg for each analytes. The verified method was successfully applied to the quantitative determination of commercial samples. This developed procedure will help to control food animal products with MEQ and QCT residues, and facilitate further pharmacokinetic and residue studies of similar quinoxaline-1,4-dioxide veterinary drugs. PMID:24799224

  19. 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]. PMID:27222866

  20. Identification and quantitation of new glutamic acid derivatives in soy sauce by UPLC/MS/MS.

    PubMed

    Frerot, Eric; Chen, Ting

    2013-10-01

    Glutamic acid is an abundant amino acid that lends a characteristic umami taste to foods. In fermented foods, glutamic acid can be found as a free amino acid formed by proteolysis or as a non-proteolytic derivative formed by microorganisms. The aim of the present study was to identify different structures of glutamic acid derivatives in a typical fermented protein-based food product, soy sauce. An acidic fraction was prepared with anion-exchange solid-phase extraction (SPE) and analyzed by UPLC/MS/MS and UPLC/TOF-MS. α-Glutamyl, γ-glutamyl, and pyroglutamyl dipeptides, as well as lactoyl amino acids, were identified in the acidic fraction of soy sauce. They were chemically synthesized for confirmation of their occurrence and quantified in the selected reaction monitoring (SRM) mode. Pyroglutamyl dipeptides accounted for 770 mg/kg of soy sauce, followed by lactoyl amino acids (135 mg/kg) and γ-glutamyl dipeptides (70 mg/kg). In addition, N-succinoylglutamic acid was identified for the first time in food as a minor compound in soy sauce (5 mg/kg). PMID:24130027

  1. 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

  2. Assessment of peeling of Astragalus roots using 1H NMR- and UPLC-MS-based metabolite profiling.

    PubMed

    Jung, Jee-Youn; Jung, Youngae; Kim, Jin-Sup; Ryu, Do Hyun; Hwang, Geum-Sook

    2013-10-30

    A metabolomic analysis was performed to examine the postharvest processing of Astragalus membranaceus roots with a focus on the peeling procedure using (1)H NMR and UPLC-MS analyses. Principal component analysis (PCA) score plots from the (1)H NMR and UPLC-MS data showed clear separation between peeled and unpeeled Astragalus roots. Peeled roots exhibited significant losses of several primary metabolites, including acetate, alanine, arginine, caprate, fumarate, glutamate, histidine, N-acetylaspartate, malate, proline, sucrose, trigonelline, and valine. In contrast, the peeled roots contained higher levels of asparagine, aspartate, and xylose, which are xylem-related compounds, and formate, which is produced in response to wound stress incurred during postharvest processing. In addition, the levels of isoflavonoids and astragalosides were significantly reduced in peeled Astragalus root. These results demonstrate that metabolite profiling based on a combination of (1)H NMR and UPLC-MS analyses can be used to evaluate peeling procedures used in the postharvest processing of herbal medicines. PMID:24073592

  3. Methylmalonic acid quantification in low serum volumes by UPLC-MS/MS.

    PubMed

    Pedersen, Theresa L; Keyes, William R; Shahab-Ferdows, Setareh; Allen, Lindsay H; Newman, John W

    2011-06-01

    Methylmalonic acid (MMA) is a metabolic intermediate transformed to succinic acid (SA) by a vitamin B(12)-dependent catalytic step, and is broadly used as a clinical biomarker of functional vitamin B12 status. However, reported methods use between 100 and 1000 μL of serum or plasma making them sub-optimal for sample-limited studies, including those with neonates and infants. LC-MS/MS based protocols to measure MMA as n-butyl esters in the presence of tri-deuterated MMA (MMA-d(3)) were modified for use with 25 μL of human serum by scaling down sample processing volumes and analysis by UPLC-MS/MS. Plasma-based calibration solutions were found to be unnecessary, and chromatographic resolution and peak shape of SA and MMA was optimized in <4 min with isocratic 53:47 methanol/1.67 mM (pH 6.5) ammonium formate. Additionally, 1-cyclohexyl-urido-3-dodecanoic acid (CUDA) was included as internal standard allowing direct assessment of MMA recovery. Sample concentrations in the low normal range produced a signal:noise of >100:1. MMA intra- and inter-assay variability was under 10%. MMA-d(3) surrogate recovery averaged 93±14%. MMA stability exceeded three years in frozen samples and was unaffected by up to five freeze/thaw cycles. In conclusion, we report that methylmalonic acid can be measured with 25 μL of serum using water based standards. The assay signal:noise per concentration indicates that the method could perform as implemented with as little as 5 μL of serum. The reported method is applicable for studies of functional B12 status in sample limited experiments including investigations of nutritional status in neonates and in studies where low normal MMA levels are expected. PMID:21497144

  4. 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

  5. Quantitative evaluation of berberine subcellular distribution and cellular accumulation in non-small cell lung cancer cells by UPLC-MS/MS.

    PubMed

    Yuan, Zhong-Wen; Leung, Elaine Lai-Han; Fan, Xing-Xing; Zhou, Hua; Ma, Wen-Zhe; Liu, Liang; Xie, Ying

    2015-11-01

    Berberine, an isoquinoline alkaloid, has been demonstrated to be a safe anti-cancer agent with multiple effects on mitochondria. Intracellular concentration and distribution around the targeting sites are determinants of efficacy, but subcellular distribution of berberine has not been fully elucidated yet, which relies on the sensitive and robustness assay. In this study, a sensitive and robust UPLC-MS/MS method has been developed and validated with optimized extraction solvents and detection conditions. Key factors such as the purity and integrity of isolated organelle fractions, and the effects of isolation procedures on the subcellular concentration of berberine were systemically evaluated. With the developed assay, we found that the intracellular accumulations of berberine in two gefitinib resistant NSCLC cell lines H1650 and H1975 were 2-3 folds higher than that of normal epithelial cells BEAS-2B. Moreover, significantly different subcellular distribution profiles in NSCLC cancer cells from that of BEAS-2B cells with a striking increase in content in most organelles may contribute to its selective cytotoxicity to cancer cells. Furthermore, a predominant accumulation of berberine was observed for the first time in microsomal fraction for all three cell lines. Therefore, this method could be used for quantitative evaluation of subcellular distribution and cellular accumulation of berberine and for further evaluation of the concentration-effects relationship. PMID:26452787

  6. 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

  7. 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

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

    PubMed Central

    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

  9. 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

  10. Optimization and evaluation of metabolite extraction protocols for untargeted metabolic profiling of liver samples by UPLC-MS.

    PubMed

    Masson, Perrine; Alves, Alexessander Couto; Ebbels, Timothy M D; Nicholson, Jeremy K; Want, Elizabeth J

    2010-09-15

    A series of six protocols were evaluated for UPLC-MS based untargeted metabolic profiling of liver extracts in terms of reproducibility and number of metabolite features obtained. These protocols, designed to extract both polar and nonpolar metabolites, were based on (i) a two stage extraction approach or (ii) a simultaneous extraction in a biphasic mixture, employing different volumes and combinations of extraction and resuspension solvents. A multivariate statistical strategy was developed to allow comparison of the multidimensional variation between the methods. The optimal protocol for profiling both polar and nonpolar metabolites was found to be an aqueous extraction with methanol/water followed by an organic extraction with dichloromethane/methanol, with resuspension of the dried extracts in methanol/water before UPLC-MS analysis. This protocol resulted in a median CV of feature intensities among experimental replicates of <20% for aqueous extracts and <30% for organic extracts. These data demonstrate the robustness of the proposed protocol for extracting metabolites from liver samples and make it well suited for untargeted liver profiling in studies exploring xenobiotic hepatotoxicity and clinical investigations of liver disease. The generic nature of this protocol facilitates its application to other tissues, for example, brain or lung, enhancing its utility in clinical and toxicological studies. PMID:20715759

  11. 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

  12. Separation and characterization of ciprofloxacin, difloxacin, lomefloxacin, norfloxacin, and ofloxacin oxidation products under potassium permanganate treatment in acidic medium by UPLC-MS/MS.

    PubMed

    Hubicka, Urszula; Zmudzki, Paweł; Zuromska-Witek, Barbara; Zajdel, Paweł; Pawłowski, Maciej; Krzek, Jan

    2013-05-15

    A simple, sensitive and reproducible ultra-performance liquid chromatography method for determination of ciprofloxacin, difloxacin, lomefloxacin, norfloxacin and ofloxacin oxidation stability under permanganate treatment in acidic conditions at pH from 3.0 to 6.0, was developed. Chromatographic separations were carried out using the Acquity UPLC BEH C18 column; (2.1×100 mm, 1.7 μm particle size). The column was maintained at 40°C, and eluted under isocratic conditions using 83% of eluent A and 17% of eluent B over 6.5 min, at a flow rate of 0.3 mL min(-1). Eluent A: water/formic acid (0.1 v/v%); eluent B: acetonitrile/formic acid (0.1 v/v%). An oxidation process followed kinetic of the second order reaction and depended upon solution acidity. Oxidation of fluoroquinolones proceeded at piperazine moiety yielding respective hydroxy and oxo analogs, and remaining the quinolone fragment intact. Structures of products formed were assigned on a basis of UPLC/MS/MS fragmentation pathways. PMID:23618144

  13. Development and validation of a UPLC-MS/MS method for quantitation of droxidopa in human plasma: Application to a pharmacokinetic study.

    PubMed

    Wang, Haidong; Yang, Guangsheng; Zhou, Jinyu; Pei, Jiang; Zhang, Qiangfeng; Song, Xingfa; Sun, Zengxian

    2016-08-01

    In this study, a simple and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for quantitation of droxidopa in human plasma for the first time. A simple plasma protein precipitation method using methanol containing 3% formic acid was selected, and the separation was achieved by an Acquity UPLC™ BEH Amide column (2.1mm×50mm, 1.7μm) with a gradient elution using acetonitrile, ammonium formate buffer and formic acid as mobile phase. The detection of droxidopa and benserazide (internal standard, IS) was performed using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The precursor-to-product ion transitions m/z 214.2→m/z 152.0 for droxidopa, and m/z 258.1→m/z 139.1 for IS were used for quantification. A lower limit of quantification of 5.00ng/mL was achieved and the linear curve range was 5.00-4000ng/mL using a weighted (1/x(2)) linear regression model. Intra-assay and inter-assay precision was less than 10.2%, and the accuracy ranged from 0.1% to 2.1%. Stability, recovery and matrix effects were within the acceptance criteria recommended by the regulatory bioanalytical guidelines. The method was successfully applied to a pharmacokinetic study of droxidopa in healthy Chinese volunteers. PMID:27311027

  14. Microdialysis combined with UPLC-MS/MS method for determination of tetramethylpyrazine and ferulic acid in striatum of awake and anesthetic rats subjected to cerebral ischemia.

    PubMed

    Liao, Weiguo; Yu, Jianye; Guo, Zhonglin; Ba, Wenqiang; Wang, Ding; Li, Zhou; Fan, Wentao; Liao, Fengyun; Wu, Yinai; Wang, Lisheng

    2016-09-01

    A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination and pharmacokinetic investigation of Tetramethylpyrazine (TMP) and Ferulic acid (FA) in rat striatum. The method was validated over the concentration range of 1.15-505ng/mL for TMP and 3.23-101ng/mL for FA, with a lower limit of quantitation (LLOQ) of 1.15ng/mL and 3.23ng/mL, respectively. This method can be successfully applied in pharmacokinetic studies of TMP and FA in striatum of awake and anesthetic rats. The cerebral blood flow velocity (CBF) during middle cerebral artery occlusion (MCAO) was monitored by Laser speckle contrast imaging, to observe whether the compatibility of TMP and FA could improve CBF against cerebral ischemia/reperfusion (I/R) injury. Infarct volume was examined to evaluate severity of ischemic brain injury. The pharmacokinetic study indicated that T1/2, Cmax, MRT and AUC0-inf were changed after combined administration of TMP and FA, when compared with either drug alone both in awake and anesthetic groups. The pharmacodynamics results showed that co-administration of drugs could enhance the CBF during middle cerebral artery occlusion and reduced the infarct volume. Taken together, the compatibility treatment of TMP and FA might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize the compatibility proportion. PMID:27389185

  15. 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. PMID:26207321

  16. Separation and quantitation of three acidic herbicide residues in tobacco and soil by dispersive solid-phase extraction and UPLC-MS/MS.

    PubMed

    Xiong, Wei; Tao, Xiaoqiu; Pang, Su; Yang, Xue; Tang, GangLing; Bian, Zhaoyang

    2014-01-01

    A method for the determination of three acidic herbicides, dicamba, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in tobacco and soil has been developed based on the use of liquid-liquid extraction and dispersive solid-phase extraction (dispersive-SPE) followed by UPLC-MS/MS. Two percentage of (v/v) formic acid in acetonitrile as the extraction helped partitioning of analytes into the acetonitrile phase. The extract was then cleaned up by dispersive-SPE using primary secondary amine as selective sorbents. Quantitative analysis was done in the multiple-reaction monitoring mode using stable isotope-labeled internal standards for each compound. A separate internal standard for each analyte is required to minimize sample matrix effects on each analyte, which can lead to poor analyte recoveries and decreases in method accuracy and precision. The total analysis time was <4 min. The linear range of the method was from 1 to 100 ng mL(-1) with a limit of detection of each herbicide varied from 0.012 to 0.126 ng g(-1). The proposed method is faster, more sensitive and selective than the traditional methods and more accurate and robust than the published LC-MS/MS methods. PMID:24366907

  17. 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

  18. 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

  19. Analysis of the Enantioselective Effects of PCB95 in Zebrafish (Danio rerio) Embryos through Targeted Metabolomics by UPLC-MS/MS

    PubMed Central

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

    2016-01-01

    As persistent organic pollutants, polychlorinated biphenyls (PCBs) accumulate in the bodies of animals and humans, resulting in toxic effects on the reproductive, immune, nervous, and endocrine systems. The biological and toxicological characteristics of enantiomers of chiral PCBs may differ, but these enantioselective effects of PCBs have not been fully characterized. In this study, we performed metabolomics analysis, using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the enantioselective toxic effects of PCB95 in zebrafish (Danio rerio) embryos after exposure to three dose levels of 0.1, 1, and 10 μg/L for 72 h. Multivariate analysis directly reflected the metabolic perturbations caused by PCB95. The effects of (-)-PCB95 and (+)-PCB95 were more prominent than those of the racemate in zebrafish embryos. A total of 26 endogenous metabolites were selected as potential marker metabolites with variable importance at projection values larger than 1 and significant differences (p<0.05). These metabolites included amino acids, organic acids, nucleosides, betaine, and choline. The changes in these biomarkers were dependent on the enantiomer-specific structures of PCB95. Fifteen metabolic pathways were significantly affected, and several nervous and immune system-related metabolites were significantly validated after exposure. These metabolic changes indicated that the toxic effects of PCB95 may be associated with the interaction of PCB95 with the nervous and immune systems, thus resulting in disruption of energy metabolism and liver function. PMID:27500732

  20. Development and full validation of an UPLC-MS/MS method for the quantification of the plant-derived alkaloid indirubin in rat plasma.

    PubMed

    Jähne, Evelyn A; Sampath, Chethan; Butterweck, Veronika; Hamburger, Matthias; Oufir, Mouhssin

    2016-09-01

    An UPLC-MS/MS method for the quantification of indirubin in lithium heparinized rat plasma was developed and validated according to current international guidelines. Indirubin was extracted from rat plasma by using Waters Ostro™ pass-through sample preparation plates. The method was validated with a LLOQ of 5.00ng/mL and an ULOQ of 500ng/mL. The calibration curve was fitted by least-square quadratic regression, and a weighting factor of 1/X was applied. Recoveries of indirubin and I.S. were consistent and ≥75.5%. Stability studies demonstrated that indirubin was stable in lithium heparinized rat plasma for at least 3 freeze/thaw cycles, for 3h at RT, for 96h in the autosampler at 10°C, and for 84days when stored below -65°C. Preliminary pharmacokinetic (PK) data were obtained from Sprague Dawley rats after intravenous administration of indirubin (2mg/kg b.w.) and blood sampling up to 12h after injection. PK parameters were determined by non-compartmental analysis. Indirubin had a half-life (t1/2) of 35min, and a relatively high clearance (CL) of 2.71L/h/kg. PMID:27281580

  1. Simultaneous determination and pharmacokinetic study of Atractylenolide I, II and III in rat plasma after intragastric administration of Baizhufuling extract and Atractylodis extract by UPLC-MS/MS.

    PubMed

    Yan, Han; Sun, Yuanyuan; Zhang, Qili; Yang, Mingjing; Wang, Xiaorui; Wang, Yang; Yu, Zhiguo; Zhao, Yunli

    2015-07-01

    A simple and rapid ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of Atractylenolide I, II and III in rat plasma. Plasma samples were processed by liquid-liquid extraction with ethyl acetate, using schisandrin as internal standard (IS). Chromatographic separation was accomplished on a Thermo Hypersil GOLD C18 column (2.1mm×50mm, 1.9μm) with mobile phase consisting of acetonitrile and 0.1% formic acid-water (50:50, v/v). The detection was carried out by ESI-MS (positive ionization mode) and low-energy collision dissociation tandem mass spectrometric analyses using the multiple-reaction monitoring (MRM) scan mode. The quantification was performed using the transitions of the protonated molecule→product ion at m/z 231.0→185.1 for Atractylenolide I, at m/z 233.1→187.1 for Atractylenolide II and at m/z 249.1→231.1 for Atractylenolide III, respectively. Method validation revealed excellent linearity over investigated range together with satisfactory intra- and inter-day precision, accuracy, matrix effects and extraction recoveries. This method was successfully applied to the comparative pharmacokinetic study of Atractylenolide I, II and III in rat plasma after intragastric administration of Baizhufuling extract and Atractylodis extract. PMID:26001909

  2. Fast identification of lipase inhibitors in oolong tea by using lipase functionalised Fe3O4 magnetic nanoparticles coupled with UPLC-MS/MS.

    PubMed

    Zhu, Yuan-Ting; Ren, Xiao-Yun; Yuan, Li; Liu, Yi-Ming; Liang, Jian; Liao, Xun

    2015-04-15

    Oolong tea is an important member in tea family, which claims for various health benefits such as preventing obesity and improving lipid metabolism. In this work, using pancreatic lipase (PL) functionalised magnetic nanoparticles (PL-MNPs) as solid phase extraction absorbent in combination with ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS), we developed a method for rapid screening and identification of lipase inhibitors from oolong tea. Three PL ligands were selectively extracted and identified as (-)-epigallocatechin-3-O-gallate (EGCG), (-)-gallocatechin-3-O-gallate (GCG) and (-)-epicatechin-3-O-gallate (ECG). Their lipase inhibitory activities were significantly higher than those non-ligands. Structure-activity analysis revealed that the presence of a galloyl moiety in the structure was required for binding to PL-MNPs, and therefore, exhibiting a strong inhibition on the enzyme. Taking advantages of the specificity in enzyme binding and the convenience of magnetic separation, this method has great potential for fast screening of lipase inhibitors from natural resources. PMID:25466054

  3. Analysis of the Enantioselective Effects of PCB95 in Zebrafish (Danio rerio) Embryos through Targeted Metabolomics by UPLC-MS/MS.

    PubMed

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

    2016-01-01

    As persistent organic pollutants, polychlorinated biphenyls (PCBs) accumulate in the bodies of animals and humans, resulting in toxic effects on the reproductive, immune, nervous, and endocrine systems. The biological and toxicological characteristics of enantiomers of chiral PCBs may differ, but these enantioselective effects of PCBs have not been fully characterized. In this study, we performed metabolomics analysis, using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the enantioselective toxic effects of PCB95 in zebrafish (Danio rerio) embryos after exposure to three dose levels of 0.1, 1, and 10 μg/L for 72 h. Multivariate analysis directly reflected the metabolic perturbations caused by PCB95. The effects of (-)-PCB95 and (+)-PCB95 were more prominent than those of the racemate in zebrafish embryos. A total of 26 endogenous metabolites were selected as potential marker metabolites with variable importance at projection values larger than 1 and significant differences (p<0.05). These metabolites included amino acids, organic acids, nucleosides, betaine, and choline. The changes in these biomarkers were dependent on the enantiomer-specific structures of PCB95. Fifteen metabolic pathways were significantly affected, and several nervous and immune system-related metabolites were significantly validated after exposure. These metabolic changes indicated that the toxic effects of PCB95 may be associated with the interaction of PCB95 with the nervous and immune systems, thus resulting in disruption of energy metabolism and liver function. PMID:27500732

  4. Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies.

    PubMed

    Gray, Nicola; Adesina-Georgiadis, Kyrillos; Chekmeneva, Elena; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

    2016-06-01

    A rapid gradient microbore ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC-MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC-MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC-MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC-MS method. PMID:27116471

  5. [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

  6. 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...

  7. 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

  8. 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...

  9. Application of a UPLC-MS/MS method for the analysis of alosetron in human plasma to support a bioequivalence study in healthy males and females.

    PubMed

    Chaudhary, Darshan V; Patel, Daxesh P; Shah, Jaivik V; Shah, Priyanka A; Sanyal, Mallika; Shrivastav, Pranav S

    2015-10-01

    A simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of alosetron (ALO) in human plasma. The assay method involved solid-phase extraction of ALO and ALO 13C-d3 as internal standard (IS) on a LichroSep DVB-HL (30 mg, 1 cm(3) ) cartridge. The chromatography was performed on an Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 µm) column using acetonitrile and 2.0 mm ammonium formate, pH 3.0 adjusted with 0.1% formic acid (80:20, v/v) as the mobile phase in an isocratic mode. For quantitative analysis, the multiple reaction monitoring transitions studied were m/z 295.1/201.0 for ALO and m/z 299.1/205.1 for IS in the positive ionization mode. The method was validated over a concentration range of 0.01-10.0 ng/mL for ALO. Post-column infusion experiment showed no positive or negative peaks in the elution range of the analyte and IS after injection of extracted blank plasma. The extent of ion-suppression/enhancement, expressed as IS-normalized matrix factor, varied from 0.96 to 1.04. The assay recovery was within 97-103% for ALO and IS. The method was successfully applied to support a bioequivalence study of 1.0 mg alosetron tablets in 28 healthy Indian male and female subjects. PMID:25761551

  10. Development and application of a UPLC-MS/MS method for the pharmacokinetic study of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats.

    PubMed

    Li, Guofei; Cai, Cuifang; Ren, Tianyang; Tang, Xing

    2014-01-01

    With the purpose to carry out the pharmacokinetic studies of 10-hydroxy camptothecin (10-HCPT) and hydroxyethyl starch (10-HCPT-HES) conjugate, an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated. The analytes, 10-HCPT and the internal standard, Diphenhydramine hydrochloride were extracted with ethyl acetate-isopropanol (95:5, v/v) and separated on an ACQUITY UPLC™ BEH C18 column using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) with a linear gradient program. With positive ion electrospray ionization (ESI), the analytes were monitored on a triple quadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained over the concentration ranges of 0.5-2500ng/mL. The intra- and inter-day precisions were less than 9.8% and 10.8%, respectively. The accuracy was within 12.1%. The mean recoveries of 10-HCPT at three concentrations of 2.5, 100, 2000ng/mL were higher than 87.2%. Commercial 10-HCPT injection and 10-HCPT-HES conjugate were administered intravenously at an equal dose of 10-HCPT at 0.5mg/kg. The biological half-life of conjugate was increased significantly from 10min to 3.15h and the bioavailability was 40 times higher than 10-HCPT injection. Consequently, the proposed UPLC-ESI-MS/MS method was proved to be sensitive, specific and reliable to analyze 10-HCPT in biological samples; 10-HCPT and HES conjugate is a promising strategy for delivery of 10-HCPT with prolonged half time and improved bioavailability. PMID:24140449

  11. Rapid and simple UPLC-MS/MS method for precise phytochelatin quantification in alga extracts.

    PubMed

    Bräutigam, Anja; Wesenberg, Dirk; Preud'homme, Hugues; Schaumlöffel, Dirk

    2010-09-01

    Quantitative phytochelatin (PC) analysis is, due to oxidation sensitivity of the PCs, matrix effects, and time consuming sample preparation, still a challenging analytical task. In this study, a rapid, simple, and sensitive method for precise determination of native PCs in crude extracts of the green alga Chlamydomonas reinhardtii was developed. Algae were exposed 48 h to 70 μM Cd. Coupling of ultra performance liquid chromatography and electrospray ionization tandem mass spectrometry with multi-reaction mode transitions for detection permitted the required short-time, high-resolution separation and detection specificity. Thus, under optimized chromatographic conditions, 10 thiol peptides were baseline-separated within 7 min. Relative detection limits in the nanomolar range in microliter sample volumes were achieved (corresponding to absolute detection limits at femtomole level). Next to glutathione (GSH), the most abundant cadmium-induced PCs in C. reinhardtii, namely CysGSH, PC(2), PC(3), CysPC(2), and CysPC(3), were quantified with high reproducibility at concentrations between 15 and 198 nmol g(-1) fresh weight. The biological variation of PC synthesis of nine independently grown alga cultures was determined to be on average 13.7%. PMID:20632163

  12. The wild Egyptian artichoke as a promising functional food for the treatment of hepatitis C virus as revealed via UPLC-MS and clinical trials.

    PubMed

    Elsebai, Mahmoud Fahmi; Abass, Khaled; Hakkola, Jukka; Atawia, Ahmed Rezk; Farag, Mohamed A

    2016-07-13

    Infection by hepatitis C virus (HCV) and its subsequent complications are a major cause of mortality worldwide. The water extract of the wild Egyptian artichoke (WEA) (Cynara cardunculus L. var. sylvestris (Lam.) Fiori) leaves is a freely available herbal product that is used for treatment of HCV-infection complications such as jaundice and ascites. The purpose of this study was to evaluate whether WEA exhibits activity against HCV, identify bioactive chemicals in its extract and to tentatively examine the potential inhibitory interactions of WEA with human drug-metabolizing enzymes. The current pilot clinical trial revealed that the water extract of a WEA plant decreased the HCV viral load below the detection level in 12 out of 15 patients. Furthermore, the liver enzymes ALT and AST, as well as the level of bilirubin were normalized. The total WEA extract inhibited CYP2B6 (OH-BUP) and CYP2C19 (5-OH-OME) with high affinity, IC50 ∼ 20 μg ml(-1), while moderate inhibitory interactions were observed for CYP1A2, CYP2D6, CYP2E1 and CYP3A4. Results presented herein suggest that the WEA exhibits strong antiviral activity against HCV and may be useful for its treatment. Compared to the artichoke product "Hepar SL Forte(®)", WEA was found to be more enriched in sesquiterpenes versus the abundance of phenolic compounds, especially flavonoids in Hepar SL Forte(®) as revealed via UPLC-MS analysis coupled to chemometrics. PMID:27296047

  13. 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

  14. An UPLC-MS/MS method for separation and accurate quantification of tamoxifen and its metabolites isomers.

    PubMed

    Arellano, Cécile; Allal, Ben; Goubaa, Anwar; Roché, Henri; Chatelut, Etienne

    2014-11-01

    A selective and accurate analytical method is needed to quantify tamoxifen and its phase I metabolites in a prospective clinical protocol, for evaluation of pharmacokinetic parameters of tamoxifen and its metabolites in adjuvant treatment of breast cancer. The selectivity of the analytical method is a fundamental criteria to allow the quantification of the main active metabolites (Z)-isomers from (Z)'-isomers. An UPLC-MS/MS method was developed and validated for the quantification of (Z)-tamoxifen, (Z)-endoxifen, (E)-endoxifen, Z'-endoxifen, (Z)'-endoxifen, (Z)-4-hydroxytamoxifen, (Z)-4'-hydroxytamoxifen, N-desmethyl tamoxifen, and tamoxifen-N-oxide. The validation range was set between 0.5ng/mL and 125ng/mL for 4-hydroxytamoxifen and endoxifen isomers, and between 12.5ng/mL and 300ng/mL for tamoxifen, tamoxifen N-desmethyl and tamoxifen-N-oxide. The application to patient plasma samples was performed. PMID:25173109

  15. 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

  16. 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

  17. UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers.

    PubMed

    Graça, Gonçalo; Goodfellow, Brian J; Barros, António S; Diaz, Sílvia; Duarte, Iola F; Spagou, Konstantina; Veselkov, Kirill; Want, Elizabeth J; Lindon, John C; Carreira, Isabel M; Galhano, Eulália; Pita, Cristina; Gil, Ana M

    2012-04-01

    We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed. PMID:22294348

  18. 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

  19. 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

  20. Determination of rhynchophylline and hirsutine in rat plasma by UPLC-MS/MS after oral administration of Uncaria rhynchophylla extract.

    PubMed

    Wu, Yu-Tse; Lin, Lie-Chwen; Tsai, Tung-Hu

    2014-03-01

    An ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to concurrently determine rhynchophylline and hirsutine in rat plasma. The sample preparation of rat plasma was achieved by alkalization and liquid-liquid extraction. The mass transition of precursor ion → product ion pairs were monitored at m/z 385.2 → 160.0 for rhynchophylline, m/z 369.3 → 144.0 for hirsutine and m/z 414.0 → 220.0 for noscapine (internal standard). This method revealed linear relationships from 2.5 to 50 ng/mL (r(2)  > 0.997) for rhynchophylline and from 2.5 to 50 ng/mL (r(2)  > 0.998) for hirsutine. The limit of quantification values for rhynchophylline and hirsutine in rat plasma were both 2.5 ng/mL. Intra-day and inter-day precisions were within 10.6% and 12.5%, respectively, for rhynchophylline and hirsutine, and the accuracy (bias) was <10%. Liquid-liquid extraction of rat plasma samples resulted in insignificant matrix effect, and the extraction recoveries were >83.6% for rhynchophylline, 73.4% for hirsutine and 90.7% for the internal standard. This method was applied successfully to a pharmacokinetic study of rhynchophylline and hirsutine in rats after oral administration. PMID:24122787

  1. Simultaneous Determination of Bosentan, Glimepiride, HYBOS and M1 in Rat Plasma by UPLC-MS-MS and its Application to Pharmacokinetic Study.

    PubMed

    Chen, Mengchun; Song, Wenjie; Wang, Shuanghu; Chen, Qiulei; Pan, Peipei; Xu, Tao; Hu, Guoxin; Zheng, Zhiqiang

    2016-08-01

    A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the simultaneous determination of bosentan (BOS), glimepiride (GLP), hydroxyl bosentan (HYBOS) and hydroxyl glimepiride (M1) in rat plasma using one-step protein precipitation was developed and validated. After addition of ambrisentan as an internal standard (IS), protein precipitation by acetonitrile was used in sample preparation. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm particle size, Waters Corp., Milford, MA, USA) and inline 0.2 μm stainless steel frit filter (Waters Corp.) with acetonitrile-0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min with gradient elution. The column temperature was maintained at 40°C. Only 4 min was needed for an analytical run. The retention times were ∼3.29 min for BOS, 3.56 min for GLP, 1.42 min for HYBOS, 1.53 min for M1 and 3.22 min for IS. Electrospray ionization source was employed and operated in positive-ion mode; multiple reaction monitoring mode was applied to target fragment ions m/z 552 → 202, m/z 568 → 202, m/z 491 → 352, m/z 507 → 352 and m/z 379 → 347 for BOS, HYBOS, GLP, M1 and IS, respectively. The assay was validated over concentration ranges of 25-5,000 ng/mL (r(2) = 0.9984) for BOS, 1-200 ng/mL (r(2) = 0.9999) for GLP, 0.5-100 ng/mL (r(2) = 0.9999) for HYBOS and 0.1-20 ng/mL (r(2) = 0.9984) for M1. Intra- and interday precision values for replicate quality control samples were within 14.2% for all analytes during the assay validation. Mean quality control accuracy values were within -3.3 to 14.4% of nominal values for all analytes. The mean recoveries of BOS, GLP, HYBOS, M1 and ambrisentan from the plasma exceeded 90.4%. The analytes were stable in rat plasma for at least 2 h at room temperature, 30 days at -40°C and following at least three freeze-thaw cycles (-40°C to room temperature). This method was

  2. 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

  3. An improved UPLC-MS/MS platform for quantitative analysis of glycerophosphoinositol in mammalian cells.

    PubMed

    Grauso, Laura; Mariggiò, Stefania; Corda, Daniela; Fontana, Angelo; Cutignano, Adele

    2015-01-01

    The glycerophosphoinositols constitute a class of biologically active lipid-derived mediators whose intracellular levels are modulated during physiological and pathological cell processes. Comprehensive assessment of the role of these compounds expands beyond the cellular biology of lipids and includes rapid and unambiguous measurement in cells and tissues. Here we describe a sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative analysis of the most abundant among these phosphoinositide derivatives in mammalian cells, the glycerophosphoinositol (GroPIns). The method has been developed in mouse Raw 264.7 macrophages with limits of quantitation at 3 ng/ml. Validation on the same cell line showed excellent response in terms of linear dynamic range (from 3 to 3,000 ng/ml), intra-day and inter-day precision (coefficient of variation ≤ 7.10%) and accuracy (between 98.1 and 109.0%) in the range 10-320 ng/ml. As proof of concept, a simplified analytical platform based on this method and external calibration was also tested on four stimulated and unstimulated cell lines, including Raw 264.7 macrophages, Jurkat T-cells, A375MM melanoma cells and rat basophilic leukemia RBL-2H3 cells. The results indicate a wide variation in GroPIns levels among different cell lines and stimulation conditions, although the measurements were always in line with the literature. No significant matrix effects were observed thus indicating that the here proposed method can be of general use for similar determinations in cells of different origin. PMID:25860666

  4. UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses.

    PubMed

    Auray-Blais, Christiane; Lavoie, Pamela; Tomatsu, Shunji; Valayannopoulos, Vassili; Mitchell, John J; Raiman, Julian; Beaudoin, Maxime; Maranda, Bruno; Clarke, Joe T R

    2016-09-14

    Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients). The main objective of our project was to devise and validate a reliable tandem mass spectrometry multiplex analysis for the urine quantitation of four GAGs (dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)) for an eventual technological transfer to the clinic. The developed methodology is rapid (7 min) and our results showed good intraday and interday precision (RSDs ≤ 8.7%) and accuracy (Biases range: -12.0%-18.4%). Linearity was good (r(2) > 0.995) for DS, HS, CS, and KS calibration curves. In comparison with the DMB spectrophotometric method, this multiplex tandem mass spectrometry method allows GAG fractionation, thus a differentiation of MPS types, except for MPS I and II which are characterized by the same GAG profile. The devised method is a useful and reliable tool for diagnosis of MPS patients, as well as their monitoring and follow up, as shown by longitudinal studies. PMID:27566349

  5. Simultaneous determination of erlotinib and tamoxifen in rat plasma using UPLC-MS/MS: Application to pharmacokinetic interaction studies.

    PubMed

    Maher, Hadir M; Alzoman, Nourah Z; Shehata, Shereen M

    2016-08-15

    Tamoxifen (TAM) is a non-steroidal estrogen receptor antagonist that enhances erlotinib (ERL)-induced cytotoxicity in the treatment of NSCLC. ERL and TAM are metabolized by CYP3A4 enzymes. In addition, both drugs have the potential of altering the enzymatic activity through either inhibition (ERL) or induction (TAM). Thus it was expected that pharmacokinetics (PK) drug-drug interactions (DDIs) could be encountered following their co-administration. In this respect, a bioanalytical UPLC-MS/MS method has been developed and validated for the simultaneous determination of ERL and TAM in rat plasma samples, using ondansetron (OND) as an internal standard (IS). Plasma samples were prepared using mixed mode cationic solid phase extraction (SPE) STRATA™ -X-C 33μm cartridges with good extraction recovery of both drugs from rat plasma (Er% from -13.92 to -3.32). The drugs were separated on a Waters BEH™ C18 column with an isocratic elution using a mobile phase composed of a mixture of acetonitrile and water, each with 0.15% formic acid, in the ratio of 80: 20, v/v. Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM) at m/z 394.20>278.04 (ERL), m/z 372.25>72.01 (TAM), and m/z 294.18>170.16 (OND). The method was fully validated as per the FDA guidelines over the concentration range of 0.2-50ng/mL with very low lower limit of quantification (LLOQ) of 0.2ng/mL for both ERL and TAM. The intra- and inter-day assay precision (in terms of relative standard deviation, RSD) and accuracy (in terms of percentage relative error, % Er) were evaluated for both drugs and the calculated values evaluated at four different concentration levels were within the acceptable limits (<15%) for concentrations other than LLOQ and 20% for LLOQ. The method was successfully applied to the study of possible PK-DDI following the oral administration of ERL and TAM in a combination, compared to their single administration. PMID:27336702

  6. Development of a UPLC-MS/MS bioanalytical method for the pharmacokinetic study of (-)-epiafzelechin, a flavan-3-ol with osteoprotective activity, in C57BL/6J mice.

    PubMed

    Wong, Ka Chun; Law, Man Chun; Wong, Man Sau; Chan, Tak Hang

    2014-09-15

    (-)-Epiafzelechin is a flavan-3-ol commonly found in plant source. Biological studies suggested that (-)-epiafzelechin may have anti-inflammatory, anti-oxidant and bone-protective effect. However, it's in vivo efficacy remains to be demonstrated. A specific detection method for (-)-epiafzelechin was successfully developed by using UPLC-MS/MS to quantify the amount of (-)-epiafzelechin present in mice plasma after a liquid-liquid extraction by ethyl acetate. The separation was achieved by using a reversed-phase C18 column with a 16 min gradient elution protocol consisting of water (0.1%, v/v, formic acid) and 0-70% ACN (0.1%, v/v, formic acid). The lower limit of quantitation for (-)-epiafzelechin was found to be 12.5 ng/mL. This method exhibited a good linearity (r(2)=0.992). The intra-day and inter-day precision were within 12%, while the accuracy was between 97.6 and 113. 4%. A quantity of 10mg/kg synthetic (-)-epiafzelechin was administered to C57BL/6J mice by intravenous (i.v.) and intraperitoneal (i.p.) injections and the blood was collected at different time points. The plasma was then analyzed by the UPLC-MS/MS method, and the plasma drug concentration-time curves for i.v. and i.p. (-)-epiafzelechin injection were constructed. The maximum concentrations (Cmax) of (-)-epiafzelechin in blood by i.v. and i.p. injection were found to be 10.6 and 6.0 μg/mL, respectively, while the time for reaching Cmax in i.p. injection was found to be 15 min. The distribution half-lives of (-)-epiafzelechin after i.v. and i.p. injection were found to be 7.0 and 12.6 min, respectively. Some of the PK parameters were found to be similar in both i.v. and i.p. injections of (-)-epiafzelechin owing to its high solubility in water. PMID:25108364

  7. Rutaecarpine and evodiamine selected as β1-AR inhibitor candidates using β1-AR/CMC-offline-UPLC/MS prevent cardiac ischemia-reperfusion injury via energy modulation.

    PubMed

    Xue, Hui; Cheng, Yongjie; Wang, Xin; Yue, Yuan; Zhang, Weifang; Li, Xiaoni

    2015-11-10

    In the present study, an offline analytical method combining β1-adrenergic receptor/cell membrane chromatography (β1-AR/CMC) with ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used for direct recognition, separation, and identification of β1-AR inhibitors from Evodia rutaecarpa (Juss) Benth, by which rutaecarpine and evodiamine were screened and identified as potential β1-AR antagonists and the β1-AR inhibition activity of them was confirmed by downregulation of cAMP and PKA in vitro test. In addition, the results of in vivo pharmacological trials revealed that rutaecarpine (1.1mg/ml) and evodiamine (1.1mg/ml) attenuated myocardial infarct size injured by myocardial ischemia/reperfusion, improved metabolism disorders between fatty acid and glucose, increased the content of ATP, Ca(2+)-ATPase activity and reduced the content of peroxisome proliferator-activated receptor α (PPARα) protein level. Thus, the β1-AR/CMC-offline-UPLC/MS method developed in this study could be used as an effective alternative for screening β1-AR binding bioactive components in traditional Chinese medicines and the bioactive components could be used to remedy cardiac diseases via energy modulation. PMID:26263059

  8. Validation of a confirmatory method of salbutamol in sheep hair by UPLC-MS/MS and its application to pharmacokinetic study.

    PubMed

    Decheng, Suo; Wei, Zhang; Yu, Zhang; Genlong, Zhao; Ruigou, Wang; PeiLong, Wang; Xiaoou, Su

    2015-10-10

    A new method for determining salbutamol in hair of sheep by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was established. Samples were extracted with 0.1M of HCl solution. The mixture was heated to 60 °C in a water bath and kept at this temperature for 4h. The extracts were purified through SPE method and then dried with nitrogen. Residues were redissolved in mobile phase. The target compound was determined by UPLC-MS/MS with BEH-C18 column. The usefulness and feasibility of different treatment procedures of hair containing salbutamol were evaluated. The range of linearity was 1-100 ng/g. The LOD was 0.3 ng/g, and the LOQ was 1 ng/g. Recoveries were 89-106%, and coefficients of variation were 3.2-13.9%. Pharmacokinetics of salbutamol was studied in healthy sheep after oral administration of 150 μg/kg body weight salbutamol for 21 consecutive days. Salbutamol residues in hair were still detected after 21 days of administration. PMID:25988297

  9. QuEChERS-based purification method coupled to ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine six quaternary ammonium compounds (QACs) in dairy products.

    PubMed

    Xian, Yanping; Dong, Hao; Wu, Yuluan; Guo, Xindong; Hou, Xiangchang; Wang, Bin

    2016-12-01

    QuEChERS-based purification coupled with UPLC-MS/MS method, was developed for six quaternary ammonium compounds (QACs) determination in dairy products. Powder samples were firstly dispersed by water. Protein in liquid milk was precipitated and sample solution was extracted by acetonitrile. QuEChERS-based purification was used to purify the solution. QACs were finally separated by HILIC column and detected in MRM mode of MS/MS under ESI(+). The stable isotope benzyl-2,3,4,5,6-d5-dimethyltetradecylammonium bromide (C14-BAC-d5) was used as an internal standard. This method was validated in terms of linearity, sensitivity, precision, accuracy. Linear relations were favorable for QACs over the selected concentration ranges of 0.2-50μg/L, with correlation coefficients greater than 0.999. The limits of detection (LODs) were in the range of 0.4-14.5μg/kg. Recoveries were between 91.2% and 115% with RSDs of 2.8-7.5% for intra-day precision and 3.7-6.7% for inter-day precision. This validated method was successfully applied to determine the QACs concentrations in dairy products. PMID:27374511

  10. Development and validation of a UPLC-MS/MS method for quantification of SKLB010, an investigational anti-inflammatory compound, and its application to pharmacokinetic studies in beagle dogs.

    PubMed

    Ye, Xia; Tang, Minghai; Liu, Juan; Wang, Xianhuo; Ma, Liang; Zheng, Hao; Hu, Jia; Chen, Xiang; Duan, Xingmei; Chen, Lijuan

    2011-09-10

    SKLB010 is currently under development as a potential therapeutic agent for the treatment of acute hepatitis and rheumatoid arthritis. The purpose of this paper was to investigate the pre-clinical pharmacokinetics of SKLB010 in beagle dogs. An ultra performance liquid chromatographic tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the quantitative determination of SKLB010 in dog plasma, using rosiglitazone as the internal standard (I.S.). Plasma samples were prepared by a simple solid phase extraction (SPE) method. The analyte and internal standard were separated by an Acquity UPLC BEH C18 (2.1 mm × 50 mm) column with a mobile phase of methanol-water (80/20, v/v) over 2 min. Detection was based on the multiple reaction monitoring with the precursor-to-product ion transitions m/z 234.10→147.92 (SKLB010) and m/z 356.15→150.00 (I.S.). The method was validated according to FDA guidelines on bio-analytical method validation. The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression and stability were within the acceptable ranges. The method described above was successfully applied to reveal the single- and multi-pharmacokinetic profiles of SKLB010 in beagle dogs and should be extendable to pharmacokinetic studies in other species as well. PMID:21680128

  11. 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

  12. Fast and sensitive quantification of human liver cytosolic lithocholic acid sulfation using ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Bansal, Sumit; Lau, Aik Jiang

    2016-02-01

    Detoxification of lithocholic acid (LCA) to lithocholic acid sulfate (LCA-S) is catalyzed by sulfotransferases, mainly SULT2A1. We developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify human liver cytosolic-dependent LCA sulfation. Chromatographic separation was achieved on an UPLC C18 column (2.1×50mm, 1.7μm) and a gradient elution of 0.1% formic acid in water and acetonitrile. Negative electrospray ionization with multiple reaction monitoring (MRM) mode was used to quantify LCA-S (455.3→97.0) and cholic acid (407.2→343.3; internal standard). The retention time was 3.51min for LCA-S and 3.08min for cholic acid. The lower limit of quantification of LCA-S was 0.5nM (or 0.23ng/ml in 400μl total volume) and the assay was linear from 0.2 to 200pmol. Intra-day and inter-day accuracy and precision were <14%. The quality control samples were stable at room temperature for 4h, 4°C for 24h, -20°C for 14 days, and after three freeze-thaw cycles. The matrix (20-100μg cytosolic protein) did not affect LCA-S quantification. This is the first UPLC-MS/MS method applied to optimization of the human liver cytosolic LCA sulfation assay. The optimal levels of MgCl2 and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) cofactor were 2.5mM and 20μM, respectively. Addition of reducing agents (2-mercaptoethanol and DL-dithiothreitol) did not affect LCA-S formation. Human liver cytosolic LCA sulfation was linear with 20-100μg of cytosolic protein and 5-30min incubation time. This UPLC-MS/MS approach offers a specific, sensitive, fast, and direct approach for quantifying human liver cytosolic LCA sulfation. PMID:26773894

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

    PubMed

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

    2015-05-01

    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

  14. 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

  15. 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

  16. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    PubMed

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. PMID:25497892

  17. 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

  18. 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

  19. Pharmacokinetic comparisons by UPLC-MS/MS of isomer paeoniflorin and albiflorin after oral administration decoctions of single-herb Radix Paeoniae Alba and Zengmian Yiliu prescription to rats.

    PubMed

    Gong, Can; Yang, Hong; Wei, Hai; Qi, Cong; Wang, Chang-Hong

    2015-03-01

    Zengmian Yiliu (ZMYL), a traditional Chinese formula, is designed to improve clinical efficacy and reduce adverse effects in combination with cisplatin in ovarian cancer chemotherapy. In ZMYL, Radix Paeoniae Alba (RPA, made from root of Paeonia lactiflora Pall.) acts as an adjunctive drug in cancer treatment by ameliorating side effects induced by radio- and chemotherapy. The pharmacokinetics differences between isomer albiflorin and paeoniflorin, the main components of RPA, after oral administration decoction of single-herb RPA and ZMYL were compared using a sensitive and accurate UPLC-MS/MS. The results indicate that there are statistically significant differences between the pharmacokinetic parameters: decreasing area under the plasma concentration-time curve (AUC), maximum concentration (Cmax ), elimination rate constant (Ke ) and increasing apparent volume of distribution (Vd ) and clearance (CL) for albiflorin, increasing distribution half-life (T1/2d ) and decreasing elimination half-life (T1/2e ), distribution rate constant (Kd ) and absorption rate constant (Ka ) for paeoniflorin in the ZMYL group compared with the single-herb RPA group. In comparison with albiflorin, the pharmacokinetic parameters of paeoniflorin included significantly increasing mean residence time (MRT) and Vd , decreasing CL and Ke in the single-herb RPA group and increasing MRT and T1/2d and decreasing CL, Ke and Kd in the ZMYL group. Both paeoniflorin and albiflorin are more likely, as the main active ingredients in RPA and ZMYL, to play a variety of pharmacological effects, and herb-herb interactions occur, resulting in different pharmacokinetics of albiflorin and paeoniflorin in RPA and ZMYL. PMID:25042570

  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. Development and validation of a 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

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

    2013-12-01

    A simple, sensitive and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was 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(TM) BEH C18 (1.7 µm, 2.1 × 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 time 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 10-4000 ng/mL (r(2) = 0.999) with a lower limit of quantification of 10 ng/mL. The extraction recoveries ranged from 62.0 to 67.3% at concentrations of 20, 600 and 3200 ng/mL). Intra- and inter-day assay precisions (relative standard deviation) were <15% and the accuracy was within 96.5-104.0%. This validated method was successfully applied to quantify 7-hydroxymitragynine in rat plasma following intravenous administration. PMID:23893615

  3. 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

  4. Development and application of a UPLC-MS/MS method for simultaneous determination of fenofibric acid and berberine in rat plasma: application to the drug-drug pharmacokinetic interaction study of fenofibrate combined with berberine after oral administration in rats.

    PubMed

    Li, Guofei; Yang, Fan; Liu, Mei; Su, Xianying; Zhao, Mingming; Zhao, Limei

    2016-07-01

    With the purpose of carrying out pharmacokinetic interaction studies ofnberberine (BBR) and fenofibrate (FBT), an UPLC-MS/MS method has been developed and validated. The analytes, BBR and fenofibric acid (FBA, metabolite of FBT) and the internal standard, tetrahydropalmatine, were extracted with dichloromethane-diethyl ether (3:2, v/v) and separated on an Agilent Eclipse XDB C18 column using a mobile phase composed of acetonitrile and water. With positive ion electrospray ionization, the analytes were monitored on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. Linear calibration curves were obtained over the concentration ranges of 0.1-100.0 ng/mL for BBR and 10.0-50,000.0 ng/mL for FBA. For BBR and FBA, the intra- and inter-day precisions were <11.5 and 11.9%, respectively. The accuracy was within 11.7% and 11.3%. The mean recoveries of BBR at three concentrations of 0.2, 20.0, 80.0 ng/mL were >85.6%, and those of FBA at three concentrations of 20.0, 2500.0, 40,000.0 ng/mL were >87.9%. Consequently, the proposed method was applied to the pharmacokinetic interaction study of FBT combined with BBR after oral administration in rats and was proved to be sensitive, specific and reliable to analyze BBR and FBA in biological samples simultaneously. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26577601

  5. Development and validation of methods for the extraction of phenolic acids from plasma, urine, and liver and analysis by UPLC-MS.

    PubMed

    de Oliveira, Daniela M; Pinto, Carolina B; Sampaio, Geni R; Yonekura, Lina; Catharino, Rodrigo R; Bastos, Deborah H M

    2013-06-26

    This study developed and validated a method for the extraction and determination of 11 phenolic acids in rat plasma, urine, and liver by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). A system suitability test (instrumental linearity, area, and retention time precision) was performed and recovery, intraday and between-day precisions, detection limits (LOD), and quantification limits (LOQ) were determined for all compounds in each biological matrix. Recoveries varied between 88 and 117% in plasma, between 87 and 102% in urine, and between 38 and 100% in liver. Precision was higher than 13.7% intraday and 14.0% interday in all matrices, at three concentration levels. To demonstrate the applicability, the method was used to estimate the concentrations of phenolic acids in samples from animals that received 5-caffeoylquinic acid (5-CQA) by gavage. The excellent validation results and the applicability of the method to real samples confirmed the suitability for studies on absorption, bioavailability, and pharmacokinetics of phenolic acids derived from foods rich in phenolic compounds. PMID:23711305

  6. Prediction of variability in CYP3A4 induction using a combined 1H NMR metabonomics and targeted UPLC-MS approach.

    PubMed

    Rahmioglu, Nilufer; Le Gall, Gwénaëlle; Heaton, James; Kay, Kristine L; Smith, Norman W; Colquhoun, Ian J; Ahmadi, Kourosh R; Kemsley, E Kate

    2011-06-01

    The activity of Cytochrome P450 3A4 (CYP3A4) enzyme is associated with many adverse or poor therapeutic responses to drugs. We used (1)H NMR-based metabonomics to identify a metabolic signature associated with variation in induced CYP3A4 activity. A total of 301 female twins, aged 45--84, participated in this study. Each volunteer was administered a potent inducer of CYP3A4 (St. John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate (300 mg). Pre- and postintervention fasting urine samples were used to obtain metabolite profiles, using (1)H NMR spectroscopy, and were analyzed using UPLC--MS to obtain a marker for CYP3A4 induction, via the ratio of 3-hydroxyquinine to quinine (3OH-Q:Q). Multiple linear regression was used to build a predictive model for 3OH-Q:Q values based on the preintervention metabolite profiles. A combination of seven metabolites and seven covariates showed a strong (r = 0.62) relationship with log(3OH-Q:Q). This regression model demonstrated significant (p < 0.00001) predictive ability when applied to an independent validation set. Our results highlight the promise of metabonomics for predicting CYP3A4-mediated drug response. PMID:21491888

  7. 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

  8. 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

  9. An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats.

    PubMed

    Huang, Yue; Bo, Yunhai; Wu, Xiao; Wang, Qiuyi; Qin, Feng; Zhao, Longshan; Xiong, Zhili

    2016-08-01

    Gushudan, a Chinese compound formulation based on the theory of traditional Chinese medicine and desgined to treat osteoporosis. However, its intergated intervention effective mechanism in vivo is not well understood. In this study, an intergated serum and urinary metabonomic strategy based on UPLC-MS technique have been developed to increase the understanding of the metabolism characters of osteoporosis and to investigate the holistic therapeutic efficacy of Gushudan on prednisolone-induced osteoporosis rat model. Principle component analysis (PCA) was utilized to identify differences in metabolic profiles of rats in the control group, prednisolone-induced osteoporosis model group and Gushudan-treatment group and clear separation was achieved among three groups. Furthermore, 17 potential biomarkers from urine and 10 potential biomarkers from serum were identified, primiarily related to amino acid metabolism, energy metabolism, lipid metabolism, intestinal flora metabolism and kidney damage. Gushudan has therapeutic effects on rat with osteoporosis via the regulation of multiple metabolic pathways. It's worth mentioning that some new biomarkers associated with osteoporosis such as 3-methoxydopa, 2,8-digydroxyadenine have been discovered in this study for the first time. This study provides a useful approach to get insight into the intergated metabonomic mechanism of prednisolone-induced osteoporosis and to assess the efficacy of Gushudan on osteoporotic rats. The work also shows that the metabonomics method is a promising tool in the efficacy and mechanism research of traditional Chinese compound medicines. PMID:27281385

  10. 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

  11. 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

  12. 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

  13. 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...

  14. 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...

  15. 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

  16. 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

  17. 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

  18. Development of a multiple immunoaffinity column for simultaneous determination of multiple mycotoxins in feeds using UPLC-MS/MS.

    PubMed

    Hu, Xiaofeng; Hu, Rui; Zhang, Zhaowei; Li, Peiwu; Zhang, Qi; Wang, Min

    2016-09-01

    A sensitive and specific immunoaffinity column to clean up and isolate multiple mycotoxins was developed along with a rapid one-step sample preparation procedure for ultra-performance liquid chromatography-tandem mass spectrometry analysis. Monoclonal antibodies against aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, zearalenone, ochratoxin A, sterigmatocystin, and T-2 toxin were coupled to microbeads for mycotoxin purification. We optimized a homogenization and extraction procedure as well as column loading and elution conditions to maximize recoveries from complex feed matrices. This method allowed rapid, simple, and simultaneous determination of mycotoxins in feeds with a single chromatographic run. Detection limits for these toxins ranged from 0.006 to 0.12 ng mL(-1), and quantitation limits ranged from 0.06 to 0.75 ng mL(-1). Concentration curves were linear from 0.12 to 40 μg kg(-1) with correlation coefficients of R (2) > 0.99. Intra-assay and inter-assay comparisons indicated excellent repeatability and reproducibility of the multiple immunoaffinity columns. As a proof of principle, 80 feed samples were tested and several contained multiple mycotoxins. This method is sensitive, rapid, and durable enough for multiple mycotoxin determinations that fulfill European Union and Chinese testing criteria. PMID:27225172

  19. UPLC-MS-MS Method for the Determination of Vilazodone in Human Plasma: Application to a Pharmacokinetic Study.

    PubMed

    El-Bagary, Ramzia; Hashem, Hanaa; Fouad, Marwa; Tarek, Sally

    2016-09-01

    A sensitive, rapid and simple liquid chromatographic-electrospray ionization tandem mass spectrometric (LC-ESI-MS-MS) method was developed for the quantitative determination of vilazodone in human plasma and for the study of the pharmacokinetic behavior of vilazodone in healthy Egyptian volunteers. With escitalopram as internal standard (IS), liquid-liquid extraction was used for the purification and preconcentration of analytes from human plasma matrix using diethyl ether. The separation was performed on an Acquity UPLC BEH shield RP C18 column (1.7 µm, 2.1 × 150 mm). Isocratic elution was applied using methanol-0.2% formic acid (90:10, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via an electrospray ionization source at m/z 442.21 → 155.23 for vilazodone and m/z 325.14 → 109.2 for escitalopram. Linear calibration curves were obtained over the range of 1-200 ng/mL with the lower limit of quantification at 1 ng/mL. The intra- and inter-day precision showed relative standard deviation ≤3.3%. The total run time was 1.5 min. This method was successfully applied for clinical pharmacokinetic investigation, and a preliminary metabolic study was also carried out. PMID:27209054

  20. Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study.

    PubMed

    Wang, Ying; Liu, Shi-Ping; Guo, Mei-Hua; Wang, Zhuo

    2016-09-01

    A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS-IVa) in rat plasma was established and validated. Plasma samples were pre-treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 × 50 mm, i.d., 3.5 μm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M - H](-) were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5-1000 ng/mL for CHS-IVa. The recoveries of CHS-IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS-IVa in rats. For oral administration, the plasma concentrations of CHS-IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS-IVa decreased quickly (t1/2 , 1.59 ± 0.25 h). The absolute bioavailability of CHS-IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26864353

  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. Distribution and persistence of cephalosporins in cephalosporin producing wastewater using SPE and UPLC-MS/MS method.

    PubMed

    Yu, Xin; Tang, Xinyao; Zuo, Jiane; Zhang, Mengyu; Chen, Lei; Li, Zaixing

    2016-11-01

    An investigation to study the distribution and persistence of cephalosporins in the cephalosporin producing wastewater was carried out in this paper. The target cephalosporins included ceftriaxone (CRO), cefalexin (CEF), cefotaxime (CTX), cefazolin (CZO), cefuroxime (CXM), cefoxitin (CFX) and cefradine (CF). A rapid and reliable detection method for cephalosporins was established based on solid phase extraction and ultra-performance liquid chromatography - tandem mass spectrometry. In the cephalosporin producing wastewater effluent (CPWWeff), the limit of quantification for the targets ranged from 27.5ng/L to 131.8ng/L, and the recoveries for all of the analytes ranged from 73% to 102%. The mean concentrations of the seven cephalosporins were 12.85-141.55μg/L and 0.05-24.38μg/L in cephalosporin producing wastewater influent and effluent, respectively. Although high removal efficiencies were achieved for the cephalosporins (78.8-99.7%), up to 1.9kg of cephalosporins was discharged per day from the investigated C-WWTP. The degradation processes of CRO, CEF, CZO and CXM followed first-order kinetics in CPWWeff under all of the testing conditions. The degradation rates of tested cephalosporins were accelerated by high temperature and light. Persistence of CXM was the highest among the four tested cephalosporins in CPWWeff. PMID:27328396

  3. Separation and identification of diarylheptanoids in supercritical fluid extract of Alpinia officinarum by UPLC-MS-MS.

    PubMed

    Luo, Jingchao; Rui, Wen; Jiang, Miaomiao; Tian, Qinglong; Ji, Xing; Feng, Yifan

    2010-11-01

    In the present study, ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization (ESI(+)) tandem mass spectrometry (MS) was developed to identify and characterize the diarylheptanoids in the supercritical fluid extract (SFE) of Alpinia officinarum. The method established provides good reproducibility of UPLC and shows high precision with all the mass accuracy of less than 5 ppm. The ESI-MS-MS fragmentation behavior of every group and their appropriate characteristic pathways were proposed. On the basis of analyzing the fragmentation pathways, elemental composition provided by software Masslynx, mass data of the standard compounds and the information regarding polarity obtained from retention time data, in all, 23 diarylheptanods were characterized. All of them have been reported in Alpinia officinarum. They were classified into six distinct groups (homologous series). Compared to the references, the fragmentation pathways of the first and second group were detailed much more and complementary. Further more, the fragmentation pathways of the last four groups were firstly discussed. The fragmentation rules deduced and the data provided could aid in the characterization of other diarylheptanoids of these types and would be useful for the further research of diarylheptanoids in Alpinia officinarum or the other plants. PMID:21044408

  4. Development and validation of an UPLC-MS/MS method for the determination of ionophoric and synthetic coccidiostats in vegetables.

    PubMed

    Broekaert, N; Van Peteghem, C; Daeseleire, E; Sticker, D; Van Poucke, C

    2011-12-01

    In poultry farming, anticoccidial drugs are widely used as feed additives for the prevention and treatment of coccidiosis. Because coccidiostats and veterinary medicines, in general, are often poorly absorbed, manure from treated animals may contain high concentrations of these compounds. Experimental studies have shown that the uptake of veterinary medicines by plants from soil containing contaminated manure may occur. This leads to several questions regarding the impact on the environment, resistance problems, and public health and allergy issues. This work describes the development of a quantification method for coccidiostats in vegetables. Vegetables were spiked at 100 μg kg(-1) (dry weight) with coccidiostats (monensin, narasin, lasalocid A, salinomycin, diclazuril, and nicarbazin) in order to optimize the extraction and clean-up. Possible critical factors (e.g., extraction solvent) were statistically examined by linear regression with the use of Plackett-Burman and full factorial designs. Final extracts were analyzed with ultra-performance liquid chromatography tandem mass spectrometry operating in multiple-reaction monitoring mode. Both the synthetic and ionophoric coccidiostats could be determined in a single run with an analysis time of 5 min. The developed method was validated taking into account the requirements of the Commission Decision 2002/657/EC as a guideline. The method is regarded as applicable for its intended purposes with quantification limits between 0.30 and 2.98 μg kg(-1). This method could be used to establish possible maximum residue limits for coccidiostats in vegetables, as already exist for eggs, meat, and milk. PMID:21984012

  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 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

  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. 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

  8. 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

  9. 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

  10. 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.…

  11. 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

  12. Validation of a novel in vitro assay using ultra performance liquid chromatography-mass spectrometry (UPLC/MS) to detect and quantify hydroxylated metabolites of BDE-99 in rat liver microsomes.

    PubMed

    Erratico, Claudio A; Szeitz, András; Bandiera, Stelvio M

    2010-06-01

    The purpose of this study was to develop and validate an ultra performance liquid chromatography-mass spectrometry (UPLC/MS) method to investigate the hepatic oxidative metabolism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), a widely used flame retardant and ubiquitous environmental contaminant. Hydroxylated metabolites were extracted using liquid-to-liquid extraction, resolved on a C18 column with gradient elution and detected by mass spectrometry in single ion recording mode using electrospray negative ionization. The assay was validated for linearity, accuracy, precision, limit of quantification, range and recovery. Calibration curves were linear (R2 > or = 0.98) over a concentration range of 0.010-1.0 microM for 4-OH-2,2',3,4',5-pentabromodiphenyl ether (4-OH-BDE-90), 5'-OH-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE-99) and 6'-OH-2,2',4,4',5-pentabromodiphenyl ether (6'-OH-BDE-99), and a concentration range of 0.0625-12.5 microM for 2,4,5-tribromophenol (2,4,5-TBP). Inter- and intra-day accuracy values ranged from -2.0% to 6.0% and from -7.7% to 7.3%, respectively, and inter- and intra-day precision values ranged from 2.0% to 8.5% and from 2.2% to 8.6% (n=6), respectively. The limits of quantification were 0.010 microM for 4-OH-BDE-90, 5'-OH-BDE-99 and 6'-OH-BDE-99, and 0.0625 microM for 2,4,5-TBP. Recovery values ranged between 85 and 100% for the four analytes. The validated analytical method was applied to identify and quantify hydroxy BDE-99 metabolites formed in vitro. Incubation of BDE-99 with rat liver microsomes yielded 4-OH-BDE-90 and 6'-OH-BDE-99 as major metabolites and 5'-OH-BDE-99 and 2,4,5-TBP as minor metabolites. To our knowledge, this is the first validated UPLC/MS method to quantify hydroxylated metabolites of PBDEs without the need of derivatization. PMID:20451473

  13. 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

  14. A rapid and reliable UPLC-MS/MS method for the identification and quantification of fourteen synthetic anti-diabetic drugs in adulterated Chinese proprietary medicines and dietary supplements.

    PubMed

    Li, Ning; Cui, Mei; Lu, Xiumei; Qin, Feng; Jiang, Kun; Li, Famei

    2010-11-01

    An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for simultaneous qualitative and quantitative analysis of 14 synthetic anti-diabetic drugs in adulterated Chinese proprietary medicines (CPMs) and dietary supplements. The samples were prepared by ultrasonic extraction with methanol and separated on a C₁₈ column with mobile phase consisting of acetonitrile and water (both containing 0.10% formic acid). Gradient elution was applied with a flow rate of 0.20 mL/min. Two transitions from protonated molecules were monitored for each synthetic anti-diabetic drug in positive mode of electrospray ionization (ESI). The two transitions, the peak area ratio of the two transitions and the retention time were used for identification. The more intensive transition was used for quantification. The analysis time was 6 min per sample. Satisfactory linear relationships were estimated between the peak area and the concentration with correlation coefficients higher than 0.995. The limit of detection ranged from 0.03 to 5.45 ng/mL. The relative standard deviation of intra-day precision was below 7.6%, the RSD of inter-day precision was below 15% and the relative error of accuracy was between -10 and 7.8%. The proposed method is rapid, selective, reliable and was successfully applied to the analysis of 30 real samples of 22 CPMs and eight dietary supplements from the local market in China. PMID:20954219

  15. A rapid and simple UPLC-MS-MS method for determination of glipizide in human plasma and its application to bioequivalence study.

    PubMed

    Qiu, Xiangjun; Zheng, Shuang-li; Wang, Yingfei; Wang, Rong; Ye, Lei

    2015-01-01

    In this study, a simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method is described for the determination of glipizide in human plasma samples using carbamazepine as the internal standard (IS) from bioequivalence assays. Sample preparation was accomplished through protein precipitation with methanol, and chromatographic separation was performed on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with gradient profile at a flow rate of 0.4 mL/min. Mass spectrometric analysis was performed using an QTrap5500 mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 446.1 → 321.0 and m/z 237.1 → 194.2 were used to quantify for glipizide and IS. The linearity of this method was found to be within the concentration range of 10-1,500 ng/mL for glipizide in human plasma. Only 1.0 min was needed for an analytical run. The method was applied to a bioequivalence study of two drug products containing glipizide in human plasma samples. PMID:24771054

  16. Comparative pharmacokinetics of active alkaloids after oral administration of Rhizoma Coptidis extract and Wuji Wan formulas in rat using a UPLC-MS/MS method.

    PubMed

    Chen, Ying; Li, Yuejie; Wang, Yajie; Yang, Qing; Dong, Yu; Weng, Xiaogang; Zhu, Xiaoxin; Wang, Yiwei; Gong, Zipeng; Zhang, Ruijie

    2015-03-01

    Wuji Wan (WJW), containing Rhizoma Coptidis (Huanglian in Chinese, HL), Frutus Evodiae Rutaecarpae (Wuzhuyu, WZY) and Radix Paeoniae Alba (Baishao, BS), is a classical traditional Chinese medical formula employed in treating intestinal disorders. Berberine (BBR) and palmatine (PMT) are the major active alkaloids in HL and have analgesic and anti-microbial effects. A sensitive, specific and validated ultra-performance liquid chromatography-tandem mass spectrometric method was developed to investigate the pharmacokinetic profiles of BBR and PMT in rat plasma and in situ intestinal perfusion solution. In comparison with the pharmacokinetic parameters of BBR and PMT, t(1/2), C(max), T(max), AUC, CL and MRT after intragastric (i.g.) administration with HL extract alone, those remarkably changed after i.g. administration with WJW formulas 1 and 2 (herb proportions are 12:2:3 and 12:1:12). Particularly, the oral bioavailability of PMT in WJW formula 1 was significantly increased. In rat intestinal perfusion experiments, the apparent permeability coefficient value of PMT was (1.45 ± 0.72) × 10(-5) cm/s when perfusion with HL was performed, and the value was significantly increased to (3.92 ± 0.52) × 10(-5) cm/s on perfusion with WJW formula 1. These results indicate that the pharmacokinetic parameters and absorption of BBR and PMT are affected by the other herbs or ingredients from WJW formulas. PMID:24577954

  17. Quantification of sofosbuvir and ledipasvir in human plasma by UPLC-MS/MS method: Application to fasting and fed bioequivalence studies.

    PubMed

    Rezk, Mamdouh R; Bendas, Ehab R; Basalious, Emad B; Karim, Iman A

    2016-08-15

    A rapid and sensitive LC-MS/MS method was developed, optimized and validated for quantification of sofosbuvir (SF) and ledipasvir (LD) in human plasma using eplerenone as an internal standard (IS). Analytes and IS were extracted from plasma by simple liquid-liquid extraction technique using methyl tertiary butyl ether. The prepared samples were chromatographed on Acquity UPLC BEH C18 column. Separation was done using a mobile phase formed of 0.1% formic acid and acetonitrile (50:50, v/v) in an isocratic mode at a flow rate of 0.4ml/min. The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. A full validation of the method was performed according to the FDA guidelines. Linearity was found to be in the range of 0.25-3500ng/ml for SF and 5-2000ng/ml for LD. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A short run time of 2min allows analysis of more than 400 plasma samples per day. The developed method was successfully applied to both fasting and fed bioequivalence studies in healthy human volunteers. PMID:27322631

  18. Simultaneous determination of five components in rat plasma by UPLC-MS/MS and its application to a comparative pharmacokinetic study in Baihe Zhimu Tang and Zhimu extract.

    PubMed

    Li, Guolong; Tang, Zhishu; Yang, Jie; Duan, Jinao; Qian, Dawei; Guo, Jianming; Zhu, Zhenhua; Liu, Hongbo

    2015-01-01

    Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components in Zhimu are flavonoids such as neomangiferin, mangiferin, and steroid saponins (e.g., timosaponin BII, anemarsaponin BIII, timosaponin AIII). The aim of this study was to compare the pharmacokinetics of mangiferin, neomangiferin, timosaponin BII, anemarsaponin BIII and timosaponin AIII in rat plasma after oral administration of BZT and Zhimu extract (ZME). A sensitive, reliable and robust LC-MS/MS method to simultaneously determine steroid saponins and flavonoids in rat plasma was successfully validated. Significant differences (p < 0.05) were found in the pharmacokinetic parameters of timosaponin BII, anemarsaponin BIII and timosaponin AIII between BZT and ZME. It was surmised that formula compatibility could significantly influence the pharmacokinetics of BZT and our study is the first to study the administration of BZT based on pharmacokinetic studies. PMID:25884551

  19. 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. PMID:26753983

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.…

  5. 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

  6. An ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of hederacoside C, a drug candidate for respiratory disorder, in rat plasma.

    PubMed

    Rehman, Shaheed Ur; Choi, Min Sun; Kim, In Sook; Kim, Seung Hyun; Yoo, Hye Hyun

    2016-09-10

    Hederacoside C is a principal bioactive pharmaceutical ingredient of Hedera helix leaf extracts. H. helix extracts have long been used in folk medicine for the treatment of respiratory disorders. Currently, hederacoside C is investigated as a promising candidate for the treatment of respiratory diseases. In this study, an accurate, sensitive, rapid, and reliable bioanalytical method was developed for the determination of hederacoside C in rat plasma using ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). For sample preparation, plasma proteins were precipitated with 0.1% acetic acid in acetonitrile. Waters UPLC BEH C18 (2.1mm I.D.×100mm, 1.7μm) column was used for chromatographic separation. A gradient elution of mobile phases consisting of 0.02% acetic acid in distilled water (solvent A) and 0.02% acetic acid in acetonitrile (solvent B) was used at a flow rate of 0.3mL/min. The multiple reaction monitoring (MRM) mode was used for mass spectrometric detection; the MRM transitions were m/z 1219.7→m/z 469.2 for hederacoside C and m/z 1108.3→m/z 221.2 for ginsenoside Rb1 (internal standard) in the negative ionization mode. A calibration curve was constructed in the range of 10-1000ng/mL. The intra- and inter-day precision and accuracy were within 5%. The developed UPLC-MS/MS method was successfully applied in a pharmacokinetic study of hederacoside C in rats. Hederacoside C was quickly but inadequately absorbed from the gastrointestinal tract of rats resulting in extremely low bioavailability and relatively slow clearance. PMID:27411171

  7. [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

  8. A high sensitivity THz detector

    NASA Astrophysics Data System (ADS)

    Su, Bo; Duan, Guoteng

    2011-08-01

    We have developed a novel THz detector which uses the cantilever technology and surface plasmon resonance (SPR) technology to achieve a high sensitivity. The Micro Electro Mechanical System (MEMS) technology is adopted to fabricate the detector, which comprise thermo-sensitive bi-material micro-cantilever, prism and optical readout system. The bi-material of Si3N4 and Al is used to fabricate the micro-cantilever because of the good absorption characteristic for THz of Si3N4 and the great difference in thermal expansion coefficient of the bi-material for the deformation of the micro-cantilever. In order to increase the deformation of micro-cantilever, the method of computer simulation is used to obtain the optimal structure of micro-cantilever and the thickness of Si3N4 and Al. The function of the glass prism is to make the incident light generate total reflection under certain conditions. The gold film is sputtering on the top of glass slide using the method of magnetron sputtering and it is necessary for the generation of SPR performance. The optical readout system can make the change of cantilever bending convert to the change of reflection luminous intensity proportionally. The heat on the micro-cantilever coming from the THz radiation can lose easily in the air, so the detector is placed vertically in a cylindrical vacuum chamber which is sealed with quartz glasses and polyethylene lamina at the two end surfaces respectively. The quartz glass is used for the incidence of visible polarized light and the polyethylene lamina for the THz radiation. In order to maintain the vacuum performance of the chamber, the mechanical pump and molecular pump are adopted. In static mode, THz radiation absorption raises the temperature of micro-cantilever, so it bends proportionally. The micro-cantilever bending changes the thicknesses of the gap between the micro-cantilever and the metallic thin film on the micro-prism. It will result in a shift of the SPR angle. Therefore, the

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. High sensitivity cymbal-based accelerometer

    SciTech Connect

    Sun Chengliang; Lam, K.H.; Choy, S.H.; Chan, H.L. W.; Zhao, X.-Z.; Choy, C.L.

    2006-03-15

    A high sensitivity piezoelectric accelerometer has been developed by replacing the conventional piezoelectric rings with a cymbal transducer. The sensitivity of the cymbal-based accelerometers containing cymbal transducers with different endcap thicknesses and different seismic masses has been measured as a function of driving frequency. Due to the high d{sub 33}{sup '} coefficient of the cymbal transducers, the cymbal-based accelerometers have a high sensitivity of {approx}97 pC/ms{sup -2} with the amplitude rise of 2.85% (<1 dB) at one-third of the mounted resonance frequency (3.38 kHz). The effect of the seismic mass, the resonance frequency, and d{sub 33}{sup '} coefficient of the cymbal transducers on the sensitivity and the frequency range of the cymbal-based accelerometers are reported.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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 Central

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

    2015-01-01

    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 on an Acquity UPLC BEH C18 (2.1 mm X 50 mm) with 1.7 μm particle size and 130Å pore size. Flow rate was 0.5 mL/min and total chromatographic run time was 2.2 minutes. Mobile phase consisted of 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 102-118% with CV less than 6% for all matrices. The calibration curves for all matrices were linear over the studied concentration range (R2 ≥ 0.998, n = 3). 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 accuracy were between 85–115% 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. UPLC-MS/MS method with automated on-line SPE for the isomer-specific quantification of the first-generation anti-HCV protease inhibitors in peripheral blood mononuclear cells.

    PubMed

    De Nicolò, Amedeo; Abdi, Adnan Mohamed; Boglione, Lucio; Baiett, Lorena; Allegra, Sarah; Di Perri, Giovanni; D'Avolio, Antonio

    2015-11-10

    HCV infection affects over 170 million people worldwide. The current standard for treatment of genotype 1 infection is the association of the first generation protease inhibitors boceprevir or telaprevir to ribavirin and peginterferon α. Although the response rate has been improved with these new drugs, some pharmacokinetic/pharmacodinamic issues emerged in the past years. To date, some analytical methods are available for the quantification of these drugs in plasma; however, the real active concentrations of the two drugs are those in hepatocytes. Being the withdrawal of hepatocytes too invasive, in this work we aimed to develop and validate a chromatographic method coupled with tandem mass spectrometry capable of quantifying boceprevir and telaprevir isomers in peripheral blood mononuclear cells, used as an "in-vivo" cellular model of compartmentalization. The method used an on-line solid phase extraction protocol based on the new OSM(®) platform and was fully validated following FDA guidelines. This method showed mean intra- and inter-day inaccuracy and imprecision both lower than 15%, high and stable recovery and contained matrix effect, with a run time of 6min, comprehensive of SPE extraction. The method was then applied on 35 real samples from patients treated with boceprevir or telaprevir, with good analytical performances, thus assessing its eligibility for a possible future routine use. Peculiar pharmacokinetic data have been observed, suggesting the usefulness of investigating intracellular pharmacokinetics of these drugs. Further studies will be required to test the correlation of intracellular concentrations with effectiveness and toxicity of triple therapy. PMID:26291788

  7. Diaphragm based high sensitive FBG pressure sensor

    NASA Astrophysics Data System (ADS)

    Vengal Rao, P.; Srimannarayana, K.; Sai Shankar, M.; Kishore, P.

    2013-06-01

    A high sensitive pressure sensor based on Fiber Bragg grating (FBG) integrated with a thin metal diaphragm was designed and demonstrated. To enhance the pressure sensitivity FBG is firmly glued across the diameter of the diaphragm. Under pressure, the diaphragm deforms and produces an induced strain along the length of the fiber causes shift in Bragg wavelength of the FBG. Pressure measurement is made by measuring the Bragg wavelength shift against change in pressure. The sensor was tested up to the maximum pressure of 140 psi and the corresponding pressure sensitivity was found to be 0.0204 nm/psi, which is approximately 970 times higher than that can be achieved with a bare FBG. The experimental results show good agreement with the theoretical results and possess good linearity and repeatability. This sensor can be used for the measurement of medium pressure, liquid level and depth of underwater.

  8. 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.

  9. 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

    2016-02-18

    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

  10. Highly sensitive catalytic spectrophotometric determination of ruthenium

    NASA Astrophysics Data System (ADS)

    Naik, Radhey M.; Srivastava, Abhishek; Prasad, Surendra

    2008-01-01

    A new and highly sensitive catalytic kinetic method (CKM) for the determination of ruthenium(III) has been established based on its catalytic effect on the oxidation of L-phenylalanine ( L-Pheala) by KMnO 4 in highly alkaline medium. The reaction has been followed spectrophotometrically by measuring the decrease in the absorbance at 526 nm. The proposed CKM is based on the fixed time procedure under optimum reaction conditions. It relies on the linear relationship where the change in the absorbance (Δ At) versus added Ru(III) amounts in the range of 0.101-2.526 ng ml -1 is plotted. Under the optimum conditions, the sensitivity of the proposed method, i.e. the limit of detection corresponding to 5 min is 0.08 ng ml -1, and decreases with increased time of analysis. The method is featured with good accuracy and reproducibility for ruthenium(III) determination. The ruthenium(III) has also been determined in presence of several interfering and non-interfering cations, anions and polyaminocarboxylates. No foreign ions interfered in the determination ruthenium(III) up to 20-fold higher concentration of foreign ions. In addition to standard solutions analysis, this method was successfully applied for the quantitative determination of ruthenium(III) in drinking water samples. The method is highly sensitive, selective and very stable. A review of recently published catalytic spectrophotometric methods for the determination of ruthenium(III) has also been presented for comparison.

  11. Highly sensitive beam steering with plasmonic antenna

    PubMed Central

    Rui, Guanghao; Zhan, Qiwen

    2014-01-01

    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. PMID:25091405

  12. 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.

  13. 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.

  14. The high sensitivity double beta spectrometer TGV

    NASA Astrophysics Data System (ADS)

    Briancon, Ch.; Brudanin, V. B.; Egorov, V. G.; Janout, Z.; Koníček, J.; Kovalík, A.; Kovalenko, V. E.; Kubašta, J.; Pospíšil, S.; Revenko, A. V.; Rukhadze, N. I.; Salamatin, A. V.; Sandukovsky, V. G.; Štekl, I.; Timkin, V. V.; Tsupko-Sitnikov, V. V.; Vorobel, V.; Vylov, Ts.

    1996-02-01

    A high sensitivity double beta spectrometer TGV (Telescope Germanium Vertical) has been developed. It is based on 16 HPGe detectors of volume 1200 × 6 mm 3 each in the same cryostat. The TGV spectrometer was proposed for the study of ultrarare nuclear processes (e.g. 2νββ, 0νββ, 2νEC/EC). Details of the TGV spectrometer construction are described, the principles of background suppression, the results of Monte Carlo simulations and the results of test background measurements (in Dubna and Modane underground laboratory) are provided.

  15. [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

  16. 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.

  17. 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

  18. 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.

  19. High-sensitivity detection of TNT

    PubMed Central

    Pushkarsky, Michael B.; Dunayevskiy, Ilya G.; Prasanna, Manu; Tsekoun, Alexei G.; Go, Rowel; Patel, C. Kumar N.

    2006-01-01

    We report high-sensitivity detection of 2,4,6-trinitrotoluene (TNT) by using laser photoacoustic spectroscopy where the laser radiation is obtained from a continuous-wave room temperature high-power quantum cascade laser in an external grating cavity geometry. The external grating cavity quantum cascade laser is continuously tunable over ≈400 nm around 7.3 μm and produces a maximum continuous-wave power of ≈200 mW. The IR spectroscopic signature of TNT is sufficiently different from that of nitroglycerine so that unambiguous detection of TNT without false positives from traces of nitroglycerine is possible. We also report the results of spectroscopy of acetylene in the 7.3-μm region to demonstrate continuous tunability of the IR source. PMID:17164325

  20. A simple sheathless CE-MS interface with a sub-micrometer electrical contact fracture for sensitive analysis of peptide and protein samples.

    PubMed

    Nguyen, Tam T T N; Petersen, Nickolaj J; Rand, Kasper D

    2016-09-14

    Online coupling of capillary electrophoresis (CE) to electrospray ionization mass spectrometry (MS) has shown considerable potential, however, technical challenges have limited its use. In this study, we have developed a simple and sensitive sheathless CE-MS interface based on the novel concept of forming a sub-micrometer fracture directly in the capillary. The simple interface design allowed the generation of a stable ESI spray capable of ionization at low nanoliter flow-rates (45-90 nL/min) for high sensitivity MS analysis of challenging samples like those containing proteins and peptides. By analysis of a model peptide (leucine enkephalin), a limit of detection (LOD) of 0.045 pmol/μL (corresponding to 67 attomol in a sample volume of ∼15 nL) was obtained. The merit of the CE-MS approach was demonstrated by analysis of bovine serum albumin (BSA) tryptic peptides. A well-resolved separation profile was achieved and comparable sequence coverage was obtained by the CE-MS method (73%) compared to a representative UPLC-MS method (77%). The CE-MS interface was subsequently used to analyse a more complex sample of pharmaceutically relevant human proteins including insulin, tissue factor and α-synuclein. Efficient separation and protein ESI mass spectra of adequate quality could be achieved using only a small amount of sample (30 fmol). In addition, analysis of ubiquitin samples under both native and denatured conditions, indicate that the CE-MS setup can facilitate native MS applications to probe the conformational properties of proteins. Thus, the described CE-MS setup should be useful for a wide range of high-sensitivity applications in protein research. PMID:27566351

  1. 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.

  2. 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.

  3. High sensitivity ancilla assisted nanoscale DC magnetometry

    NASA Astrophysics Data System (ADS)

    Liu, Yixiang; Ajoy, Ashok; Marseglia, Luca; Saha, Kasturi; Cappellaro, Paola

    2016-05-01

    Sensing slowly varying magnetic fields are particularly relevant to many real world scenarios, where the signals of interest are DC or close to static. Nitrogen Vacancy (NV) centers in diamond are a versatile platform for such DC magnetometry on nanometer length scales. Using NV centers, the standard technique for measuring DC magnetic fields is via the Ramsey protocol, where sensitivities can approach better than 1 μ T/vHz, but are limited by the sensor fast dephasing time T2*. In this work we instead present a method of sensing DC magnetic fields that is intrinsically limited by the much longer T2 coherence time. The method exploits a strongly-coupled ancillary nuclear spin to achieve high DC field sensitivities potentially exceeding that of the Ramsey method. In addition, through this method we sense the perpendicular component of the DC magnetic field, which in conjunction with the parallel component sensed by the Ramsey method provides a valuable tool for vector DC magnetometry at the nanoscale.

  4. Rapid and sensitive hormonal profiling of complex plant samples by liquid chromatography coupled to electrospray ionization tandem mass spectrometry

    PubMed Central

    2011-01-01

    Background Plant hormones play a pivotal role in several physiological processes during a plant's life cycle, from germination to senescence, and the determination of endogenous concentrations of hormones is essential to elucidate the role of a particular hormone in any physiological process. Availability of a sensitive and rapid method to quantify multiple classes of hormones simultaneously will greatly facilitate the investigation of signaling networks in controlling specific developmental pathways and physiological responses. Due to the presence of hormones at very low concentrations in plant tissues (10-9 M to 10-6 M) and their different chemistries, the development of a high-throughput and comprehensive method for the determination of hormones is challenging. Results The present work reports a rapid, specific and sensitive method using ultrahigh-performance liquid chromatography coupled to electrospray ionization tandem spectrometry (UPLC/ESI-MS/MS) to analyze quantitatively the major hormones found in plant tissues within six minutes, including auxins, cytokinins, gibberellins, abscisic acid, 1-amino-cyclopropane-1-carboxyic acid (the ethylene precursor), jasmonic acid and salicylic acid. Sample preparation, extraction procedures and UPLC-MS/MS conditions were optimized for the determination of all plant hormones and are summarized in a schematic extraction diagram for the analysis of small amounts of plant material without time-consuming additional steps such as purification, sample drying or re-suspension. Conclusions This new method is applicable to the analysis of dynamic changes in endogenous concentrations of hormones to study plant developmental processes or plant responses to biotic and abiotic stresses in complex tissues. An example is shown in which a hormone profiling is obtained from leaves of plants exposed to salt stress in the aromatic plant, Rosmarinus officinalis. PMID:22098763

  5. 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.

  6. Face Transplantation in a Highly Sensitized Recipient.

    PubMed

    Chandraker, Anil; Arscott, Ramon; Murphy, George; Lian, Christine; Bueno, Ericka; Marty, Francisco; Rennke, Helmut; Milford, Edgar; Tullius, Stefan; Pomahac, Bodhan

    2016-05-01

    Face transplantation was performed in a highly sensitized recipient with positive preoperative crossmatch and subsequent antibody-mediated rejection. The recipient was a 45-year-old female with extensive conventional reconstructions after chemical burns over the majority of the body. Residual quality of life and facial functions were poor. Levels of circulating anti-human leukocyte antigen (HLA) antibodies were high, and panel reactive antibody score was 98%. A potential donor was identified; however, with positive T and B cell flow crossmatches. The transplant team proceeded with face transplantation from this donor, under tailored immune suppression and with available salvage options. The operation was successful. Plasmapheresis and induction immune suppression (i.e., thymoglobulin followed by mycophenolate mofetil, tacrolimus, and steroids) were provided. Five days later, there was significant facial swelling, rising anti-HLA antibody titers, and unprecedented evidence of C4d deposits on skin. High doses of steroids and thymoglobulin were provided; however, rejection increased such that by day 19 it was diagnosed grade III in the BANFF scale. After stopping thymoglobulin because of serum sickness, combination therapy of plasmapheresis, eculizumab, bortezomib, and alemtuzumab was provided. HLA antibody levels decreased while swelling and redness improved. At 3 months, there were no longer signs of rejection on biopsy. PMID:27168576

  7. Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques

    PubMed Central

    Fang, Jing; Doneanu, Catalin; Alley, William R.; Yu, Ying Qing; Beck, Alain; Chen, Weibin

    2016-01-01

    ABSTRACT In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. Some differences were observed for the lower abundance glycans. Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. PMID:27260215

  8. 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.

  9. Demonstration of high sensitivity laser ranging system

    NASA Technical Reports Server (NTRS)

    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.

  10. Quantitative determination of mithramycin in human plasma by a novel, sensitive ultra-HPLC-MS/MS method for clinical pharmacokinetic application.

    PubMed

    Roth, Jeffrey; Peer, Cody J; Widemann, Brigitte; Cole, Diane E; Ershler, Rachel; Helman, Lee; Schrump, David; Figg, William D

    2014-11-01

    Mithramycin is a neoplastic antibiotic synthesized by various Streptomyces bacteria. It is under investigation as a chemotherapeutic treatment for a wide variety of cancers. Ongoing and forthcoming clinical trials will require pharmacokinetic analysis of mithramycin in humans, both to see if target concentrations are achieved and to optimize dosing and correlate outcomes (response/toxicity) with pharmacokinetics. Two published methods for mithramycin quantitation exist, but both are immunoassays that lack current bioanalytical standards of selectivity and sensitivity. To provide an upgraded and more widely applicable assay, a UPLC-MS/MS method for quantitation of mithramycin in human plasma was developed. Solid-phase extraction allowed for excellent recoveries (>90%) necessary for high throughput analyses on sensitive instrumentation. However, a ∼55% reduction in analyte signal was observed as a result of plasma matrix effects. Mithramycin and the internal standard chromomycin were separated on a Waters Acquity BEH C18 column (2.1×50 mm, 1.7 μm) and detected using electrospray ionization operated in the negative mode at mass transitions m/z 1083.5→268.9 and 1181.5→269.0, respectively, on an AB Sciex QTrap 5500. The assay range was 0.5-500 ng/mL and proved to be linear (r(2)>0.996), accurate (≤10% deviation), and precise (CV<15%). Mithramycin was stable in plasma at room temperature for 24 h, as well as through three freeze-thaw cycles. This method was subsequently used to quantitate mithramycin plasma concentrations from patients enrolled on two clinical trials at the NCI. PMID:25247492

  11. Quantitative Determination of Mithramycin in Human Plasma by a Novel, Sensitive ultra-HPLC-MS/MS Method for Clinical Pharmacokinetic Application

    PubMed Central

    Roth, Jeffrey; Peer, Cody J.; Widemann, Brigitte; Cole, Diane E.; Ershler, Rachel; Helman, Lee; Schrump, David; Figg, William D.

    2014-01-01

    Mithramycin is a neoplastic antibiotic synthesized by various Streptomyces bacteria. It is under investigation as a chemotherapeutic treatment for a wide variety of cancers. Ongoing and forthcoming clinical trials will require pharmacokinetic analysis of mithramycin in humans, both to see if target concentrations are achieved and to optimize dosing and correlate outcomes (response/toxicity) with pharmacokinetics. Two published methods for mithramycin quantitation exist, but both are immunoassays that lack current bioanalytical standards of selectivity and sensitivity. To provide an upgraded and more widely applicable assay, a UPLC-MS/MS method for quantitation of mithramycin in human plasma was developed. Solid phase extraction allowed for excellent recoveries (>90%) necessary for high throughput analyses on sensitive instrumentation. However, a ~55% reduction in analyte signal was observed as a result of plasma matrix effects. Mithramycin and the internal standard chromomycin were separated on a Waters Acquity BEH C18 column (2.1x50mm, 1.7um) and detected using electrospray ionization operated in the negative mode at mass transitions m/z 1083.5→268.9 and 1181.5→269.0, respectively, on an AB Sciex QTrap 5500. The assay range was 0.5–500 ng/mL and proved to be linear (r2>0.996), accurate (≤10% deviation), and precise (CV<15%). Mithramycin was stable in plasma at room temperature for 24 hours, as well as through three freeze-thaw cycles. This method was subsequently used to quantitate mithramycin plasma concentrations from patients enrolled on two clinical trials at the NCI. PMID:25247492

  12. 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.

  13. 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

  14. A high sensitive phosphor for dosimetric applications

    NASA Astrophysics Data System (ADS)

    Kore, Bhushan P.; Dhoble, N. S.; Lochab, S. P.; Dhoble, S. J.

    2015-06-01

    In this study a novel TL phosphor CaMg3(SO4)4:Dy3+ was prepared by acid distillation method. The TL response of this phosphor towards γ-rays and carbon ion beam was tested. Good dosimetric glow curve was observed which is stable against both the type of radiations. The CaMg3(SO4)4:Dy3+ phosphor doped with 0.2 mol% of Dy3+, irradiated with γ-ray shows nearly equal sensitivity to that of commercially available CaSO4:Dy TLD phosphor whereas 3.5 times more sensitivity than CaSO4:Dy, when irradiated with carbon ion beam. The change in glow peak intensities and glow peak temperature with variation in irradiation species and energy of ion beam is discussed here. The effect of these on trapping parameters is also illustrated.

  15. 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.

  16. 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.

  17. A high sensitive phosphor for dosimetric applications

    SciTech Connect

    Kore, Bhushan P. Dhoble, S. J.; Dhoble, N. S.; Lochab, S. P.

    2015-06-24

    In this study a novel TL phosphor CaMg{sub 3}(SO{sub 4}){sub 4}:Dy{sup 3+} was prepared by acid distillation method. The TL response of this phosphor towards γ-rays and carbon ion beam was tested. Good dosimetric glow curve was observed which is stable against both the type of radiations. The CaMg{sub 3}(SO{sub 4}){sub 4}:Dy{sup 3+} phosphor doped with 0.2 mol% of Dy{sup 3+}, irradiated with γ-ray shows nearly equal sensitivity to that of commercially available CaSO{sub 4}:Dy TLD phosphor whereas 3.5 times more sensitivity than CaSO{sub 4}:Dy, when irradiated with carbon ion beam. The change in glow peak intensities and glow peak temperature with variation in irradiation species and energy of ion beam is discussed here. The effect of these on trapping parameters is also illustrated.

  18. 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.

  19. Fabrication of High Sensitive Immunochromato Kit Using Au Colloid

    NASA Astrophysics Data System (ADS)

    Okamoto, Koji

    Au colloid have characteristics of surface plasmon resonance with absorption at 500 nm~600 nm wavelength. Surface on the citric acid Au colloid can be conjugated with protein eg. antibody. Various particle size of Au colloid makes it high sensitive immunochromato as diagnostics. High sensitive immunochromato will be useful for application of cancer marker eg. prostate specific antigen and influenza early diagnosis.

  20. 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.

  1. 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

  2. Novel high-sensitivity fluorescence polarization reader

    NASA Astrophysics Data System (ADS)

    Hoyt, Clifford C.; Levenson, Richard M.; Banks, Peter

    2001-05-01

    We have developed a new fluorescence polarization (FP) reader suitable for high-throughput screening (HST) and ultra-HTS whose assay-performance and sample-throughput are both considerably improved over present state-of-the-art instrumentation. The SymmetryTM reader possesses a number of features that differ from conventional HTS FP readers. These include: laser-based excitation, liquid crystal polarization optics that rapidly and accurately measure polarization states; and CCD detectors to capture emission from multiple wells. We show that the performance in assays relevant to the drug discovery process, such as G- protein coupled receptor-based assays, is significantly enhanced due to a dramatic improvement in precision. Furthermore, the CCD-detection system used can substantially improve sample throughput compared to sequential readers while maintaining high performance.

  3. High sensitivity accelerometers for high performance seismic attenuators

    NASA Astrophysics Data System (ADS)

    Bertolini, A.; de Salvo, R.; Fidecaro, F.; Francesconi, M.; Sannibale, V.; Takamori, A.

    2000-06-01

    We present concepts and features of a new horizontal accelerometer whose mechanical design and machining process aim to improve the sensitivity in the frequency region between 10 mHz and 1 Hz. The expected sensitivity, less than 10-11 m/s2/Hz around 100 mHz, is a couple of orders of magnitude below the state of art limits. This accelerometer could be integrated in the active control of the LIGO II mirror seismic isolators. .

  4. High sensitivity silicon single nanowire junctionless phototransistor

    NASA Astrophysics Data System (ADS)

    Das, Samaresh; Dhyani, Veerendra; Georgiev, Yordan M.; Williams, David A.

    2016-02-01

    A high-gain photodetector based on junctionless MOSEFT has been presented in this work. Tri-gate junctionless nanowire phototransistors were fabricated on (100) silicon-on-insulator wafers with a buried oxide of thickness 145 nm and top silicon layer of thickness 10 nm. The gate stack consisted of a 10 nm SiO2 dielectric and a 50 nm poly-Si gate electrode. The channel length and doping concentration of junctionless n-MOSFETs was 1 μm and 3 × 1019 cm-3, respectively. The dark current of this device measured at room temperature was less than 1 pA. The measured internal gain of the device was about 35 for 860 nm light illumination. The photocurrent was 300 times larger than the dark current for only 30 nW incident power on the nanowire at 300 mV drain bias.

  5. 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.

  6. Fabrication of High Sensitivity Carbon Microcoil Pressure Sensors

    PubMed Central

    Su, Chih-Chung; Li, Chen-Hung; Chang, Neng-Kai; Gao, Feng; Chang, Shuo-Hung

    2012-01-01

    This work demonstrates a highly sensitive pressure sensor that was fabricated using carbon microcoils (CMCs) and polydimethylsiloxane (PDMS). CMCs were grown by chemical vapor deposition using various ratios of Fe-Sn catalytic solution. The pressure sensor has a sandwiched structure, in which the as-grown CMCs were inserted between two PDMS layers. The pressure sensor exhibits piezo-resistivity changes in response to mechanical loading using a load cell system. The yields of the growth of CMCs at a catalyst proportion of Fe:Sn = 95:5 reach 95%. Experimental results show that the sensor achieves a high sensitivity of 0.93%/kPa from the CMC yield of 95%. The sensitivity of the pressure sensor increases with increasing yield of CMCs. The demonstrated pressure sensor shows the advantage of high sensitivity and is suitable for mass production. PMID:23112586

  7. High sensitivity optical waveguide accelerometer based on Fano resonance.

    PubMed

    Wan, Fenghua; Qian, Guang; Li, Ruozhou; Tang, Jie; Zhang, Tong

    2016-08-20

    An optical waveguide accelerometer based on tunable asymmetrical Fano resonance in a ring-resonator-coupled Mach-Zehnder interferometer (MZI) is proposed and analyzed. A Fano resonance accelerometer has a relatively large workspace of coupling coefficients with high sensitivity, which has potential application in inertial navigation, missile guidance, and attitude control of satellites. Due to the interference between a high-Q resonance pathway and a coherent background pathway, a steep asymmetric line shape is generated, which greatly improves the sensitivity of this accelerometer. The sensitivity of the accelerometer is about 111.75 mW/g. A 393-fold increase in sensitivity is achieved compared with a conventional MZI accelerometer and is approximately equal to the single ring structure. PMID:27556984

  8. 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

  9. 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

  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. 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

  12. Highly sensitive bovine serum albumin biosensor based on liquid crystal

    NASA Astrophysics Data System (ADS)

    Sharma, Vikash; Kumar, Ajay; Ganguly, Prasun; Biradar, A. M.

    2014-01-01

    A highly sensitive liquid crystal (LC) based bovine serum albumin (BSA) protein biosensor is designed. A uniform homeotropic alignment of nematic LC was observed in BSA free substrate which changed into homogeneous in presence of BSA. The change in the LC orientation is found to depend strongly on BSA concentration. This change in the LC alignment is attributed to the modification in the surface conditions which is verified by contact angle measurements. We have detected an ultra low concentration (0.5 μg/ml) of BSA. The present study demonstrates the utilization of LC in the realization of high sensitivity biosensors.

  13. 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

  14. High-sensitivity SQUIDs with dispersive readout for scanning microscopy

    NASA Astrophysics Data System (ADS)

    Mol, J. M.; Foroughi, F.; Arps, J.; Kammerloher, E.; Bethke, P.; Gibson, G. W., Jr.; Fung, Y. K. K.; Klopfer, B.; Nowack, K.; Kratz, P. A.; Huber, M. E.; Moler, K. A.; Kirtley, J. R.; Bluhm, H.

    2014-03-01

    In a scanning SQUID microscope, the high magnetic flux sensitivity is utilized to image magnetic properties of sample surfaces. As an alternative to the widely used DC SQUIDs, we present Nb SQUIDs for scanning with dispersive microwave readout, featuring significantly higher bandwidth and sensitivity. An on-chip shunt capacitor in parallel with the junction and flux pickup loops forms an LC resonator whose resonance depends on the flux in the SQUID. The readout utilizes a phase-sensitive detection of the reflected drive signal at the SQUID's resonance frequency. Highest sensitivities are achieved by making use of the inherent nonlinearity of the device at high excitation powers. We present a study of the characteristics and noise measurements of our sensors at 4 K. Extrapolations from our results to 300 mK indicate that flux sensitivities as low as 50 nΦ0Hz- 1 / 2 could be possible. Using high-resolution lithography, our sensors promise sub-micron spatial resolution. Integrated into a scanning microscope, they will provide a powerful tool for the study of weak magnetic effects and quantum coherent phenomena. This work was supported by NSF IMR-MIP grant No. 0957616 and the Alfried Krupp von Bohlen und Halbach - Foundation.

  15. Large pi-aromatic molecules as potential sensitizers for highly efficient dye-sensitized solar cells.

    PubMed

    Imahori, Hiroshi; Umeyama, Tomokazu; Ito, Seigo

    2009-11-17

    Recently, dye-sensitized solar cells have attracted much attention relevant to global environmental issues. Thus far, ruthenium(II) bipyridyl complexes have proven to be the most efficient TiO(2) sensitizers in dye-sensitized solar cells. However, a gradual increment in the highest power conversion efficiency has been recognized in the past decade. More importantly, considering that ruthenium is a rare metal, novel dyes without metal or using inexpensive metal are desirable for highly efficient dye-sensitized solar cells. Large pi-aromatic molecules, such as porphyrins, phthalocyanines, and perylenes, are important classes of potential sensitizers for highly efficient dye-sensitized solar cells, owing to their photostability and high light-harvesting capabilities that can allow applications in thinner, low-cost dye-sensitized solar cells. Porphyrins possess an intense Soret band at 400 nm and moderate Q bands at 600 nm. Nevertheless, the poor light-harvesting properties relative to the ruthenium complexes have limited the cell performance of porphyrin-sensitized TiO(2) cells. Elongation of the pi conjugation and loss of symmetry in porphyrins cause broadening and a red shift of the absorption bands together with an increasing intensity of the Q bands relative to that of the Soret band. On the basis of the strategy, the cell performance of porphyrin-sensitized solar cells has been improved intensively by the enhanced light absorption. Actually, some push-pull-type porphyrins have disclosed a remarkably high power conversion efficiency (6-7%) that was close to that of the ruthenium complexes. Phthalocyanines exhibit strong absorption around 300 and 700 nm and redox features that are similar to porphyrins. Moreover, phthalocyanines are transparent over a large region of the visible spectrum, thereby enabling the possibility of using them as "photovoltaic windows". However, the cell performance was poor, owing to strong aggregation and lack of directionality in the

  16. 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.

  17. 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...

  18. Determination of impact sensitivity of materials at high pressures

    NASA Technical Reports Server (NTRS)

    Davis, L.; Pippen, D.; Stradling, J.; Whitaker, D.

    1972-01-01

    Compact device is used to determine impact sensitivity of material in static, high pressure, gaseous environment. It can also be instrumented to monitor and record pressure, temperature, and striker impact force. Device is used in conjunction with commercially available liquid oxygen impact tester which provides impact energy.

  19. Microelectromechanical Resonant Accelerometer Designed with a High Sensitivity.

    PubMed

    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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Highly mass-sensitive thin film plate acoustic resonators (FPAR).

    PubMed

    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

  5. High sensitivity of positron annihilation to thermal oxidation of polyethylene

    NASA Astrophysics Data System (ADS)

    Ito, Kenji; Kobayashi, Yoshinori; Nanasawa, Atsushi

    2003-01-01

    We demonstrate the high sensitivity of positron annihilation to compositional changes related to the thermal degradation of polyethylene (PE). Positron annihilation γ-ray and lifetime measurements were conducted for PE films with and without antioxidant (1000-ppm Ciba® IRGANOX® 1076), subjected to heat treatment at 100 °C for different periods, to a maximum of 30 days. For the film without antioxidant, the positron Doppler parameter (S) and ortho-positronium formation probability (Io-Ps) appreciably decreased with increased heat treatment times, whereas they barely changed for the film with antioxidant. This, together with the Fourier transform infrared measurements, demonstrated that the variations of S and Io-Ps are caused by the thermal oxidation of PE. The S parameter was found to be sensitive to the early stage of degradation, where the carbonyl concentration is inferred to be lower than 100 ppm. The high sensitivity results from the large positron mobility in PE and from the high positron affinity of oxygen-containing polar groups. This work provides the basis for an application of positron annihilation to sensitive detection of the initial degradation of PE and other nonpolar polymers.

  6. 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.

  7. Integrated compact optical current sensors with high sensitivity

    NASA Astrophysics Data System (ADS)

    Huang, Duanni; Pintus, Paolo; Srinivasan, Sudharsanan; Bowers, John E.

    2016-02-01

    We demonstrate a Sagnac based fiber optic current sensor using only 10cm of terbium doped fiber with a high Verdet constant of 15.5 rad/Tm at a wavelength of 1300nm. Measurements of the fiber inside a solenoid show over 40dB of open loop dynamic range as well as a minimum detectable current of 0.1mA. In order to decrease size while increasing sensitivity even further, we consider integrated magneto-optic waveguides as the sensing element. Using silicon waveguides alongside magneto-optic material such as cerium doped yttrium iron garnet (Ce:YiG), we model the Verdet constant to be as high as 10,000 rad/Tm. This improvement by three orders of magnitude shows potential for magnetooptic waveguides to be used in ultra-high sensitivity optical magnetometers and current sensors. Finally, we propose a fully integrated optical current sensor using heterogeneous integration for silicon photonics.

  8. 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

  9. 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.

  10. High-sensitivity microfluidic calorimeters for biological and chemical applications

    PubMed Central

    Lee, Wonhee; Fon, Warren; Axelrod, Blake W.; Roukes, Michael L.

    2009-01-01

    High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described. PMID:19706406

  11. 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

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

    NASA Astrophysics Data System (ADS)

    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.

  13. 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.

  14. 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

  15. Determination of a highly selective mixed-affinity sigma receptor ligand, in rat plasma by ultra performance liquid chromatography mass spectrometry and its application to a pharmacokinetic study

    PubMed Central

    Jamalapuram, Seshulatha; Vuppala, Pradeep K.; Mesangeau, Christophe; McCurdy, Christopher R.; Avery, Bonnie A.

    2014-01-01

    A selective, rapid and sensitive ultra performance liquid chromatography mass spectrometry (UPLC/MS) method was developed and validated to quantitate a highly selective mixed-affinity sigma receptor ligand, CM156 (3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo[d] thiazole-2(3H)-thione), in rat plasma. CM156 and the internal standard (aripiprazole) were extracted from plasma samples by a single step liquid–liquid extraction using chloroform. The analysis was carried out on an ACQUITY UPLCTM BEH HILIC column (1.7 µm, 2.1 mm × 50 mm) with isocratic elution at flow rate of 0.2 mL/min using 10 mM ammonium formate in 0.1% formic acid and acetonitrile (10:90) as the mobile phase. The detection of the analyte was performed on a mass spectrometer operated in selected ion recording (SIR) mode with positive electrospray ionization (ESI). The validated analytical method resulted in a run time of 4 min and the retention times observed were 2.6 ± 0.1 and 2.1 ± 0.1 min for CM156 and the IS, respectively. The calibration curve exhibited excellent linearity over a concentration range of 5–4000 ng/mL with the lower limit of quantification of 5 ng/mL. The intra- and inter-day precision values were below 15% and accuracy ranged from −6.5% to 5.0%. The mean recovery of CM156 from plasma was 96.8%. The validated method was applied to a pilot intravenous pharmacokinetic study in rats. PMID:22406103

  16. 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.

  17. Anticipation of interoceptive threat in highly anxiety sensitive persons.

    PubMed

    Melzig, Christiane A; Michalowski, Jaroslaw M; Holtz, Katharina; Hamm, Alfons O

    2008-10-01

    Anticipatory anxiety plays a major role in the etiology of panic disorder. Although anticipatory anxiety elicited by expectation of interoceptive cues is specifically relevant for panic patients, it has rarely been studied. Using a population analogue in high fear of such interoceptive arousal sensations (highly anxiety sensitive persons) we evaluated a new experimental paradigm to assess anticipatory anxiety during anticipation of interoceptive (somatic sensations evoked by hyperventilation) and exteroceptive (electric shock) threat. Symptom reports, autonomic arousal, and defensive response mobilization (startle eyeblink response) were monitored during threat and matched safe conditions in 26 highly anxiety sensitive persons and 22 controls. The anticipation of exteroceptive threat led to a defensive and autonomic mobilization as indexed by a potentiation of the startle response and an increase in skin conductance level in both experimental groups. During interoceptive threat, however, only highly anxiety sensitive persons but not the controls exhibited a startle response potentiation as well as autonomic activation. The anticipation of a hyperventilation procedure thus seems a valid paradigm to investigate anticipatory anxiety elicited by interoceptive cues in the clinical context. PMID:18723161

  18. 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

  19. Quantum-Dot-Sensitized Solar Cell with Unprecedentedly High Photocurrent

    NASA Astrophysics Data System (ADS)

    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 (JSC) of PbS quantum dot (QD)-sensitized solar cell was less than 19 mA/cm2 despite the capability to generate 38 mA/cm2, 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 JSC of 30 mA/cm2. By Hg2+ doping into PbS, JSC is almost doubled with improved stability. Femtosecond transient study confirms that the improved JSC 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 Hg2+, which is responsible for the enhanced electron injection, suppressed recombination and stability. Thanks to the extremely high JSC, power conversion efficiency of 5.6% is demonstrated at one sun illumination.

  20. 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.

  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. Quantum-Dot-Sensitized Solar Cell with Unprecedentedly High Photocurrent

    PubMed Central

    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 (JSC) of PbS quantum dot (QD)-sensitized solar cell was less than 19 mA/cm2 despite the capability to generate 38 mA/cm2, 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 JSC of 30 mA/cm2. By Hg2+ doping into PbS, JSC is almost doubled with improved stability. Femtosecond transient study confirms that the improved JSC 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 Hg2+, which is responsible for the enhanced electron injection, suppressed recombination and stability. Thanks to the extremely high JSC, power conversion efficiency of 5.6% is demonstrated at one sun illumination. PMID:23308343

  3. 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

  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. 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.

  6. 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.

  7. 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.

  8. High efficiency neutron sensitive amorphous silicon pixel detectors

    SciTech Connect

    Mireshghi, A.; Cho, G.; Drewery, J.S.; Hong, W.S.; Jing, T.; Lee, H.; Kaplan, S.N.; Perez-Mendez, V.

    1993-11-01

    A multi-layer a-Si:H based thermal neutron detector was designed, fabricated and simulated by Monte Carlo method. The detector consists of two PECVD deposited a-Si:H pin detectors interfaced with coated layers of Gd, as a thermal neutron converter. Simulation results indicate that a detector consisting of 2 Gd films with thicknesses of 2 and 4 {mu}m, sandwiched properly with two layers of sufficiently thick ({approximately}30{mu}m) amorphous silicon diodes, has the optimum parameters. The detectors have an intrinsic efficiency of about 42% at a threshold setting of 7000 electrons, with an expected average signal size of {approximately}12000 electrons which is well above the noise. This efficiency will be further increased to nearly 63%, if we use Gd with 50% enrichment in {sup 157}Gd. We can fabricate position sensitive detectors with spatial resolution of 300 {mu}m with gamma sensitivity of {approximately}1 {times} 10{sup {minus}5}. These detectors are highly radiation resistant and are good candidates for use in various application, where high efficiency, high resolution, gamma insensitive position sensitive neutron detectors are needed.

  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. Novel high sensitivity EUV photoresist for sub-7nm node

    NASA Astrophysics Data System (ADS)

    Nagai, Tomoki; Nakagawa, Hisashi; Naruoka, Takehiko; Tagawa, Seiichi; Oshima, Akihiro; Nagahara, Seiji; Shiraishi, Gosuke; Yoshihara, Kosuke; Terashita, Yuichi; Minekawa, Yukie; Buitrago, Elizabeth; Ekinci, Yasin; Yildirim, Oktay; Meeuwissen, Marieke; Hoefnagels, Rik; Rispens, Gijsbert; Verspaget, Coen; Maas, Raymond

    2016-03-01

    Extreme ultraviolet lithography (EUVL) has been recognized as the most promising candidate for the manufacture of semiconductor devices for the 7 nm node and beyond. A key point in the successful introduction of EUV lithography in high volume manufacture (HVM) is the effective EUV dose utilization while simultaneously realizing ultra-high resolution and low line edge roughness (LER). Here we show EUV resist sensitivity improvement with the use of a photosensitized chemically amplified resist PSCARTM system. The evaluation of this new chemically amplified resist (CAR) as performed using EUV interference lithography (EUV-IL) is described and the fundamentals are discussed.

  14. Approaches to a broad range of high performance PDT sensitizers

    NASA Astrophysics Data System (ADS)

    d'A. Rocha Gonsalves, António M.; Serra, Arménio C.; Pineiro, Marta; Botelho, M. Filomena

    2009-02-01

    Starting from expertise in the area of chemical synthesis, particularly in tetrapyrrolic macrocycles and an interest in modelling structures for particular objectives, we came to the point of aiming at modelling photochemical sensitizers designed for photodynamic therapy (PDT) purposes. Our endeavours were gratifying when it was proved that our synthetic methodologies allowed for the easy availability of properly halogenated porphyrins with high quantum yield singlet oxygen efficiency. Joining the presence of this heavy atom and other functionalities as substituents in selected positions of macrocyclic structures we were able to generate novel porphyrin structures whose photophysical and photochemical properties, singlet oxygen formation quantum yields, photobleaching and logP were measured. Cellular uptake measurements and cytotoxicity assays on WiDr adenocarcinoma and A375 tumor cell lines were carried out and some of our porphyrins demonstrated very high performance as PDT sensitizers comparatively to known compounds approved for clinical use and in the market. Further developments of our studies allowed for the generation of different and more efficient structures, easily made available by our own synthetic methodologies. Our studies in this area allowed us to reach a stage which we believe to correspond to a significant knowledge and capacity to synthesise a broad range of simple structures, whose selectivity and efficiency as PDT sensitizers can be modulated for different cellular and tissue specificities. Our most recent developments in this area will be presented in this communication.

  15. High-sensitivity strain visualization using electroluminescence technologies

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Jo, Hongki

    2016-04-01

    Visualizing mechanical strain/stress changes is an emerging area in structural health monitoring. Several ways are available for strain change visualization through the color/brightness change of the materials subjected to the mechanical stresses, for example, using mechanoluminescence (ML) materials and mechanoresponsive polymers (MRP). However, these approaches were not effectively applicable for civil engineering system yet, due to insufficient sensitivity to low-level strain of typical civil structures and limitation in measuring both static and dynamic strain. In this study, design and validation for high-sensitivity strain visualization using electroluminescence technologies are presented. A high-sensitivity Wheatstone bridge, of which bridge balance is precisely controllable circuits, is used with a gain-adjustable amplifier. The monochrome electroluminescence (EL) technology is employed to convert both static and dynamic strain change into brightness/color change of the EL materials, through either brightness change mode (BCM) or color alternation mode (CAM). A prototype has been made and calibrated in lab, the linearity between strain and brightness change has been investigated.

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

    SciTech Connect

    Murakami, Hironaru; Tonouchi, Masayoshi

    2010-01-15

    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 3.47x10{sup -5} rad/{mu}m Oe shows a magnetic sensitivity of about 5 {mu}T, 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{sub 2}Cu{sub 3}O{sub 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.

  17. 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

  18. Highly sensitive Fourier transform spectroscopy with LED sources

    NASA Astrophysics Data System (ADS)

    Serdyukov, V. I.; Sinitsa, L. N.; Vasil'chenko, S. S.

    2013-08-01

    It is shown that the use of high luminance LED emitters as a light source for Fourier transform spectrometers permits to enhance their threshold sensitivity in the visible range by orders of magnitude. Using a 2.5 W Edixeon EDEI-1LS3 emitter in the range of 11,350-11,700 cm-1 as a light source for the spectrometer with a 60-cm multipass cell during a 24-h measurement time, we have achieved a signal-to-noise ratio of 4.5 × 104 which corresponds to the minimal detectable absorption coefficient of 1.2 × 10-8 cm-1. Such enhanced sensitivity spectrometer has been used to measure the transition frequencies of CO2 vibrational bands 00051-00001 and 01151-01101 in the range of 11,400-11,500 cm-1.

  19. 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

  20. High-sensitivity permeation measurements on flexible OLED substrates

    NASA Astrophysics Data System (ADS)

    Paetzold, Ralph; Henseler, Debora; Heuser, Karsten; Cesari, Valentina; Sarfert, Wiebke; Wittmann, Georg; Winnacker, Albrecht

    2004-02-01

    We describe a novel method to measure permeation rates for oxidizing agents with very high sensitivity. The technique is based on monitoring the resistance of a degrading Ca sensor in situ, inside a climate chamber. A sensitivity limit below 10-6 g/m2 day is reported for accelerated measurement conditions of 38°C and 90% relative humidity. The benefits of the method are demonstrated for single- and double-sided barrier foils, and the temperature and humidity dependence of the transport through PET is analyzed in detail. The method is also applied to obtain permeation rates for a barrier-coated substrate after as well as during bending. Theoretical simulations are used to evaluate the influence of a defect-dominated transport mechanism on the experimental results and to model the time evolution of the concentration profile in a double-barrier stack. Implications for the development of barrier-enhanced substrates for flexible OLED applications are discussed.

  1. 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

  2. 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.

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

    PubMed Central

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

    2012-01-01

    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/cm2 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/cm2. 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/cm2 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

  4. A high sensitivity inductive sensor for blade tip clearance measurement

    NASA Astrophysics Data System (ADS)

    Du, Li; Zhu, Xiaoliang; Zhe, Jiang

    2014-06-01

    A multiplexed inductive sensor consisting of multiple mini-sized planar spiral coils for detecting multiple tip clearances of rotor blades is presented. The sensor measures the tip clearances by monitoring the inductance changes of planar spiral coils caused by the passage of the rotor blades. A resonance frequency division multiplexing technique and parallel LC resonance measurement were applied to the multiple sensor coils, making it feasible to measure multiple tip clearances using only one set of measurement electronics with high sensitivity and resolution. The results from tests conducted on a bench-top test rig have demonstrated that the sensor is capable of simultaneously measuring multiple tip clearances from 0 to 5 mm with a 10 μm resolution at a high rotary speed up to 80 000 RPM. With its high resolution, high sensitivity and capability of monitoring a large number of tip clearances simultaneously, this sensor can potentially be used for advanced active tip clearance control in turbine machinery.

  5. 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.

  6. 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

  7. High-sensitivity molecular organometallic resist for EUV (MORE)

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    We have developed organometallic carboxylate compounds [RnM(O2CR')2] capable of acting as negativetone EUV resists. Overall, the best and fastest resists contain antimony, are pentavalent and the carboxylate group contains a polymerizable olefin (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 molecules of the type RnM(O2CR')2 where we have studied seven R groups, four main group metals (M), and three polymerizable carboxylate groups (O2CR'). We found that the greatest predictor of sensitivity of the RnSb(O2CR')2 resists is their level of polymerizable olefins. We mathematically define the polymerizable olefin loading (POL) as the ratio of the number of olefins vs. the number of non-hydrogen atoms. Linear and log plots of Emax vs. POL for a variety of molecules of the type R3Sb(O2CR')2 lend insight into the behaviour of these resists.

  8. Miniaturized superconducting quantum interference magnetometers for high sensitivity applications

    NASA Astrophysics Data System (ADS)

    Granata, C.; Vettoliere, A.; Russo, M.

    2007-09-01

    A miniaturized niobium based dc superconducting quantum interference device (SQUID) magnetometer for high magnetic field sensitivity applications has been developed. The sensing coil consists of an integrated square superconducting coil with a length of 3mm, involving a device area much smaller with respect to the standard SQUID magnetometers with a comparable magnetic field sensitivity; so it allows increasing the spatial resolution keeping the magnetic field sensitivity unaltered. Furthermore, a small pickup coil minimizes its antenna gain, reducing the radio frequency interference. At T =4.2K, the sensors have shown smooth and resonance free V-Φ characteristics and an intrinsic white magnetic field noise spectral density as low as 5.8fT /Hz1/2, measured in flux locked loop configuration. The good agreement with the theoretical predictions guarantees the reliability and the controllability of the sensors. Due to their compactness and good characteristic parameters, such sensors are suitable for large multichannel systems used in biomagnetic imaging.

  9. 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

  10. 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.

  11. Ultra-high sensitivity moment magnetometry of geological samples

    NASA Astrophysics Data System (ADS)

    Andrade Lima, E.; Weiss, B. P.

    2012-12-01

    Scanning SQUID microscopy offers a unique combination of high spatial resolution and magnetic field sensitivity that allows for the detection of magnetic moments as weak as 10^-16 Am2. This opens the possibility of extending paleomagnetic analyses to samples that have not been accessible to standard moment magnetometry, for which the detection limit is 10^-12 Am2. Of particular interest are individual terrestrial and extraterrestrial particles of small size (< 500 μm) that may preserve records of planetary dynamos and early nebular magnetic fields. Example targets include impact melt spherules, zircon and other silicate crystals, micrometeorites, cosmic dust, chondrules and refractory inclusions. These grains may be adequately modeled as small uniformly magnetized volumes, such that retrieving their magnetic moments from measured magnetic field maps does not require solving non-unique inverse problems. As a consequence, SQUID microscopes can be utilized as ultra-high sensitivity moment magnetometers. We show alternating field and thermal demagnetization data for several grains that demonstrate the performance of this technique. In addition, we compare scanning SQUID microscopy data with net moment measurements of the same samples performed by a commercial superconducting rock magnetometer. The results agree for stronger moments, as expected, but rapidly diverge as net moments fall below the lower 10^-10 Am2 range. These studies underscore the inability of conventional instruments not only to detect very weak moments but also to isolate contamination originating from background sources such as sample holders and mounts. We expect ultra-high sensitivity moment magnetometry using scanning SQUID microscopy will be a powerful tool in helping elucidate the formation of the solar system and planetary history.

  12. 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.

  13. 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.

  14. Highly sensitive automated setup for measuring surface photovoltage spectra

    NASA Astrophysics Data System (ADS)

    Germanova, K.; Nikolov, L.; Hardalov, Ch.

    1989-04-01

    We present an automated experimental setup for dc measurement of surface photovoltage (SPV) spectra in wide spectral and/or temperature ranges. A Pt boss, sealed on a bimorphic piezoelement, has been used as a small area vibrating electrode and a programmable digital-to-analog convertor (DAC) as a source of compensation. In addition, a combination of automatic data acquisition and statistical analysis has been applied, thus ensuring reliability and stability of SPV measurements. Moreover, the automated setup provides a high sensitivity and objectivity of SPV investigations.

  15. 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

  16. Highly sensitive electronically modulated photoacoustic spectrometer for ozone detection.

    PubMed

    Gondal, M A; Yamani, Z H

    2007-10-10

    An ozone (O(3)) gas sensor with a sensitivity of parts per 10(9) (ppb) level and a high level of selectivity based on the resonant photoacoustic effect was developed using an electronically modulated cw CO(2) laser beam. Quite different from the standard chopper modulation of a laser beam, here the laser source was electronically modulated to overcome the inherent problem of frequency instability associated with chopper modulation. With electronic modulation, in conjunction with the fast Fourier transform (FFT) of transient signals, we were able to improve significantly the sensitivity of the photoacoustic (PA) system for the detection of O(3). In addition to the improved sensitivity, our method proved that the FFT of a laser modulated PA signal could suppress the noise signal generated by spurious window diffused absorption, which in the case of most commonly used lock-in techniques is rather unavoidable. The dependence of the PA signal on various experimental parameters such as buffer gas, laser power, modulation frequency, and trace gas concentration was investigated. In the case of buffer gas, argon proved to be more suitable than nitrogen and helium in terms of enhancing the sensitivity of the system. The limits of detection of O(3) using the 9 P(14) CO(2) laser line in our PA system are 5 parts per 10(9) by volume (ppbv) and 14 ppbv with electronic and standard chopper modulation, respectively. This detection limit of O(3) is quite applicable for detection of safe levels of O(3), at ground level. PMID:17932514

  17. High Sensitivity Surface Enhanced Raman Scattering Detection of Tryptophan

    NASA Astrophysics Data System (ADS)

    Kandakkathara, Archana

    Raman spectroscopy has the capability of providing detailed information about molecular structure, but the extremely small cross section of Raman scattering prevents this technique from applications requiring high sensitivity. Surface enhanced Raman scattering (SERS) on the other hand provides strongly increased Raman signal from molecules attached to metallic nanostructures. SERS is thus a promising technique for high sensitivity analytical applications. One particular area of interest is the application of such techniques for the analysis of the composition of biological cells. However, there are issues which have to be addressed in order to make SERS a reliable technique such as the optimization of conditions for any given analyte, understanding the kinetic processes of binding of the target molecules to the nanostructures and understanding the evolution and coagulation of the nanostructures, in the case of colloidal solutions. The latter processes introduce a delay time for the observation of maximum enhancement factors which must be taken into account for any given implementation of SERS. In the present thesis the goal was to develop very sensitive SERS techniques for the measurement of biomolecules of interest for analysis of the contents of cells. The techniques explored could be eventually be applicable to microfluidic systems with the ultimate goal of analyzing the molecular constituents of single cells. SERS study of different amino acids and organic dyes were performed during the course of this thesis. A high sensitivity detection system based on SERS has been developed and spectrum from tryptophan (Trp) amino acid at very low concentration (10-8 M) has been detected. The concentration at which good quality SERS spectra could be detected from Trp is 4 orders of magnitude smaller than that previously reported in literature. It has shown that at such low concentrations the SERS spectra of Trp are qualitatively distinct from the spectra commonly reported in

  18. High pressure-sensitive gene expression in Lactobacillus sanfranciscensis.

    PubMed

    Vogel, R F; Pavlovic, M; Hörmann, S; Ehrmann, M A

    2005-08-01

    Lactobacillus sanfranciscensis is a Gram-positive lactic acid bacterium used in food biotechnology. It is necessary to investigate many aspects of a model organism to elucidate mechanisms of stress response, to facilitate preparation, application and performance in food fermentation, to understand mechanisms of inactivation, and to identify novel tools for high pressure biotechnology. To investigate the mechanisms of the complex bacterial response to high pressure we have analyzed changes in the proteome and transcriptome by 2-D electrophoresis, and by microarrays and real time PCR, respectively. More than 16 proteins were found to be differentially expressed upon high pressure stress and were compared to those sensitive to other stresses. Except for one apparently high pressure-specific stress protein, no pressure-specific stress proteins were found, and the proteome response to pressure was found to differ from that induced by other stresses. Selected pressure-sensitive proteins were partially sequenced and their genes were identified by reverse genetics. In a transcriptome analysis of a redundancy cleared shot gun library, about 7% of the genes investigated were found to be affected. Most of them appeared to be up-regulated 2- to 4-fold and these results were confirmed by real time PCR. Gene induction was shown for some genes up-regulated at the proteome level (clpL/groEL/rbsK), while the response of others to high hydrostatic pressure at the transcriptome level seemed to differ from that observed at the proteome level. The up-regulation of selected genes supports the view that the cell tries to compensate for pressure-induced impairment of translation and membrane transport. PMID:16082466

  19. 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

  20. 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.

  1. High refractive index and temperature sensitivity LPGs for high temperature operation

    NASA Astrophysics Data System (ADS)

    Nascimento, I. M.; Gouveia, C.; Jana, Surnimal; Bera, Susanta; Baptista, J. M.; Moreira, Paulo; Biwas, Palas; Bandyopadhyay, Somnath; Jorge, Pedro A. S.

    2013-11-01

    A fiber optic sensor for high sensitivity refractive index and temperature measurement able to withstand temperature up to 450 °C is reported. Two identical LPG gratings were fabricated, whereas one was coated with a high refractive index (~1.78) sol-gel thin film in order to increase its sensitivity to the external refractive index. The two sensors were characterized and compared in refractive index and temperature. Sensitivities of 1063 nm/RIU (1.338 - 1.348) and 260 pm/°C were achieved for refractive index and temperature, respectively.

  2. High-sensitivity acoustic sensors from nanofibre webs

    PubMed Central

    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

  3. 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

  4. 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

  5. Ultra-Sensitive, High Throughput and Quantitative Proteomics Measurements

    SciTech Connect

    Jacobs, Jon M.; Monroe, Matthew E.; Qian, Weijun; Shen, Yufeng; Anderson, Gordon A.; Smith, Richard D.

    2005-02-01

    We describe the broad basis and application of an approach for very high throughput, ultra-sensitive, and quantitative proteomic measurements based upon the use of ultra-high performance separations and mass spectrometry. An overview of the accurate mass and time (AMT) tag approach and a description of the incorporated data analysis pipeline necessary for efficient proteomic studies are presented. Adjunct technologies, including stable-isotope labeling methodologies and improvements in the utilization of LC-MS peak intensity information for quantitative purposes are discussed. Related areas include the use of automated sample handling for improving analysis reproducibility, methods for using information from the separation for more confident peptide peak identification, and the utilization of smaller diameter capillary columns having lower volumetric flow rates to increase electrospray ionization efficiency and allow for more predictable and quantitative results. The developments are illustrated in the context of studies of complex biological systems.

  6. Wide bandwidth transimpedance amplifier for extremely high sensitivity continuous measurements

    NASA Astrophysics Data System (ADS)

    Ferrari, Giorgio; Sampietro, Marco

    2007-09-01

    This article presents a wide bandwidth transimpedance amplifier based on the series of an integrator and a differentiator stage, having an additional feedback loop to discharge the standing current from the device under test (DUT) to ensure an unlimited measuring time opportunity when compared to switched discharge configurations while maintaining a large signal amplification over the full bandwidth. The amplifier shows a flat response from 0.6Hzto1.4MHz, the capability to operate with leakage currents from the DUT as high as tens of nanoamperes, and rail-to-rail dynamic range for sinusoidal current signals independent of the DUT leakage current. Also available is a monitor output of the stationary current to track experimental slow drifts. The circuit is ideal for noise spectral and impedance measurements of nanodevices and biomolecules when in the presence of a physiological medium and in all cases where high sensitivity current measurements are requested such as in scanning probe microscopy systems.

  7. Hydrophilic packaging of iron oxide nanoclusters for highly sensitive imaging.

    PubMed

    Smith, Cartney E; Ernenwein, Dawn; Shkumatov, Artem; Clay, Nicholas E; Lee, JuYeon; Melhem, Molly; Misra, Sanjay; Zimmerman, Steven C; Kong, Hyunjoon

    2015-11-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging probes to provide contrast in magnetic resonance images. Successful use of SPIONs in targeted applications greatly depends on their ability to generate contrast, even at low levels of accumulation, in the tissue of interest. In the present study, we report that SPION nanoclusters packaged to a controlled size by a hyperbranched polyglycerol (HPG) can target tissue defects and have a high relaxivity of 719 mM(-1) s(-1), which was close to their theoretical maximal limit. The resulting nanoclusters were able to identify regions of defective vasculature in an ischemic murine hindlimb using MRI with iron doses that were 5-10 fold lower than those typically used in preclinical studies. Such high relaxivity was attributed to the molecular architecture of HPG, which mimics that of the water retentive polysaccharide, glycogen. The results of this study will be broadly useful in sensitive imaging applications. PMID:26291408

  8. Highly efficient monolithic dye-sensitized solar cells.

    PubMed

    Kwon, Jeong; Park, Nam-Gyu; Lee, Jun Young; Ko, Min Jae; Park, Jong Hyeok

    2013-03-01

    Monolithic dye-sensitized solar cells (M-DSSCs) provide an effective way to reduce the fabrication cost of general DSSCs since they do not require transparent conducting oxide substrates for the counter electrode. However, conventional monolithic devices have low efficiency because of the impediments resulting from counter electrode materials and spacer layers. Here, we demonstrate highly efficient M-DSSCs featuring a highly conductive polymer combined with macroporous polymer spacer layers. With M-DSSCs based on a PEDOT/polymer spacer layer, a power conversion efficiency of 7.73% was achieved, which is, to the best of our knowledge, the highest efficiency for M-DSSCs to date. Further, PEDOT/polymer spacer layers were applied to flexible DSSCs and their cell performance was investigated. PMID:23432389

  9. Highly sensitive detection of urinary cadmium to assess personal exposure.

    PubMed

    Argun, Avni A; Banks, Ashley M; Merlen, Gwendolynne; Tempelman, Linda A; Becker, Michael F; Schuelke, Thomas; Dweik, Badawi M

    2013-04-22

    A series of Boron-Doped Diamond (BDD) ultramicroelectrode arrays were fabricated and investigated for their performance as electrochemical sensors to detect trace level metals such as cadmium. The steady-state diffusion behavior of these sensors was validated using cyclic voltammetry followed by electrochemical detection of cadmium in water and in human urine to demonstrate high sensitivity (>200 μA ppb(-1) cm(-2)) and low background current (<4 nA). When an array of ultramicroelectrodes was positioned with optimal spacing, these BDD sensors showed a sigmoidal diffusion behavior. They also demonstrated high accuracy with linear dose dependence for quantification of cadmium in a certified reference river water sample from the U.S. National Institute of Standards and Technology (NIST) as well as in a human urine sample spiked with 0.25-1 ppb cadmium. PMID:23561905

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. High-sensitivity quantitative phase microcopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhou, Renjie; Kuang, Cuifang; Hosseini, Poorya; Chowdhary, Ravi; Yaqoob, Zahid; So, Peter T. C.

    2016-03-01

    In the past decade, various quantitative phase microscopy (QPM) techniques have emerged, driven by the need to study biological samples non-invasively. However, the fundamental limit for phase noise is scarcely discussed in the literature. In a typically off-axis phase microscope system, the phase noise is limited to a few milliradians using a moderate camera. Common-path QPMs offer much reduced phase noise compared to typical Mach-Zehnder-based systems. However, further scaling down the phase noise becomes difficult. Here we propose a high-sensitivity common-path QPM that promises to reduce the phase noise by a factor of 10 (assuming the mechanical noise is negligible). This is achieved by a specifically designed signal filter, leaving only the subtle phase fluctuations coming from the dynamics sample scattering. By working at photon shot-noise limited detection, we can magnify the subtle phase contrast which is proportional to the camera well depth. We expect this system to have the height sensitivity similar to an atomic force microcopy, while measuring biological structures with a full field of view in a single-shot. We plan to use this system to study cell dynamics, particularly lamellipodial height fluctuations as well as stiffer cell membrane fluctuations.

  15. 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.

  16. 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.

  17. 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.

  18. Nanoparticle-Structured Highly Sensitive and Anisotropic Gauge Sensors.

    PubMed

    Zhao, Wei; Luo, Jin; Shan, Shiyao; Lombardi, Jack P; Xu, Yvonne; Cartwright, Kelly; Lu, Susan; Poliks, Mark; Zhong, Chuan-Jian

    2015-09-16

    The ability to tune gauge factors in terms of magnitude and orientation is important for wearable and conformal electronics. Herein, a sensor device is described which is fabricated by assembling and printing molecularly linked thin films of gold nanoparticles on flexible microelectrodes with unusually high and anisotropic gauge factors. A sharp difference in gauge factors up to two to three orders of magnitude between bending perpendicular (B(⊥)) and parallel (B(||)) to the current flow directions is observed. The origin of the unusual high and anisotropic gauge factors is analyzed in terms of nanoparticle size, interparticle spacing, interparticle structure, and other parameters, and by considering the theoretical aspects of electron conduction mechanism and percolation pathway. A critical range of resistivity where a very small change in strain and the strain orientation is identified to impact the percolation pathway in a significant way, leading to the high and anisotropic gauge factors. The gauge anisotropy stems from molecular and nanoscale fine tuning of interparticle properties of molecularly linked nanoparticle assembly on flexible microelectrodes, which has important implication for the design of gauge sensors for highly sensitive detection of deformation in complex sensing environment or on complex curved surfaces such as wearable electronics and skin sensors. PMID:26037089

  19. High-sensitivity dilatometer for quality-control use

    NASA Astrophysics Data System (ADS)

    Tomer, G. S.; Schlegel, G. L.; Gaal, P. S.

    1988-03-01

    A simple-to-operate dilatometer, intended for rapid quality-control testing of low-expansion materials in a single temperature interval, is described. The instrument employs a thermoelectric heat/cool element to supply the thermal environment for the sample and a high-sensitivity linear variable differential transformer (LVDT) for displacement measurement. The mechanical configuration is made so as to eliminate the need for quartz correction and to provide a 4∶1 mechanical advantage to the displacement signal for improved accuracy. Operating between 0 and 100°C, the machine proved to give consistently good results with materials having expansion coefficients as low as 0.5×10-6 °C-1. Representative data on some carbonaceous materials and fused silica (quartz) are given.

  20. 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.

  1. Sensitivity of LHC experiments to exotic highly ionising particles

    NASA Astrophysics Data System (ADS)

    De Roeck, A.; Katre, A.; Mermod, P.; Milstead, D.; Sloan, T.

    2012-04-01

    The experiments at the Large Hadron Collider (LHC) are able to discover or set limits on the production of exotic particles with TeV-scale masses possessing values of electric and/or magnetic charge such that they behave as highly ionising particles (HIPs). In this paper the sensitivity of the LHC experiments to HIP production is discussed in detail. It is shown that a number of different detection methods are required to investigate as fully as possible the charge-mass range. These include direct detection as the HIPs pass through either passive or active detectors and, in the case of magnetically charged objects, the so-called induction method with which magnetic monopoles which stop in accelerator and detector material could be observed. The benefit of using complementary approaches to HIP detection is discussed.

  2. 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.

  3. Radiation noise in a high sensitivity star sensor

    NASA Technical Reports Server (NTRS)

    Parkinson, J. B.; Gordon, E.

    1972-01-01

    An extremely accurate attitude determination was developed for space applications. This system uses a high sensitivity star sensor in which the photomultiplier tube is subject to noise generated by space radiations. The space radiation induced noise arises from trapped electrons, solar protons and other ionizing radiations, as well as from dim star background. The solar activity and hence the electron and proton environments are predicted through the end of the twentieth century. The available data for the response of the phototube to proton, electron, gamma ray, and bremsstrahlung radiations are reviewed and new experimental data is presented. A simulation was developed which represents the characteristics of the effect of radiations on the star sensor, including the non-stationarity of the backgrounds.

  4. High-sensitivity broadband microwave spectroscopy with small nonresonant coils

    NASA Astrophysics Data System (ADS)

    Mahdjour, H.; Clark, W. G.; Baberschke, K.

    1986-06-01

    The use of a small, nonresonant, coil of micron dimensions as the microwave magnetic field structure of a broadband electron-spin-resonance (ESR) spectrometer is described. The coil is driven by a broadband microwave generator which operates between 0.1 and 8.5 GHz. The samples may fill the coil to approximately 100 percent. It is shown that for small size samples this system offers higher sensitivity than a conventional cavity spectrometer. Because the system is broadband, either frequency scans or the conventional magnetic field scans can be used to traverse the resonance. Examples for DPPH and for the spin glass AgMn using this method are reported. Since the sample coil is small, it has many potential applications, such as insertion into the mixing chamber of dilution refrigerator or high-pressure cell, efficient use of power in ENDOR and other double resonance experiments, and rapid recovery from transients in pulsed ESR experiments.

  5. High-sensitivity and high-dry-etching durability positive-type electron-beam resist

    NASA Astrophysics Data System (ADS)

    Tamura, Akira; Yonezawa, Masaji; Sato, Mitsuyoshi; Fujimoto, Yoshiaki

    1991-08-01

    As feature sizes of semiconductors grow smaller, a resist having dry etching durability and high sensitivity is required for electron beam lithography. However, the positive type electron beam resist having both high sensitivity and high dry etching durability, which suits for practical use, has not been developed yet. In order to solve this problem, a homologous series of poly(alkyl 2-cyanoacrylate) has been investigated. As a result, the new positive type electron beam resist having high sensitivity, high dry etching durability, and high thermal resistance has been developed. This new type of resist consists of poly(cyclohexyl 2- cyanoacrylate), and these features of this resist are due to the cyano and the cyclohexyl groups. The dry etching durability of this resist is 2.19 times as high as that of poly(mthyl methacrylate) (PMMA). The sensitivity is 1.7 (mu) C/cm2 at accelerating voltage of 20 kV, which is about the same as that of poly(butene-1-sulfone) (PBS). Moreover, poly(cyclohexyl 2-cyanoacrylate) has the glass transition of 152 degree(s)C, and then it is thermally stable. Using this resist in photomask fabrication by dry etching, the chrome linewidth uniformity of 0.034 micrometers 3 (sigma) can be obtained.

  6. Innovative nanostructures for highly sensitive vibrational biosensing (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Popp, Juergen; Mayerhöfer, Thomas; Cialla-May, Dana; Weber, Karina; Huebner, Uwe

    2016-03-01

    Employing vibrational spectroscopy (IR-absorption and Raman spectroscopy) allows for the labelfree detection of molecular specific fingerprints of inorganic, organic and biological substances. The sensitivity of vibrational spectroscopy can be improved by several orders of magnitude via the application of plasmonic active surfaces. Within this contribution we will discuss two such approaches, namely surface enhanced Raman spectroscopy (SERS) as well as surface enhanced IR absorption (SEIRA). It will be shown that SERS using metal colloids as SERS active substrate in combination with a microfluidic lab-on-a-chip (LOC) device enables high throughput and reproducible measurements with highest sensitivity and specificity. The application of such a LOC-SERS approach for therapeutic drug monitoring (e.g. quantitative detection of antibiotics in a urine matrix) will be presented. Furthermore, we will introduce innovative bottom-up strategies to prepare SERS-active nanostructures coated with a lipophilic sensor layer as one-time use SERS substrates for specific food analysis (e.g. quantitative detection of toxic food colorants). The second part of this contribution presents a slit array metamaterial perfect absorber for IR sensing applications consisting of a dielectric layer sandwiched between two metallic layers of which the upper layer is perforated with a periodic array of slits. Light-matter interaction is greatly amplified in the slits, where also the analyte is concentrated, as the surface of the substrate is covered by a thin silica layer. Thus, already small concentrations of analytes down to a monolayer can be detected by refractive index sensing and identified by their spectral fingerprints with a standard mid-infrared lab spectrometer.

  7. Graphene nanomesh as highly sensitive chemiresistor gas sensor.

    PubMed

    Paul, Rajat Kanti; Badhulika, Sushmee; Saucedo, Nuvia M; Mulchandani, Ashok

    2012-10-01

    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) of a grown p-type semiconducting large-area monolayer graphene film was patterned into a nanomesh by the combination of nanosphere lithography and reactive ion etching and evaluated as a field-effect transistor and chemiresistor gas sensors. The resulting neck-width of the synthesized nanomesh was about ∼20 nm and was comprised of the gap between polystyrene (PS) spheres that was formed during the reactive ion etching (RIE) process. The neck-width and the periodicities of the graphene nanomesh (GNM) could be easily controlled depending on the duration/power of the RIE and the size of the PS nanospheres. The fabricated GNM transistor device exhibited promising electronic properties featuring a high drive current and an I(ON)/I(OFF) ratio of about 6, significantly higher than its film counterpart. Similarly, when applied as a chemiresistor gas sensor at room temperature, the graphene nanomesh sensor showed excellent sensitivity toward NO(2) and NH(3), significantly higher than their film counterparts. The ethanol-based graphene nanomesh sensors exhibited sensitivities of about 4.32%/ppm in NO(2) and 0.71%/ppm in NH(3) with limits of detection of 15 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

  8. 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

  9. Wide bandwidth transimpedance amplifier for extremely high sensitivity continuous measurements.

    PubMed

    Ferrari, Giorgio; Sampietro, Marco

    2007-09-01

    This article presents a wide bandwidth transimpedance amplifier based on the series of an integrator and a differentiator stage, having an additional feedback loop to discharge the standing current from the device under test (DUT) to ensure an unlimited measuring time opportunity when compared to switched discharge configurations while maintaining a large signal amplification over the full bandwidth. The amplifier shows a flat response from 0.6 Hz to 1.4 MHz, the capability to operate with leakage currents from the DUT as high as tens of nanoamperes, and rail-to-rail dynamic range for sinusoidal current signals independent of the DUT leakage current. Also available is a monitor output of the stationary current to track experimental slow drifts. The circuit is ideal for noise spectral and impedance measurements of nanodevices and biomolecules when in the presence of a physiological medium and in all cases where high sensitivity current measurements are requested such as in scanning probe microscopy systems. PMID:17902966

  10. High olfactory sensitivity for dimethyl sulphide in harbour seals

    PubMed Central

    Kowalewsky, Sylvia; Dambach, Martin; Mauck, Björn; Dehnhardt, Guido

    2005-01-01

    Productive areas are patchily distributed at sea and represent important feeding grounds for many marine organisms. Although pinnipeds are known to travel on direct routes and return regularly to particular feeding sites, the environmental information seals use to perform this navigation is as yet unknown. As atmospheric dimethyl sulphide (DMS) has been demonstrated to be a reliable indicator for profitable foraging areas, we tested seals for their ability to smell DMS at concentrations typical for the marine environment. Using a go/no-go response paradigm we determined the DMS detection threshold in two harbour seals (Phoca vitulina vitulina). DMS stimuli from 8.05×108 to 8 pmol (DMS) m−3(air) were tested against a control stimulus using a custom-made olfactometer. DMS-thresholds determined for both seals (20 and 13 pmol m−3) indicate that seals can detect ambient concentrations associated with high primary productivity, e.g. in the North Atlantic. Thus, seals possess an extraordinarily high olfactory sensitivity for DMS, which could provide a sensory basis for identifying or orienting to profitable foraging grounds. PMID:17148339

  11. High-sensitivity thermoluminescence applied to environmental monitoring

    NASA Astrophysics Data System (ADS)

    Velbeck, K. J.; Zhang, L.; Rotunda, Joe E.; Moscovitch, Marko

    1999-02-01

    We describe the development of a new environmental TLD Dosemeter Badge and dose computation algorithm based on the new LiF:Mg,Cu,P material. LiF:Mg,Cu,P, with its high sensitivity, tissue equivalence, energy independence, and low fading characteristics, is a natural choice for environmental dosimetry. The badge consists of a card and a plastic holder. The card contains four LiF:Mg,Cu,P elements, each 3.2 mm square and 0.4 mm thick, encapsulated in TeflonR. The badge is symmetrical and uses four filters to discriminate low and high energy photons and to determine Directional Dose Equivalent, H'(0.07,(alpha) ), and Ambient Dose Equivalent, H*(10). Extensive data was taken based on irradiations of 920 dosemeters to both single and mixed fields of photons and betas. In addition, angular incidence data of various fields was taken. The approach to the algorithm is empirical and is based on this data. While most algorithms are based solely on perpendicular incidence exposure, this algorithm is being developed to account for the angular response of the dosemeter. This paper will present the algorithm for perpendicular irradiation; the angular response portion is in development. The dosemeter is designed to meet the criteria of the new draft standard ANSI N13.29, 'Environmental Dosimetry Performance -- Criteria for Testing.'

  12. High sensitivity, low power, microfabricated electrochemical sensor for CO

    SciTech Connect

    Neuzil, P.; Kayvani, D.; Maclay, G.J.

    1996-12-31

    CO is a toxic byproduct of incomplete combustion. Improperly vented fireplaces and faulty furnaces cause a estimated 400 deaths in the US each year. The presence of high CO levels may also indicate the presence of a fire. Hence, improved CO detection is of great interest and in the last several years commercial CO detectors have been released. The two most common methods of CO detection in commercial systems for residential use are (1) optical colorometric method, and (2) tin oxide sensor. The colorometric method has the advantage of low power, but the devices tend to give an alarm condition when exposed to low CO levels for a long time period, are difficult to reset, and have a lifetime of about 1 year. The tin oxide sensors have limited stability and high power requirement since the sensor must be heated. There is a need for a stable, sensitive, low power, low cost CO sensor. The authors have developed a planar amperometric sensor for CO detection using microfabrication technology.

  13. A batteryless temperature sensor based on high temperature sensitive material

    NASA Astrophysics Data System (ADS)

    Bakkali, Asma; Pelegri-Sebastia, José; Laghmich, Youssef; Lyhyaoui, Abdelouahid

    2016-05-01

    The major challenge in wireless sensor networks is the reduction of energy consumption. Passive wireless sensor network is an attractive solution for measuring physical parameters in harsh environment for large range of applications requiring sensing devices with low cost of fabrication, small size and long term measurement stability. Batteryless temperature sensing techniques are an active research field. The approach developed in our work holds a promising future for temperature sensor applications in order to successfully reduce the energy consumption. The temperature sensor presented in this paper is based on the electromagnetic transduction principle using the integration of the high temperature sensitive material into a passive structure. Variation in temperature makes the dielectric constant of this material changing, and such modification induces variation in the resonant frequencies of high-Q whispering-gallery modes (WGM) in the millimeter-wave frequency range. Following the results achieved, the proposed device shows a linear response to the increasing temperature and these variations can be remotely detected from a radar interrogation. Contribution to the topical issue "Materials for Energy Harvesting, Conversion and Storage (ICOME 2015) - Elected submissions", edited by Jean-Michel Nunzi, Rachid Bennacer and Mohammed El Ganaoui

  14. 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.

  15. 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

  16. 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

  17. Capillary photoionization: a high sensitivity ionization method for mass spectrometry.

    PubMed

    Haapala, Markus; Suominen, Tina; Kostiainen, Risto

    2013-06-18

    We present a capillary photoionization (CPI) method for mass spectrometric (MS) analysis of liquid and gaseous samples. CPI utilizes a heated transfer capillary with a vacuum ultraviolet transparent MgF2 window, through which vacuum UV light (10 eV) from an external source enters the capillary. The liquid or gaseous sample, together with dopant, is introduced directly into the heated transfer capillary between the atmosphere and the vacuum of the MS. Since the sample is vaporized and photoionized inside the capillary, ion transmission is maximized, resulting in good overall sensitivity for nonpolar and polar compounds. As in atmospheric pressure photoionization, ionization in CPI occurs either by proton transfer or by charge exchange reactions. The feasibility of CPI was demonstrated with selected nonpolar and polar compounds. A particular advantage of CPI is that it enables the analysis of nonvolatile and nonpolar compounds in liquid samples with high ionization efficiency. This is not possible with existing capillary ionization methods. The performance of CPI as an interface between GC and MS and its applicability for the analysis of steroids in biological samples are also demonstrated. The GC-CPI-MS method shows good chromatographic resolution, linearity (R(2) > 0.993), limits of detection (LOD) in the range of 2-6 pg/mL and repeatability of injection with relative standard deviations of 4-15%. PMID:23713722

  18. 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.

  19. Physical activity and high-sensitivity C-reactive protein.

    PubMed

    Plaisance, Eric P; Grandjean, Peter W

    2006-01-01

    Cardiovascular disease (CVD) remains one of the leading causes of death and disability in developed countries around the world despite the documented success of lifestyle and pharmacological interventions. This illustrates the multifactorial nature of atherosclerosis and the use of novel inflammatory markers as an adjunct to risk factor reduction strategies. As evidence continues to accumulate that inflammation is involved in all stages of the development and progression of atherosclerosis, markers of inflammation such as high-sensitivity C-reactive protein (CRP) may provide additional information regarding the biological status of the atherosclerotic lesion. Recent investigations suggest that physical activity reduces CRP levels. Higher levels of physical activity and cardiorespiratory fitness are consistently associated with 6-35% lower CRP levels. Longitudinal training studies that have demonstrated reductions in CRP concentrations range from 16% to 41%, an effect that may be independent of baseline levels of CRP, body composition or weight loss. The average change in CRP associated with physical activity appears to be at least as good, if not better, than currently prescribed pharmacological interventions in similar populations. The primary purpose of this review will be to present evidence from both cross-sectional and longitudinal investigations that physical activity lowers CRP levels in a dose-response manner. Finally, this review will examine factors such as body composition, sex, blood sample timing, diet and smoking, which may influence the CRP response to physical activity. PMID:16646631

  20. A Highly Sensitive Genetic Protocol to Detect NF1 Mutations

    PubMed Central

    Carmen Valero, María; Martín, Yolanda; Hernández-Imaz, Elisabete; Marina Hernández, Alba; Meleán, Germán; María Valero, Ana; Javier Rodríguez-Álvarez, Francisco; Tellería, Dolores; Hernández-Chico, Concepción

    2011-01-01

    Neurofibromatosis type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene. Detecting mutation in NF1 is hindered by the gene's large size, the lack of mutation hotspots, the presence of pseudogenes, and the wide variety of possible lesions. We developed a method for detecting germline mutations by combining an original RNA-based cDNA-PCR mutation detection method and denaturing high-performance liquid chromatography (DHPLC) with multiplex ligation-dependent probe amplification (MLPA). The protocol was validated in a cohort of 56 blood samples from NF1 patients who fulfilled NIH diagnostic criteria, identifying the germline mutation in 53 cases (95% sensitivity). The efficiency and reliability of this approach facilitated detection of different types of mutations, including single-base substitutions, deletions or insertions of one to several nucleotides, microdeletions, and changes in intragenic copy number. Because mutational screening for minor lesions was performed using cDNA and the characterization of mutated alleles was performed at both the RNA and genomic DNA level, the analysis provided insight into the nature of the different mutations and their effect on NF1 mRNA splicing. After validation, we implemented the protocol as a routine test. Here we present the overall unbiased spectrum of NF1 mutations identified in 93 patients in a cohort of 105. The results indicate that this protocol is a powerful new tool for the molecular diagnosis of NF1. PMID:21354044

  1. 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.

  2. Hi-net: High sensitivity seismograph network, Japan

    NASA Astrophysics Data System (ADS)

    Obara, Kazushige

    The high sensitivity seismograph network in Japan (Hi-net), composed of around 600 seismic stations, is a part of the project made by ‘The Headquarter for Earthquake Research Promotion’ after 1995 Hyogoken-nanbu Earthquake and has been constructed and operated by National Research Institute for Earth Science and Disaster Prevention (NIED). Seismic stations are distributed homogeneously covering whole Japan Islands with an average spacing of 20 30 km. Three-component short period velocity seismometers are installed at the bottom of boreholes with depth of 100 m or deeper. Seismic data are digitized by 24-bit A/D converter and decimated to 27bit data with the sampling frequency of 100Hz. Stations are connected to the Hi-net data center, NIED in Tsukuba by a frame relay network service. TCP/IP and SNMP are used for data transmission and network management, respectively. The data are continuously transmitted to the data center and local offices of Japan Meteorological Agency for routine monitoring of seismic activity. The data receiving, monitoring, processing, and archiving system is controlled by a database management system in the data center. Event detection, phase picking, hypocentral determination, spectra analyses, and extracting waveform parameters are processed automatically. Event information and continuous waveform data are available through the world-wide-web.

  3. Highly sensitive hot electron bolometer based on disordered graphene.

    PubMed

    Han, Qi; Gao, Teng; Zhang, Rui; Chen, Yi; Chen, Jianhui; Liu, Gerui; Zhang, Yanfeng; Liu, Zhongfan; Wu, Xiaosong; Yu, Dapeng

    2013-01-01

    A bolometer is a device that makes an electrical resistive response to the electromagnetic radiation resulted from a raise of temperature due to heating. The combination of the extremely weak electron-phonon interactions along with its small electron heat capacity makes graphene an ideal material for applications in ultra-fast and sensitive hot electron bolometer. However, a major issue is that the resistance of pristine graphene weakly depends on the electronic temperature. We propose using disordered graphene to obtain a strongly temperature dependent resistance. The measured electrical responsivity of the disordered graphene bolometer reaches 6 × 10(6) V/W at 1.5 K, corresponding to an optical responsivity of 1.6 × 10(5) V/W. The deduced electrical noise equivalent power is 1.2 fW/√Hz, corresponding to the optical noise equivalent power of 44 fW/√Hz. The minimal device structure and no requirement for high mobility graphene make a step forward towards the applications of graphene hot electron bolometers. PMID:24346418

  4. Highly sensitive hot electron bolometer based on disordered graphene

    PubMed Central

    Han, Qi; Gao, Teng; Zhang, Rui; Chen, Yi; Chen, Jianhui; Liu, Gerui; Zhang, Yanfeng; Liu, Zhongfan; Wu, Xiaosong; Yu, Dapeng

    2013-01-01

    A bolometer is a device that makes an electrical resistive response to the electromagnetic radiation resulted from a raise of temperature due to heating. The combination of the extremely weak electron-phonon interactions along with its small electron heat capacity makes graphene an ideal material for applications in ultra-fast and sensitive hot electron bolometer. However, a major issue is that the resistance of pristine graphene weakly depends on the electronic temperature. We propose using disordered graphene to obtain a strongly temperature dependent resistance. The measured electrical responsivity of the disordered graphene bolometer reaches 6 × 106 V/W at 1.5 K, corresponding to an optical responsivity of 1.6 × 105 V/W. The deduced electrical noise equivalent power is 1.2 , corresponding to the optical noise equivalent power of 44 . The minimal device structure and no requirement for high mobility graphene make a step forward towards the applications of graphene hot electron bolometers. PMID:24346418

  5. ASIC for High Rate 3D Position Sensitive Detectors

    SciTech Connect

    Vernon, E.; De Geronimo, G.; Ackley, K.; Fried, J.; He, Z.; Herman, C.; Zhang, F.

    2010-06-16

    We report on the development of an application specific integrated circuit (ASIC) for 3D position sensitive detectors (3D PSD). The ASIC is designed to operate with pixelated wide bandgap sensors like Cadmium-Zinc-Telluride (CZT), Mercuric Iodide (Hgl2) and Thallium Bromide (TIBr). It measures the amplitudes and timings associated with an ionizing event on 128 anodes, the anode grid, and the cathode. Each channel provides low-noise charge amplification, high-order shaping with peaking time adjustable from 250 ns to 12 {micro}s, gain adjustable to 20 mV/fC or 120 mV/fC (for a dynamic range of 3.2 MeV and 530 keV in CZT), amplitude discrimination with 5-bit trimming, and positive and negative peak and timing detections. The readout can be full or sparse, based on a flag and single- or multi-cycle token passing. All channels, triggered channels only, or triggered with neighbors can be read out thus increasing the rate capability of the system to more than 10 kcps. The ASIC dissipates 330 mW which corresponds to about 2.5 mW per channel.

  6. 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.

  7. High throughput modular chambers for rapid evaluation of anesthetic sensitivity

    PubMed Central

    Sun, Yi; Chen, Jingqiu; Pruckmayr, Gregory; Baumgardner, James E; Eckmann, David M; Eckenhoff, Roderic G; Kelz, Max B

    2006-01-01

    Background Anesthetic sensitivity is determined by the interaction of multiple genes. Hence, a dissection of genetic contributors would be aided by precise and high throughput behavioral screens. Traditionally, anesthetic phenotyping has addressed only induction of anesthesia, evaluated with dose-response curves, while ignoring potentially important data on emergence from anesthesia. Methods We designed and built a controlled environment apparatus to permit rapid phenotyping of twenty-four mice simultaneously. We used the loss of righting reflex to indicate anesthetic-induced unconsciousness. After fitting the data to a sigmoidal dose-response curve with variable slope, we calculated the MACLORR (EC50), the Hill coefficient, and the 95% confidence intervals bracketing these values. Upon termination of the anesthetic, Emergence timeRR was determined and expressed as the mean ± standard error for each inhaled anesthetic. Results In agreement with several previously published reports we find that the MACLORR of halothane, isoflurane, and sevoflurane in 8–12 week old C57BL/6J mice is 0.79% (95% confidence interval = 0.78 – 0.79%), 0.91% (95% confidence interval = 0.90 – 0.93%), and 1.96% (95% confidence interval = 1.94 – 1.97%), respectively. Hill coefficients for halothane, isoflurane, and sevoflurane are 24.7 (95% confidence interval = 19.8 – 29.7%), 19.2 (95% confidence interval = 14.0 – 24.3%), and 33.1 (95% confidence interval = 27.3 – 38.8%), respectively. After roughly 2.5 MACLORR • hr exposures, mice take 16.00 ± 1.07, 6.19 ± 0.32, and 2.15 ± 0.12 minutes to emerge from halothane, isoflurane, and sevoflurane, respectively. Conclusion This system enabled assessment of inhaled anesthetic responsiveness with a higher precision than that previously reported. It is broadly adaptable for delivering an inhaled therapeutic (or toxin) to a population while monitoring its vital signs, motor reflexes, and providing precise control over environmental

  8. High sensitivity Moire interferometry with phase shifting at nano resolution

    NASA Astrophysics Data System (ADS)

    Chen, Bicheng

    Due to insatiate demand for miniaturization of electronics, there is a need for new techniques to measure full-field strain at micro-scale structures. In addition, Micro-Electronic-Mechanical-Systems (MEMS) require a high resolution and high sensitivity material property characterization technique. In this study, a theoretic model for a high sensitivity Moire Interferometry (MI) for measuring nano-scale strain field has been developed. The study also includes the application of the proposed measurement technique for the study of reliability of next generation nano-electronics/power electronics. The study includes both theoretical and experimental work. In the theoretical part, a far field modeling of a Moire Interferometer (MI) using the mode decomposition method is proposed according to the analytical formulation from the scalar diffraction theory. The wave propagation within the defined MI far field domain is solved analytically for a single frequency surface relieved grating structure following the Rayleigh-Sommerfeld formulation under the paraxial approximation. It is shown that the far-field electrical field and the intensity interferogram can be calculated using the mode decomposition method. Furthermore, the near-field (propagation distance < 1 mum) assumptions are validated using exact electromagnetic (EM) theory; and the EM fields are simulated in a few microns region above the surface of the diffraction grating. The study shows that there is a strong correlation (correlation factor R = 0.869) of spatial frequency response between EM field and strain field at the nanoscale. Experimentally, a 164 nm/pixel spatial resolution Moire Interferometer with automated full strain field calculation is proposed. Accurate full strain field maps are generated automatically by a combination of phase shifting technique (temporal data redundancy) and Continuous Wavelet Transform (CWT) (spatial data redundancy). A thermal experiment on BGA packaging is used to demonstrate

  9. High-sensitivity high-throughput chip based biosensor array for multiplexed detection of heavy metals

    NASA Astrophysics Data System (ADS)

    Yan, Hai; Tang, Naimei; Jairo, Grace A.; Chakravarty, Swapnajit; Blake, Diane A.; Chen, Ray T.

    2016-03-01

    Heavy metal ions released into the environment from industrial processes lead to various health hazards. We propose an on-chip label-free detection approach that allows high-sensitivity and high-throughput detection of heavy metals. The sensing device consists of 2-dimensional photonic crystal microcavities that are combined by multimode interferometer to form a sensor array. We experimentally demonstrate the detection of cadmium-chelate conjugate with concentration as low as 5 parts-per-billion (ppb).

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. Highly sensitive and unbiased approach for elucidating antibody repertoires.

    PubMed

    Lin, Sherry G; Ba, Zhaoqing; Du, Zhou; Zhang, Yu; Hu, Jiazhi; Alt, Frederick W

    2016-07-12

    Developing B lymphocytes undergo V(D)J recombination to assemble germ-line V, D, and J gene segments into exons that encode the antigen-binding variable region of Ig heavy (H) and light (L) chains. IgH and IgL chains associate to form the B-cell receptor (BCR), which, upon antigen binding, activates B cells to secrete BCR as an antibody. Each of the huge number of clonally independent B cells expresses a unique set of IgH and IgL variable regions. The ability of V(D)J recombination to generate vast primary B-cell repertoires results from a combinatorial assortment of large numbers of different V, D, and J segments, coupled with diversification of the junctions between them to generate the complementary determining region 3 (CDR3) for antigen contact. Approaches to evaluate in depth the content of primary antibody repertoires and, ultimately, to study how they are further molded by secondary mutation and affinity maturation processes are of great importance to the B-cell development, vaccine, and antibody fields. We now describe an unbiased, sensitive, and readily accessible assay, referred to as high-throughput genome-wide translocation sequencing-adapted repertoire sequencing (HTGTS-Rep-seq), to quantify antibody repertoires. HTGTS-Rep-seq quantitatively identifies the vast majority of IgH and IgL V(D)J exons, including their unique CDR3 sequences, from progenitor and mature mouse B lineage cells via the use of specific J primers. HTGTS-Rep-seq also accurately quantifies DJH intermediates and V(D)J exons in either productive or nonproductive configurations. HTGTS-Rep-seq should be useful for studies of human samples, including clonal B-cell expansions, and also for following antibody affinity maturation processes. PMID:27354528

  16. High-intensity xenon plasma discharge lamp for bulk-sensitive high-resolution photoemission spectroscopy

    SciTech Connect

    Souma, S.; Sato, T.; Takahashi, T.; Baltzer, P.

    2007-12-15

    We have developed a highly brilliant xenon (Xe) discharge lamp operated by microwave-induced electron cyclotron resonance (ECR) for ultrahigh-resolution bulk-sensitive photoemission spectroscopy (PES). We observed at least eight strong radiation lines from neutral or singly ionized Xe atoms in the energy region of 8.4-10.7 eV. The photon flux of the strongest Xe I resonance line at 8.437 eV is comparable to that of the He I{alpha} line (21.218 eV) from the He-ECR discharge lamp. Stable operation for more than 300 h is achieved by efficient air-cooling of a ceramic tube in the resonance cavity. The high bulk sensitivity and high-energy resolution of PES using the Xe lines are demonstrated for some typical materials.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Self-concentrating buoyant glass microbubbles for high sensitivity immunoassays.

    PubMed

    Juang, Duane S; Hsu, Chia-Hsien

    2016-02-01

    Here, we report the novel application of a material with self-concentrating properties for enhancing the sensitivity of immunoassays. Termed as glass microbubbles, they are antibody functionalized buoyant hollow glass microspheres that simultaneously float and concentrate into a dense monolayer when dispensed in a liquid droplet. This self-concentrating charactaristic of the microbubbles allow for autonomous signal localization, which translates to a higher sensitivity compared to other microparticle-based immunoassays. We then demonstrated a "microbubble array" platform consisting of the glass microbubbles floating in a microfluidic liquid hemisphere array for performing multiplex immunoassays. PMID:26620967

  2. 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)

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. High-sensitivity and wide-directivity ultrasound detection using high Q polymer microring resonators

    PubMed Central

    Ling, Tao; Chen, Sung-Liang; Guo, L. Jay

    2011-01-01

    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. PMID:21673832

  10. High-sensitivity high-resolution dual-function signal and time digitizer

    NASA Astrophysics Data System (ADS)

    Sarwana, Saad; Gupta, Deepnarayan; Kirichenko, Alex F.; Oku, Takayuki; Otani, Chiko; Sato, Hiromi; Shimizu, Hirohiko M.

    2002-03-01

    We have developed a dual-function high sensitivity/high-resolution digitizer. It consists of a superconducting digital integrated circuit, which can operate both as a time-to-digital converter (TDC) and a flux counting analog-to-digital converter (ADC). The TDC has a 30 ps multihit time resolution. The ADC has been designed with a superconducting quantum interference device based detector for a 1 μA full scale range. This digitizer is extremely useful in many applications, e.g., for time-of-flight measurements, or as a radiation resistant, low-noise, low-power ADC for detector readout.

  11. Further study on highly sensitive AMS measurement of 53Mn

    NASA Astrophysics Data System (ADS)

    Kejun, Dong; Hao, Hu; Xianggao, Wang; Chaoli, Li; Ming, He; Zhenyu, Li; Shaoyong, Wu; Jiancheng, Liu; Guowen, Zheng; Heng, Li; Zhigang, Chen; Guangshan, Liu; Jian, Yuan; Shan, Jiang

    2012-08-01

    The AMS facility at China Institute of Atomic Energy has been equipped with a ΔE-Q3D detection system for the measurements of 53Mn. While the sample material of MnO2 and the extraction ions of MnO- were used previously in AMS measurement of 53Mn with fairly good results, a method has recently been developed with the extraction of MnF- from ion source using MnF2 and MnO2 + PbF2 as sample materials. As a result, a sensitivity of 10-14 (53Mn/Mn) has been achieved. Compared with the original MnO-/MnO2 approach, the method of MnF- extraction, combined with ΔE-Q3D detection technique, demonstrated an improved sensitivity for AMS measurement of 53Mn.

  12. A High Sensitivity Laser-Pumped Cesium Magnetometer

    NASA Astrophysics Data System (ADS)

    Huang, Kai-Kai; Li, Nan; Lu, Xuan-Hui

    2012-10-01

    An atomic magnetometer based on optically detected magnetic resonance is investigated and demonstrated experimentally. We build an 894 nm external cavity diode laser which is frequency locked to the F = 4 → F' = 3 transition of Cs D1 line with DAVLL spectroscopy. With the phase-locked loop, the frequency of the rf coils is actively locked to the Larmor frequency and the magnetometer tracks the magnetic field variations in a phase coherent manner. An ultimate sensitivity of 19 fT/Hz1/2 and an intrinsic sensitivity of 8.6 pT/Hz1/2 in the magnetic environment which is close to geomagnetic field have been achieved with the spatial resolution smaller than 2 cm.

  13. 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.

  14. 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.

  15. 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.

  16. 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…

  17. High Resolution, High Sensitivity Detectors for Molecular Imaging of Small Animals and Tumor Detection

    NASA Astrophysics Data System (ADS)

    Magliozzi, M. L.; Cisbani, E.; Colilli, S.; Cusanno, F.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lo Meo, S.; Lucentini, M.; Santavenere, F.; Veneroni, P.; Schillaci, O.; Simonetti, G.; Majewsky, S.; Cinti, M. N.; de Vincentis, G.; Pani, R.; Pellegrini, R.; Scopinaro, F.

    2006-04-01

    Imaging techniques with radionuclides provide very sensitive measures of a wide range of specific processes underying disease in the body. Detection of very small tumors with high specificity is therefore possible but the tecnique requires both high spatial resolution and high sensitivity. We present the first simulations, performed by means of GEANT4 code, of breast tumors, imaged by different configurations of a compact discrete gamma camera, in order to optimize the performances of dedicated detectors for these tasks. Simulated planar images from 6 to 10 mm diameter tumors, placed at 5 mm from the collimator, were generated for NaI scintillator pixel sizes of 1.0×1.0 and 1.2×1.2 mm2, hexagonal hole Pb collimators with hole size of 1.5 and 1.9 mm. The generated photons have been sampled by two modelled Hamamatsu H8500 and H9500 PMT. Tumor to background uptake ratio from 1:6 to 1:12 has been considered. The preliminary results in terms of spatial resolution and SNR show a slightly better performance of the high efficiency collimator, larger crystal size and H9500 combination.

  18. 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

  19. High-sensitivity capillary and microchip electrophoresis using electrokinetic supercharging.

    PubMed

    Dawod, Mohamed; Chung, Doo Soo

    2011-10-01

    Electrokinetic supercharging (EKS) is considered as one of the most powerful online preconcentration techniques in electrophoresis. It combines the efficient preconcentration power of field-amplified sample injection and the exceptional selective nature of transient isotachophoresis. It has a wide range of applications to different types of analytes ranging from small ions to large proteins and DNA fragments. This comprehensive review--up to date--provides listing for all the works, developments, and advances in EKS. The review will pay particular attention to innovations, new methodologies for manipulation, challenges for improving the detection sensitivity, and various applications of EKS in capillaries and microchips. PMID:21793208

  20. 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.

  1. 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.

  2. 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

  3. A protein multiplex microarray substrate with high sensitivity and specificity

    PubMed Central

    Fici, Dolores A.; McCormick, William; Brown, David W.; Herrmann, John E.; Kumar, Vikram; Awdeh, Zuheir L.

    2010-01-01

    The problems that have been associated with protein multiplex microarray immunoassay substrates and existing technology platforms include: binding, sensitivity, a low signal to noise ratio, target immobilization and the optimal simultaneous detection of diverse protein targets. Current commercial substrates for planar multiplex microarrays rely on protein attachment chemistries that range from covalent attachment to affinity ligand capture, to simple adsorption. In this pilot study, experimental performance parameters for direct monoclonal mouse IgG detection were compared for available two and three dimensional slide surface coatings with a new colloidal nitrocellulose substrate. New technology multiplex microarrays were also developed and evaluated for the detection of pathogen specific antibodies in human serum and the direct detection of enteric viral antigens. Data supports the nitrocellulose colloid as an effective reagent with the capacity to immobilize sufficient diverse protein target quantities for increased specificory signal without compromising authentic protein structure. The nitrocellulose colloid reagent is compatible with the array spotters and scanners routinely used for microarray preparation and processing. More importantly, as an alternate to fluorescence, colorimetric chemistries may be used for specific and sensitive protein target detection. The advantages of the nitrocellulose colloid platform indicate that this technology may be a valuable tool for the further development and expansion of multiplex microarray immunoassays in both the clinical and research laborat environment. PMID:20974147

  4. 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

  5. High precision, high sensitivity distributed displacement and temperature measurements using OFDR-based phase tracking

    NASA Astrophysics Data System (ADS)

    Gifford, Dawn K.; Froggatt, Mark E.; Kreger, Stephen T.

    2011-05-01

    Optical Frequency Domain Reflectometry is used to measure distributed displacement and temperature change with very high sensitivity and precision by measuring the phase change of an optical fiber sensor as a function of distance with high spatial resolution and accuracy. A fiber containing semi-continuous Bragg gratings was used as the sensor. The effective length change, or displacement, in the fiber caused by small temperature changes was measured as a function of distance with a precision of 2.4 nm and a spatial resolution of 1.5 mm. The temperature changes calculated from this displacement were measured with precision of 0.001 C with an effective sensor gauge length of 12 cm. These results demonstrate that the method employed of continuously tracking the phase change along the length of the fiber sensor enables high resolution distributed measurements that can be used to detect very small displacements, temperature changes, or strains.

  6. 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.

  7. 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.

  8. Ultra-high sensitive and high resolution optical coherence tomography using a laser induced electromagnetic dipole

    NASA Astrophysics Data System (ADS)

    Kuroda, Hiroto; Baba, Motoyoshi; Suzuki, Masayuki; Yoneya, Shin

    2013-09-01

    Utilizing an optical coherence tomography measurement, we have developed a technique that actively uses a dielectric response due to an induced dipole moment caused by a mode-locked pulsed laser light source. Irradiated laser light in the material induces a photo-induced electric dipole resulting in a refractive index change for its strong electric field. Using this technique, we obtained a highly sensitive fundus retina tomogram of a human eye in vivo with a resolution of 1.3 μm by single scanning for 20 ms using 8 fs mode-locked pulse laser light with a 350 nm spread spectrum.

  9. 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

  10. 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.

  11. 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. PMID:26014851

  12. 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

  13. 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

  14. Highly sensitive detection of nitroaromatic explosives at discrete nanowire arrays.

    PubMed

    Barry, Sean; Dawson, Karen; Correa, Elon; Goodacre, Royston; O'Riordan, Alan

    2013-01-01

    We show a photolithography technique that permits gold nanowire array electrodes to be routinely fabricated at reasonable cost. Nanowire electrode arrays offer the potential for enhancements in electroanalysis such as increased signal-to-noise ratio and increased sensitivity while also allowing quantitative detection at much lower concentrations. We explore application of nanowire array electrodes to the detection of different nitroaromatic species. Characteristic reduction peaks of nitro groups are not observed at nanowire array electrodes using sweep voltammetric methods. By contrast, clear and well-defined reduction peaks are resolved using potential step square wave voltammetry. A Principle Component Analysis technique is employed to discriminate between nitroaromatic species including structural isomers of DNT. The analysis indicates that all compounds are successfully discriminated by unsupervised cluster analysis. Finally, the magnitude of the reduction peak at -671 mV for different concentrations of TNT exhibited excellent linearity with increasing concentrations enabling sub-150 ng mL(-1) limits of detection. PMID:24466670

  15. High sensitivity infrared 10.6 micrometer heterodyne receiver development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The results are presented for a study on the design of an infrared 10.6-micrometer quantum-noise-limited optical receiver subsystem. Performance measurements of the HgCdTe photomixer preamplifier combination were carried out for photomixer temperatures up to 152 K and a photomixer frequency response of up to 420 MHz was obtained. Results of temperature and bias cycling of HgCdTe photomixers are reported. Design considerations for an operational 10.6 micrometer heterodyne receiver are presented. These consist of design data on required laser LO illumination, heat load levels for photomixer cooler, photomixer uniformity and the effects of photomixer impedance match on receiver sensitivity. Analysis and measurements of 10.6 micrometer heterodyne detection in an extrinsic photoconductive (p-type) HgCdTe photomixer are also presented.

  16. 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

    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.

  17. Metallophthalocyanines as triplet sensitizers for highly efficient photon upconversion based on sensitized triplet-triplet annihilation.

    PubMed

    Han, J L; You, J; Yonemura, H; Yamada, S; Wang, S R; Li, X G

    2016-08-01

    Soluble palladium and platinum phthalocyanines with coumarin moieties were synthesized with Q bands in the red and near-IR regions, in which the molar extinction coefficients were up to 1.01 × 10(5) cm(-1) mol(-1). These metallophthalocyanines were coupled with rubrene and applied in photon upconversion systems based on triplet-triplet annihilation. The highest upconversion efficiency of the palladium phthalocyanine was 5.6%, which is higher than that of the platinum phthalocyanine-rubrene system. The larger molar extinction coefficient resulted in high upconversion capability (>10(5) cm(-1) mol(-1)) and low saturation incident power (<20 mW cm(-2)). PMID:27431880

  18. 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

  19. High-sensitivity in situ QCLAS-based ammonia concentration sensor for high-temperature applications

    NASA Astrophysics Data System (ADS)

    Peng, W. Y.; Sur, R.; Strand, C. L.; Spearrin, R. M.; Jeffries, J. B.; Hanson, R. K.

    2016-07-01

    A novel quantum cascade laser (QCL) absorption sensor is presented for high-sensitivity in situ measurements of ammonia (hbox {NH}_3) in high-temperature environments, using scanned wavelength modulation spectroscopy (WMS) with first-harmonic-normalized second-harmonic detection (scanned WMS-2 f/1 f) to neutralize the effect of non-absorption losses in the harsh environment. The sensor utilized the sQ(9,9) transition of the fundamental symmetric stretch band of hbox {NH}_3 at 10.39 {\\upmu }hbox {m} and was sinusoidally modulated at 10 kHz and scanned across the peak of the absorption feature at 50 Hz, leading to a detection bandwidth of 100 Hz. A novel technique was used to select an optimal WMS modulation depth parameter that reduced the sensor's sensitivity to spectral interference from hbox {H}_2hbox {O} and hbox {CO}_2 without significantly sacrificing signal-to-noise ratio. The sensor performance was validated by measuring known concentrations of hbox {NH}_3 in a flowing gas cell. The sensor was then demonstrated in a laboratory-scale methane-air burner seeded with hbox {NH}_3, achieving a demonstrated detection limit of 2.8 ± 0.26 ppm hbox {NH}_3 by mole at a path length of 179 cm, equivalence ratio of 0.6, pressure of 1 atm, and temperatures of up to 600 K.

  20. High sensitivity of northeastern broadleaf forest trees to water availability

    NASA Astrophysics Data System (ADS)

    Levesque, M.; Pederson, N.; Andreu-Hayles, L.

    2015-12-01

    Temperate deciduous forests of eastern US provide goods and services to millions of people and play a vital role in the terrestrial carbon and hydrological cycles. However, ongoing climate change and increased in CO2 concentration in the atmosphere (ca) are expected to alter growth and gas exchange of trees, and ultimately forest productivity. Still, the magnitude of these effects is unclear. A better comprehension of the species-specific responses to environmental changes will better inform models and managers on the vulnerability and resiliency of these forests. Tree-ring analysis was combined with δ¹³C and δ18O measurements to investigate growth and physiological responses of red oak (Quercus rubra L.) and tulip poplar (Liriodendron tulipifera L.) in northeastern US to changes in water availability and ca for the period 1950-2014. We found very strong correlations between summer climatic water balance (June-August) and isotopic tree-ring series for δ¹³C (r = -0.65 and -0.73), and δ18O (r = -0.59 and -0.70), for red oak and tulip poplar, respectively. In contrast, tree-ring width was less sensitive to summer water availability (r = 0.33-0.39). Prior to the mid 1980s, low water availability resulted in low stomatal conductance, photosynthesis, and growth. Since that period, pluvial conditions occurring in northeastern US have increased stomatal conductance, carbon uptake, and growth of both species. These findings demonstrate that broadleaf trees in this region could be more sensitive to drought than expected. This appears especially true since much of the calibration period looks wet in a multi-centennial perspective. Further, stronger spatial correlations were found between climate data with tree-ring isotopes than with tree-ring width and the geographical area of the observed δ18O-precipitation response (i.e. the area over which correlations are > 0.5) covers most of the northeastern US. Given the good fit between the isotopic time series and water

  1. Highly heat-sensitive luminophor for recording IR radiation

    SciTech Connect

    Zaitsev, L.M.; Martyshova, N.E.; Pospelova, L.A.; Senashenko, M.V.; Timofeev, Yu.P.

    1988-12-01

    The purpose of this study was to develop and predict the properties of a single-phase crystalline phosphor with an extended range of temperature sensitivity. The luminophors ZnS /times/ CdS mentioned above were used as a matrix to synthesize a luminophor of the new type. Substances exhibiting a different temperature dependence - Ag and Eu - were chosen for activation. The choice of the composition of the base made it possible to rely on the fact that the emission bands of both activators will mutually overlap and that a spectrally uniform crystalline phosphor will be obtained. It was shown that the dynamic range of the power density of the recorded IR radiation can be substantially expanded (up to 30). The receiving luminescent screen is made of a single-phase crystalline phosphor ZnS /times/ CdS with Ag, Eu, and Ni with thermal extinction of both centers of luminescence in different temperature regions, making it possible to obtain a series of screens with well-reproducible characteristics.

  2. 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.

  3. Missing Iron-Oxidizing Acidophiles Highly Sensitive to Organic Compounds

    PubMed Central

    Ueoka, Nagayoshi; Kouzuma, Atsushi; Watanabe, Kazuya

    2016-01-01

    The genus Acidithiobacillus includes iron-oxidizing lithoautotrophs that thrive in acidic mine environments. Acidithiobacillus ferrooxidans is a representative species and has been extensively studied for its application to the bioleaching of precious metals. In our attempts to cultivate the type strain of A. ferrooxidans (ATCC 23270T), repeated transfers to fresh inorganic media resulted in the emergence of cultures with improved growth traits. Strains were isolated from the resultant culture by forming colonies on inorganic silica-gel plates. A representative isolate (strain NU-1) was unable to form colonies on agarose plates and was more sensitive to organics, such as glucose, than the type strain of A. ferrooxidans. Strain NU-1 exhibited superior growth traits in inorganic iron media to those of other iron-oxidizing acidithiobacilli, suggesting its potential for industrial applications. A draft genome of NU-1 uncovered unique features in catabolic enzymes, indicating that this strain is not a mutant of the A. ferrooxidans type strain. Our results indicate that the use of inorganic silica-gel plates facilitates the isolation of as-yet-unexamined iron-oxidizing acidithiobacilli from environmental samples and enrichment cultures. PMID:27356527

  4. Multi-residue and multi-class determination of antibiotics in gilthead sea bream (Sparus aurata) by ultra high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Freitas, Andreia; Leston, Sara; Rosa, João; Castilho, Maria da Conceição; Barbosa, Jorge; Rema, Paulo; Pardal, Miguel Ângelo; Ramos, Fernando

    2014-01-01

    This paper describes a method for the determination of 41 antibiotics from seven different classes in gilthead sea bream (Sparus aurata) by ultra-high-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). Sulfonamides, trimethoprim, tetracyclines, macrolides, quinolones, penicillins and chloramphenicol were simultaneously determined. Fourteen procedures for sample treatment were tested and an extraction with acetonitrile and ethylenediaminetetra acetic acid was found to be the best option. The methodology was validated in accordance with Decision 2002/657/EC. Precision in terms of relative standard deviation (RSD) was under 17% for all compounds, and the recoveries ranged from 92% to 111%. CCα and CCβ were determined according to the maximum residue limit or the minimum required performance limit, when necessary. The validation provided evidence that the method was suitable for application in routine analysis for the detection and confirmation of antibiotics in muscle of gilthead sea bream, an important and intensively produced fish in aquaculture. PMID:24512256

  5. 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

  6. Laser-induced breakdown spectroscopy with high detection sensitivity

    NASA Astrophysics Data System (ADS)

    Shen, X. K.; Ling, H.; Lu, Y. F.

    2009-02-01

    Laser-induced breakdown spectroscopy (LIBS) with spatial confinement and LIBS combined with laser-induced fluorescence (LIF) have been investigated to improve the detection sensitivity and selectivity of LIBS. An obvious enhancement in the emission intensity of Al atomic lines was observed when a cylindrical wall was placed to spatially confine the plasma plumes. The maximum enhancement factor for the emission intensity of Al atomic lines was measured to be around 10. Assuming local thermodynamic equilibrium conditions, the plasma temperatures are estimated to be in the range from 4000 to 5800 K. It shows that the plasma temperature increased by around 1000 K when the cylindrical confinement was applied. Fast imaging of the laser-induced Al plasmas shows that the plasmas were compressed into a smaller volume with a pipe presented. LIBS-LIF has been investigated to overcome the matrix effects in LIBS for the detection of trace uranium in solids. A wavelength-tunable laser with an optical parametric oscillator was used to resonantly excite the uranium atoms and ions within the plasma plumes generated by a Q-switched Nd:YAG laser. Both atomic and ionic lines can be selected to detect their fluorescence lines. A uranium concentration of 462 ppm in a glass sample can be detected using this technique at an excitation wavelength of 385.96 nm for resonant excitation of U II and a fluorescence line wavelength of 409.01 nm from U II. The mechanism of spatial confinement effects and the influence of relevant operational parameters of LIBS-LIF are discussed.

  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. A Simple, High-Precision, High-Sensitivity Tracer Assay for N(inf2) Fixation

    PubMed Central

    Montoya, J. P.; Voss, M.; Kahler, P.; Capone, D. G.

    1996-01-01

    We describe a simple, precise, and sensitive experimental protocol for direct measurement of N(inf2) fixation using the conversion of (sup15)N(inf2) to organic N. Our protocol greatly reduces the limit of detection for N(inf2) fixation by taking advantage of the high sensitivity of a modern, multiple-collector isotope ratio mass spectrometer. This instrument allowed measurement of N(inf2) fixation by natural assemblages of plankton in incubations lasting several hours in the presence of relatively low-level (ca. 10 atom%) tracer additions of (sup15)N(inf2) to the ambient pool of N(inf2). The sensitivity and precision of this tracer method are comparable to or better than those associated with the C(inf2)H(inf2) reduction assay. Data obtained in a series of experiments in the Gotland Basin of the Baltic Sea showed excellent agreement between (sup15)N(inf2) tracer and C(inf2)H(inf2) reduction measurements, with the largest discrepancies between the methods occurring at very low fixation rates. The ratio of C(inf2)H(inf2) reduced to N(inf2) fixed was 4.68 (plusmn) 0.11 (mean (plusmn) standard error, n = 39). In these experiments, the rate of C(inf2)H(inf2) reduction was relatively insensitive to assay volume. Our results, the first for planktonic diazotroph populations of the Baltic, confirm the validity of the C(inf2)H(inf2) reduction method as a quantitative measure of N(inf2) fixation in this system. Our (sup15)N(inf2) protocols are comparable to standard C(inf2)H(inf2) reduction procedures, which should promote use of direct (sup15)N(inf2) fixation measurements in other systems. PMID:16535283

  9. Variable high pressure processing sensitivities for GII human noroviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is one of the most promising non-thermal technologies for decontamination of viral pathogens in foods. However, the survival of HuNoVs by HPP is poorly understood because these viruses cann...

  10. 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...

  11. High-sensitivity mass spectrometry with a tandem accelerator

    SciTech Connect

    Henning, W.

    1983-01-01

    The characteristic features of accelerator mass spectrometry are discussed. A short overview is given of the current status of mass spectrometry with high-energy (MeV/nucleon) heavy-ion accelerators. Emphasis is placed on studies with tandem accelerators and on future mass spectrometry of heavier isotopes with the new generation of higher-voltage tandems.

  12. Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells

    NASA Astrophysics Data System (ADS)

    Tan, Juntao; Yang, Nuo; Hu, Zixi; Su, Jing; Zhong, Jianhong; Yang, Yang; Yu, Yating; Zhu, Jianmeng; Xue, Dabin; Huang, Yingying; Lai, Zongqiang; Huang, Yong; Lu, Xiaoling; Zhao, Yongxiang

    2016-06-01

    A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells.

  13. Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells.

    PubMed

    Tan, Juntao; Yang, Nuo; Hu, Zixi; Su, Jing; Zhong, Jianhong; Yang, Yang; Yu, Yating; Zhu, Jianmeng; Xue, Dabin; Huang, Yingying; Lai, Zongqiang; Huang, Yong; Lu, Xiaoling; Zhao, Yongxiang

    2016-12-01

    A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells. PMID:27299653

  14. Highly stable and sensitive glucose biosensor based on covalently assembled high density Au nanostructures.

    PubMed

    Si, Peng; Kannan, Palanisamy; Guo, Longhua; Son, Hungsun; Kim, Dong-Hwan

    2011-05-15

    We describe the development of a highly stable and sensitive glucose biosensor based on the nanohybrid materials derived from gold nanoparticles (AuNPs) and multi-walled carbon nanotubes (MWCNT). The biosensing platform was developed by using layer-by-layer (LBL) self-assembly of the nanohybrid materials and the enzyme glucose oxidase (GOx). A high density of AuNPs and MWCNT nanocomposite materials were constructed by alternate self assembly of thiol functionalized MWCNTs and AuNPs, followed by chemisoption of GOx. The surface morphology of multilayered AuNPs/MWCNT structure was characterized by field emission-scanning electron microscope (FE-SEM), and the surface coverage of AuNPs was investigated by cyclic voltammetry (CV), showing that 5 layers of assembly achieves the maximum particle density on electrode. The immobilization of GOx was monitored by electrochemical impedance spectroscopy (EIS). CV and amperometry methods were used to study the electrochemical oxidation of glucose at physiological pH 7.4. The Au electrode modified with five layers of AuNPs/MWCNT composites and GOx exhibited an excellent electrocatalytic activity towards oxidation of glucose, which presents a wide liner range from 20 μM to 10 mM, with a sensitivity of 19.27 μA mM(-1) cm(-2). The detection limit of present modified electrode was found to be 2.3 μM (S/N=3). In addition, the resulting biosensor showed a faster amperometric current response (within 3 s) and low apparent Michaelis-Menten constant (K(m)(app)). Our present study shows that the high density of AuNPs decorated MWCNT is a promising nanohybrid material for the construction of enzyme based electrochemical biosensors. PMID:21454070

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. High-speed asynchronous optical sampling for high-sensitivity detection of coherent phonons

    NASA Astrophysics Data System (ADS)

    Dekorsy, T.; Taubert, R.; Hudert, F.; Schrenk, G.; Bartels, A.; Cerna, R.; Kotaidis, V.; Plech, A.; Köhler, K.; Schmitz, J.; Wagner, J.

    2007-12-01

    A new optical pump-probe technique is implemented for the investigation of coherent acoustic phonon dynamics in the GHz to THz frequency range which is based on two asynchronously linked femtosecond lasers. Asynchronous optical sampling (ASOPS) provides the performance of on all-optical oscilloscope and allows us to record optically induced lattice dynamics over nanosecond times with femtosecond resolution at scan rates of 10 kHz without any moving part in the set-up. Within 1 minute of data acquisition time signal-to-noise ratios better than 107 are achieved. We present examples of the high-sensitivity detection of coherent phonons in superlattices and of the coherent acoustic vibration of metallic nanoparticles.

  20. Dynamics and sensitivity analysis of high-frequency conduction block

    NASA Astrophysics Data System (ADS)

    Ackermann, D. Michael; Bhadra, Niloy; Gerges, Meana; Thomas, Peter J.

    2011-10-01

    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) depolarizing currents promote conduction block via inactivation of sodium channels and (2) 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

  1. Highly sensitive passive radio frequency identification based sensor systems

    NASA Astrophysics Data System (ADS)

    Wissenwasser, J.; Vellekoop, M.; Heer, R.

    2010-02-01

    A novel platform for sensor applications based on radio frequency (rf) identification technology, where passive tags are powered by the rf-field of a reader, is presented. The sophisticated energy harvesting system of the tag enables a blanking of the rf-field for a defined period, while supplying the tag electronics with a highly stable voltage and a power of 25 mW for 100 ms. During this time, span measurements can be performed without interferences of the rf-field. The presented tags work without batteries and are designed for impedance measurements on microbiological cell cultures under physiological relevant conditions as well as in harsh environments.

  2. Highly sensitive passive radio frequency identification based sensor systems.

    PubMed

    Wissenwasser, J; Vellekoop, M; Heer, R

    2010-02-01

    A novel platform for sensor applications based on radio frequency (rf) identification technology, where passive tags are powered by the rf-field of a reader, is presented. The sophisticated energy harvesting system of the tag enables a blanking of the rf-field for a defined period, while supplying the tag electronics with a highly stable voltage and a power of 25 mW for 100 ms. During this time, span measurements can be performed without interferences of the rf-field. The presented tags work without batteries and are designed for impedance measurements on microbiological cell cultures under physiological relevant conditions as well as in harsh environments. PMID:20192517

  3. Purification of ethanol for highly sensitive self-assembly experiments

    PubMed Central

    Barbe, Kathrin; Kind, Martin; Pfeiffer, Christian

    2014-01-01

    Summary Ethanol is the preferred solvent for the formation of self-assembled monolayers (SAMs) of thiolates on gold. By applying a thin film sensor system, we could demonstrate that even the best commercial qualities of ethanol contain surface-active contaminants, which can compete with the desired thiolates for surface sites. Here we present that gold nanoparticles deposited onto zeolite X can be used to remove these contaminants by chemisorption. This nanoparticle-impregnated zeolite does not only show high capacities for surface-active contaminants, such as thiols, but can be fully regenerated via a simple pyrolysis protocol. PMID:25161861

  4. 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

  5. Porous tungsten oxide nanoflakes for highly alcohol sensitive performance

    NASA Astrophysics Data System (ADS)

    Xiao, J.; Liu, P.; Liang, Y.; Li, H. B.; Yang, G. W.

    2012-10-01

    Porous tungsten oxide (WO3) nanoflakes have been synthesized by a simple and green approach in an ambient environment. As a precursor solution a polycrystalline hydrated tungstite (H2WO4.H2O) nanoparticles colloid was first prepared by pulsed-laser ablation of a tungsten target in water. The H2WO4.H2O nanoflakes were produced by 72 h aging treatment at room temperature. Finally, porous WO3 nanoflakes were synthesized by annealing at 800 °C for 4 h. Considering the large surface-to-volume ratio of porous nanoflakes, a porous WO3 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.

  6. 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

  7. A novel high resolution, high sensitivity SPECT detector for molecular imaging of cardiovascular diseases

    NASA Astrophysics Data System (ADS)

    Cusanno, F.; Argentieri, A.; Baiocchi, M.; Colilli, S.; Cisbani, E.; De Vincentis, G.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M. L.; Majewski, S.; Marano, G.; Musico, P.; Musumeci, M.; Santavenere, F.; Torrioli, S.; Tsui, B. M. W.; Vitelli, L.; Wang, Y.

    2010-05-01

    Cardiovascular diseases are the most common cause of death in western countries. Understanding the rupture of vulnerable atherosclerotic plaques and monitoring the effect of innovative therapies of heart failure is of fundamental importance. A flexible, high resolution, high sensitivity detector system for molecular imaging with radionuclides on small animal models has been designed for this aim. A prototype has been built using tungsten pinhole and LaBr3(Ce) scintillator coupled to Hamamatsu Flat Panel PMTs. Compact individual-channel readout has been designed, built and tested. Measurements with phantoms as well as pilot studies on mice have been performed, the results show that the myocardial perfusion in mice can be determined with sufficient precision. The detector will be improved replacing the Hamamatsu Flat Panel with Silicon Photomultipliers (SiPMs) to allow integration of the system with MRI scanners. Application of LaBr3(Ce) scintillator coupled to photosensor with high photon detection efficiency and excellent energy resolution will allow dual-label imaging to monitor simultaneously the cardiac perfusion and the molecular targets under investigation during the heart therapy.

  8. 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.

  9. Stretchable and highly sensitive graphene-on-polymer strain sensors

    PubMed Central

    Li, Xiao; Zhang, Rujing; Yu, Wenjian; Wang, Kunlin; Wei, Jinquan; Wu, Dehai; Cao, Anyuan; Li, Zhihong; Cheng, Yao; Zheng, Quanshui; Ruoff, Rodney S.; Zhu, Hongwei

    2012-01-01

    The use of nanomaterials for strain sensors has attracted attention due to their unique electromechanical properties. However, nanomaterials have yet to overcome many technological obstacles and thus are not yet the preferred material for strain sensors. In this work, we investigated graphene woven fabrics (GWFs) for strain sensing. Different than graphene films, GWFs undergo significant changes in their polycrystalline structures along with high-density crack formation and propagation mechanically deformed. The electrical resistance of GWFs increases exponentially with tensile strain with gauge factors of ~103 under 2~6% strains and ~106 under higher strains that are the highest thus far reported, due to its woven mesh configuration and fracture behavior, making it an ideal structure for sensing tensile deformation by changes in strain. The main mechanism is investigated, resulting in a theoretical model that predicts very well the observed behavior. PMID:23162694

  10. (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.

  11. 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.

  12. 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

  13. 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…

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. High-resolution and high-sensitivity tephra-inferred fingerprints in stalagmite geochemistry

    NASA Astrophysics Data System (ADS)

    Wu, Chung-Che; Burger, Marcel; Günther, Detlef; Hattendorf, Bodo; Shen, Chuan-Chou

    2016-04-01

    High-resolution and high-sensitivity rare earth elements (REEs) profiles of Holocene stalagmites collected from East Timor (8° 47' S, 126° 23' E) provide detailed fluctuation information which can be inferred to super volcano eruptions. Since REEs are enriched in igneous rocks (~ μg/g) but depleted in carbonates (~ ng/g to pg/g), REEs preserved in stalagmites are acted as an ideal proxy of tephra-inferred signature; however, due to the low REE abundances in most natural stalagmite samples (1-100s ng/g), overall applicability has been sharply limited. Here we develop and apply an improved LA-GED-ICPMS methodology to determine REEs in such low concentration stalagmites. Two pronounced REE peaks occur where their concentrations sharply increased by 1-2 order of magnitudes, from 10s of ng/g to 100s of ng/g. This event was dated at 80 thousand years ago by U-Th methods. Nevertheless, the accurate timing of this REE anomalous event should be examined carefully. Also more multi-proxies evidences such as stable isotopes δ13C, δ18O, and S isotope, should be provided in the future.

  19. Development of a 300,000-pixel ultrahigh-speed high-sensitivity CCD

    NASA Astrophysics Data System (ADS)

    Ohtake, H.; Hayashida, T.; Kitamura, K.; Arai, T.; Yonai, J.; Tanioka, K.; Maruyama, H.; Etoh, T. Goji; Poggemann, D.; Ruckelshausen, A.; van Kuijk, H.; Bosiers, Jan T.

    2006-02-01

    We are developing an ultrahigh-speed, high-sensitivity broadcast camera that is capable of capturing clear, smooth slow-motion videos even where lighting is limited, such as at professional baseball games played at night. In earlier work, we developed an ultrahigh-speed broadcast color camera1) using three 80,000-pixel ultrahigh-speed, highsensitivity CCDs2). This camera had about ten times the sensitivity of standard high-speed cameras, and enabled an entirely new style of presentation for sports broadcasts and science programs. Most notably, increasing the pixel count is crucially important for applying ultrahigh-speed, high-sensitivity CCDs to HDTV broadcasting. This paper provides a summary of our experimental development aimed at improving the resolution of CCD even further: a new ultrahigh-speed high-sensitivity CCD that increases the pixel count four-fold to 300,000 pixels.

  20. 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...

  1. Interoceptive threat leads to defensive mobilization in highly anxiety sensitive persons.

    PubMed

    Melzig, Christiane A; Holtz, Katharina; Michalowski, Jaroslaw M; Hamm, Alfons O

    2011-06-01

    To study defensive mobilization elicited by the exposure to interoceptive arousal sensations, we exposed highly anxiety sensitive students to a symptom provocation task. Symptom reports, autonomic arousal, and the startle eyeblink response were monitored during guided hyperventilation and a recovery period in 26 highly anxiety sensitive persons and 22 controls. Normoventilation was used as a non-provocative comparison condition. Hyperventilation led to autonomic arousal and a marked increase in somatic symptoms. While high and low anxiety sensitive persons did not differ in their defensive activation during hyperventilation, group differences were detected during early recovery. Highly anxiety sensitive students exhibited a potentiation of startle response magnitudes and increased autonomic arousal after hyper- as compared to after normoventilation, indicating defensive mobilization evoked by the prolonged presence of feared somatic sensations. PMID:21073480

  2. 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 80°C 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

  3. Impact sensitivity of materials in contact with liquid and gaseous oxygen at high pressure

    NASA Technical Reports Server (NTRS)

    Schwinghamer, R. J.

    1972-01-01

    As a result of the Apollo 13 incident, increased emphasis is being placed on materials compatibility in a high pressure GOX environment. It is known that in addition to impact sensitivity of materials, approximately adiabatic compression conditions can contrive to induce materials reactivity. Test runs at high pressure using the ABMA tester indicate the following: (1) The materials used in the tests showed an inverse relationship between thickness and impact sensitivity. (2) Several materials tested exhibited greater impact sensitivity in GOX than in LOX. (3) The impact sensitivity of the materials tested in GOX, at the pressures tested, showed enhanced impact sensitivity with higher pressure. (4) The rank ordering of the materials tested in LOX up to 1000 psia is the same as the rank ordering resulting from tests in LOX at 14.7 psia.

  4. Human cortical sensitivity to interaural level differences in low- and high-frequency sounds.

    PubMed

    Salminen, Nelli H

    2015-02-01

    Interaural level difference (ILD) is used as a cue in horizontal sound source localization. In free field, the magnitude of ILD depends on frequency: it is more prominent at high than low frequencies. Here, a magnetoencephalography experiment was conducted to test whether the sensitivity of the human auditory cortex to ILD is also frequency-dependent. Robust cortical sensitivity to ILD was found that could not be explained by monaural level effects, but this sensitivity did not differ between low- and high-frequency stimuli. This is consistent with previous psychoacoustical investigations showing that performance in ILD discrimination is not dependent on frequency. PMID:25698049

  5. High-sensitive and broad-dynamic-range quantitative phase imaging with spectral domain phase microscopy.

    PubMed

    Yan, Yangzhi; Ding, Zhihua; Shen, Yi; Chen, Zhiyan; Zhao, Chen; Ni, Yang

    2013-11-01

    Spectral domain phase microscopy for high-sensitive and broad-dynamic-range quantitative phase imaging is presented. The phase retrieval is realized in the depth domain to maintain a high sensitivity, while the phase information obtained in the spectral domain is exploited to extend the dynamic range of optical path difference. Sensitivity advantage of phase retrieved in the depth domain over that in the spectral domain is thoroughly investigated. The performance of the proposed depth domain phase based approach is illustrated by phase imaging of a resolution target and an onion skin. PMID:24216799

  6. Toward high-sensitivity and high-resolution submillimeter-wave video imaging

    NASA Astrophysics Data System (ADS)

    Heinz, Erik; May, Torsten; Born, Detlef; Zieger, Gabriel; Thorwirth, Günter; Anders, Solveig; Zakosarenko, Vyacheslav; Krause, Torsten; Krüger, André; Schulz, Marco; Meyer, Hans-Georg; Schubert, Marco; Starkloff, Michael

    2011-11-01

    Against a background of newly emerged security threats, the well-established idea of utilizing submillimeter-wave radiation for personal security screening applications has recently evolved into a promising technology. Possible application scenarios demand sensitive, fast, flexible and high-quality imaging techniques. At present, best results are obtained by passive imaging using cryogenic microbolometers as radiation detectors. Building upon the concept of a passive submillimeter-wave stand-off video camera introduced previously, we present the evolution of this concept into a practical application-ready imaging device. This has been achieved using a variety of measures such as optimizing the detector parameters, improving the scanning mechanism, increasing the sampling speed, and enhancing the image generation software. The camera concept is based on a Cassegrain-type mirror optics, an optomechanical scanner, an array of 20 superconducting transition-edge sensors operated at a temperature of 450 to 650 mK, and a closed-cycle cryogen-free cooling system. The main figures of the system include: a frequency band of 350+/-40 GHz, an object distance of 7 to 10 m, a circular field of view of 1.05 m diameter, and a spatial resolution in the image center of 2 cm at 8.5 m distance, a noise equivalent temperature difference of 0.1 to 0.4 K, and a maximum frame rate of 10 Hz.

  7. Slow light engineering for high Q high sensitivity photonic crystal microcavity biosensors in silicon

    PubMed Central

    Chakravarty, Swapnajit; Zou, Yi; Lai, Wei-Cheng; Chen, Ray T.

    2012-01-01

    Current trends in photonic crystal microcavity biosensors in silicon-on-insulator (SOI), that focus on small and smaller sensors have faced a bottleneck trying to balance two contradictory requirements of resonance quality factor and sensitivity. By simultaneous control of the radiation loss and optical mode volumes, we show that both requirements can be satisfied simultaneously. Microcavity sensors are designed in which resonances show highest Q ~9,300 in the bio-ambient phosphate buffered saline (PBS) as well as highest sensitivity among photonic crystal biosensors. We experimentally demonstrated mass sensitivity 8.8 atto-grams with sensitivity per unit area of 0.8 picograms/mm2 Highest sensitivity, irrespective of the dissociation constant Kd, is demonstrated among all existing label-free optical biosensors in silicon at the concentration of 0.1μg/ml. PMID:22748964

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Variable sensitivity of US maize yield to high temperatures across developmental stages

    NASA Astrophysics Data System (ADS)

    Butler, E. E.; Huybers, P. J.

    2013-12-01

    The sensitivity of maize to high temperatures has been widely demonstrated. Furthermore, field work has indicated that reproductive development stages are particularly sensitive to stress, but this relationship has not been quantified across a wide geographic region. Here, the relationship between maize yield and temperature variations is examined as a function of developmental stage. US state-level data from the National Agriculture Statistics Service provide dates for six growing stages: planting, silking, doughing, dented, mature, and harvested. Temperatures that correspond to each developmental stage are then inferred from a network of weather station observations interpolated to the county level, and a multiple linear regression technique is employed to estimate the sensitivity of county yield outcomes to variations in growing-degree days and an analogous measure of high temperatures referred to as killing-degree days. Uncertainties in the transition times between county-level growth stages are accounted for. Results indicate that the silking and dented stages are generally the most sensitive to killing degree days, with silking the most sensitive stage in the US South and dented the most sensitive in the US North. These variable patterns of sensitivity aid in interpreting which weather events are of greatest significance to maize yields and provide some insight into how shifts in planting time or changes in developmental timing would influence the risks associated with exposure to high temperatures.

  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 and reconfigurable fiber optic current sensor by optical recirculating in a fiber loop.

    PubMed

    Du, Jiangbing; Tao, Yemeng; Liu, Yinping; Ma, Lin; Zhang, Wenjia; He, Zuyuan

    2016-08-01

    An advanced fiber optic current sensor (FOCS) is proposed based on recirculating fiber loop architecture for significantly enhancing the current sensitivity. The recirculating loop is constructed by a 2X2 optical switch and the standard single mode fiber (SSMF) is used as the sensing head. The proposed FOCS is coupler-free with low insertion loss which results in a significantly improved current sensitivity. We experimentally obtained a sensitivity of 11.5 degrees/A for 1-Km SSMF FOCS and a sensitivity of 21.2 degrees/A for 500-m SSMF FOCS, both of which have been enhanced by more than ten times. The flexible switch control of recirculating can support the FOCS to work for different current scenarios with the same system and thus reconfigurable operation of the FOCS has been achieved. The significantly enhanced high sensitivity with reconfigurable operation capability makes the proposed FOCS a promising method for practical applications. PMID:27505765

  15. 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

  16. 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

  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. Towards high-sensitivity and high-resolution submillimeter-wave video imaging

    NASA Astrophysics Data System (ADS)

    Heinz, Erik; May, Torsten; Born, Detlef; Zieger, Gabriel; Anders, Solveig; Zakosarenko, Viatcheslav; Schubert, Marco; Krause, Torsten; Krüger, André; Schulz, Marco; Meyer, Hans-Georg

    2011-05-01

    Against a background of newly emerged security threats the well-established idea of utilizing submillimeter-wave radiation for personal security screening applications has recently evolved into a promising technology. Possible application scenarios demand sensitive, fast, flexible and high-quality imaging techniques. At present, best results are obtained by passive imaging using cryogenic microbolometers as radiation detectors. Building upon the concept of a passive submillimeter-wave stand-off video camera introduced previously, we present the evolution of this concept in a practical application-ready imaging device. This has been achieved using a variety of measures such as optimizing the detector parameters, improving the scanning mechanism, increasing the sampling speed, and enhancing the camera software. The image generation algorithm has been improved and an automatic sensor calibration technique has been implemented taking advantage of redundancy in the sensor data. The concept is based on a Cassegrain-type mirror optics, an opto-mechanical scanner providing spiraliform scanning traces, and an array of 20 superconducting transition-edge sensors (TES) operated at a temperature of 450-650 mK. The TES are cooled by a closed-cycle cooling system and read out by superconducting quantum interference devices (SQUIDs). The frequency band of operation centers around 350 GHz. The camera can operate at an object distance of 7-10 m. At 9m distance it covers a field of view of 110 cm diameter, achieves a spatial resolution of 2 cm and a pixel NETD (noise equivalent temperature difference) of 0.1-0.4 K. The maximum frame rate is 10 frames per second.

  19. 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 388 nm/Refractive Index Unit. The resonant wavelength is sensitive to background temperature by 18.5 pm/°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

  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. Polycrystalline CVD diamond detector: Fast response and high sensitivity with large area

    SciTech Connect

    Liu, Linyue Zhang, Xianpeng; Zhong, Yunhong; Ouyang, Xiaoping Zhang, Jianfu

    2014-01-15

    Polycrystalline diamond was successfully used to fabricate a large area (diameter up to 46 mm) radiation detector. It was proven that the developed detector shows a fast pulsed response time and a high sensitivity, therefore its rise time is lower than 5 ns, which is two times faster than that of a Si-PIN detector of the same size. And because of the large sensitive area, this detector shows good dominance in fast pulsed and low density radiation detection.

  2. High-sensitivity Fabry-Perot interferometric pressure sensor based on a nanothick silver diaphragm.

    PubMed

    Xu, Feng; Ren, Dongxu; Shi, Xiaolong; Li, Can; Lu, Weiwei; Lu, Lu; Lu, Liang; Yu, Benli

    2012-01-15

    We present a fiber-optic extrinsic Fabry-Perot interferometer pressure sensor based on a nanothick silver diaphragm. The sensing diaphragm, with a thickness measured in a few hundreds of nanometers, is fabricated by the electroless plating method, which provides a simple fabrication process involving a high-quality diaphragm at a low cost. The sensor exhibits a relatively linear response within the pressure variation range of 0-50 kPa, with a high pressure sensitivity of 70.5 nm/kPa. This sensor is expected to have potential applications in the field of highly sensitive pressure sensors. PMID:22854444

  3. Application of ordered mesoporous carbon in solid phase microextraction for fast mass transfer and high sensitivity.

    PubMed

    Zheng, Juan; Wang, Kun; Liang, Yeru; Zhu, Fang; Wu, Dingcai; Ouyang, Gangfeng

    2016-05-21

    Due to unique high-surface-area ordered mesoporous channels interconnected with 3D network-like mesopores and π-π interactions between carbon frameworks and analytes, the as-prepared ordered mesoporous carbon-coated fiber exhibited a large adsorption amount, fast mass transport and high sensitivity. PMID:27137527

  4. 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.

  5. 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

  6. 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.

  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. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. Photon Counting System for High-Sensitivity Detection of Bioluminescence at Optical Fiber End.

    PubMed

    Iinuma, Masataka; Kadoya, Yutaka; Kuroda, Akio

    2016-01-01

    The technique of photon counting is widely used for various fields and also applicable to a high-sensitivity detection of luminescence. Thanks to recent development of single photon detectors with avalanche photodiodes (APDs), the photon counting system with an optical fiber has become powerful for a detection of bioluminescence at an optical fiber end, because it allows us to fully use the merits of compactness, simple operation, highly quantum efficiency of the APD detectors. This optical fiber-based system also has a possibility of improving the sensitivity to a local detection of Adenosine triphosphate (ATP) by high-sensitivity detection of the bioluminescence. In this chapter, we are introducing a basic concept of the optical fiber-based system and explaining how to construct and use this system. PMID:27424915

  16. 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.

  17. Human cortical sensitivity to interaural time difference in high-frequency sounds.

    PubMed

    Salminen, Nelli H; Altoè, Alessandro; Takanen, Marko; Santala, Olli; Pulkki, Ville

    2015-05-01

    Human sound source localization relies on various acoustical cues one of the most important being the interaural time difference (ITD). ITD is best detected in the fine structure of low-frequency sounds but it may also contribute to spatial hearing at higher frequencies if extracted from the sound envelope. The human brain mechanisms related to this envelope ITD cue remain unexplored. Here, we tested the sensitivity of the human auditory cortex to envelope ITD in magnetoencephalography (MEG) recordings. We found two types of sensitivity to envelope ITD. First, the amplitude of the auditory cortical N1m response was smaller for zero envelope ITD than for long envelope ITDs corresponding to the sound being in opposite phase in the two ears. Second, the N1m response amplitude showed ITD-specific adaptation for both fine-structure and for envelope ITD. The auditory cortical sensitivity was weaker for envelope ITD in high-frequency sounds than for fine-structure ITD in low-frequency sounds but occurred within a range of ITDs that are encountered in natural conditions. Finally, the participants were briefly tested for their behavioral ability to detect envelope ITD. Interestingly, we found a correlation between the behavioral performance and the neural sensitivity to envelope ITD. In conclusion, our findings show that the human auditory cortex is sensitive to ITD in the envelope of high-frequency sounds and this sensitivity may have behavioral relevance. PMID:25668126

  18. High temperature sensitivity is intrinsic to voltage-gated potassium channels.

    PubMed

    Yang, Fan; Zheng, Jie

    2014-01-01

    Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors. PMID:25030910

  19. High temperature sensitivity is intrinsic to voltage-gated potassium channels

    PubMed Central

    Yang, Fan; Zheng, Jie

    2014-01-01

    Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors. DOI: http://dx.doi.org/10.7554/eLife.03255.001 PMID:25030910

  20. Effect of particle size in the TL response of natural quartz sensitized with high gamma dose

    NASA Astrophysics Data System (ADS)

    Carvalho, A. B., Jr.; Guzzo, P. L.; Sullasi, H. L.; Khoury, H. J.

    2010-11-01

    The aim of this study is to investigate the effect of particle size in the thermoluminescence (TL) response of natural quartz sensitized with high gamma dose. For this, fragments of a single crystal taken from the Solonópole district (Brazil) were crushed and classified into ten size fractions ranging from 38 μm to 5 mm. Aliquots of each size fraction were sensitized with 25 kGy of gamma dose of 60Co and heat-treated in a muffle furnace at 400oC. The non-sensitized samples were exposed to test doses between 50 Gy and 5 kGy and the sensitized samples were exposed to a unique test dose equal to 50 mGy. For non-sensitized samples, the TL peak near 325 °C increases with the particle size decreasing. However, in the case of sensitized samples, the TL output near 280 °C increases with the increasing of particle size up to mean grain size equal to 308 μm. Above 308 μm, an abrupt reduction in the TL intensity was noticed. These effects are discussed in relation to the specific surface area and the different interaction of high gamma doses with fine and coarse particles of quartz.